EUROPEAN FEDERATION OF BIOTECHNOLOGY
SERVING BIOTECHNOLOGISTS IN EVERY COUNTRY OF THE CONTINENT OF EUROPE
WORKING PARTY ON SAFETY IN BIOTECHNOLOGY

A Strengthened

Biological and Toxin Weapons Convention

Potential Implications for Biotechnology

28. - 29. May 1998

Institute of Applied Microbiology

University for Agricultural Science

Vienna, Austria

International information and discussion forum on the potential implications for biotechnology [research and production] of the legally binding protocol being negotiated to strengthen the BTWC.

Organizers:

Working Party Safety in Biotechnology of the European Federation Biotechnology (EFB)

Institute for Applied Microbiology of the University of Agricultural Sciences, Vienna

Austrian Federal Ministry for Foreign Affairs and the Austrian Federal Ministry for Economic Affairs

Organizing Committee:

Otto Doblhoff-Dier, EFB WP Safety in Biotechnology

Bernhard Kainradl, Austrian Federal Ministry for Economic Affairs

Willy Kempel, Austrian Federal Ministry of Foreign Affairs

Graham S. Pearson, University of Bradford, UK

Program

THURSDAY

08:30 - 10:00

Registration

10:00-10:15

Opening Ceremony

10:15 - 10:45

Biological and toxin weapons: Introduction and overview

Dr. Brad Roberts, Institute for Defense Analyses, Washington,DC, USA ( Editor, "Biological Weapons: Weapons of the Future")

10:45 - 11:15

The Biological and Toxin Weapons Convention- A historic and political perspective

Willy Kempel, Ministry of Foreign Affairs, Austria

11:15 - 11:45

UNSCOM : Lessons for Biological Arms Control arising from the experience of the UN Special Commission on Iraq (UNSCOM)

Johannes Rath, UNSCOM Chief Inspector, University Vienna, Austria

11:45 - 12:15

The current status of the Geneva negotiations on the protocol to strengthen the BTWC

Tibor Toth, Chairman Ad Hoc Groupof the States Parties to the BTWC, Hungary

12:15 - 14:00

Lunch and

Tutorial: Biosafety information on the Internet

14:00 - 14:30

The Chemical Weapons Convention (CWC) verification regime: Implications for Biotechnology

Julian Perry Robinson, Director Havard Sussex Program on CBW Armament and Arms Limitation, Science Policy Research Unit, University of Sussex - Lecture was held by Graham S. Pearson

14:30 - 15:15

The likely practical aspects of the strengthened BWTC protocol

Graham S. Pearson, Visiting Professor of International Security, University of Bradford, former Director General and Chief Executive of the UK Chemical and Biological Defence Establishment at Porton Down

15:15 - 15:45

Coffee Break

15:45 - 16:30

Plenary Discussion - Introductory Statements

Implications for biotechnology

Malcolm Dando, Professor of International Security,

Department of Peace Studies, University of Bradford, UK

Implications for academic R&D

O. Doblhoff-Dier, Chairman WP Safety in

Biotechnology of the European Federation Biotechnology, Inst. for Applied Microbiology, Austria

Implications for industrial operations

Helmut Bachmayer, Cooporate Biosafety, Novartis

Meeting U.S. Industry Concerns within a Strong BTWC Compliance Regime

Lynn C. Klotz, Ph. D. Federation of American Scientists Working Group on BW Verification

16: 30 - 17:00

Plenary discussion

FRIDAY

09:00 - 09:30

Comparison of the strengthened BTWC protocol with other regulatory systems

Rudolf Bliem, Tarac Consulting, Consultant for the Bioindustries specializing on FDA and European approvals

09:30 - 10:00

The EC Biosafety Regulations

David Bosworth, European Commission, Brussels

10:00 - 10:30

The US Biological Safety and Requirements for Facilities Transferring or Receiving Select Agents

Jonathan Y. Richmond, Director, Office of Health and Safety, Centers for Disease Control and Prevention,

10:30 - 11:00

Coffee break

11:00 - 11:30

The Biosafety Regulations in the fromer Eastern Block Contries

George Tzotzos, UNIDO Biotechnology Network and Advisory Service, Vienna

11:30 - 12:00

The Convention on Biological Diversity: Possible implications of the International Biosafety / Advance Informed Agreement Protocol

Mr P J Van der Meer, Ministry of Housing, Spatial Planning and the Environment, The Netherlands

12:00 - 13:45

Lunch

and

Tutorial: Biosafety information on the Internet

13:45 -14:30

Biotechnology Controls: What are the technical requirements? Protective equipment and containment validation, documentation, storage and access control, identification of pathogens and pathogenic characteristics

Howard Tranter, CAMR, UK

14:30 - 15:00

Maintaining awareness of developments in biosafety

regulations and controls

O. Doblhoff

15:00 - 15:45

Closing Statement and Discussion:

International harmonisation of biosafety protocols

Biological and toxin weapons: Introduction and overview
Brad Roberts, Institute for Defense Analyses, Washington,DC, USA

ABSRACT:

For much of the 20th century the threat of biological warfare has been given a low priority by policymakers and others concerned with international security. Looking to the past, many analysts have dismissed biological weapons as virtually unknown in the experience of modern warfare and as having little or no military utility. But looking to the future, there is a growing fear of the impact of proliferation and biotechnology--of the possibility that the 21st century could see the much broader acquisition and use of such weapons. This fear motivates policymakers to do what they can in the present to strengthen controls over biological weapons. Key aspects of the BW problem include the following.

First, biological weapons have proliferated in recent years. When the Biological and Toxin Weapons Convention (BTWC) entered into force in 1975, it was generally believed that only one or two countries other than the two superpowers had such weapons. Today, approximately a dozen countries are believed to possess such weapons, or to be actively seeking them. Reportedly, these countries are located in the Middle East, South Asia, and East Asia. The continuing revelations about the biological arsenal of Iraq are a wake-up call about the sophistication of proliferator programs and the risks that will confront international coalitions responding to acts of aggression by BW-armed states. The global diffusion of biotechnologies means that virtually every country of the world has the means to produce advanced biological weapons.

Second, the BW problem is not just a proliferation problem. Russian President Boris Yeltsin has acknowledged that the USSR never complied with its treaty obligations to destroy its BW arsenal. Moreover, he reported his own difficulties in closing down the vestiges of the old program. Strong doubts remain about ongoing work on Russian BW facilities, with recent defectors illuminating the pernicious exploitation of biotechnology to engineer advanced biological weapons. China too is frequently charged with being in violation of the BTWC. It is important to note that the United States, Britain, and France all abandoned biological weapons during the Cold War.

Third, non-state actors--terrorists--are increasingly interested in biological warfare agents. The Japanese/Russian sect Aum Shinrikyo experimented with anthrax and botulinum toxin before turning to the nerve agent Sarin. Militia groups in the United States are known to be experimenting with BW agents. Transnational criminal organizations have reportedly hired out BW expertise to terrorist groups.

The BTWC has served as a useful expression of the international norm against biological warfare. It has codified restraint shown by most of the nations of the world. But it has not proven to be particularly effective at restraining proliferation, disarming known BW possessors, or inhibiting terrorist interest. If the anti-BW legal regime is to remain viable for the future, it must be strengthened. The costs and risks associated with specific measures to strengthen the treaty must be weighed against the costs and risks of allowing recent trends to go unchecked.

Further information

special issue of the Journal of the American Medical Association, focusing

on biological warfare issues, August 6, 1997, Vol. 278, No. 5, pp. 347-446.

Brad Roberts, editor, "Biological Weapons: Weapons of the Future?"

(Washington, D.C.: Center for Strategic and International Studies, 1993).

Brad Roberts, editor, "Terrorism With Chemical and Biological Weapons:

Calibrating Risks and Responses" (Alexandria, Va.: Chemical and Biological

Arms Control Institute, 1997).

Graham Pearson, "Why Biological Warfare Matters" (Alexandria, Va.: Chemical

and Biological Arms Control Institute, 1995).

Malcolm Dando, "Biological Warfare in the 21st Century: Biotechnology and

the Proliferation of Biological Weapons" (London: Brassey's, 1994).

Richard Preston, "The Cobra Event" (New York: Random House, 1997).

Oliver Thraenert, editor, "Enhancing the Biological Weapons Convention"

(Bonn: Dietz, 1996).

Web site for the Chemical and Biological Arms Control Institute:

http://www.pressroom.com/~cbaci

SLIDES:

Biological Weapons & International Security: Why is it Necessary to Strengthen the Existing Arms Control Regime?

The BW Problem

Historically, little concern about biological weapons. Among security specialists, typically seen as far less important than nuclear weapons. Among industry leaders, typically seen as completely irrelevant to scientific or commercial activities.
Why then do diplomats seek a strengthening of the Biological and Toxin Weapons Convention of 1975, and ask science and industry to run some risks and absorb some costs? Three interconnected reasons:

#1: proliferation

#2: Russia

#3: terrorism

Reason #1: BW Proliferation

When the BWC was signed in 1972, experts generally believed that only 1 or 2 states other than the superpowers had armed themselves with biological weapons.
Today, public reports assert that between 10 and 15 countries have such weapons or actively seek them.
Moreover, government sources emphasize that the number of states could be larger, given the difficulty of actually detecting such programs in the absence of any on-site inspections.
The proliferation of chemical weapons to between 20 and 24 states and the ongoing diffusion of advanced biotechnologies suggest that BW may proliferate further.

Iraqi BW [Internet source: www.un.org/peace and security/UNSCOM]

1974: program begun, funded by Iraqi Intelligence Ministry, with new facility at Salman Pak in 1978.
1979-85: may have suspended program to develop BW for military applications, instead focusing on BW for clandestine ops
1987: construction of production facilities and expansion of research program on military applications
Gulf War: Iraq acknowledges large-scale production of bot tox and anthrax and claims to have filled 100 bombs with bot tox, 50 with anthrax, 7 with aflatoxin and filling 25 missile warheads (5 anthrax, 4 aflatoxin, 16 bot).
Were they deterred? BW attack predelegated but release point not reached in combat operations.

Iraqi Deception

From its original 3-page declaration in early 1991 to July 1995, Iraq maintained it had no offensive BW program. A defector triggered new revelations.
Since then, 6 official "full, final, and complete disclosures" by Iraq (and various other drafts)
3rd technical experts meeting of spring 1998 finds latest FFCD deficient in its descriptions of:
- the history of the program, including evolution and funding
- program organization, including reporting structures
- acquisition of supplies, materials, seed strains, munitions, growth media
- research and development. (Iraq denies any program planning)
- production (Iraq claims to have unilaterally destroyed all records)
- weaponization
- material balances

Reason #2: Russia

BW is not strictly a problem of proliferation to small or medium sized states in regions of instability.
Historically, in the period between World War I and the early Cold War, many of the major powers possessed biological weapons or maintained active programs aimed at future production. During the Cold War, the Western powers all abandoned BW.
But the Soviet Union did not. Nor reportedly did China.
Despite a trilateral inspections process under the BWC, doubts remain about whether Russia is fully in compliance with its treaty BWC obligations.

Soviet BW--as publicly reported by Ken Alibek

Started in 1920s, some limited use of endemic diseases in WWII, capture and integration of Japanese Unit 721 items in Manchuria
1950s: mobilization facilities for manufacture during "special period"
Biopreparat established at time of USSR signature of BWC to exploit new biotechnologies for commercial and military purposes, ultimately involving "dozens of thousands" of people in "hundreds" of institutes
sizable research and production infrastructures built around specific BW agents; developed spray tank and ICBM delivery techniques
Gorbachev decreed closure, not implemented--new production facilities and delivery systems (multiple BW warhead for ICBM)
Yeltsin decree has closed more of program, but some of what was destroyed in 1980s is being recreated (e.g., documentation); evidence in Russian journals of ongoing work on genetically altered strains

Reason #3: Terrorism

Historically, terrorists have seen attacks aimed at generating mass casualties as either unnecessary or counterproductive. Such attacks might have delegitimized their cause or made concessions by the targeted state more difficult.
In the current era, traditional terrorist organizations are in decline. But new terrorist actors are emerging, many of which seem unconcerned with political goals of a traditional kind or unrestrained by their use of violence to exact revenge, strike at a hated symbol, or accelerate the apocalypse.

Example: Aum Shinrikyo

Better known for its sarin attack on the Tokyo subway system, Aum also had a substantial BW program.
Aum developed its own BW labs, purchased BW assistance from the KGB and Spetsnaz forces and sent technicians to Africa in search of Ebola.
It conducted at least 9 BW attacks on targets in Tokyo, including the parliament, imperial palace, and US military headquarters. It also planned CBW attacks outside Japan.
At the time, Aum members believed that their attacks had succeeded in killing literally millions. But the attacks failed for technical reasons.

Conclusions

The examples provided by Iraq, Russia, and Aum may or may not be representative of the broader BW problem. Other proliferation programs may be less sophisticated than Iraq's. The Soviet program may have been unique. Other terrorists may not mimic Aum. On the other hand, these may prove only to be harbingers of further revelations yet to come.
Either way, these are wake-up calls. They are the reason that diplomats ask leaders in science and industry to support the negotiation and implementation of an improved prohibition against biological warfare.

The Biological and Toxin Weapons Convention: A historic and political perspective
Willy Kempel, Ministry of Foreign Affairs, Austria

ABSTRACT

Gases and asphyxiating substances were initially used to limit or eliminate military capabilities of enemy troops. Other forms of "biological weapons" encompassed the spreading of sicknesses or plagues, partially engaging primitive means such as rats.

Technical progress allowed for more sophisticated forms of warfare in the 19^th century and especially also in WW I. Both sides had invested tremendous resources in developing germ warfare programs which were used during the war with terrifying and deadly consequences (Verdun, Ypres).

In light of these experiences, the international community endorsed the prohibition of the use of chemical and biological weapons in the Geneva Protocol 1925, which should remain in force until today, even if partially superseded by later legal instruments. The Geneva Protocol prohibits only the use of biological weapons, not their production, storage, or transfer, as the then legal and political environment did not allow for any more comprehensive regulations. Moreover, a number of countries introduced reservations regarding a second use option.

While biological warfare was not resorted to in WW II, research programs both in defensive and offensive uses continued world-wide. In later years, these activities also led to planned releases of biological warfare agents for testing purposes, resulting in some areas being rendered uninhabitable for years to come.

Even at the height of the Cold War, both sides still looked for rationalisations in the arms control and disarmament field. These attempts led to the BWC 1972, which not only prohibits the use of biological weapons by endorsing the Geneva Protocol 1925, but also encompasses the obligation to destroy all existing stocks as well as the prohibition to stockpile, develop, or transfer such weapons. The sole exceptions for transfers of agents and toxins adopted were for medical or defensive purposes in limited quantities.

While the international community reviewed the BWC treaty in 5-term intervals since its entry into force, and was of the clear opinion that all stocks would be destroyed in due time, the treaty proved to leave some loop-holes for potential perpetrators. In fact, no verification measures were agreed upon, only reporting duties have been adopted. Furthermore, defensive programs were not always easily distinguishable from offensive ones. Moreover, a number of countries remained outside the regime or found ways to circumvent export control procedures put in place by mostly Western countries, joined only in the eighties and nineties by Eastern European countries.

Trust in the regime was severely undermined by the so-called Sverdlovsk incident in the then Soviet Union in 1978 which was only admitted as a breach of the BWC by the Russian Government in the 90s. Further impetus for taking action was found in the use of Iraqi biological weapons in the war with Iran as well as in the extent of the Iraqi BW program found out under the UNSCOM inspections. Moreover, the use of Sarin by terrorists in the Japanese subway added momentum. The UN-SG obtained a mandate for on-site verification measures in case of use or threat of use of biological weapons, but not beyond.

The international community realised that the 1972 treaty remained too limited in its application, as it did not allow for verification measures which have become the new standards of international arms control and disarmament in the 80s and 90s. Especially the Chemical Weapons Convention of 1991 provides for full access to military and civil sites and thereby comprehensive verification measures. In order to elaborate such verification standards also in the BWC context, the international community took action in 1994 in convening a special conference which led to the establishment of an expert group and later-on to the continuous convening of an Ad Hoc Expert Group to negotiate a verification protocol to the treaty.

FULL TEXT

The nuke of the poor man! The biological weapons program of Iraq! Terrorist attacks in the Tokyo subway! 25 countries are believed to have biological weapons! Events and statements like this bring back the horror of the past, whereby the menace of BW should, in fact, no longer be with us at all!

Gases and asphyxiating substances, referred to as chemical and biological weapons, were used to some extent throughout history to hamper the enemy, to force political and other advantages, to retaliate or just to destroy. In fact, these were also the main motives for the enhanced attention given to them prior to World War I. The war itself led to the first large-scale use of chemical weapons, causing over one million casualties. Names like Verdun and Yper are sadly associated with this mass killing. Later uses were US utilisation of herbicides in Vietnam, Iraqi chemical weapons used against Iran and its own Kurdish population, estimated to have caused around 10,000 casualties.

Biological weapons, though intensively researched, developed, produced, and stockpiled during and after World War II, have never been used openly in armed conflict, although their possible strategic, tactical and covert uses have been explored by military planners. Several charges of use or experiments, however, have been brought forward, and at least one case of covert use - by Japan against China in 1940-44 - has been well documented.

Despite tremendous resources put into research and development of BW, both psychological as well as factual reluctance to use such weapons prevailed. The main reasons for this might have been the lack of control once such weapons were used as well as the reluctance to spread diseases of which mankind has been trying to rid itself for centuries. Therefore, in 1925 the international community took a major step, although limited when compared with today's world, to ban the use of such weapons: the Geneva Protocol of 1925 was concluded. It prohibited the use of chemical and biological weapons, however, it did not forbid the possession, production, stockpiling or transfer of such weapons. Moreover, the number of reservations with regard to a second-use option made it primarily an interdiction of first-use of such weapons. Still, the international norm was established, paving the way for consecutive steps to be taken.

As mentioned before, World War II did not witness any use of biological warfare, even if Nazi Germany came close to such use when its military demanded it vigorously. But also allied countries had continued their research programs and the development of weaponry, even experimenting with open-air releases. This inhibited test areas from being populated for years to come. Reseach activities continued during the sixties. A golden window of opportunity offered itself in the midst of the Cold War, allowing for the conclusion of the Convention on the Prohibition of Biological and Toxin Weapons in 1972 (BWTC). What had happened that the precious genii was put back in the bottle?

Military planners realised that biological weapons might offer less advantages than had been thought before. In case of their use, they might also endanger and kill one's own troops if not heavily protected. The contaminated areas might not be able to be used in an acceptable or suitable time-frame. The disease might spread further, making a given situation uncontrollable for the user of such weapons. Moreover, public opinion took a clear stance against this form of weapons and pushed policy makers to outlaw them. At the same time, fears were invoked of massive proliferation of such weapons to developing countries which had entered world stage in the past 20 years as new players. Last but not least, chemical weapons were considered as an optimal alternative, as they seemed less problematic in handling, storage and use.

Still, the convention of 1972 had limitations, as it could only achieve what was possible at that time. On the positive side, the destruction of all existing stocks was foreseen. Furthermore, a comprehensive prohibition of production, possession, stockpiling, transfer and use of such weapons, with the sole - but important - exception for legitimate purposes, was endorsed. These allowed purposes included medical and protective uses in small quantities, whereby the latter remained ambiguous as any defensive program automatically offered the insight into offensive options. On the negative side, no provision was made for any kind of verification mechanism, leaving the implementation of the Convention a sole national prerogative.

Doubts about the full and comprehensive implementation of the convention by all States Parties led the international community to look for ways and means of enhancing confidence in the regime. The First Review Conference of 1980 was looking at the overall scope of the Convention's Article I and found that it covered all technological developments possible. Background of this reaffirmation of the scope of the convention was the growing military interest in the biological sciences and advances in genetic engineering and other biogenetic technologies. Moreover, the growing tensions between the superpowers as well as the release of anthrax spores into the atmosphere during an unexplained accident in 1979 in Sverdlovsk in the former Soviet Union added further anxiety.

The Second Review Conference of 1986, however, took up the issue of the doubts expressed regarding the implementation of the treaty and accepted a range of Confidence Building Measures (CBMs). These foresaw voluntary annual reporting of relevant activities and facilities and increased transparency to a large extent. However, only 30-40 countries have reported regularly on an annual basis ever since, leaving a large number of questions unanswered. Moreover, the content of information provided differed to a large extent, making it difficult to allow for adequate comparison.

Further actions were taken by the international community in order to cope with growing concerns regarding the proliferation of such weapons, their precursors and their delivery systems (i.a. spraying equipment). The so-called Australia Group intensified its efforts to control a comprehensive list, rendering it difficult for potential perpetrators to amass a comprehensive BW program. However, the world community as a whole had to admit its failure when Iraq used chemical weapons against Iran and even more so as the extent of the Iraqi BW program become known in the aftermath of the Iraq-Kuwait war.

As a consequence of the Iraqi use of chemical weapons, the UN-Secretary General was provided with an elaborate mandate to investigate possible cases of BW and CW use or threat of use. For the Iraqi program, the UNSCOM inspections added a new dimension to international arms control and disarmament efforts, leading to further thinking concerning the strengthening of the BWTC.

The conclusion of the Chemical Weapons Convention in 1991 constituted a major breakthrough in international negotiations, allowing for the ban of an entire category of weapons and strict verification measures. Its entry into force in 1997 paved the way for the future destruction of all existing chemical weapons stocks over a 10-year period as well as strict control both of civilian industry and military sites. This major undertaking was followed by the extension of the nuclear safeguards regime to the control of all nuclear activities of a given country as well as its related industry and research activities (the so-called program 93+2), which was adopted in May 1997 by the IAEA Board of Governors. Still, the BWTC was the one treaty pertaining to weapons of mass destruction that awaited further strengthening.

The Third Review Conference in 1991 acknowledged the need for urgent action by instituting a Verification Expert Group (VEREX), which identified over the next 3 years a number of proposals aimed at implementing the Convention in a comprehensive manner, particularly in the field of verifying its major prohibitions. A Special Conference in 1994 established the so-called Ad Hoc Group, mandated to conclude negotiations of an implementing Protocol to the 1972 Convention. Without any doubt, the CWC served as a role model, even if a number of differences in the areas of verification and co-operation between the two undertakings had to be taken into account.

The Fourth Review Conference in 1997 was mostly devoted to already addressing key elements and negotiating positions of the states participating in the Ad Hoc Group. Major attention was given to the possible time-table to conclude the negotiations, the possibilities to enhance technological co-operation among states parties, the role of export controls, the various verification options, the future control organisation and a proposal by Iran to amend the Convention. However, the political strengthening of the negotiating process sought for could not be achieved in light of differing positions as to the details mentioned.

A number of initiatives have been taken since. The European Union has adopted a legally binding Common Position, referring to the four major issues it deems most important, which are declarations of relevant activities and facilities, facility visits, investigations in compliance concerns and a cost-effective and independent organisation. US President Clinton has outlined some key elements of the American negotiating position in a State of the Union address. Australia has proposed to hold a high level meeting to demonstrate support for the negotiations.

The new Protocol will have to offer what the international community has long sought for: a credible and comprehensive guarantee that the menace of biological warfare in all its aspects is once and for all banned.

UNSCOM: Lessons for Biological Arms Control arising from the experience of the UN Special Commission on Iraq (UNSCOM)
Johannes Rath, UNSCOM Chief Inspector, University Vienna, Austria, Jochen Bürgel, FOCUS MC, Austria

Public awareness on Iraq's potential in Biological Warfare (BW) together with Iraq's confession of having built up the infrastructure for research, production and weaponization of BW agents has fuelled an on-going discussion for an international control mechanism of biological warfare capabilities. Among others, the above factors have led to the current meetings of the BTWC Ad Hoc Group, held in Geneva, Switzerland.

Before going into specifics it might be helpful to mention that UNSCOM was created by the United Nations Security Council (UNSC) as a consequence of the Gulf War. UNSC Resolutions (UNSCRs) determined the organisation and tasks of UNSCOM, namely to verify the destruction and to monitor Iraq's capabilities in the area of Weapons for Mass Destruction (WMD). In contrast, the legal foundation for a future international biological arms control organisation will be a multilateral treaty. As such, it will have to pay attention to the sovereignty of the member countries, independence of the organisation from any national influence and trade secrets.

UNSCOM´s work has undoubtedly brought into light the historical attempts made by the government of Iraq to produce BW-agents and also resulted in an insight into Iraq's current potential in this area. A fact that can not be overlooked in this discussion, is that even though the Iraqi government until 1995 denied the existence of an offensive BW programme, UNSCOM was able with its inspection procedures to find evidence for such a programme. Evidence that allows to keep the BW-file on Iraq open, and also resulted in Iraq's confession in 1995. An example that shows that combining information gathered from on-site inspections, export-import control, and other sources can be efficiently used to verify or falsify information provided by the government under observation.

The procedures employed by UNSCOM include:

primary declaration of all dual use equipment, media, organisms
periodical declarations of dual use activities
export - import control of dual use items
on site inspections of different characters (notified, short noticed, no-noticed; verification, monitoring, "challenge inspections")
discussions and meetings on-site with site representatives and employees
cross connection of information.

The long lasting perspective of a treaty also offers the chance to include procedures not executed by UNSCOM. For example, the instrument of prevention by confidence building and co-operation have not been included into the procedures of UNSCOM, due to the above mentioned history of UNSCOM´s establishment as a consequence of a war situation. "Confidence building measurements" is a granted indefinite term and open to include measurements in the area of multinational co-operations on biosafety, communicable disease control, etc. Aspects that are (partially) already covered by various UN-organisations (WHO, FAO, UNICEF etc.) but may also be seen and co-ordinated under the aspect of BW-prevention.Finally, consequences of a treaty violation have to be carefully evaluated and should be targeted to issue: to prevent the production and use of Biological Weapons.

What is the United Nations Special Commission?

subsidiary organ of the UN Security Council
established in 1991 (UNSCR 687) as a consequence of the Gulf War mandate:
- to eliminate, under international supervision, weapons of mass destruction (nuclear, chemical, biological) in Iraq
- to establish an "On-going Monitoring and Verification" system (OMV) "in order to ensure Iraq's compliance" (UNSCR 715 - Report of the Secretary General 11. Oct. 1991)

General aspects of BW-control

DUAL USE -

legitimate vs. proscribed use

equipment

materials

organisms

fermentation

down stream processing

stabilisation

SIZE ASPECT

comparatively easy to hide

threshold discussion

BIOSAFETY STANDARDS

biosafety standards differ between countries *

What are the procedures employed by UNSCOM ?

baseline declaration
periodical declarations of activity
export / import control (UNSCR 1051)
on site inspections of different characters (notified, short notice, no-notice; "visits", verification, monitoring, "challenge inspections")
discussions and meetings on-site with site representatives and employees
real time monitoring of key equipment (cameras, sensors, ..)
compilation and combination of information

Privileges and immunities of UNSCOM (as agreed in the exchange of letters between UNSCOM and Iraq)

Unrestricted freedom of entry into the country without delay or hindrance
unrestricted freedom of movement without advanced notice
unimpeded access to any site or facility for the purpose of on-site inspection
the right to take photographs and samples
unrestricted communication
the right to designate any site whatsoever for observation

Are UNSCOM's experiences transferrable to the Geneva negotiations ?

Issue

Geneva negotiations

UNSCOM - IRAQ

impact of National Interests

sovereignity aspect

sensitive areas

confidentiality

necessity for compromises

MULTILATERAL TREATY

"DURING WAR" UNSCR

confidence building measurements

integrated approach with other organisations

LONG TERM STRATEGY

SHORT TERM STRATEGY, IMMEDIATE NEED TO ACT

future vs. past orientation

dynamic vs. stable system

PREVENTION

ELIMINATION-DESTRUCTION (PREVENTION, UNSCR 715)

Conclusion

Inspections, declarations, privileges, immunities, size and structure of the organisation, consequences of violation, confidentiality, liability, independence, list of organisms, thresholds, equipment, import/export control, national interests, confidence building measurements, sovereignity aspects, sensitive areas, interests of the biotechnology industry, should be incoroprated into an EFFICIENT BW-CONTROL SYSTEM. A system in biological weapons control has to be open for adaptions and new developments

The Chemical Weapons Convention (CWC) verification regime: Implications for Biotechnology
Julian Perry Robinson, Director Havard Sussex Program on CBW Armament and Arms Limitation, Science Policy Research Unit, University of Sussex

ABSTRACT

For the May 1998 conference in Vienna on implications for biotechnology of a strengthened Biological Weapons Convention, this paper identifies controls to which pharmaceutical and biotechnology-based industry is already subject under the 1993 Convention on the Prohibition of Chemical Weapons (the CWC), which entered into force on 29 April 1997. After a broad overview of the regime thus far instituted for verification of compliance with provisions of the CWC, the paper draws attention to the still-developing role of the Article VII National Authorities. The powers envisaged for these bodies in the treaty could affect biotechnology more strongly than they seem to at present. This is because the criterion of purpose that the treaty uses to define chemical weapons brings all toxic chemicals and their precursors, including biotechnological-process products, within reach of the treaty's controls. Yet only for the 43 species or families of chemical listed in schedules to the CWC, including three varieties of toxin in the sense of the Biological Weapons Convention, is implementation of the criterion currently a day-to-day responsibility of the OPCW Technical Secretariat, which is the treaty's The-Hague-based international authority. Control of unscheduled chemicals thus falls by default to the National Authorities, and it is not yet fully apparent how they are discharging this responsibility in regard to biotechnology. The paper goes on to describe the international controls which the Technical Secretariat operates in a division of labour with the National Authorities. These controls comprise: the mandatory declarations by states-parties of data relating to scheduled chemicals and associated industrial facilities and to plant sites where unscheduled "discrete organic chemicals" are synthesized; the routine inspections of facilities where scheduled chemicals exist in quantities exceeding specified thresholds, the inspections being done primarily in order to validate the declarations; and the short-notice challenge inspections that can in principle be conducted almost anywhere to deter cheaters from operating outside the declarations-bounded domain of routine inspection. The paper ends with an account of the legislative and administrative machinery underlying the overall verification regime. The conclusion is that the CWC verification regime affords useful parallels for the regime now being negotiated for the Biological Weapons Convention, even though some features may be inappropriate. The appropriate features would seem to include: (1) an international organization charged with overseeing implementation of the treaty in a division of labour with national authorities; (2) mandatory declarations that ensure continuing oversight of biotechnology by National Authorities that operate under the scrutiny of the international authority; and (3) an international on-site-inspection regime wherein challenge and non-challenge visits, the latter linked to the declarations, mutually reinforce one another to the detriment of potential cheaters.

FULL TEXT:

INTRODUCTION

(1) Voices can sometimes be heard from within pharmaceutical and biotechnology-based industry suggesting that a strengthened Biological Weapons Convention (BWC) would impose a whole new type of burden on the industry. Yet in fact the industry, like the rest of the chemicals industry, falls within the ambit of the 1993 Chemical Weapons Convention (CWC), which entered into force a year ago and currently has 107 states-parties, including all EU member-states and all other major industrialized countries. Another 61 states have signed but not yet completed the requisite ratification processes. The present paper sets out some of the key provisions of the CWC, including the verification regime set out in the CWC Verification Annex, the implementation of which is now getting under way in the industry. The paper draws lessons from the CWC experience for the strengthening of the BWC.

OVERVIEW OF THE CWC VERIFICATION REGIME

(2) The verification regime for the CWC is a system operated jointly by, on the one hand, the Technical Secretariat of the CWC's international authority, the The-Hague-based Organization for the Prohibition of Chemical Weapons (OPCW), and, on the other hand, the "national authorities" which, under CWC Art VII.4, each state party is required to designate or establish "[i]n order to fulfil its obligations under this Convention". The treaty defines chemical weapons in such a way as to bring within its purview any activity involving toxic chemicals, broadly defined, or substances from which toxic chemicals can be made. Some parts of pharmaceutical and biotechnology-based industry are therefore already experiencing the CWC verification regime. Moreover, the entire industry (except where located within countries not party to the treaty) is subject to the 'challenge inspection' procedures of the regime. The chief purpose of the present paper is to describe these CWC-mandated controls on biotechnology.

(3) The CWC-verification system has several components. Some are inspection activities of various types. These are the "verification measures provided for in this Convention" which the OPCW Technical Secretariat, according to CWC Art VIII.37, must carry out. More specifically, according to CWC Verification Annex Part II.3, these activities are to be performed by the Secretariat's "designated inspectors and inspection assistants", and only by them. Other components of the verification system are declaration activities: the collection, reporting and processing of specified kinds of information relating to chemical weapons or to technologies that could be used to make them. Herein lies a division of labour that underpins the entire verification regime. The National Authorities are responsible for collecting and reporting the information that the Convention obliges states parties to declare either at regular intervals or when occasion arises, depending on the type of information. The Technical Secretariat is responsible for receiving and processing the declarations and, through the 'routine inspection' procedures, for validating some of them. To be able to make the declarations, the National Authorities must have entered into an intimate monitoring relationship with all relevant parts of their countries' technological base, including civil industry. High standards of monitoring are in principal assured through the relationship of mutual scrutiny between the National Authorities and the Technical Secretariat instituted by the many international procedures of the treaty. Completing the regime is the possibility of short-notice challenge inspection at virtually any location, a threat which the Convention poses so as to deter potentially non-compliant states from exploiting technologies or facilities that lie outside the declarations-bounded domain of routine inspection.

(4) In the broad architecture of the CWC verification regime, three principal elements can thus be discerned: mandatory declarations, routine inspection, and challenge inspection. The strength of the overall construct must depend not only on system-design but also on the powers of the system-operators - the OPCW Technical Secretariat and the National Authorities - and on their respective propensities for collaboration within their assigned division of labour. The prevailing tendency in international relations today is still to minimize the autonomy and capacity for independent action of international organizations such as the OPCW. So, whether CWC-derived controls do or do not come to bear down heavily upon biotechnology would seem, at the present juncture, to depend less on what the OPCW Technical Secretariat does and more on what the National Authorities choose to do. It is important in the present paper, therefore, to identify the role and powers of the National Authorities within the overall regime.

ROLE AND POWERS OF THE ARTICLE VII NATIONAL AUTHORITIES

(5) The purpose of the verification system is to generate and sustain confidence among the states parties that they are better off inside the CWC than outside it: that it is worth their while continuing to pay their membership dues and to accept the constraints and burdens imposed by the treaty. The verification system itself contributes to those burdens, which means that, in principle, there can be both too much and too little verification. This principle was well recognised by the original negotiators of the CWC, and led them to assign a major role to the national authorities within the overall verification regime. Thus, by making individual chemical companies accountable for treaty-compliance, not in the first instance to the OPCW, but to their national authorities, the burden of bureaucracy could be reduced; and any threat that those companies might see to their confidential proprietary information in the requisite accountability could be no different from that to which they were accustomed in other areas of government-industry dealings. To reinforce this particular relative advantage (as compared with alternative forms of verification), the negotiators devised the strict information-confidentiality regime imposed upon states parties by CWC Art VII.6 and upon the OPCW Technical Secretariat by CWC Art VIII.5 and the Confidentiality Annex.

(6) The powers envisaged in the treaty for the National Authorities are extensive in that CWC Art VII.4 assigns to these bodies the responsibility for ensuring that states parties are fulfilling their obligations. Some states-parties have established their national authorities within their ministries of economics, trade, industry or commerce; others, within their ministries of foreign affairs; others still, within special commissions. Full implementation of the CWC is proving a slow process, even though the treaty did not enter into force until 29 April 1997, more than four years after it had been opened for signature. It is possible that, despite the educational efforts of the OPCW Preparatory Commission and then the Technical Secretariat, not all states-parties have yet sufficiently appreciated what is expected of their national authorities. In other respects, too, the "level playing field" on which the original negotiators sought to ensure that their industries would compete while controlled remains unrealised. This is evident in, for example, the continuing absence of consensus among states-parties on the "low concentration" issue and on the question of which biotechnological-process products should be treated as discrete organic chemicals "produced by synthesis". For the time being, it is up to each National Authority to decide for itself the positions on these and other such issues, which it will then implement in its industry. Furthermore, a number of key states-parties have still to adopt legislation empowering their National Authorities to do what the CWC requires of them. The weight of influence of the National Authorities within the overall regime is therefore still not entirely clear.

(7) Wisely, the original negotiators first devised the procedures whereby the National Authorities and the OPCW Technical Secretariat would be placed in a continuing relationship of mutual scrutiny, and, having done that, chose to leave most of the detailed specification of the duties of the National Authorities to the states parties. This is so in the case of the most onerous obligation of all, that of CWC Art VI.2. This provision of the treaty requires each state party to "adopt the necessary measures to ensure that toxic chemicals and their precursors are only developed, produced, otherwise acquired, retained, transferred, or used within its territory or in any other place under its jurisdiction or control for purposes not prohibited under this Convention." Only as regards the chemicals listed in the schedules of the CWC Annex on Chemicals does the provision go on to specify how it is to be implemented. So it is left for individual states-parties to decide what the "necessary measures" should be for the huge multitude of unscheduled chemicals (including toxins and other toxic biotechnological-process products) also subject to the Art VI.2 provision in accordance with what has come to be called its 'general purpose criterion'. This means, in effect, that it is to the National Authorities, not to the OPCW, that the CWC has assigned the task of overseeing implementation of a major provision of the treaty. The same can be said of several other primary obligations of the treaty for which the Technical Secretariat has no assigned role in monitoring compliance. Notable examples of such implementation duties falling by default to the National Authorities include the CWC Art I.1(a) obligation not to "develop" chemical weapons and the CWC Art I.1(c) obligation not to "engage in any military preparations to use chemical weapons".

(8) The extent to which National Authorities have recognised and accepted these default duties is not yet evident from the public record. The Iraq-UNSCOM relationship has no doubt given pause for thought about the propriety of an international regime becoming significantly dependent upon national agencies; likewise the behaviour of the Soviet Union towards the Biological Weapons Convention. (Iraqi authorities have been deliberately concealing from international inspectors an ambitious biological-weapons programme which the UN Security Council ceasefire resolution had outlawed in 1991, at the close of the Kuwait War. The USSR had continued development of biological weapons even after entry into force of the BWC, and built large-scale production capacity for the weapons within its civilian pharmaceutical and biotechnology-based industry.) Yet the remedy to compliance-dereliction at high governmental level is surely to strengthen the procedural links between the national and international authorities, not to diminish the role of national agencies. The fact remains that the CWC establishes an expectation that the National Authorities will both be accorded and exercise substantial powers for domestic implementation of the treaty, and that their implementation is subject to international verification.

(9) As regards particular default duties, a number of National Authorities have expressly recognised at least the guardianship of the General Purpose Criterion which CWC Art VI.2 implicitly entrusts to them. This can be seen in, for example, the statutory annual report to Parliament of the UK National Authority for 1997. The Criterion is an element of the CWC regime that is especially pertinent to the present paper, for it is what brings so much of biotechnology-based industry within the ambit of the CWC verification system.

(10) The significance of the General Purpose Criterion is described in the following paragraphs. Quite apart from the role of the CWC National Authorities in overseeing its implementation, it is evident from the preceding paragraphs that these bodies are essential to effective relations the OPCW and the states-parties. A strengthened BWC will surely also require the creation or designation of counterpart national bodies.

THE GENERAL PURPOSE CRITERION

(11) The General Purpose Criterion is the device which the original negotiators of the CWC copied from the Biological Weapons Convention in order to give adequate scope to their treaty. As set out in CWC Art II.1(a), it defines the objects prohibited by the Convention-"chemical weapons"-not in terms of intrinsic properties but in terms of purposes for which they exist: "toxic chemicals and their precursors, except where intended for purposes not prohibited under this Convention, as long as the types and quantities are consistent with such purposes". What those purposes may be are listed-rather more specifically than the "prophylactic, protective or other peaceful purposes" which the Biological Weapons Convention uses in relation to "microbial and other biological agents, and toxins whatever their method of production"-in CWC Art II.9, while in CWC Art II.2 "toxic chemical" is defined to mean "any chemical which through its action on life processes can cause death, temporary incapacitation or permanent harm to humans or animals". A chemical weapon in the sense of the CWC is therefore a considerably broader concept than the chemical weapon of, say, common military parlance. Without that breadth, chemical-warfare agents of novel but still-secret chemical identity, or toxic chemicals not yet discovered or made newly accessible through manufacturing innovation, would be unaffected by the strictures of the treaty. The General Purpose Criterion thus allows the Convention to keep up with technological change.

(12) No less important, the General Purpose Criterion is also the device that protects beneficent peaceful application of the so-called 'dual use' chemicals. These are the substances which can serve purposes not prohibited under the CWC but which can also be used as chemical-warfare agents, or as precursors in the manufacture of such agents. Examples include such widely and heavily used industrial intermediates as chlorine, phosgene and hydrogen cyanide, which also happen to be first-generation military poison-gases. The General Purpose Criterion operates to permit their industrial use instead of suppressing it, as the disarmament stipulations of the Convention would otherwise demand. Further examples of dual-use chemicals protected by the General Purpose Criterion are to be found within the pharmaceutical industry, including scheduled chemicals, such as 3-quinuclidinyl benzilate and saxitoxin, and unscheduled chemicals, such as the Clostridium botulinum toxins.

(13) The General Purpose Criterion is restated in the CWC Article VI.2 provision quoted above (in paragraph 7) as a positive obligation upon states parties to adopt the measures necessary to give it force. As regards unscheduled chemicals, one of the few areas in which the operation of such measures is evident is the work of the Australia Group, which, however, concerns only a limited number of chemicals and is restricted to export controls. As regards scheduled chemicals, Art VI.2 incorporates into the treaty both the Annex on Chemicals and the Verification Annex whereby an agreed international control regime is defined in detail, to be supervised by the OPCW Technical Secretariat. The principal features of this chemical control regime are summarized in Table 1. Article VI.2 is thus the basis for the system of mandatory declarations and routine inspections to which civil chemical industry is subject under the CWC.

(14) In summary, then, the General Purpose Criterion is vital to the future well-being of the CWC regime. Any neglect over the years ahead could bring obsolescence to the regime, opportunity for camouflaging prohibited activities, and a weakening of the safeguards against ill-considered calls for the suppression of beneficial technologies that happen also to have weapons applications. It is fortunate that the BWC contains a similar device, and it seems vital that nothing in the projected BWC Protocol be allowed to detract from it. Above all, it is surely essential that such lists as may have to be written into the BWC Protocol for verification purposes do not come to be seen as limiting the scope of the General Purpose Criterion, and therefore also the scope of the treaty itself.

THE MANDATORY DECLARATIONS

(15) The CWC obliges states parties to submit declarations and notifications of a wide variety of information, some during the period immediately succeeding entry into force of the treaty, some occasionally, and some recurrently. Article III provides for the declarations concerning past chemical-weapons programmes: data on any remaining holdings of chemical weapons, including old or abandoned chemical weapons; on facilities for development, storage, production or destruction of chemical weapons; and also on "riot control agents". These declarations enable the OPCW Technical Secretariat to identify the facilities that the CWC requires be made subject to "systematic verification". Article VI provides for the declarations of industrial rather than chemical-weapons data. The original negotiators intended the declarations of industrial information as means for identifying facilities whose 'dual use' attributes rendered them a particular threat to the "object and purpose of this Convention" - in other words facilities that might be especially attractive to potential cheaters seeking to conceal production of chemical-warfare agents behind a façade of legitimate industrial activity, or even facilities that had been deliberately constructed so as to furnish such concealment. Thus identified, the facilities would be subject to a regime of routine inspection intended to reduce their concealment potential and thus drive cheaters out to more exposed venues.

(16) For purposes of the Article VI declarations, the CWC Annex on Chemicals sets out three schedules, which together list 43 species or families of chemical: 12 in Schedule 1 (including saxitoxin and ricin, as well as blister and nerve gases and intermediates thereof), 14 in Schedule 2, and 17 in Schedule 3 (including hydrogen cyanide, which is another toxin within the meaning of the Biological Weapons Convention). Of the 43, 27 are precursors and 16 are toxicants. Each of the chemicals has been scheduled because it is deemed to pose a risk to the object and purpose of the Convention, the chemicals in Schedule 1 a "high" risk, and those in Schedule 2 a "significant" risk. The scheduling also reflects the degree of industrial application of the listed chemicals, those in Schedule 3 being ones "produced in large commercial quantities" and those in Schedule 1 "having little or no use for purposes not prohibited under this Convention". The three schedules are in fact negotiated lists, though criteria for adding new chemicals to them, or removing existing ones, are also specified in the Annex on Chemicals. Two categories of declaration are triggered by each schedule, one having to do with the chemicals per se, the other with facilities associated with them. The amount of detail required is greatest for Schedule 1 and smallest for Schedule 3, this reflecting the differing stringency of the control regime associated with each schedule. The facilities to be declared are ones in which more than threshold quantities of the chemicals are produced or, for chemicals on Schedules 1 and 2, processed or consumed. The facility declarations also extend, with certain exemptions, to plant sites where "unscheduled discrete organic chemicals" are "produced by synthesis" in more than threshold quantities. Annual declarations are made in two broad types, one reporting data for the previous year, the other reporting anticipated data for the year ahead. A summary of all these declaration requirements is given in Table 2.

(17) Information contained in the various declarations has the protection from disclosure afforded by CWC Art VIII.5, which states that the OPCW "shall take every precaution to protect the confidentiality of information on civil and military activities and facilities coming to its knowledge in the implementation of this Convention and, in particular, shall abide by the provisions set forth in the Confidentiality Annex". The Confidentiality Annex requires the OPCW Director-General to establish a special regime for protecting confidential information, for which it sets out guidelines. The confidentiality regime that is now in place actually makes it rather difficult for the outside world to know even in broad terms how well the treaty is being implemented, let alone what the content of individual facility declarations, say, might be. If a state-party wishes any information it declares to the Technical Secretariat to be protected, it simply has to designate it as `confidential' and indicate which of the three available levels of protection should be applied to it. The Secretariat is then obliged to protect the information accordingly. The Director-General has complained publicly of the tendency of some states parties to assign unnecessarily high protective markings to some or all of their declarations. The states-parties themselves, through their National Authorities, are entitled under paragraph 2(b) of the Confidentiality Annex to be "routinely provided" with such data as they require "to be assured of the continued compliance with this Convention by other States Parties". This provision goes on to state that such data may include the initial and annual reports and declarations under Articles III, IV, V and VI. According to CWC Art VII.6, it would seem that only people in government who have responsibilities for domestic implementation of the Convention may have access to confidential information supplied under paragraph 2(b).

(18) In summary, it is hard to envisage an international verification regime for the CWC which did not pivot on a system for mandatory declarations. What information should actually be declared clearly depends upon prevailing circumstances, meaning that mechanisms for reconsidering and, if necessary, amending the requirements are perhaps no less important within the overall regime. Both these conclusions seem applicable also to the projected BWC verification regime.

THE ROUTINE INSPECTIONS

(19) If the annual quantity of scheduled chemical processed, consumed and/or produced in a declared facility exceeds a specified threshold, the facility becomes liable to routine inspection by the OPCW Technical Secretariat. It is not obvious, in retrospect, that this simple quantitative method for triggering the international inspectorate into action within civil industry is really the best way of ensuring that all industrial `dual use' facilities that are especially vulnerable to abuse are brought within the ambit of routine inspection. As set out in the treaty, the trigger is clearly a compromise. The key thing about it is that it is the outcome of international negotiation in which senior representatives of chemical industry, as well as diplomats and chemical-weapons experts, were involved throughout. Important for industry representatives was the willingness of the diplomats first to write into the treaty stringent provisions for safeguarding confidential proprietary information (see paragraphs 4 and 14 above), secondly to accept that the number of routine inspections a state-party would be required to receive at declared industrial facilities each year would be rather tightly limited, and thirdly to accept that each and every routine inspection could be governed by a "facility agreement" that had been negotiated bilaterally between the OPCW Technical Secretariat and the state-party concerned. These facility agreements limit access by OPCW inspectors solely to those particular areas of a plant site that had been declared as producing, or otherwise handling, a scheduled chemical; the facility agreements preclude access to other areas. Within those parameters, the intrusiveness of routine inspection varies from schedule to schedule. A summary of the facility control regime is given in Table 3.

(20) The disclosure of information gathered by the OPCW Technical Secretariat during routine inspections is governed in the first instance by the reporting procedure set out in CWC Verification Annex Part II.60 and 62-65, and thereafter by the confidentiality regime (see paragraph 17 above). During the day following an inspection, the inspectors are to write a preliminary report on a standardized form after they have met to review the inspection with representatives of the inspected facility and the inspected state party, this also being opportunity for clarifying ambiguities. Attached to the preliminary report is to be a list of all data gathered, samples taken, written information obtained and anything else which the team will be taking off site. A copy of all this is to be given to the inspected state party. Within the next ten days a final report is to be prepared and sent to the inspected state party, whose comments, if any, will be annexed to the report when it is transmitted to the Director-General. The latter may, as he thinks fit, seek clarifications from the inspected state party, and if these prove unsatisfactory the OPCW Executive Council is to be informed without delay. Throughout this process the report is to remain confidential. The Confidentiality Annex, in paragraph 17, states that if information contained in the report has to be transmitted beyond the inspected state party and the Technical Secretariat, it may first be "processed into less sensitive forms". It was in December 1997 that routine inspection of civil chemical industry commenced, so experience with these various provisions is only now starting to accumulate. There have been glitches, but basically the system seems to be working.

(21) In summary, the key points to note here are that routine industry inspections under the CWC are carried out relatively infrequently (perhaps once every three years at a particular facility), and that they are tightly circumscribed inspections that are confined to declared areas of plant sites.

CHALLENGE INSPECTION

(22) Routine inspections are not meant to discourage production of chemical weapons or other illicit activities in undeclared facilities, nor can they be expected to deter abuse of declared facilities, such as could conceivably happen if cheaters were to find ways of evading the procedures prescribed for the routine verification regime. Moreover, routine inspections do not allow states parties much opportunity to demonstrate that particular facilities within their jurisdiction are not being abused. The challenge inspection provisions of the CWC are intended to serve the first two of these functions. They could also contribute to the third. A state-party wishing to dispel doubts or allegations concerning its own compliance may, under CWC Art IX.5, seek the assistance of the Executive Council to clarify the situation. It is up to the Council to decide what to do, but among its options will be that of organizing a special inspection by the Technical Secretariat. No challenge inspections have yet been conducted under the CWC. A number of states-parties have, however, invited the participation of the OPCW Technical Secretariat in practice challenge inspections.

(23) The challenge-inspection provisions of the treaty are as follows. When a question of compliance becomes an issue, CWC Art IX.2 requires that the states-parties concerned first make every effort to resolve the issue among themselves through exchange of information and consultations. If that does not work, the challenge procedures can be invoked. By CWC Art IX.8, "each State Party has the right to request an on-site challenge inspection of any facility or location...under the jurisdiction or control of any other State Party for the sole purpose of clarifying and resolving any questions concerning possible non-compliance...and to have this inspection conducted anywhere without delay by an inspection team designated by the Director-General ...". By CWC Art IX.11(b), the challenged state is obliged "to provide access within the requested site for the sole purpose of establishing facts relevant to the concern regarding possible non-compliance". By CWC Art IX.12, the requesting state may attach an observer to the inspection team whom the challenged state is expected but not obliged to accept. The challenged state is required by CWC Art IX.11(a) "to make every reasonable effort to demonstrate its compliance with this Convention".

(24) Three principal limitations are placed upon the challenge-inspection process by the Convention in order to provide protection against abuse. These limitations follow from CWC Art IX.9, which obliges states parties to keep inspection requests "within the scope of this Convention" and to justify their requests by including "appropriate information". The first limitation subjects requests to a filtering mechanism, the so-called `red light' procedure. By CWC Art IX.17, the OPCW Executive Council, to which the inspection request must be transmitted as well as to the Director-General of the Technical Secretariat, may block inspection if it deems the request to be "frivolous, abusive or clearly beyond the scope of this Convention". Such action requires a three-quarters majority of the Council, and must be taken within 12 hours of the request. The second and third limitations are mandated by CWC Art IX.11(c), which gives the inspected state the "right to take measures to protect sensitive installations, and to prevent disclosure of confidential information and data, not related to this Convention". One such protection is established by the procedures set out in CWC Verification Annex Part X.16-21 which allow for negotiation between the inspection team and the challenged state on where exactly the inspection is to be conducted. This will not prevent access, but it will allow the challenged state the best part of five days to prepare the site for inspection (less if it is a declared site). The second such protection is in the procedures for "managed access" set out in Part X.46-52 whereby there may be less than full access to objects within the inspected site. This may be achieved by shrouding items, removing sensitive papers, logging-off computers, agreeing on use of Random Selective Access techniques, and suchlike measures.

(25) The reporting procedure for a challenge-inspection team, set out in Verification Annex X.59-61, is somewhat similar to the procedure following routine inspections (see paragraph 16), including the requirement that the final report be limited to the factual findings. The team is most definitely not required to present an assessment of compliance or noncompliance. The final report is, however, to be disseminated to all states parties -- bowdlerized, if necessary -- in preparation for the review of the report which the Executive Council is required to conduct. It will be on the basis of this review that the Council will decide whether further action is or is not necessary.

(26) Challenge inspection represents the CWC verification regime at its most intrusive. Like the civil-industry controls, it is a precedent-setting feature of the treaty. Walter Krutzsch and Ralf Trapp, on pages 175-6 of their magnificent A Commentary on the Chemical Weapons Convention (Nijhoff, 1994), describe how, in the intrusiveness of challenge inspection and in the essentially unlimited range of sites at which it may be applied, it far surpasses such procedures as the `unannounced inspections' of the IAEA safeguards system, the CSCE inspections, the `short notice inspections' of the INF treaty and the `inspections on suspicion' of the CFE treaty. In the limitations placed by the Convention on challenge inspection are to be seen the most delicate of the compromises reached by the original negotiators: a balance between, on the one hand, the effectiveness of the central deterrent against cheating and, on the other hand, the security of information unrelated to the Convention which, for one reason or another, states parties wish to keep secret. The quest is now to strike such a balance in the "legally binding instrument" that is to strengthen the BWC. The key must surely lie, as it did with the CWC, in the degree to which the routine and the challenge on-site inspection regime can be made to support one another, thereby enhancing their overall deterrent effect.

LEGISLATIVE AND ADMINISTRATIVE MACHINERY

(27) Biotechnology is a prime example of `dual use' technology. The manner in which the CWC addresses dual use thus offers especially relevant guidance, even though the CWC model may not in all respects be a good one. The General Purpose Criterion is, as has been seen earlier in this paper, the central element in the CWC's dual-technology control, and, because the BWC also relies upon such a criterion, it will also direct the projected BWC Verification Protocol. The chief problem with the criterion is that, administratively, it is far less easy to implement than, for example, a list-based approach to what is and is not prohibited. The CWC, in its schedules-bounded regime of routine verification, in fact uses a list-based approach as well as the General Purpose Criterion. Its remedy for ensuring that states-parties do not in consequence come to neglect the criterion is to follow BWC Art IV. Thus, CWC Art VII.1 opens as follows: "Each State Party shall, in accordance with its constitutional processes, adopt the necessary measures to implement its obligations under this Convention." These obligations of course include the CWC Art VI.2 obligation to implement the General Purpose Criterion (see paragraph 7 above). In contrast to BWC Art IV, which adds nothing further of substance, CWC Art VII.1 goes on to specify what those "necessary measures" must include: "In particular, [each State Party] shall: (a) Prohibit natural and legal persons anywhere on its territory or in any other place under its jurisdiction as recognized by international law from undertaking any activity prohibited to a State Party under this Convention, including enacting penal legislation with respect to such activity; (b) Not permit in any place under its control any activity prohibited to a State Party under this Convention; and (c) Extend its penal legislation enacted under subparagraph (a) to any activity prohibited to a State Party under this Convention undertaken anywhere by natural persons, possessing its nationality, in conformity with international law."

(28) While it seems from the declarations under BWC confidence-building measure "E" that rather few BWC states parties have taken any Article IV "necessary measures", CWC Article VII cannot so easily be disregarded. In part this is because of the specificity of its provisions. In part, too, the Article has attraction as a means for reinforcing state powers against, for example, chemical terrorism. But there is also recognition that, in the absence of strong and routine national measures, the international CWC regime would be an edifice built upon sand. That much is apparent from study of at least some of the national legislation enacted in accordance with Article VII. In the UK Chemical Weapons Act 1996, for example, the general purpose criterion is implemented in full, and the steps now being taken properly to administer the Act include efforts to ensure that the relevant authorities receive the coöperation from the country's science and technology base without which enforcement of the General Purpose Criterion would be a hopelessly optimistic goal. The actual administrative device employed is a National Authority Advisory Committee whose membership includes representation from industry, the universities and professional scientific associations as well as the National Authority itself and other parts of government.

(29) The CWC thus suggests a strong need to develop BWC Article IV, and thereby, as the mandate of the BWC Ad Hoc Group puts it, "to improve the implementation of the Convention". of the BWC

CONCLUSION

(30) A conclusion to be drawn from the foregoing descriptions is that the CWC verification regime affords useful parallels for the regime now being negotiated for the Biological Weapons Convention, even though some features, such as the chemical-weapons destruction destruction provisions, might be inappropriate. The appropriate features would seem to include: (1) an international organization charged with overseeing implementation of the treaty in a division of labour with national authorities; (2) mandatory declarations that ensure continuing oversight of biotechnology by National Authorities that operate under the scrutiny of the international authority; and (3) an international on-site-inspection regime wherein challenge and non-challenge visits, the latter linked to the declarations, mutually reinforce one another to the detriment of potential cheaters. A strengthened BWC would require a verification regime in which these features were carefully integrated. It is fitting that the result would resemble the counterpart CWC regime, for there is much in common between biological and chemical weapons. Moreover, given that toxins are covered by both treaties, some overlaps are going to be essential.

Table 1. The chemical control regimes under the CWC

Elements of control regime

For Schedule 1 chemicals

For Schedule 2 chemicals

For Schedule 3 chemicals

For unscheduled discrete organic chemicals

Production limit

No more than 1000 kg of all types may be held by a state-party

None specified, but all production must be for, and in quantities consistent with, purposes not prohibited under the Convention

Data reporting (initial and annual)

Yes: detailed information on production, use, import and export

Yes: for each one, aggregate national data on production, use, import and export

Yes: for each one, aggregate national data on production, import and export

No, except for plant specific data (as with the scheduled chemicals)

Inspection of facilities producing more than threshold quantities

Yes: highly stringent and augmented with instrumented monitoring

Yes

Yes: less stringent

Not until EIF+3 yrs, if then approved by the Conference of the States Parties

Export control

Exports permitted only to states parties, with advance notification of OPCW

End-use certification required until EIF+3 yrs, after which exports permitted only to states parties

End-use certification required; and possibility of other measures after EIF+ 5 yrs

None specified

Table 2. Chemical industry declarations required of CWC states-parties

CWC element

Information to be declared by each state party

Deadline

VerAx VII.9-10 VerAx VIII.9-10

Each plant site where there is plant that has produced Schedule 2 or 3 chemicals for chemical-weapons purposes at any time since 1 January 1946

By entry into force (EIF) + 30 days

VerAx VI.17-20

Location and details of all facilities approved for production of more than 0.1 kg/yr of Schedule 1 chemicals for research, medical or pharmaceutical purposes.

Annual declarations also required: of prior-year production, consumption, storage and transfer, and of projected next-year production.

By EIF + 30 days

By year-end + 90 d & year-start - 90 d

VerAx VII.1-2

Aggregate national data on the production, processing, consumption, import and export of Schedule 2 chemicals, for each such chemical during the previous calendar year.

Declaration to be repeated annually.

By EIF + 30 days

By year-end + 90 d

VerAx VIII.1-2

Aggregate national data on the production, import and export of Schedule 3 chemicals, for each such chemical

Declaration to be repeated annually.

By EIF + 30 days

By year-end + 90 d

VerAx VII.3-8

Each plant site where Schedule 2 chemicals have recently been, or will next year be, produced, processed or consumed in amounts exceeding 1 ton/yr (or less for three of the chemicals: see Table 3), with details.

Annual declarations also required, both of prior-year and of projected next-year activities.

By EIF + 30 days

By year-end + 90 d & year-start - 60 d

VerAx VIII.3-8

Each plant site where Schedule 3 chemicals have been or will be produced in amounts exceeding 30 ton/yr, with details.

Annual declarations also required, both of prior-year and of projected next-year activities.

By EIF + 30 days

By year-end + 90 d & year-start - 60 d

VerAx IX.1-6

For unscheduled discrete organic chemicals, each plant site where more than 200 tons were synthesized during the previous year, unless the chemicals contain P, S or F, in which case the threshold is 30 tons, or unless the chemicals are exclusively explosives or hydrocarbons.

The list of sites is to be updated annually.

By EIF + 30 days

By yr-start + 90 d

Table 3. The facility control regimes under the CWC

Facility type

Number of inspectable facilities anticipated by OPCW PrepCom

Routine inspection regime

Facility agreement

Annual production threshold

Continuous monitoring

Notice of inspection

Duration of inspection

Access during inspection

Frequency of inspection

for reporting

for inspection

CWSF

33 (and 40 for oacw)

Mandatory

[not applicable]

On-site instruments

initial: 72 hrs other: 48 hrs

As agreed

Automatic to declared facilities

Not specified in the CWC

CWPF

43

Mandatory

[not applicable]

On-site instruments

initial: 72 hrs

other: 24 hrs

As agreed

Automatic to declared cw

Upto 4 per year

CWDF

4

Mandatory

[not applicable]

On-site instruments and inspectors

As agreed

Automatic to all parts of declared facilities

Not specified in the CWC

Schedule 1 facilities

ca 75

Mandatory

0.01 kg

0.01 kg

On-site instruments

As agreed

Automatic to declared facilities

Not specified in the CWC

Schedule 2 facilities

More than 300

Mandatory unless waived by both sides

bz: 1 kg

amiton: 0.1 t

pfib: 0.1 t

Others: 1 t

10 kg

1 t

1 t

10 t

No

48 hrs

96 hrs

Automatic to plant site and to specified areas within declared plants; beyond that, as agreed

Upto 2 per year per plant site

Schedule 3 facilities

ca 400

Optional

30 t

200 t

No

120 hrs

24 hrs

Upto 2 per year per plant site, with limit on combined total

UDOC facilities

More than 5000

Optional

PSF: 30 t

Others: 200 t

200 t

200 t

No

120 hrs

24 hrs

Automatic to plant site; managed, to declared plants

The strengthened BTWC protocol : the likely integrated regime
Graham S. Pearson, former Director General and Chief Executive of the UK Chemical and Biological Defence Establishment at Porton Down, Honorary Visiting Professor in International Security, Department of Peace Studies, University of Bradford, West Yorkshire

ABSTRACT

The Biological and Toxin Weapons Convention (BTWC) has no provisions forverification or for the monitoring of compliance. The Ad Hoc Groupestablished in 1994 to consider appropriate measures, including possibleverification measures, and draft proposals to strengthen the Convention, tobe included, as appropriate, in a legally binding instrument has now met 10times. The July 1997 AHG session saw the successful introduction of arolling text for the Protocol to strengthen the BTWC. All the essentialelements for the Protocol are now in the rolling text -- MandatoryDeclarations, Non-Challenge Visits (both focussed and random) andCompliance Concern Investigations together with measures to strengthen theimplementation of Article X (cooperation for peaceful purposes) and otherArticles of the BTWC. Although there has been much proliferation ofsquare brackets indicating alternatives, the essential contents of aProtocol to strengthen the BTWC are already present.

Political developments around the world in the first few months of 1998have demonstrated that there is a serious international commitment to thenegotiations and that the political will needed to complete thenegotiations is there. This paper considers the current rolling text ofthe Protocol to strengthen the BTWC and draws together the likely elementsof that Protocol in order to examine how together they will result in anintegrated regime that will strengthen effectively the BTWC.

It is concluded that the Protocol being negotiated by the Ad Hoc Group inGeneva has all the key elements required for a highly effective integratedregime already in the draft text. The additional detailed measuresidentified in this paper that have yet to be elaborated should not presentan undue difficulty -- declarations of past BW facilities, visits to BWdefence and government owned past BW facilities at about once every twoyears intervals, measures to improve implementation of Articles III, IV andX of the Convention designed to also contribute to strengthening confidencein compliance. This paper has demonstrated that all the differentelements are all inter-related and together will have a considerablesynergistic effect that will build confidence in compliance with theConvention, ensure that uncertainties, anomalies and concerns are swiftlyinvestigated and improve the implementation of the Convention.

FULL TEXT

Introduction

The Biological and Toxin Weapons Convention (BTWC) has no provisions for verification or for the monitoring of compliance. At the Third Review Conference in September 1991 following the Persian Gulf war of 1990/1991, the States Parties "determined to strengthen the effectiveness and improve the implementation of the Convention" established an Ad Hoc Group of Governmental Experts to examine possible verification measures from a scientific and technical viewpoint. This Group (known as VEREX) met twice in 1992 and twice in 1993. Its final report was considered by a Special Conference in September 1994 which established an Ad Hoc Group (AHG) to consider appropriate measures, including possible verification measures, and draft proposals to strengthen the Convention, to be included, as appropriate, in a legally binding instrument. Its mandate stated that "Measures should be formulated and implemented in a manner designed to protect sensitive commercial proprietary information and legitimate national security needs."

The AHG commenced its work in January 1995 and has now met 10 times. In September 1996 the AHG decided to intensify its work and the July 1997 session saw the successful introduction of a rolling text for the Protocol to strengthen the BTWC. All the essential elements for the Protocol are now in the rolling text -- Mandatory Declarations, Non-Challenge Visits (both focussed and random) and Compliance Concern Investigations together with measures to strengthen the implementation of Article X (cooperation for peaceful purposes) and other Articles of the BTWC. Although some parts of the rolling text are in square brackets indicating alternatives, the essential contents of a Protocol to strengthen the BTWC are already present.

In 1998 the AHG met for 3 weeks in January and 1 week in March; it will meet for 3 weeks in June/July and for 4 weeks in September/October. There is consequently a real opportunity to complete the substantive negotiations this year -- particularly as President Clinton in his State of the Union address on 27 January 1998 said "Now, we must act to prevent the use of disease as a weapon of war and terror. The Biological Weapons Convention has been in effect for 23 years. The rules are good, but the enforcement is weak -- and we must strengthen it with a new international system to detect and deter cheating." The associated Fact Sheet released by the White House at the same time said that "under the new initiative announced by the President today, the United States will seek to complete the framework of a strong BWC protocol by the end of 1998." In March 1998 the European Union issued a Common Position that commits the 15 Member States as well as the 14 Associated States to "Member States...shall actively promote decisive progress in the work of the Ad Hoc Group, with a view to concluding the substantive negotiations by the end of 1998, so that the Protocol can be adopted by a Special Conference of States Parties early in 1999." In addition, Australia announced on 2 March 1998, an initiative to strengthen the BTWC "aimed at fast-tracking the negotiations on a verification system for the Biological Weapons Convention by: - calling for the convening of a high level meeting to inject into the negotiations the necessary political commitment for urgent action,...to help secure early conclusion to the negotiations." A Statement by the Non-Aligned Movement and other countries said inter alia that "they will contribute fully to this work [of the Ad Hoc Group] in order to promote consensus on key issues which will facilitate the conclusion of this undertaking in an manner acceptable to all States Parties...". More recently, the Foreign Ministers of the G8 in the communiqué issued following their meeting in London on 8-9 May 1998 said that they "are committed to action in the following areas: - the intensification and successful conclusion of the negotiation on measures, includes those for effective deterrence and verification to strengthen the Biological and Toxin Weapons Convention with the aim of the earliest possible adoption of a legally-binding Protocol." A week ago, President Clinton said "We must strengthen the international Biological Weapons Convention with a strong system of inspections to detect and prevent cheating. This is a major priority. It was part of my State of the Union address earlier this year, and we are working with other nations and our industries to make it happen." He went on to say that "We must not cede the cutting edge of biotechnology to those who would do us harm." It is thus evident that there is a serious commitment to the negotiations and that the political will needed to complete the negotiations is there.

This paper considers the current rolling text of the Protocol to strengthen the BTWC and draws together the likely elements of that Protocol in order to examine how together they will result in an integrated regime that will strengthen effectively the BTWC. This paper aims to set out what measures the Protocol is likely to contain so that the implications for the biotechnology industry can be realistically assessed bearing in mind the mandate requirement that "Measures should be formulated and implemented in a manner designed to protect sensitive commercial proprietary information ...".

The Essential Elements for the Protocol

The central and essential elements to the future Protocol are measures which together will provide the BTWC with a compliance monitoring mechanism that will detect and deter cheaters and will build confidence over time in compliance with the Convention. These measures include:

a. Mandatory Declarations of those facilities and activities of most relevance to the Convention

b. Non-Challenge Visits, both focussed and random, to declared facilities

c. Both Facility and Field Investigations to address a compliance concern.

However, these measures in isolation will not suffice. It will be recalled that the Special Conference in its Final Declaration stated that "the Conference, determined to strengthen the effectiveness and improve the implementation of the Convention and recognizing that effective verification could reinforce the Convention, decides to establish an Ad Hoc Group." [Emphasis added]. It went on to say that "the objective of this Ad Hoc Group shall be to consider appropriate measures, including possible verification measures, and draft proposals to strengthen the Convention, to be included, as appropriate, in a legally binding instrument..."[Emphasis added]. It is thus evident that the aim of the AHG is both to strengthen the effectiveness and the implementation of the Convention.

Consequently, measures are needed also to ensure the full implementation of Article X (cooperation for peaceful purposes) as specifically required in the mandate for the Ad Hoc Group, as well as such other measures needed to improve the effectiveness and implementation of the Convention. Thus, measures to improve the implementation of Article IV (national implementation measures) and Article III (non-transfer for prohibited purposes) are also necessary. Such measures, if crafted appropriately, will also strengthen the effectiveness of the Convention.

The additional elements needed for the Protocol thus include:

a. Measures to ensure full implementation of Article X (peaceful cooperation)

b. Measures to improve the implementation of Article IV (national implementation)

c. Measures to improve the implementation of Article III (non-transfer)

together with an appropriate organisation to implement the Protocol. Measures in isolation without an appropriate organisation would be ineffective.

In addition, it is important to recognise that strengthening of the BTWC should not be considered on its own. The technologies at the heart of the BTWC -- microbiology and biotechnology -- are central to the wealth and well-being of all in the 21st Century -- and are the subject of numerous national, regional and international initiatives. Consequently, the measures for the Protocol to strengthen the BTWC need to be designed to complement and build on those activities already being implemented in other fora. This should not present a problem as these fora share common objectives -- the goal in many of these other fora is to protect human health and environmental safety whilst that of the strengthened BTWC is to ensure that human, animal and plant diseases are not used as weapons of war to cause harm to humans, animals or plants.

An Integrated Regime

In this section, the measures currently in the draft Protocol are examined in some detail together with some ideas as to how these might be further developed to see what the future regime is likely to comprise and how this would function. In doing this, it is helpful to consider schematically what the strengthened regime might comprise.

There is no credible or effective alternative to the establishment of a BTWC Organization. It has to be recognised that the function of the BTWC Organization is oversee the implementation of the BTWC Protocol and thereby to monitor and improve the implementation of the Convention. There is no other organization that could do this function. However, this is not to say that the BTWC Organization should not develop effective working relationships with other international organizations and provide and receive information to and from these organizations. Thus the OPCW, WHO, FAO and OIE are all organizations that a future BTWC Organization should establish close links with -- however, those organizations rightly have their own specific functions and they cannot be a substitute for the BTWC Organization.

Inputs to the BTWC Organization

The BTWC Organization will be dependent on information received from a wide variety of sources in order to carry out its role and function. The draft Protocol has an Annexe E Confidentiality Provisions which currently comprises some 16 pages and addresses inter alia how confidential information should be handled and protected by the future BTWC Organization; these provisions closely mirror those in the CWC Confidentiality Annex. These information sources will range from public information such as that in the media and on the internet, to information provided under the Confidence-Building Measures (whether those agreed by the BTWC Review Conferences or as part of the Protocol), to information provided by the States Parties and available information from organizations such as the OPCW and the WHO, FAO and OIE. Thus, for example, the OPCW and the BTWC Organization will not only both address toxins, they will also have a great deal of common ground in their day to day activities and both organisations will benefit from adopting best practice from each other. It must, however, be recognised that information available to the BTWC Organization from such international organisations will not be tailored to the specific requirements of the BTWC Organization as to do so would be contrary to the charter of those organizations -- and indeed could jeopardize their primary functions. It will be up to the BTWC Organization to examine and analyse this information. These various types of information will need to be analysed and assimilated by the BTWC Organization in order that it should function as an effective professional agency which has a high international standing and reputation.

BTWC Organization Functions

The BTWC Organization will be required to carry out a number of functions in implementing the Protocol and thereby strengthening the implementation of the Convention. States Parties will be required to establish National Authorities whose responsibilities will include the collection of national data and information required for declarations and submit these declarations to the BTWC Organization. The BTWC Organization will need to protect confidential information should such information be included in these declarations. Declarations will need to be examined and analysed by the BTWC Organization and by the National Authority which will both wish to check that national declarations are accurate and complete. There is much to be gained by making these declarations publicly available at least in part as this demonstrates transparency and builds confidence both nationally and internationally. Publicly available declarations can be analysed by national and international experts thereby providing additional assurances of both their accuracy and their completeness.

Declarations. The current rolling text contains language albeit in square brackets for the declaration of the following activities and facilities:

[(a) Activities

(i) The presence/absence of [military][civilian][national][biological]defence programmes [against biological and toxin weapons];

[(ii) Any additional information related to past offensive and/or defensive activities not provided in the initial declaration.]]

[(b) Facilities

(i) [Which as their main task are][taking part in][military][civilian][national][biological] defence [facilities taking part in]programme(s) [against biological and toxin weapons [as per listed agents and toxins]][and conducting work on microorganisms or toxins as well as material imitating their properties];

(ii) Which produce vaccines [and/or toxoids/anatoxins][licensed by the State Party] for the protection of humans [against listed agents or toxins][with a production capacity as specified in Annex...][with primary production containment];

(iii) Which produce vaccines [and/or toxoids/anatoxins][licensed by the State Party] for the protection of animals [against listed agents or toxins][with a production capacity as specified in Annex...][with primary production containment];

[(iv) Which produce plant inoculants and/or biological control agent(s) and have a plant quarantine capability [with primary production containment];]

(v) Which have any maximum containment laboratories meeting criteria designated as [Biosafety level 4 ((BL4) according to WHO Classification) or P4 (according to WHO Classification) or equivalent standards][maximum containment];

[(vi) Containing areas protected [by high containment][according to Biosafety Level 3 (BL3) [as specified in the 1993 WHO Laboratory Biosafety Manual]] [and working with listed agents or toxins]but excluding purely diagnostic [and medical]facilities;]

(vii) Which

[work with listed agents or toxins with the exclusion of facilities involved only in diagnostic and/or medical treatment activities;]

[have an aggregate fermenter capacity of 100 litres or more and work with or produce listed agents;]

[conduct any of the following activities with any of the agents or toxins listed in Annex A excluding those involved only in diagnostic and/or medical treatment activities:

[- research and development...

[- production of such agents and toxins...

[- maintain culture collections...

[- apply genetic modification...

[- aerobiology

[(viii) Other microbiological production facilities...not working with listed agents which have an aggregate fermenter production capacity of [100][1000]litres or more...

[(ix) Not working with listed agents or toxins which

[-possess aerosol {Explosive] test chambers of ...m3 or above for work with microorganisms or toxins;]...

In addition there is language for the declaration of transfers of listed agents or toxins and equipment, of any relevant information on outbreaks of disease caused by listed agents or toxins for humans, animals and plants, and of the implementation of Article X of the Convention.

The major omission, in what is otherwise comprehensive language, is the absence of any specific mention of declarations of past BW facilities. As it is well known from declarations made under Confidence Building Measure Form F that there are such past BW facilities in several countries, such as Canada, France, the Russian Federation, the UK and the US, there is a strong argument that such facilities should be specifically declared as they are undoubtedly of particular relevance to the Convention as they may well still contain the knowledge and in some cases some of the facilities required for BW. It is worth noting that under the Chemical Weapons Convention (CWC), chemical weapon (CW) production facilities are required to be destroyed; they may only exceptionally be converted and are then subjected to an appropriately intrusive verification regime. Whilst it is not suggested that past BW facilities should be destroyed because of their potential use for peaceful purposes, they should be subjected to an appropriately intrusive verification regime.

There is a good argument that the aim of declarations must be to have declarations of those activities and facilities of greatest relevance to the Convention and not to have declarations of all facilities of possible relevance. Indeed, it can be argued that the numbers of facilities declared by a country should be of the order of tens resulting, for 160 States Parties in a total of some 1600 to 3200 facility declarations if an average of 10 to 20 is taken per country. This total is consistent with the number of 2500 estimated by others. The Austrian/UK contribution to the EU seminar for the pharmaceutical industry on 13 May 1998 said that "the number of facilities in individual EU countries that would need to be declared can probably measured in tens rather than hundreds." Consequently, the triggers for declarations need to catch the most relevant facilities whilst not endeavouring to catch all facilities.

Bearing this in mind, it is suggested that the triggers for Declarations that should appear in the Protocol are the following:

Activities

a. Biological defence programmes

b. Past offensive/defensive programmes

Facilities

a. Biological defence facilities

b. Past BW facilities

c. Human vaccine production facilities

d. Animal vaccine production facilities

e. Plant inoculant production facilities

f. Other microbiological production facilities

g. Maximum containment (BL 4) facilities

In addition, there should be a combination trigger for

h. Facilities working with listed agents or toxins and

having an aggregate fermentation capacity of 100 litres or more.

It is judged that the reporting burden for such facilities would not be excessive -- afterall, the microbiological industry in many countries is already tightly controlled for public health and environmental safety reasons -- and would be effective in catching the facilities of most relevance to the Convention. It also appears that no confidential proprietary information will be required to complete the declarations for commercial facilities. The Austrian/UK contribution to the EU seminar for the pharmaceutical industry on 13 May 1998 said that "All are agreed that the forms should be simple and straightforward and should not seek any information which would be considered commercially sensitive."

Visits. The current rolling text contains provision for four types of visits:

(a) [Random Visits];

(b) [Clarification Visits];

(c) [Voluntary Visits];

(d) [Voluntary Confidence-Building Visits];

The negotiations relating to visits are very active and terminology and purposes are changing from AHG meeting to meeting. In the present language, Random Visits are to confirm that "declarations are consistent with obligations under this Protocol", Clarification Visits are to "resolve any ambiguity, uncertainty, anomaly or omission in the declarations of a State Party", Voluntary Visits (previously known as Request Visits) are to help States Parties "compile individual facility and national declarations" and Voluntary Confidence-Building Visits are visits carried out under procedures in the Annex on Confidence-Building Measures to the Protocol. The latter class of visits is ill-defined in the current text as they appear to have developed from the VEREX measure of exchange visits into visits that may be bilaterally arranged or may be arranged by the BTWC Organization.

The basic premise that there should be a portfolio of different types of visits -- all of which are non-challenge in nature -- is a sound one. A two-pillar regime that had only declarations and challenge investigations would be ineffective and would be likely to reach erroneous judgements and thus fall into disrepute. There is a convincing argument for a three-pillar regime comprising declarations, visits to declared facilities and challenge investigations.

An analysis of information available about the Organization for the Prohibition of Chemical Weapons (OPCW) has led to an estimate of the size of a future BTWC Organization of about 200, well under half that of the OPCW. About 70 would be inspectors, about a third of the number of OPCW inspectors. This same analysis assumes that the BTWC Organization might make about 100 visits and inspections each year, about a third of the number planned by the OPCW. If it is assumed that there as many biological defence facilities as there are chemical defence facilities (and that the chemical defence facilities are the 40 Single Small Scale Facilities (SSSF) under the CWC) and that there are perhaps 20 past BW facilities under government control or funding, then it is possible to make some estimates about the numbers of different kinds of visits might take place each year.

Such an estimate of 40 biological defence facilities is supported by analyses of the declarations made under the Confidence Building Measure (CBM) A.2 which show that although 60 such facilities were declared by States parties between 1992 and 1997 only 43 were declared in 1997. As only just over half of the States Parties provide the required CBM information, the number of 43 is a conservative estimate. Insofar as past BW facilities are concerned, CBM F does not specifically call for such declarations. Nevertheless, some 5 countries (Canada, France, Russia, UK and US) have declared past offensive BW programmes under CBM F and it is clear from various studies of these past offensive BW programmes that the numbers of facilities involved was as many as 20 in the former Soviet Union alone. Consequently, an estimate of 20 past BW facilities under government control is again conservative.

Under the CWC, the SSSF are to be visited once every two years. It would seem reasonable to adopt a similar frequency for visits by the BTWC Organization to both biological defence facilities and to past BW facilities still under government control or funding. Thus of the 100 visits and inspections each year, 20 would be to biological defence facilities and 10 to past BW facilities. The remaining 70 would be for random visits, clarification visits and voluntary visits; for this analysis, consideration of Voluntary Confidence-Building Visits has been excluded as their nature is ill-defined. In the early years of the Protocol, it is likely that there could be a number of Voluntary Visits to assist States Parties in compiling their national and facility declarations and that there could also be a number of Clarification Visits to resolve ambiguities, uncertainties, anomalies and omissions in declarations. It is suggested that there might be some 50 visits, both Voluntary and Clarification, in the early years which could be expected to reduce in number in later years as States Parties gained experience in compiling their declarations. The number of Random Visits thus might be some 20 a year in the early years and would increase as the numbers of Voluntary and Clarification Visits reduced but would be unlikely to exceed 70 a year should the numbers of Voluntary and Clarification Visits reach zero. This estimate corresponds closely to the Swedish Netherlands paper on visits at the EU seminar on 13 May 1998 which stated that "...such visits will not be carried out routinely to all declared facilities, but will be limited to a relatively low number per year, in the order of 50 to 100." The distribution of Random Visits should be such as to maximise the benefit to the Convention. The current rolling text has language in Article III F as follows:

"There shall be no more than [50] Random Visits per calendar year [with the following groups of countries receiving no more than [10] Random Visits each: [Africa, Asia, Eastern Europe, Latin America and the Caribbean, and the Western Europeans and other States...][Such visits shall be distributed [fairly] among the [5][...][regional] groups of countries - [and proportional to the number of the declared facilities of each State Party].] No State Party shall receive more than [10] Random Visits in each five year period...."

Whilst, such a geographical distribution is laudable, attention should also be paid to which States Parties have received visits to biological defence facilities and past BW facilities or Voluntary and Clarification Visits so that Random Visits can be weighted towards those States Parties that have received no Visits. It should be recalled that one of the principal reasons why Random Visits are important is that these are to confirm the accuracy of declarations. They also help to ensure that the BTWC Inspectorate has gained some appreciation of the approaches to microbiology within a State Party prior to any challenge investigation being carried out in any State Party as in the absence of any prior Visits, the chance that the Inspectorate could reach an inaccurate and incorrect judgement during a challenge investigation will be increased.

It also needs to be recognised that Random Visits are likely to be short and by small teams. Their prime purpose is to confirm the accuracy of the declaration for that site. One Working Paper presented to the Ad Hoc Group demonstrates that a group of 3 inspectors spending 2 days at a site can, without jeopardizing confidential proprietary information, gain a useful appreciation which would contribute over time to the gaining of a valuable additional level of information on activities relevant to the Convention that the BTWC organization inspectorate would not otherwise have.

It is thus considered that the future Protocol should include provisions for the following categories of Visits, all being non-challenge and all to declared facilities:

Facilities

Number of

facilities

Frequency

of visits

Visits per

year

Biological defence

40

0.5/year

20

Past BW facilities

20

0.5/year

10

Random visits

2500

< 2/year

20 -- 70

Clarification visits

2500

as necessary

20 -- 0

Voluntary visits

160

on request

30 -- 0

An order of magnitude of their frequency is indicated assuming some 160 States Parties.

Useful parallels can be drawn from the routine inspections under the CWC where a recent paper by the Chairman of the Compliance and Controls Task Group of the US Chemical Manufacturers Association concludes that the values of the CWC far outweighs its costs. It notes the importance of the good protection in the CWC for commercial proprietary information and provides useful advice on how the chemical industry can prepare for routine visits.

Although there has been much debate about visits in the BTWC Protocol and whether commercial proprietary information might be put at risk by such visits, it has to be emphasised that the prime purpose of visits is to check that declarations are accurate or, in the case of voluntary or clarification visits, to assist in preparing declarations or resolve ambiguities in declarations. It seems probable that visits, which will be very infrequent, will be short and not put commercial proprietary information at risk.

Investigations. The rolling text contains provision for three types of investigation:

(1) [Field] investigations [of the alleged use of biological weapons][, to be conducted in geographic areas where the release of, or exposure of humans, animals or plants to microbial or other biological agents and/or toxins has given rise to a concern about non-compliance with Article I of the Convention by a State Party]

(2) [Facility] investigations [of any other alleged breach of obligations under the provisions of the Convention][, to be conducted inside the perimeter of a particular facility(ies) for which there is a concern that it is involved in activities prohibited by Article I of the Convention]

[(3) Investigations where there is a concern that a transfer has taken place in violation of Article III of the Convention]

There has been considerable debate about natural outbreaks of disease with a NAM (Non-Aligned Movement) and other countries working paper in January 1998 addressing the exclusion of all natural outbreaks of disease from investigations under the Protocol. This paper states that "the investigation, diagnosis, treatment and control of disease fall primarily within the domain of the public health care system of each country...Investigation and control of disease remains its sovereign responsibility, even if that country were to seek international assistance, including from international organizations such as the World Health Organization." It then goes on to state that "All natural outbreaks of disease fall in the domain of public health and do not pose a compliance concern to the Biological and Toxin Weapons Convention (BTWC) and are therefore of no concern to the Convention or to its proposed Protocol." The paper then quite rightly recognises that unusual outbreaks of disease could have natural causes or could arise as a result of use of biological or toxin weapons. It then goes on to say that "It is essential to differentiate between natural outbreaks of disease and an event of non-compliance with the BTWC."

Whilst it is undoubtedly true that in an ideal world, unusual outbreaks resulting from an event of non-compliance with the BTWC should be differentiated from unusual outbreaks, this is not a practically simple thing to do. It will be clear from consideration of all the past alleged events of non-compliance with the BTWC that it is very difficult to obtain evidence that clearly demonstrates non-compliance without carrying out an investigation. It is also quite evident that if investigations are not carried out promptly after the initiation of the outbreak, the evidence to differentiate between an event of non-compliance and a natural, albeit unusual, outbreak may not be forthcoming.

Insofar as the protocol to strengthen the BTWC is concerned, there would appear to be a pragmatic approach that would be applicable in those cases where the State Party has been subjected to an attack by biological or toxin weapons. Such a State Party would be keen to investigate the cause of the outbreak and could be expected to welcome all possible international assistance; in such circumstances, the aid of the BTWC Organization would be positively encouraged. The only possible reservation might be if the State Party was concerned that the outbreak might have resulted from poor national health standards -- and would not wish this advertised widely. This might be overcome by an arrangement that in the event of the BTWC Organization participating in an investigation of an unusual outbreak in a State Party and concluding that this was a natural outbreak then this would suffice as the report of the BTWC Organization to the other States Parties.

The more difficult case is when an unusual outbreak has resulted in a State Party because of activities within that State Party that are non-compliant with the BTWC. Understandably, such a State Party would be unwilling to have an investigation of such an outbreak. Nevertheless, the ability to investigate such unusual outbreaks quickly lies at the heart of an effective Protocol to strengthen the BTWC.

It will be important for the BTWC Organization to build up an appreciation of the patterns of outbreaks of disease so that it has the expertise to distinguish outbreaks of disease that may result from an event of non-compliance with the BTWC and is able to focus any investigation of outbreaks on those characteristics that are most likely to demonstrate whether the outbreak was the result of a natural cause or of deliberate action. It has to be recognised that this capability has to be acquired by the BTWC Organization as other international organizations such as the WHO, FAO and OIE could not carryout such a function without jeopardizing their neutrality and hence their ability to carry out their primary functions.

The other point of debate has related to the initiation of such investigations, whether field or facility, and what type of filter mechanism should be devised. The rolling text has the following language:

[Requests for an investigation [into a non-compliance concern][may][shall]be submitted to [the United nations Security Council] for decision on whether to initiate an investigation and on the need to conduct an inspection.[[Requests for an investigation into a non-compliance concern [may][shall]be submitted to the [politically representative body of States Parties][the Director-General]. Providing the request satisfied agreed requirements, the investigation would proceed [if formally approved by [at least a two-thirds majority][a three-quarters majority][present and voting] of this representative body][unless this body decides by a three-quarters majority of all its members against carrying out the investigation.]]

This contains both the green light filter (a majority required to vote in favour of the investigation) and the red light filter (a majority required to vote to stop an investigation) mechanisms. The Chemical Weapons Convention has a red light filter mechanism as Article IX contains the following language:

The Executive Council may, not later than 12 hours after having received the inspection request, decide by a three-quarter majority of all its members against carrying out the challenge inspection, if it considers the inspection request to be frivolous, abusive or clearly beyond the scope of this Convention as described in paragraph 8. Neither the requesting nor the inspected State Party shall participate in such a decision. If the Executive Council decides against the challenge inspection, preparations shall be stopped, no further action on the inspection request shall be taken, and the States Parties concerned shall be informed accordingly. [Emphasis added]

There is much to be said for the BTWC Protocol containing a similar red light filter mechanism to that in the CWC. It would be unfortunate if an investigation relating to a toxin were to be handled differently depending on which Convention it was being investigated under. It is also apparent from recent international events such as the confrontation with Iraq earlier this year that it can be very difficult to gain an international majority even when the evidence is as clear cut as it was in the case of the Iraqi non-compliance with the United Nations Security Council Resolutions. The BTWC Protocol should have a red light filter mechanism.

It is thus considered that the future Protocol should have provision for the following investigations:

a. Field Investigations

b. Facility Investigations

c. Article III Transfer Investigations (discussed in the next section)

and that these should have a red light filter mechanism. The BTWC Organization will need to collect data on outbreaks of disease so that over time it will build expertise that it can draw upon in distinguishing an outbreak resulting from an event of non-compliance with Article I of the Convention and a natural outbreak.

Article III Measures (Non-Transfer). The current rolling text has language in Article III. F of the Protocol on measures to strengthen the implementation of Article III of the Convention:

[States Parties, in order to ensure compliance with Article III of the BTWC, shall only transfer dual-use microbial and other biological agents and toxins for purposes not prohibited by the Convention, in accordance with the following guidelines.

...the guidelines shall be as follows:

(a) Any request made by a State Party for the procurement of a specific agent/toxin reagent shall be accompanied by information on purpose, quantity required, site or facility for proposed use, quantity to be produced at the site or facility, place where intended to be stored and end-use certificate;

(b) Any request for transfer or procurement of equipment envisaged to be declared under CBMs, for use by a State participating in the compliance regime in a BL4 facility, including details of its proposed application and the site/facility for intended use, shall be intimated to [the BTWC Organization];

(c) Any transfer of technology related to means of delivery, aerosol dispersion of toxins and pathogens, stabilization of agents/toxins to environmental stress shall be intimated to [the BTWC Organization]

(d) Transfer of agents, equipment and material shall not be allowed to non-States parties of the compliance regime under the Convention without the prior approval of [the BTWC Organization];]

Alternative proposals are also elaborated in the same part of the draft Protocol. Elsewhere in the draft Protocol is language relating to declarations (Article III. D) which states that:

[Transfers

Each State Party shall declare annually all international transfers of listed agents or toxins, equipment [or means of delivery].

Each State Party declaring such transfers shall submit information according to the format in Annex...]

Whilst there is provision in the current draft for investigations where there is a concern that a transfer has taken place in violation of Article III of the Convention, there is currently no language in the relevant Annex (D. IV) of the Protocol.

The subject of measures to strengthen the implementation of Article III of the Convention is contentious because of the relationship to the Australia Group harmonization of export controls which are regarded by many developing States as being discriminatory. However, it is becoming evident that States are concerned about transfers of biological agents and toxins for prohibited purposes and some countries have introduced rigorous national controls on transfers of pathogens because of human, animal and plant health and environmental concerns, and more recently, to counter possible acquisition of agents and toxins for terrorist purposes. It is also clear that negotiations are advanced for a biosafety protocol which will introduce transborder controls for living modified organisms.

It is thus considered that the future Protocol should indeed contain measures to strengthen the implementation of Article III including:

a. Guidelines for transfers of biological agents, toxins and equipment

b. Requirement for annual declarations by States Parties

c. Provisions for the investigation of concerns that a transfer has occurred in breach of Article III of the Convention.

Article IV Measures (National Implementation). The current rolling text has language in Article X of the draft Protocol which addresses national implementation measures. This addresses both the implementation of the Protocol and implementation of the Convention in stating that:

1. Each State Party shall, in accordance with its constitutional processes, take any necessary measures [including enacting penal legislation with respect to the obligations under the Protocol] to implement its obligations under this Protocol. [In particular, it shall:

[(a) Prohibit natural and legal persons anywhere on its territory or in any other place under its jurisdiction [or control] as recognized by international law from undertaking any activity prohibited [to a State Party] under the Convention[, including enacting penal legislation with respect to such activity]; ]

[(b) Prohibit natural and legal persons from undertaking any such activity anywhere under its control; and]

[(c) Prohibit, in conformity with international law, natural persons possessing its nationality from undertaking any such activity anywhere.]]

....

[3. In order to fulfil its obligations under this Protocol [the Convention], each State Party shall designate or establish a [National Authority] and shall so inform the [Organization] [upon] entry into force of this Protocol for it. The [National Authority] shall serve as the national focal point for liaison with the [Organization] and with other States Parties.]....

Although, there is some reluctance by some States to engage in addressing how the Protocol might strengthen the implementation of the BTWC, it is clear from Final Declaration of the Special Conference that established the mandate for the Ad Hoc Group that they were "determined to strengthen the effectiveness and improve the implementation of the Convention." [Emphasis added]. When the efforts taken at the successive Review Conferences of the BTWC are considered, it becomes clear that the Protocol being negotiated by the Ad Hoc Group presents the opportunity to strengthen the implementation of Article IV of the Convention.

There would be benefits in the Protocol containing language, comparable to that which is present in respect of measures to improve the implementation of Article III, which requires States parties to provide information on the laws and regulations to implement the Article. The Article III language (in Article III. F. II of the Protocol) states that:

[(b) (i) Each State Party shall report to [the Organization] on the national laws and regulations it has adopted to implement Article III of the BTWC not later than [...] days after entry into force of this Protocol for that State Party and whenever an amendment thereto is made.

(ii) Each State Party shall report to [the Organization] on its administrative and other national measures to implement Article III of the BTWC not later than [...] days after entry into force of this protocol for that State party and whenever an amendment thereto is made.

[(iii) Such reports shall contain detailed information. If available, the information contained in these reports may be subject to examination during a visit under the Article I investigation provisions of this Protocol.]

Similar language in respect of the measures to implement Article IV would be beneficial.

It is thus considered that the future Protocol should contain measures to strengthen the implementation of Article IV including:

a. Requirements for States Parties to enact penal legislation to implement the prohibition of any activity prohibited under the Convention

b. Requirement for States Parties to set up a National Authority to implement the Protocol

c. Requirements for States Parties to report to the BTWC Organization on the national laws, regulations, administrative and other national measures that it has taken to implement Article IV of the Convention.

Article X Measures (Cooperation for Peaceful Purposes). The current rolling text has language in Article VII of the draft Protocol which addresses scientific and technological exchange for peaceful purposes in order to enhance the implementation of Article X of the Convention. Article X of the Biological Weapons Convention (BWC) promotes the peaceful use of biological materials, equipment and information for peaceful purposes as States Parties are committed as follows:

"(1) The States Parties to this Convention undertake to facilitate, and have the right to participate in, the fullest possible exchange of equipment, materials, and scientific and technological information for the use of bacteriological (biological) agents and toxins for peaceful purposes. Parties to the Convention in a position to do so shall also cooperate in contributing individually or together with other States or international organisations to the further development and application of scientific discoveries in the field of bacteriology (biology) for the prevention of disease, or for other peaceful purposes.

(2) This Convention shall be implemented in a manner designed to avoid hampering the economic or technological development of States Parties to the Convention or international cooperation in the field of peaceful bacteriological (biological) activities, including the international exchange of bacteriological (biological) agents and toxins and equipment for the processing, use or production of bacteriological (biological) agents and toxins for peaceful purposes in accordance with the provisions of the Convention."

The first paragraph of Article X is referred to as the promotional aspect and the second paragraph as the regulatory aspect. The aim is to devise measures that implement both the promotional and the regulatory elements.

At the end of the March 1998 AHG meeting, the title for Article VII had changed to:

ARTICLE VII [SCIENTIFIC AND TECHNOLOGICAL EXCHANGE FOR PEACEFUL PURPOSES][IMPLEMENTATION ASSISTANCE] AND TECHNICAL COOPERATION

The words [Implementation Assistance] had been introduced as an alternative title thus putting the title into square brackets where none had appeared before. In addition the whole section within Article VII entitled "Measures to avoid hampering the economic and technological development of States Parties" has now been placed within square brackets as has the title "International Cooperation" of another section. These are seriously retrograde steps as they unnecessarily cast doubts on the intention of the Ad Hoc Group to address the element of its mandate requiring it inter alia to consider "Specific measures designed to ensure effective and full implementation of Article X,...". As will be shown below, measures to facilitate the implementation of Article X can be devised to directly contribute to increasing transparency building confidence in compliance with the Convention. The need to consider measures relating to the implementation of Article X has been generally recognised as an issue that is of particular importance to the developing countries. It is therefore not surprising that the NAM statement at the end of the March Ad Hoc Group meeting expressed "their concerns at attempts to reduce the scope and importance of issues related to Article X of the Convention." and went on to say that "Substantive progress in strengthening the application and full operationalisation of Article X is crucial to the conclusion of a universally acceptable and legally binding instrument designed to strengthen the Convention. They reaffirm readiness to work with other delegations in order to achieve an appropriate balance in the Protocol."

The language in Article VII contains the following Sections

[(A) [General Provisions]

(B) Measures to promote scientific and technological exchanges

[(C) Measures to avoid hampering the economic and technological development of States Parties

(D) [[Institutional Mechanisms and] International Cooperation] [Protocol Implementation Assistance]

[(E) Cooperative Relationships with other international organizations]

(F) [Safeguards and limitations

In addition, there is language in Article III. D Declarations of the Protocol that requires:

Each State Party shall declare annually the measures taken individually or together with other States and international organizations in implementing Article X of the Convention.

Each State party shall submit a declaration on the implementation of Article X of the Convention according to the format in Annex...

Thus far, there has been little consideration by the Ad Hoc Group of specific measures that might be taken to enhance the implementation of Article X as the Ad Hoc group has understandably concentrated on compliance measures which lie at the heart of the Protocol to strengthen the BTWC. As, however, the Protocol text advances it is becoming timely to consider specific measures to enhance the implementation of Article X. In doing this, it is important to consider initiatives being taken in other fora that are separate from yet are relevant to the BTWC. The challenge is to identify measures that will enhance the implementation of Article X whilst at the same time contributing to the building of confidence that States Parties are compliant with the Convention and avoiding duplication with activities in other fora.

Whilst it will be important to avoid duplication of activities such as those under Agenda 21 and the Convention on Biological Diversity, it is becoming apparent that there are common goals in respect of both international security and public health and environmental safety that can complement the moves being taken by the Ad Hoc Group to increase transparency and build confidence. Two recent studies have examined possible building blocks that might be utilised in devising measures to enhance the implementation of Article X.

These show that there is already considerable international effort to harmonize national and international regulations relating to pathogens that present danger to public and animal health and to the environment. It is evident in that in many countries, for public health and environmental safety reasons, national authorities are already establishing regulations, collecting relevant information about facilities and activities and inspecting these facilities and activities. Similar measures are also being taken to counter the possible acquisition of such materials for terrorist purposes. As the BTWC Protocol is likely to contain declarations and inspections of facilities and activities together with national implementation measures, as well as measures to improve implementation of Articles III and X of the Convention, there is potential for a two way synergy between the strengthening of the BTWC and the strengthening of national procedures for the handling, use and transfer of harmful pathogens for reasons of public health and environmental safety. Consequently, in regard to the strengthening of the implementation of Article X of the BTWC, there appears to be scope for measures that are both promotional and regulatory to facilitate the harmonization of national, regional and international safety rules for pathogens involving both the collection of data and the inspection of facilities thereby enhancing both national public confidence as well as regional and international security.

Another area in which there is scope for measures to strengthen Article X whilst at the same time strengthening confidence in compliance with the BTWC is that related to the licensing of pharmaceutical and biotechnological production facilities. It is apparent that the guidelines for Good Manufacturing Practice (GMP) for medicinal products issued by the European Community, by the Pharmaceutical Inspection Cooperation Scheme and by the World Health Organization have successfully been harmonised. These guidelines, or equivalent standards, are required to be met in order for the regulatory authority of one country to accept the reports of inspections of manufacturers carried out by the inspectorate of another country. Such international acceptance is already accepted within the European Community and between the members of the Pharmaceutical Inspection Convention. Mutual Recognition Agreements have been negotiated between countries to achieve the same goal. The incentives for the harmonization of GMP and for the international acceptance of inspections is the facilitation of trade which is becoming increasingly more international.

The relevance of these harmonised guidelines for GMP for medicinal products and the international acceptance of inspections is that facilities which meet these standards for GMP for medicinal products are subject to repeated inspections about once every two years by national inspectorates. The GMP requirements are such that it would not be easy for a GMP inspected manufacturing facility to carry out covert manufacture of prohibited products. Consequently, pharmaceutical and biotechnological facilities that meet these harmonised international standards and are subject to regular inspection are unlikely to present a risk to the Convention -- in other words, there are grounds for confidence that such GMP inspected facilities are engaged in activities that are in compliance with the BTWC. Consequently, measures to assist developing countries to adopt national standards for GMP of pharmaceutical products that are the same as those that have been internationally harmonised and adopted and to establish national inspectorates to carry out regular inspections of pharmaceutical manufacturers would be a specific measure that would enhance the implementation of Article X whilst at the same time contributing to increased confidence in compliance.

There are benefits to be gained from the future Protocol containing both promotional and regulatory measures to strengthen the implementation of Article X:

Promotional Measures. The OPCW experience has shown that the setting up of National Authorities to implement the CWC is a non-trivial activity. There are immense benefits to be gained for the implementation of a strengthened BTWC Protocol through measures to assist in the setting up of national Authorities covering aspects such as draft enacting legislation for States to adapt for their own national systems, the training of personnel for National Authorities and assistance in setting up systems for the collection and collation of the data needed for the mandatory annual declarations and in receiving incoming visits and investigations from the future BTWC Organisation.

As biological warfare is a deliberate outbreak of disease in humans, animals or plants, an important element of the future BTWC regime requires the continuing surveillance worldwide of outbreaks of disease in humans, animals and plants. It would be unrealistic to expect such a surveillance system to be set up by the personnel of the future BTWC organisation. Rather the BTWC organisation will need to be a recipient of information arising from surveillance carried out by the existing WHO, FAO and OIE international organisations. As the existing surveillance arrangements have various deficiencies, measures to implement Article X through the improvement in States Parties of national components of the WHO, FAO and OIE surveillance networks would contribute both to the improved implementation of the BTWC and would serve as an important incentive to encourage States to accede to the Protocol (and the Convention) in order to gain these benefits. It is encouraging that the G8 Foreign Ministers in May 1998 recognised that "the impact of infectious and parasitic diseases continue to cause concern. The G8 is committed to helping countries respond to these challenges...through improving surveillance capacity...". They went on to say that "experts from G8 countries and WHO will meet later this month to review surveillance systems throughout the world, and examine options for assisting WHO as it helps to develop global surveillance networks."

Regulatory Measures Worldwide concerns about the potential dangers to public health and to the environment have led States to introduce national regulatory systems to ensure that dangerous pathogens, toxins and living modified organisms are handled, stored and transferred in ways that protect the public and the environment. Increasingly in order to promote trade, these systems and biosafety standards are being improved and harmonised regionally and internationally. Consequently, such measures could contribute to both the regulatory and the promotional elements of Article X. In addition, as a counter to the possible acquisition of pathogens and toxins for terrorist purposes, some States Parties such as the United States have introduced controls on the facilities in which such materials can be handled and stored as well as on their transfers. All of these regulatory controls help to ensure that such materials are only used for permitted, peaceful purposes. Measures to implement Article X through actions to promote the harmonisation of such regulatory systems internationally will contribute to enhancing confidence that dangerous pathogens and toxins are being used for controlled and peaceful purposes and thus over time to building confidence in the Convention.

In addition, to ensure the safety of the humans and animals to whom human medicinal products and veterinary products are administered, national and regional regulatory systems are increasingly requiring that manufacturer's authorizations or licences are issued for the facilities in which such products are produced. These authorizations are based on repeated inspections by national inspectorates of such facilities to ensure that internationally harmonised standards of Good Manufacturing Practice for pharmaceuticals are being met. Article X measures to assist States Parties to establish equivalent regulatory authorities and regimes would both implement Article X thereby bringing significant trade benefits to States Parties and would build confidence that such production facilities are being used for permitted purposes.

Conclusions Such measures, which would facilitate the implementation of both the promotional and regulatory elements of Article X of the BTWC, would also contribute to the effective implementation of the Protocol to strengthen the BTWC. Article X promotional measures could include ones to assist States Parties in the setting up of national Authorities to implement the Protocol to the BTWC, to improve their biosafety standards and controls and to assist States Parties in improving their national components of the WHO, FAO and OIE surveillance networks. Article X regulatory measures could include ones to assist the establishment of national systems to ensure that dangerous pathogens, toxins and living modified organisms are handled, stored and transferred in ways that present no danger to the public or to the environment and the setting up of regulatory systems to ensure that human medicinal and veterinary products are manufactured safely and will not present a danger to the humans and animals to whom they are administered.

Article X implementation measures such as these will provide both clear benefits and incentives for States to become Parties to the Protocol (and the Convention). Over time, they will serve as a first stage towards the creation of a climate in which States Parties have gained the necessary degree of confidence in the compliance of other States Parties with the Convention that present trade restrictions between States Parties can be relaxed. The benefits to States Parties from these proposed measures to implement Article X are summarised below.

Article X Measure

Benefits to States Parties

Promotional

Assistance in setting up National Authorities and in implementing the BTWC Protocol

Enhanced world-wide confidence in the implementation of the BTWC Protocol (and thus of the Convention) by all States Parties

Assistance to national elements of WHO, FAO and OIE Surveillance Networks

Improved national, regional and international surveillance of outbreaks of disease enabling counters to outbreaks to be rapidly instituted

Information from the WHO, FAO and OIE Surveillance Networks will be important for the effective operation of the BTWC Organisation in its oversight of the implementation of the BTWC Protocol

Regulatory

Regulatory frameworks for dangerous pathogens, toxins and living modified organisms

Improved public confidence that such materials are only being used for controlled and permitted purposes

Contribute to ensuring that such materials are not available for terrorist purposes

Regulatory pharmaceutical inspectorates and licences

Improved assurance of safety for humans and animals receiving the medicinal/veterinary products

Promotion of trade in pharmaceuticals

Enhanced confidence that pharmaceutical production facilities are only being used to produce licensed permitted products

Such measures will also bring significant benefits to the States Parties that do not already have such national health and safety or GMP standards and inspectorates. These measures would be additional to the proposals already in the draft Protocol for the BTWC Organization to establish cooperative arrangements with relevant organizations such as the OPCW, WHO, FAO, OIE, UNIDO, ICGEB, and UNEP and for the promotion of scientific and technological exchanges.

Analysis

It is useful to examine how the various elements of the integrated regime for the strengthened BTWC will complement one another and enhance the effectiveness of the overall regime. There are at least two main functions of the Protocol -- to strengthen confidence in compliance and to address concerns in a timely way.

Building Confidence in Compliance. Several elements of the Protocol will contribute to this:

Public information whether from the media, the internet, official communications or from academic and other publications provides a baseline of understanding within the BTWC Organization about the standing of a particular country in respect to its perceived compliance with the BTWC. It will be recalled that at the Fourth Review Conference in November 1996 the Final Declaration on Article I made an appeal through the States Parties to their scientific communities "to lend their support only to activities that have justification for prophylactic, protective and other peaceful purposes, and refrain from undertaking or supporting activities which are in breach of the obligations deriving from the provisions of the Convention." There is thus a clear need for States parties to provide public information to inform the scientific community about the Convention. Furthermore, there are benefits to be gained from involving the scientific community in contributing to the implementation of the Convention. Public information is augmented by the information provided by States Parties in the declarations made under the Confidence Building Measures (CBMs) agreed at the Second Review Conference in 1986 and extended at the Third Review Conference in 1991; under the Protocol to strengthen the BTWC, additional CBMs may be agreed which could require either the mandatory or voluntary provision of information. Thus far, the Ad Hoc Group has paid little attention to CBMs as emphasis has rightly been focussed on the central mandatory measures to strengthen the Convention. One advantage of a future BTWC Organization will be the collation and analysis of CBM information together with the reminding of States Parties of the need to provide CBM declarations.

WHO, FAO and OIE information will be an important input to the future BTWC organization which will need to analyse this information so as to build up an expertise and understanding over time of the pattern of natural outbreaks of disease within States Parties against which the BTWC Organization will be able to evaluate outbreaks that appear to be unusual. Close links will need to be established with these organisations (WHO, FAO, OIE) so that maximum benefit is derived by the BTWC Organization from the analyses carried out by these other organizations, always recognizing that these other organizations will not be able to point out outbreaks that might be caused by a BTWC non-compliant event.

OPCW information will also be important to the BTWC Organization as the CWC also covers the prohibition of toxins and there is likely to be, and rightly so, an overlap between the two Conventions in this respect. A close link between the two Organizations will also be valuable because of the links between chemical and biological weapons which mean that the two Conventions will have more in common with one another than with any other international treaty or convention. Both Organizations will benefit from exchanging information on their experience in implementing the similar, albeit different in detail, provisions in the two Conventions so that both can benefit from best practices and avoid common difficulties. It is also true that traditionally States which have sought chemical weapons have often gone on to seek biological weapons. Consequently, close liaison between the two Organizations will help to ensure that there is an effective prohibition to all chemical and biological weapons. It will, however, be important if the two organizations are to maximise their benefits to ensure that appropriate provisions are made for the handling of confidential information. It is good that the draft Protocol already contains language which in both Articles VII and IX refers to the BTWC Organization concluding "agreements and arrangements with relevant organizations" such as the OPCW.

Declarations made by States Parties will complement the information already mentioned. These declarations are likely to be not only of activities and facilities of relevance to the Convention but also of measures taken by States Parties to implement Articles III (non-transfer), IV (national implementation) and X (peaceful cooperation) of the Convention. Together these will provide the Organization with an appreciation of the approaches being taken by the State Party to implement the Convention and the quality of these declarations will be indicative of the importance ascribed by that country to compliance with the BTWC and the Protocol.

Confidence in these declarations and all other information available to the BTWC organization, such as publicly available information or information provided under Multilateral Information Sharing -- a possible CBM for which language is included in Annex G IV of the Protocol -- will be significantly augmented by Visits carried out by the BTWC Organization. Random Visits to declared sites will ensure that declarations are accurate whilst Clarification Visits will address ambiguities, uncertainties, anomalies or omissions in declarations and Voluntary Visits will help States Parties in their compilation of individual and national declarations.

It is anticipated that the BTWC Organization will produce an annual report in which it will set out its appreciation of the building of confidence in compliance with the BTWC resulting from its analysis of all information available to it. Such a report could be similar to that which the OPCW has produced on the implementation of the CWC.

Addressing Concerns about Compliance

The second key function of the Protocol will be to provide a mechanism through which inconsistencies, anomalies and concerns can be addressed in a timely fashion. It is important that concerns be addressed rapidly as if these are left unaddressed for a period of time they are likely to grow and become of greater concern. The Protocol will enable a graduated response to concerns through consultation and clarification which may take place directly between the States Parties concerned, with the assistance of the Director-General of the BTWC Organization, or by requesting the Executive Council to obtain clarification. The Protocol also contains provision for the Technical Secretariat to seek clarification from any State Party of any ambiguity, uncertainty, anomaly or omission. Should such consultation and clarification not resolve the issue, then a Clarification Visit may take place to address any ambiguity, uncertainty, anomaly or omission; the extent to which such Clarification Visits can be initiated by the BTWC Organization or by a request of a State Party is all in square brackets in the current text as is the question as to whether such Clarification Visits should be after appropriate review by the Executive Council. Should a Clarification Visit not satisfactorily resolve the concern, it will then be open for States Parties to lodge a request for an Investigation. This is shown schematically in summary form below.

The building of confidence and the addressing of concerns are closely connected. Whilst the accumulation of information over time about activities and facilities within a State Party will build confidence within the BTWC Organization that they have an accurate appreciation of that State Party, the building of confidence in compliance will depend on the consistency of the information being accumulated, the quality of the declarations by the State Party and the response by the State Party to any queries whether about when declarations will arrive or about any aspect of a declaration as well as the way in which visits to that State Party by the BTWC Organization have been received.

The heart of the building of confidence lies in the analysis of declarations and the carrying out of visits by the BTWC Inspectorate. In essence, the integrated regime can be represented as a combination of the two principal activities of building confidence and addressing concerns:

Conclusions

The Protocol being negotiated by the Ad Hoc Group in Geneva has all the key elements required for a highly effective integrated regime already in the draft text. The additional detailed measures identified here that have yet to be elaborated should not present an undue difficulty -- declarations of past BW facilities, visits to BW defence and government owned past BW facilities at about once every two years intervals, measures to improve implementation of Articles III, IV and X of the Convention designed to also contribute to strengthening confidence in compliance. This paper has demonstrated that all the different elements are all inter-related and together will have a considerable synergistic effect that will build confidence in compliance with the Convention, ensure that uncertainties, anomalies and concerns are swiftly investigated and improve the implementation of the Convention.

It is important to recall that the Chemical Weapons Convention which is already in force has implications for biotechnology. There are close parallels between the CWC verification regime which is already in force for 108 States Parties and the draft BTWC Protocol:

CWC Verification Regime

Draft BTWC Protocol

Mandatory declarations of relevant facilities

Mandatory declarations of relevant facilities

Routine inspections under facility agreements

Non-challenge visits to confirm declarations

Challenge inspections

Facility & Field Investigations

Confidentiality Annex

Confidentiality Annex

National Authorities

National Authorities

Implementing including penal legislation

Implementing including penal legislation

It is encouraging that the US Chemical Manufacturers Association state that "The values of the treaty in minimizing the likelihood of misuse of legitimate products and building the confidence of the public in the chemical industry far outweigh the costs of compliance." This augurs well for the BTWC Protocol, which closely reflects the elements of the CWC and has benefited from the lessons learnt from the negotiation and implementation of the CWC.

The measures within the draft Protocol are being designed to be effective in strengthening the BTWC without putting commercial proprietary information at risk. Although the final elaboration of the integrated regime has yet to occur, it does appear that the additional burden for the biotechnology industry will be modest and such as not to jeopardize commercial proprietary information. The biotechnology industry is already highly regulated in many countries; measures that seek to harmonise such regulations will contribute both to the promotion of trade and the building of confidence that dual purpose materials and facilities are only being used for permitted peaceful purposes.

The benefits to national and international security are clear. It is also evident that a strengthened BTWC will build international confidence which will facilitate and encourage international trade safe in the knowledge that the dual purpose biological agents and toxins, equipment and facilities will not be misused for prohibited weapons. The recent political initiatives to encourage completion of the substantive negotiations of the Protocol this year are welcomed and it behoves us all to do what we can to facilitate and aid the negotiations of the Ad Hoc Group during its final few months.

Implications of a strengthened biological and toxin weapons convention for the biotechnology and pharmaceutical industry
Professor Malcolm Dando, University of Bradford, UK

ABSTRACT:

The support of the US chemical industry was crucial in achieving ratification of the Chemical Weapons Convention (CWC) by the Senate last year, and therefore to the effective entry into force of that convention. The position taken by the dominant US biotechnology and pharmaceutical industry could likewise be crucial to the outcome of current efforts to strengthen the Biological and Toxin Weapons Convention (BTWC). This paper is based, in part, on interviews carried out in the United States in mid-1997.

There is no agreed definition of the US biotechnology industry. It encompasses both 'old' industries such as baking and brewing and 'new' industries based on modern revolutionary biology. Negotiations on the BTWC are being monitored by the various industry associations, but the lead is being taken by the major pharmaceutical companies through the Pharmaceutical Research and Manufacturers of America (PhRMA) association. This is linked to the International Federation of Pharmaceutical Manufacturers Associations (IFPMA) based in Geneva.

The US government, of course, having had a major offensive biological weapons programme from the time of the Second World War through to the late 1960s, has extensive knowledge of the problems that verification of the BTWC might present. Elements within the government have long held that it is not possible to verify the Convention. Against that background, it is not surprising that PhRMA also has expressed concerns, particularly over the potential loss of Confidential Business Information (CBI). Such concerns are obviously shared by the biotechnology industries of other countries. Unfortunately, the proposals put forward by PhRMA for strengthening the Convention are unlikely to result in effective restraint on further proliferation of biological weapons. The paper therefore sets out to discover if there could be any flexibility in the PhRMA position.

Intellectual property can be protected by patent, and the pharmaceutical industry seems generally satisfied with the development of international law in regard to patents over the last decade. Concern seems to be centered more on the potential loss of (unpatented) trade secrets. Trade secrets, in order to have legal protection in domestic law, must be identified and steps taken to protect them. Indeed, US lawyers argue that regular trade secret audits are essential to safeguard against commercial malpractice. There is no doubt, however, that as arms control agreements increasingly deal with the proliferation of dual-use technology rather than simply weapons systems, the CBI of private industry will be more at risk. Certainly, despite all the built-in restraints, CBI could still be at risk under the CWC and the research-intensive biotechnology industry feels that it has much more to lose than the chemical industry - particularly proprietary micro-organisms. On the other hand, the UK has carried out a range of practice inspections and feels that CBI can be protected by proper preparation and the use of managed access techniques.

It is argued that the PhRMA position results from a much more complex process than just an intra-industry concern over the potential loss of CBI. Indeed, whilst scientists working in the industry do not appear to be particularly well-informed about the BTWC, there is a genuine desire to help prevent the proliferation of biological weapons. The problems appear to have originated from PhRMA's interaction with the federal government and in particular the Trilateral visits from Russian officials. The fact that the US administration was unable, until this year, to reach an agreed position on strengthening the BTWC caused unease, and the handling of the Russian visits and their outcome in 1994 compounded industry fears that its views would not necessarily be considered. These factors, it is argued, led the industry to adopt a hard-line initial bargaining position in 1996-97. This explanation accords with that of another investigator, which is based on interviews in late 1997. She also points out that by that the US industry was seeking support for its position from industries in other countries. However, foreign industrialists might not understand the particular context that had given rise to the US industry's position.

In early 1998 the US government announced its position on strengthening the BTWC. Whilst making clear gestures to the biotechnology industry's concerns, this does seem to go beyond PhRMA's position in allowing for some non-challenge visits. The European Union also put forward its common position in early 1998 and, despite some difficult issues that remain to be resolved, negotiations are intensifying and could be concluded within a year. The latest PhRMA position available indicates some flexibility, but not on the core issues of concern such as non-challenge visits.

There appear to be three clear implications for the biotechnology industry, both within and outside of the United States. First, the industry must realise that the chemical industry's beneficial influence on the CWC resulted from long-term, high-level engagement with the negotiation process. It seems that the biotechnology industry has to catch up quickly and engage top-level personnel now that the endgame of the negotiations may be approaching. Second, the industry must appreciate the tension between its need to protect CBI and the need to prevent proliferation of biological weapons. The industry could 'win' in the sense of guarding its CBI, but later have to face the unpalatable fact that the Convention had not been adequately strengthened. Third, in making the difficult judgements that will be necessary on this issue over the next year, it is suggested that industry should be aware that the basis of international security, in an era of rapidly evolving science and technology, will have to change from (military) balance of power to treaty-based transparency. This will necessarily require increasingly intrusive measures of industrial verification. Strengthening the BTWC is but a early step in this general societal process. The alternative is increasingly destructive warfare.

FULL TEXT:

Introduction

In April 1997 the US Senate approved ratification of the Chemical Weapons Convention (CWC). This major step forward for those supporting effective multilateral control of the proliferation of chemical weapons was achieved in the face of strenuous opposition, including that of three former US Defense Secretaries.1 The approval of the Senate was only achieved in the end with the agreement of 28 conditions to the resolution. Some of these conditions clearly reflected potential concerns that might have been held by US chemical industry organisations. Thus:2

"Condition 16 requires notification of the Senate if an OPCW [Organisation for the Prohibition of Chemical Weapons] employee has disclosed confidential business information and certification to the Senate that the OPCW Director General has waived the employee's immunity from jurisdiction..."

and:

"Condition 28 requires that in cases where consent to the inspection is withheld by a facility owner, a criminal search warrant must be obtained for a challenge inspection and an administrative warrant must be obtained for a routine inspection..."

The underlying issues in regard to the protection of confidential business information (CBI) had, of course, been extensively debated in the US during the negotiation of the CWC over the previous decade.3,4,5

Chemical manufacturers certainly had real concerns about the potential loss of confidential business information. As one representative stated at a round-table discussion:6

"...My concern is that we do not give away the store, so to speak, and thereby make ourselves even increasingly non-competitive in a global business context. Four highly-knowledgeable people can learn an astounding amount in a plant in one hour.."

Yet, as the President and Chief Executive of the (US) Chemical Manufacturers Association (CMA) pointed out, the industry had a lot to lose if the US did not ratify:7

"There are clearly trade implications to abstaining from participation in the CWC. The Convention forces parties to halt business in Schedule 2 materials with non-parties, effective three years from entry-into-force. The parties will consider a similar requirement for Schedule 3 chemicals within five years of entry-into-force..."

He estimated that at least $600 million a year in export sales from the US could be affected if a ban came into force. It could also be argued that an industry still struggling to present a better public image, in the face of environmental concerns dating back at least to the 1984 Bhopal disaster, could ill afford to stand out against the CWC.

The facts of the matter are, however, that the CMA strongly supported the ratification of the CWC. It did so on the basis of eighteen years of involvement and it is probably true,8 given the opposition in the United States, that the President of the CMA was correct when he said:9

"...I am convinced the treaty would not have passed without strong chemical industry support."

Certainly the CMA took a full part in the ratification debate, both in the Senate and in the media.

This paper is based on the assumption that there might well be similarly strong opposition to a strengthened Biological and Toxin Weapons Convention (BTWC) in the US, and that the position of the biotechnology and pharmaceutical industry could be important to the successful outcome of a ratification debate. The paper sets out the position taken by the industry and the reasons given for that position. It then compares that position with the requirements for strengthening the BTWC. Finally, an attempt is made to assess whether any further evolution of the industry's position, and its effects on the stance of other countries' industries, is possible. The paper is based in part on a series of interviews carried out in the United States during the summer and early autumn of 1997**.

The US industry

As Taylor and Johnson pointed out in their survey of facilities in the US:10

"There is no universally agreed definition of what constitutes the biotechnology industry in the United States. For example, the Department of Commerce does not classify it as a separate industry for the purpose of collecting statistics..."

They therefore resorted to classifying industries that might be affected by a strengthening of the BTWC (through the addition of verification measures) as those that used key equipment identified in the VEREX negotiations which led to agreement to try to strengthen the BTWC.

Table 1: US biotechnology facilities 10

Group/Sub-group Number of Facilities

Drugs

A. Medical chemicals and 250

botanical products

B. Pharmaceutical preparations 750

C. In vivo and in vitro 236

diagnostic substances

D. Biological products 268

(except those in C)

Food

A. Yoghurt 100

B. Breweries 480

Agriculture

A. Microbial pesticides 12

B. Industrial ethanol 57

On this basis (Table 1), they concluded that at least 2,000 facilities could be affected, but added that several other industries were worth further study, in the main because of their use of fermentation processes.

In its 1991 study, Biotechnology in a Global Economy, the US Congress Office of Technology Assessment (OTA) had adopted a similar view, arguing that:12

"Biotechnology is not an industry. It is, instead, a set of biological techniques developed through decades of basic research, that are now being applied to research and product development in several existing industrial sectors..."

The OTA put forward two definitions of biotechnology. The first which they had used previously was broad in scope and:

"...described biotechnology as any technique that used living organisms (or parts of organisms) to make or modify products, to improve plants or animals, or to develop micro-organisms for specific purposes..."

This definition obviously encompassed old industrial practices such as baking and brewing. The OTA's second, "more narrow" definition:

"...refers only to 'new' biotechnology: the industrial use of rDNA, cell fusion, and novel bioprocessing techniques..."

and it was in this narrow sense that they used the term in their 1991 study. The OTA study stressed US pre-eminence in this new biotechnology:

"...the United States remains preeminent in biotechnology, based on strong research programs and well-established foundations in pharmaceuticals and agriculture. Broad-based, federally funded basic research - especially in biomedicine - is a hallmark of U.S. capability in biotechnology..."

It also stressed that commercial benefits were flowing first from pharmaceutical products:

"...the development of biotechnology-based pharmaceutical products is flourishing. To date, 15 biotechnology-based drugs and vaccines are on the market....Biotechnology is likely to be the principal scientific driving force for the discovery of new drugs and therapeutic chemical entities as the industry enters the 21st century."

Despite the importance of small, dedicated, biotechnology companies in this market in the the United States, the OTA also stressed the significance of the major pharmaceutical companies, both in regard to their own capabilities and in strategic alliances with small companies.

Biotechnology industries, both old and new, are represented by trade associations located in Washington D.C. which, as part of their remit, monitor and assess ongoing government legislation. For example, the International Dairy Foods Association represents milk, cheese and ice-cream manufacturers.13 Similarly, the Biotechnology Industry Organization represents more than 600 US companies and institutions involved in modern biotechnology. Most US biotechnology companies are small businesses which employ less than 50 people.14 The leading research-based pharmaceutical and biotechnology companies are represented by the Pharmaceutical Research and Manufacturers of America (PhRMA) organisation. This had some 60 members in 1997, all of which were very large, internationally recognised, companies.15 PhRMA, like other national organisations such as the Association of the British Pharmaceutical Industry,15 is also part of the International Federation of Pharmaceutical Manufacturers Associations (IFPMA), located in Geneva.17 IFPMA works closely with the Brussels-based European Federation of Pharmaceutical Industry Associations (EFPIA), but is a separate organisation. IFPMA represents some 50 national associations, particularly in their dealings with United Nations bodies such as the World Health Organization.

Before analysing the position of US industry in regard to current attempts to strengthen the BTWC, it must be understood that elements within the US, with considerable knowledge of the subject, have long stressed the difficulty of verifying compliance with the BTWC.18,19,20,21 Dr. Edward Lacey, then Acting Assistant Director, Bureau of Verification and Implementation, US Arms Control and Disarmament Agency (ACDA), expressed this view when he told the Fall meeting of the Biology and Biotechnology Section of the earlier Pharmaceutical Manufacturers Association in 1992:22

"...our own analyses indicate that the B[T]WC cannot be made more effective by adding verification measures known to us. The small size and complex structure of microorganisms, and the dual-purpose nature of many items used in biological production, make verification of a ban on biological weapons problematic, to say the least..."

He continued:

"...Our concerns about the verifiability of the B[T]WC are the primary reason the United States delegation opposed the proposals for specific verification regimes made at the September 1991 review conference. But it should also be noted that the United States opposes any measures that would limit our ability to pursue a biological defense program or unduly burden American industry."

Whilst the official US view had moderated somewhat by the time of the Fourth Review Conference of the BTWC in 1996,23 scepticism about the possibility of effective verification probably remains strong in many influential US circles.24 There could also obviously be concern over possible leakage of national security information from defence sites25 during BTWC verification.

Against that background, it would hardly be surprising if the US industry did not express some concerns. The core concern was pinpointed in a joint article by Alan Holmberg (from a major pharmaceutical company) and Alan Goldhammer, Director of Technical Affairs at the Biotechnology Industry Organization. In their view:26

"...Any implementation of a declaration and verification protocol under the B[T]WC must protect proprietary information for the pharmaceutical and biotechnology industries where the U.S. is the undisputed world-leader."

The reasons for concern over the loss of confidential information were clear from a detailed joint industry briefing which noted that:27

"...It takes an average of 10-12 years from the time the first laboratory studies are conducted until a drug is successfully marketed. It is estimated that the research and development costs to develop a single new drug (which includes the cost of 100,000 failures) is $350 million alone. This figure does not include the cost of the facilities and equipment to manufacture it."

As patents run out in about 20 years, there are only 8-10 years in which profits can be made before generic 'copies' are legally available. Thus loss of critical information could be extremely damaging for a company. Whilst manufacturing plant in particular is subject to regulatory inspection, the document argues that the agencies involved have a proven record of "not sharing proprietary information with competitors". The same was obviously not thought to necessarily hold true for international inspections.

In May 1996, after four years of discussing the possible Verification Protocol to the BTWC with its government, the PhRMA board approved a position statement.28 This stressed PhRMA's support for the BTWC, and for strengthening it where possible. However, PhRMA had considerable concerns, as stated in May 1997:

"...The areas of greatest concern to PhRMA companies are: (1) the loss of legitimate confidential business information; (2) the loss of good name by being linked to the manufacture of biological weapons, and (3) the adoption of onerous implementing regulations."

Table 2: Key elements of PhRMA's position 27

1. Current confidence building measures may become mandatory but what is declared

must not be expanded.

2. On-site inspections must be limited to challenge inspections.

3. Allegations leading to a challenge inspection must be reviewed using the 'green light'

process before proceeding.

4. Managed access must be employed during any on-site inspection.

5. A non-governmental inspected facility has the final determination of what is

proprietary.

The main elements of PhRMA's views on how the BTWC should be strengthened are set out in Table 2.

It is obvious that the concerns, at least over loss of confidential business information, are shared by industry executives outside of the US.29 Thus the conclusion to PhRMA's statement:

"...PhRMA wants to be an active participant in working to reduce the threat of biological warfare, but will oppose any compliance Protocol that does not fully protect the confidential business information of its member companies..." (emphasis added).

has to be taken seriously both within and outside of the US. The problem, however, is that the measures proposed by PhRMA, if implemented in a Protocol to the BTWC, would be very unlikely to provide adequate assurance that parties were living up to their obligations. Clearly, the Confidence Building Measures agreed in 1986 and 1991 would be less of a failure if all states were required to provide the annual data,30 but they surely do not cover all of the facilities necessary for adequate transparency since the only aspect of production covered is that of vaccines. Moreover, whilst there seems little likelihood that large-scale routine inspections of the type agreed for the CWC will be incorporated in a strengthened BTWC,31 it is difficult to see how a 'two-pillar' scheme based only on declarations and challenge inspections could be adequate. How, for example, could misunderstandings or serious misinterpretations in declarations be cleared up in such a scheme? In short, there are persuasive arguments for a Verification Protocol incorporating non-challenge visits in addition to challenge investigations.32 In regard to challenge investigations, the deterrent effect can only come from a relatively automatic short-notice inspection. The adoption of a 'green light' procedure (under which, say, three-quarters of executive council votes would be required to allow a challenge inspection), would mean that there was a good chance of obstructing a challenge even when there was good reason to proceed. This weakening of the proposed protocol of the BTWC seems particularly odd as all facilities are potentially subject to challenge under the CWC 'red light' procedure anyway.33

The question therefore arises as to whether there is any way of addressing the legitimate, core concerns of the US industry whilst at the same time achieving a strong Verification Protocol to the BTWC. Investigation of that question is the objective of the rest of this paper.

What is Confidential Business Information and how is it standardly protected?

As the OTA study of Biotechnology in a Global Economy pointed out,12 intellectual property law is of crucial importance to the development of the industry. The industry's own publications stress the importance of patent protection. The IFPMA position was stated starkly in 1997:34

"The research based pharmaceutical industry is highly dependent on intellectual property (IP), especially patent protection. Quite simply, without patent protection the world would have been deprived of the innovative medicines which have saved countless lives...because the industry as we know it today would not exist."

Patent protection in this rapidly evolving area of technology is not without difficulties and disputes even within the US,35 but international law relating to patent protection dates back to the last century.12 Moreover, whilst the industry has been concerned over the losses caused by patent piracy in some countries, it has welcomed recent international legal developments. The IFPMA, for example, noted that:34

"Industry has welcomed the two major international agreements: the intellectual property chapter of the Uruguay Round Agreement (GATT), the 'Trade Related Aspects of Intellectual Property Rights' (TRIPs) and the North American Free Trade Agreement (NAFTA) which require that all technologies, including pharmaceuticals be protected..."

PhRMA itself commented that "measurable progress has been made in strengthening intellectual property protection over the past decade".36 Patents, of course, provide a means by which the manufacturer can benefit from the vast expenditure on research, but they are also a means by which the wider society can benefit from the innovation encouraged. Eventually, when the patent runs out, the innovation can also be used by other manufacturers. However, patents are not the only way in which intellectual property can be protected by the industry.

Protection by confidentiality of trade secrets is the other main method of protecting intellectual property.37 The law relating to confidential business information remains fragmented, but a trade secret:38

"...whether a method of manufacture, the ingredients of a product, the names of actual or prospective customers, may for one reason or another not be capable of protection by the mainstream law of intellectual property, but may be of great commercial value to a company and of equal value to its competitors..."

and legal actions taken in regard to trade secret protection are prevalent in the United States.39 The crucial point to note, from this paper's perspective, is that to be a protected trade secret in the US the secret must be identified and steps taken to protect it. As the OTA noted:12

"If a trade secret is disclosed in a non-confidential manner, it is lost forever. Trade secret rights require that a trade secret be disclosed in confidence only to those having a reasonable need to know (e.g. employees). Measures must be taken to prevent disclosure of the trade secret to the public or to competitors (e.g., expressly identifying the information as a trade secret and prohibiting its disclosure)."

Indeed, intellectual property lawyers argue strongly for regular trade secret audits to be carried out by companies which wish to protect intellectual property by this method.39,40 So we have to assume that the confidential business information that the industry considers to be at risk in a strengthened BTWC has been identified and that steps have already been taken to protect it against normal routes of loss such as commercial malpractice. We are not dealing with amorphous, ill-defined possibilities of potential loss.

Arms control agreements and CBI

There can be no doubt that as modern arms control increasingly has to deal with the restraint of proliferation of weaponry derived from dual-use technology the Confidential Business Information of private companies is potentially under threat. As Kellman and his colleagues noted in their extended study, Disarmament and Disclosure: How Arms Control Verification Can Proceed Without Threatening Confidential Business Information:41

"...While past arms control efforts focused on deployed weaponry at government installations and military sites, more recent agreements focus on dual-use technology and substances that are widely possessed by private entities. Consequently, arms contral verification entails obtaining data from private industries."

Thus the industry's concern over the strengthening of the BTWC is part of a larger generic problem that will be important for many industries in the next century.

Despite the extensive measures taken in the recently negotiated Chemical Weapons Convention (CWC) to protect CBI (see, for example, reference 42) it remains the case that "[e]ven if preventive measures are implemented, CBI could still be lost".41 From the perspective of the modern biotechnology industry, it is worse - they have even more to lose. As Tucker expressed it, in a recent review of the relevance of the CWC to the BTWC:43

"...Although the chemical industry was initially concerned about how the CWC would protect proprietary information, sensitivities are even greater in the pharmaceutical and biotechnology industries, which are more research-intensive and on the cutting edge of scientific innovation..."

He elaborated as follows:

"...fears of industrial espionage are well-founded. Companies are most concerned about the loss or compromise of a proprietary microorganism that may be worth hundreds of millions of dollars. Indeed, the genetically engineered bacterium that mass produces human insulin has been valued at more than $1 billion..."

On the other hand, the UK, a depositary state which has carried out four practice challenge inspections and two practice visits related to the BTWC (in addition to its extensive experience leading up to the CWC), appears to be convinced that proper preparation and managed access techniques can guard CBI whilst BTWC inspectors gain enough information to fulfil their mandate.44 The fact that sampling and analysis appear likely to play an extremely limited role, in the BTWC regime, in regard to industry45 strengthens this viewpoint considerably.

The question that naturally arises is whether concern over the possible loss of CBI is the predominant reason for the position adopted by PhRMA (and by implication the rest of the US biotechnology industry) towards strengthening of the BTWC.

The views of US industry

At Lawrence Livermore National Laboratory, in May 1997, at a meeting of 30 experts from US and other governments, US industry, and non-governmental organisations, the objections raised by PhRMA - primarily the potential loss of CBI but also the risk to good name from false accusations and imposition of onerous regulations - were raised by industry representatives.46 US officials also presented results of a small number of trial inspections they had recently carried out. This led to much more pessimistic conclusions than the UK had drawn (Table 3).

Table 3: Summary of US findings on trial inspections 46

1. "The trial inspections did not build confidence and, on the contrary, raised a

number of suspicions that could not be resolved..."

2. "A 'BW template' can be overlaid on any complex biodefense site..."

3. "Adequate site preparation is difficult to achieve. Even after multiple briefings,

the sites were generally unprepared to meet the inspectors' requests for

information..."

On the other hand Australian, Canadian and Dutch trials were said to have reached similar conclusions to those of the UK. Industry representatives suggested that in-depth discussions of the reasons for such differences would be useful. The interaction between US officials, US industry representatives and non-US government officials, however, points to the complexity of the process by which PhRMA came to issue its position paper on the BTWC. The point was made dramatically in a recent set of essays. The author, Amy Smithson, noted that the quicksand of nightmares which swallows anything that falls into it was made up of individual grains of sand and then suggested an analogy:47

"...Over the past several years, developments related to monitoring a biological weapons ban have been taking place within the US pharmaceutical industry, among the delegations working on the B[T]WC protocol in Geneva, and within the US government. Taken individually, these events and positions, like grains of sand, would seem to be more irritating than disastrous. Collectively, they could sink the chances for the negotiation of a meaningful B[T]WC protocol." [emphasis added]

Clearly, the argument here is that the reasons for the position taken by PhRMA are much more complex than just a predominant intra-industry concern over the potential loss of CBI.

Following attendance at the meeting of experts at Lawrence Livermore 46, I interviewed a total of 20 people in Washington in May 1997 and in the Boston area in September 1997. Most of the interviewees in Boston were working in modern biotechnology companies and the interviewees in Washington were from government or industry associations or were experts in research institutes or other non-governmental organisations with interests in the problem of strengthening the BTWC. As I had expected, the scientists actively involved in modern biotechnology companies did not know a great deal about what was happening in the Geneva negotiations. They were, however, happy to help prevent the proliferation of biological weapons (as is clear from the PhRMA statement), despite the well-known crucial importance of protecting CBI in the modern biotechnology industry.48 Given that the industry is very heavily regulated, they did not envisage there being strong resistance to well-explained, reasonable implementation of a protocol to the BTWC. Industry representatives from the wider biotechnology industry, located in Washington, were aware of the negotiations in Geneva, but were prepared to have PhRMA take the lead in putting the industry's position. It was made clear to me, however, that the industry was well used to working in Congress, and could readily be activated if that was necessary at any stage.

As a visitor from the UK, a number of interviewees pointed out to me the different scale of distance industry felt from its own State Government and from the Federal Government in Washington D.C. It was impressed on me that the issue of the BTWC was but part of ongoing interaction between industrial companies and what was often felt to be a very distant, 'big' government in Washington. Hence the background to the issue of concern to me was considerable suspicion - that industrial companies had to be very careful in case Washington harmed their interests incidentally whilst pursuing national policies. Against that background, the inability of the US Government to decide on a definite position in relation to strengthening the BTWC was a cause of considerable concern to industry. A number of interviewees suggested that there was insufficient attention being given to the BTWC at a high enough level of government to force a resolution on the different agencies of the Government. Unease was certainly compounded by the large number of diverse proposals that seemed to be under discussion in Geneva, but one clear factor seemed to have greatly magnified the industry's suspicion that their need to protect CBI might not be properly taken into account. This was the Russian visit to two industrial sites in 1994 under the Trilateral Agreement.49

This agreement appears to have been set up as a discreet way of allowing the Russians to demonstrate that they had given up the massive, offensive biological weapons programme they had carried out in contradiction to their obligations under the BTWC. The agreement allowed for Russian reciprocal visits to US sites and, following a lack of adequate preparation, a US company was pressed to accept two such visits. The Russians caused considerable problems for the company by saying that they were not convinced that all its activities were legal. These events undoubtedly coloured the industry's views and actions in relation to the Government from that time. In my view, therefore, whilst the PhRMA position in regard to strengthening the BTWC was, at base, motivated by a concern over the potential loss of CBI, it was also greatly influenced - for the worse - by past interactions with the Federal Government. As I was told by interviewees, it followed that the PhRMA position was an initial, hard-line bargaining position that could change. In the right circumstances the industry might become more flexible, but it could also get tougher if relations degenerated further. Amy Smithson, in interviews in late 1997 and early 1998, found (quite independently) the same viewpoint. As she put it:47

"For the US pharmaceutical industry, these trilateral inspections constituted an ominous introduction to what efforts to monitor compliance with the B[T]WC might be like....[They] became crystallising experiences for some in industry, who vowed that a future BWC protocol would not be a repeat of the trilaterals. To compound the situation, a negative atmosphere seeped into the interactions between some US governments and industry officials..."

Moreover,

"Both verbally and in writing, the US government told the Pharmaceutical Research and Manufacturers of America that a US position would be forthcoming by January 1997, then by July 1997, or, at the latest, by September 1997."

The failure to agree a US position was obviously taken as a serious sign by the industry. Smithson therefore notes that "[i]n 1997, American industry officials began approaching their counterparts overseas to express their concerns and to seek their support of the US industry position". It has to be at least possible that non-American officials do not understand the full context in which these concerns about the potential loss of CBI under a strengthened BTWC have been generated in the US.

More recent developments

In late January 1998 the United States announced its position in regard to the strengthening of the BTWC.50 The main elements of this position are set out in Table 4. In addition to its main provisions, the statement clearly rejects the notion of routine visits (of the type built into the CWC) and stresses the importance of managed access procedures during any on-site activity. However, it clearly allows for non-challenge clarifying visits in addition to challenge inspections. Then, in late February 1998, the European Union issued a statement of its common position in regard to the BTWC.51 The main elements of this statement are set out in Table 5. In addition to its main provisions, the European Union's statement is marked by the sense of urgency conveyed, for example, in provisions for demarches by the Presidency to be sent to other States Parties urging their support of the position set out.

There is clearly a real chance that a protocol to the BTWC could be agreed quite rapidly, despite the complexity of the negotiations underway52 and some deep-rooted differences that require resolution.31 Moreover, the issues being negotiated include those of central concern to industry, such as the protection of CBI.53,54

Table 4: The US position in regard to the BTWC 50

"...Under the new initiative announced by the President...the United States will seek to complete the framework of a strong BWC protocol by the end of 1998. The United States will work closely with US industry to develop and reach international agreement on the following tools:

Declarations: BWC Parties would be required to submit annual declarations to the BWC implementing organisation about facilities and/or activities that are especially suited for possible BW purposes...

Voluntary Visits: BWC Parties would be encouraged to allow a visit to any of their facilities declared under the protocol to address questions regarding the BWC or the protocol. These voluntary visits would be at the discretion of the facility concerned...

Non-Challenge Clarifying Visits: BWC Parties would be required to accept a reasonable number of on-site visits by the BWC implementing organisation to clarify an ambiguity, uncertainty, anomaly, omission or other issue related to their annual declaration...

Challenge Investigations: BWC Parties would be required to accept an investigation by the BWC implementing organisation of any location under their jurisdiction....Such investigations should be subject to a 'green light' filter, under which a simple majority of the governing body...must vote to approve an investigation before it can proceed.

In negotiating these measures, the United States will ensure that the protocol includes strong provisions for protecting constitutional rights, Confidential Business Information (CBI) and National Security Information (NSI) during any on-site activity....The protocol should also require the BWC implementing organisation to protect any sensitive information it receives from BWC Parties."

Table 5: Common position of the European Union 51

"...Member States consider that the negotiations on a Protocol to the BTWC should be a high priority for the international community in 1998, and shall actively promote decisive progress in the work of the ad hoc Group, with a view to concluding the substantive negotiations by the end of 1998...

Member States shall, in particular work together to promote agreement in the negotiations on the following measures...

- declarations of a range of facilities and activities of potential relevance under the Convention, inter alia so as to enhance transparency;

- provision for visits to facilities in order to promote accurate and complete declarations and thus further enhance transparency and confidence;

- provision for rapid and effective investigations into concerns over non-compliance, including both facility and field investigations;

- a cost-effective and independent organisation, including a small permanent staff, capable of implementing the Protocol effectively. "

Implications for industry

By all accounts, the US chemical industry had many years of high-level involvement in the CWC negotiations.8,9,47 The US and world-wide chemical industry signalled its approval of the results of the negotiations by strongly supporting the ratification processes following the agreement of the CWC. It is clear that the US biotechnology industry has been involved in the recent interagency discussions about strengthening of the BTWC in the US,55 but there appears to be a pressing need for increased, active, high-level involvement because the negotiations could now be at quite a late, and critical, stage. The point was emphasised, in May 1996, in a paper co-authored by the Chair of the US Chemical Industry's Committee on the CWC which argued:56

"Participation of the trade organizations PhRMA and BIO is needed on a long term basis in the negotiation, ratification, and implementation of the verification protocol..."

In order to achieve that, the paper continued:

"...Experience with the Chemical Weapons Convention...has shown that it will be essential for the industry to identify one or two high-level officials who will keep abreast of the issues, consult with government officials and act as spokesperson(s) for the industry. A group of industry representatives and trade association officials will also be needed to provide expertise and assistance."

The same point could surely be made in regard to the industry in Europe. Such high level involvement would be particularly valuable now because the text of the Verification Protocol does seem to be evolving in ways which appear to address industrial concerns,53 and it is therefore quite possible for the outcome to become as acceptable to the biotechnology industry as the CWC has been to the chemical industry.

Moreover, given the past interactions between government and industry in the US, it is important that European industrialists do not misunderstand the nature and context of proposals originating from US industrial sources. There is an obvious tension between the industrial need to protect CBI and for intrusive verification to prevent proliferation of weapons of mass destruction. As Kellman and his colleagues noted in their thorough review of the problem:41

"The threat to CBI stems from the need to gather reliable and objective intelligence in order to monitor the weapons production and acquisition of other nations, either through data reporting requirements or through on-site monitoring and inspections." [ emphasis added]

Clearly, European governments believe that an effective Protocol can be crafted in a way which also strongly protects the CBI of their industries. A powerful industry, which did not accept this, could end up believing that it had won a battle to protect its CBI but be in a much worst position than it would wish because, in the process, it had also emasculated the central element in the web of deterrence against future proliferation of biological weapons of mass destruction.57 Whilst there does seem to be more flexibility in the most recent statement of PhRMA's position,58 as far as I can see this does not affect the central worrying elements (for example in regard to visits) discussed earlier. Thus a second implication for the world-wide biotechnology industry is that great care should be taken in crafting its position to ensure the effectiveness of the final agreement to strengthen the BTWC.

To my mind, it is very difficult to make the required detailed judgements on such a complex issue without some clear idea of where we intend to go. In that regard we must sometimes listen carefully to wiser and older statesmen. As Ambassador Leonard, the US negotiator for the original BTWC, argued last year:59

"During the long, slow transition to a new system of international relations, the global and regional arms control treaties of the past 40 years will be complemented by additional treaty regimes covering the full range of conventional weapons. Together, these treaties will provide a framework of norms, obligations, procedures, rules and interactions that will foster political advances..."

He continued, in regard to our specific interests here:

"...These treaties will bring with them a matrix of verification procedures so penetrating, so ubiquitous, and so intensive as to be unimaginable today. Total transparency in military matters will be the norm that is steadily and inexorably approached. Military secrecy will be seen increasingly as an unhealthy remnant of a previous era in which military security was protected by the balance of power."

A final implication for the world-wide biotechnology industry, therefore, is that it should grasp the nature of the larger transition in international security processes of which it is part and do what it can to contribute to a benign, peaceful outcome. In an age of modern technology the alternative is more war, which is good for "absolutely nothing", as John Keegan pointed out vividly in his recent Reith Lectures.60

**The work reported here was financed in part by a grant from the Nuffield Foundation. I would like to thank Jonathan Tucker for the invitation to the workshop on 'Inspection Procedures for Compliance Monitoring of the Biological Weapons Convention' held at Lawrence Livermore National Laboratory in May 1997, Michael Moodie for the invitation to work at CBACI whilst carrying out interviews in Washington, Marie Chevrier for the invitation to work at the Center for Science and International Affairs, John F. Kennedy School of Government, Harvard University whilst carrying out interviews in Boston, and Lyn Klotz and other members of FAS for help with industrial contacts.

References

1. Schlesinger, J. Weinberger, C. and Rumsfeld, D. (1997) No to the Chemical Arms Treaty. Washington Post, 5 March, p A21.

2. Gordon, A. (1997) Implications of the US Resolution of Ratification. The CBW Conventions Bulletin, 38, 1-6.

3. Tanzman, E. A. and Kellman, B. (1990) Legal implementation of the multilateral Chemical Weapons Convention: Integrating international security with the constitution. International Law and Politics, 22, 475-518.

4. Carnahan, B. M. (1991) Chemical arms control, trade secrets, and the constitution: Facing the unresolved issues. The International Lawyer, 25 (1), 167-86.

5. Aldrich, Maj. R. W. and Thompson, Maj. N. K. (1994) Verifying chemical and biological weapons treaties: Is the constitution a stumbling block? Airpower Journal, VIII, 11-27.

6. Smithson, A. E. (1994) Implementing the Chemical Weapons Convention: Counsel from Industry. Report No. 10, Henry L. Stimson Center, Washington D.C.

7. Webber, F. L. (1996) The US chemical industry stake in the Chemical Weapons Convention. Chemical Weapons Convention Bulletin, 34, 1-2.

8. Carpenter, W. D. and Moodie, M. (1997) Industry and International Biological Arms Control. Mimeo.

9. Heylin, M. (1997) CMA celebrates 125th anniversary. Chemical and Engineering News, 2 June, 12-16.

10. Taylor, T. and Johnson, L. C. (1995) The Biotechnology Industry of the United States: A Census of Facilities. Center for International Security and Arms Control, Stanford University.

11. United Nations (1994) Final Report of the Special Conference of the States Parties to the Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on Their Destruction, 19-30 September, BWC/SP.CONF/1. United Nations, Geneva.

12. Office of Technology Assessment (1991) Biotechnology in a Global Economy. OTA-BA-494, October. United States Congress, Washington D.C.

13. International Dairy Foods Association (1997) The Voice of the Dairy Foods Industry. IDFA, Washington D.C.

14. Biotechnology Industry Organization (1997) US Biotechnology Industry Profile. BIO, Washington D.C.

15. Pharmaceutical Research and Manufacturers of America (1997) Reporter's Handbook. PhRMA, Washington D.C.

16. Association of the British Pharmaceutical Industry (1998) Directory of Members. ABPI, London.

17. International Federation of Pharmaceutical Manfacturers Associations (1997) IFPMA Structure and Activities. IFPMA, Geneva.

18. US Army Chemical Corps (1961) Arms Control of CBR Weapons. I - Military Aspects. Operations Research Group Study No. 23, Army Chemical Center, Maryland.

19. Zilinskas, R. A. (1986) Verification of the Biological Weapons Convention. In E. Geissler (ed.), Biological and Toxin Weapons Today. Oxford University Press, Oxford (for SIPRI).

20. Atlas, R. M. and Goldberg, M. (1993) Biological warfare: Examining verification strategies. ASM News, 59 (8), 393-96.

21. Bailey, K. (1994) Problems with verifying a ban on biological weapons. In Director's Series on Proliferation, No. 3. UCRL-LR-114070-3, 5 January. Lawrence Livermore National Laboratory, USA.

22. Lacey, E. J. (1992) Official Text , Address given to the Fall Meeting of the Biology and Biotechnology Section of the Pharmaceutical Manufacturers Association, Baltimore, Maryland. US Arms Control and Disarmament Agency, Washington D.C.

23. Dando, M. R. and Pearson, G. S. (1997) The Fourth Review Conference of the Biological and Toxin Weapons Convention: Issues, outcomes and unfinished business. Politics and the Life Sciences, 16 (1), 105-26.

24. Porteous, H. (1997) Laxity in lab controls raises questions on bioweapons verification. Inside the Pentagon, 13 (19), 8 May, 1 and 10-12.

25. General Accounting Office (1991) Defense Research: Protecting Sensitive Data and Materials at 10 Chemical and Biological Laboratories. GAO/NSIAD-91-57. General Accounting Office, Washington D.C.

26. Holmberg, A. E. and Goldhammer, A. (1996) Strengthening the Biological Weapons Convention: An industrial perspective. Chemical and Biological Defense Information Analysis Center Newsletter, 2 (3), 1 and 10.

27. Anon. (1993) Industrial Information Paper on Concerns Regarding Disclosure of Proprietary Information to the International Community. Industrial Biotechnology Association and the Pharmaceutical Manufacturers Association, Washington D.C.

28. PhRMA (1997) PhRMA position on a compliance protocol to the Biological Weapons Convention. In Industry Issues International at the PhRMA Website (http://www.phrma.org/issues/compliance.html).

29. Imrie, R. C. (1996) An industry view of BTWC verification. Paper presented to a NATO Advanced Research Workshop on 'The Technology of Biological Arms Control and Disarmament', 28-30 May, Budapest .

30. Hunger, I. (1996) Confidence-building measures. Pp 77-92 in G. S. Pearson and M. R. Dando (eds) , Strengthening the Biological Weapons Convention: Key Points for the Fourth Review Conference. QUNO, Geneva.

31. Dando M. R. (1997) The Biological Weapons Convention: Prospects for an effective protocol. Disarmament Diplomacy, 21, 10-14.

32. Pearson, G. S. (1997) Strengthening the Biological Weapons Convention: The Necessity for Non-Challenge Visits. Briefing Paper No. 2, September. Department of Peace Studies, University of Bradford, UK.

33. Pearson, G. S. (1997) Strengthening the Biological Weapons Convention: The Importance of On-site Investigations. Briefing Paper No. 1, July. Department of Peace Studies, University of Bradford, UK.

34. International Federation of Pharmaceutical Manufacturers Associations (1997) Issues Handbook: Intellectual Property: Patents and Pharmaceuticals. IFPMA, Geneva (February).

35. Marshall, E. (1997) A bitter battle over insulin gene. Science, 277, 1028-30.

36. Pharmaceutical Research and Manufacturers of America (1997) Industry Profile. PhRMA, Washington D.C. (March).

37. Biotol (1992) A Compendium of Good Practices in Biotechnology. Butterworth-Heinemann, London.

38. Marett, P. (1996) Intellectual Property Law. Sweet and Maxwell, London.

39. Halligan, M. (1996) Recent Developments in Trade Secrets Law (1994-1996): Archive of Over 100 Cases. At WorldWideWebsite (http://www.execpc.com/~mhalligan/ tradesec.html).

40. Bacal, G. S. (1996) Law of Trade Secrets, Non-competes, and Antipiracy Agreements - A Practical Guide for Businesses and In-House Lawyers. At WorldWideWebsite (http://www.azlink.com/lawyers/articles/secrets.htm#barrie).

41. Kellman, B. et al. (1995) Disarmament and disclosure: How arms control verification can proceed without threatening Confidential Business Information. Harvard International Law Journal, 36 (1), 71-126.

42. Kellman, B. and Tanzman, E. A. (1998) Manual for National Implementation of the Chemical Weapons Convention. International Criminal Justice and Weapons Control Center, College of Law, DePaul University, Chicago.

43. Tucker, J. B. (1998) Verification provisions of the Chemical Weapons Convention and their relevance to the Biological Weapons Convention. In A. E. Smithson (ed.), Biological Weapons Proliferation: Reasons for Concern, Courses of Action. The Henry L. Stimson Center, Washington D.C.

44. Walker, J. R. (1997) Industry and inspections. Presentation at a meeting on 'The Biological Weapons Convention and the Pharmaceutical Industry', 25 November. Foreign and Commonwealth Office, London.

45. Dando, M. R. (1997) Technologies for monitoring the Biological and Toxin Weapons Convention: An emerging consensus? Paper presented to the NATO ARW on 'Monitoring the Environment for Biological Hazards', 19-22 May. Staszica Palace, Warsaw.

46. Tucker, J. B. (ed.) (1997) Inspection Procedures for Compliance Monitoring of the Biological Weapons Convention. CGSR-97-002, December. Monterey Institute of International Studies Center for Global Security Research, Lawrence Livermore National Laboratory.

47. Smithson, A. E. (1998) Man versus microbe: The negotiations to strengthen the Biological Weapons Convention. In A. E. Smithson (ed.), Biological Weapons Proliferation: Reasons for Concern, Courses of Action. The Henry L. Stimson Center, Washington D.C.

48. Dibner, M. D. (1997) Overview: 3rd International Conference on Strategic Business Information in Biotechnology, 26-28 October. Research Triangle Park, North Carolina.

49. Boucher, R. (1993) Joint US/UK Statement on Biological Weapons, 14 September. Office of the Assistant Secretary, US Department of State, Washington D.C.

50. Office of the Press Secretary (1998) Fact Sheet: The Biological Weapons Convention, 27 January. The White House, Washington D.C.

51. Council of the European Union (1998) Common Position of the Council of the European Union Relating to Progress Towards a Legally Binding Protocol to Strengthen Compliance with the BTWC and the Intensification of Work in the Ad Hoc Group to that End, 25 February. European Union, Brussels.

52. Pearson, G. S. (1998) Strengthening the Biological and Toxin Weapons Convention: Progress in Geneva Quarterly Review No. 2. The CBW Conventions Bulletin, 39, 20-23.

53. Fidler, D. P. (1998) Legal Measures for the Protection of Confidential Information in the January 1998 Rolling Text of the Proposed BWC Protocol. Federation of American Scientists, Washington D.C. (12 March).

54. Klotz, L. C. (1997) Confidentiality Can be Protected During Sampling and Analysis in a BWC Compliance Regime. Federation of American Scientists, Washington D.C. (September).

55. Technical Advisory Committee Unit (1997) Minutes of Open Session, 9 January: Overview of the BWC Inspection Proposals. Materials Technical Advisory Committee, Bureau of Expert Administration, Department of Commerce, Washington D.C.

56. Leonard, Ambassador J. F., Carpenter, W. et al. (1996) Strengthening the Biological Weapons Convention: The Impact on Confidential Proprietary Information and Property. Federation of American Scientists, Washington D.C. (May).

57. Dando, M. R. (1994) Biological Warfare in the 21st Century. Brassey's, London.

58. Woollett, G. R. (1998) Industry's role, concerns, and interests in the negotiation of a BWC compliance protocol. In A. E. Smithson (ed.), Biological Weapons Proliferation: Reasons for Concern, Courses of Action. The Henry L. Stimson Center, Washington D.C.

59. Leonard, Ambassador J. F. (1997) Keynote Address: The Control of Biological Weapons: Restrospect and Prospect. In Inspection Procedures for Compliance Monitoring of the Biological Weapons Convention. CGSR-97-002, December. Monterey Institute of International Studies Center for Global Security Research, Lawrence Livermore National Laboratory.

60. Swain, H. (1998) War, what is it good for? Absolutely nothing. The Times Higher Education Supplement, 3 April, pp 18-19.

Possible implications for R&D
Otto Doblhoff, Chairman Working Party "Safety in Biotechnology" of the European Federation Biotechnology

The foremost question to be answered, is how to find individuals or institutions in the R&D area, trying to develop BTWs. Is there any such activity to be expected from academic institutions? Is the rather open and accessible structure of academic R&D in states with stable democracies a sufficient protections against perpetrators? What role does national defense research and development play in this area? What type of control will be necessary to balance the need for protection and at the same time putting minimum restraint on R&D?

Information:

R&D institutions will very probably have to provide information on equipment, the type of research and the biological agents used.

Confidentiality will be vital to protect new technologies and products. Information might be used to gain insight into strategic decisions a R&D institution has taken.

Work load: Due to the larger number of projects being normally run at one given R&D institutions, as compared to production, the work load of providing information to the competent authorities may be significant.

Inspections:

Due to the larger amount of concurrent activities in R&D units inspecting will be more difficult than production units. Large scale equipment is very often not available in R&D, but significant amounts of biological agents could also be produced in lab scale. The depth and frequency of inspections in R&D is difficult to estimate. Academic R&D as compared to industrial R&D will be faced by the problem of less developed legal departments and lobbying activities.

Material, equipment and know-how transfer:

One of the major concerns of R&D institutions is the free exchange of materials and know-how. Will transfer restrictions complicate material exchange even more than now? The national and international guidelines on the transport of infectious materials, hygiene and quarantine, the international agreement on the protection of endangered species, etc. are already making life exceedingly difficult for R&D institutions. In most states there are a number of competent authorities involved in regulating biological material transfers, making it necessary to apply for import permits at more than one place. For institutions with limited administrative resources this could become increasingly difficult.

Will R&D institutions have problems buying equipment that may be considered dual-use (and most equipment in the biosciences could be considered as such).

Industry Position on a Compliance Protocol to the BTWC
Prof. Dr. Helmut Bachmayer, Head of Corporate Biosafety, Novartis International Basel

Industry supports the overall goals and objectives of the BTWC aiming at strengthened compliance with this Convention to reduce the threat of any misuses of biological material (to produce biological weapons or for acts of terrorism).

The legitimate uses of microbiology and biotechnology in general and recombinant DNA technology in particular are vital for new developments in the areas of health care, agribusiness, nutrition, and environmental remediation. Any compliance protocol must prevent misuses of these key technologies without impairing their legitimate exploitation not only by industry but also during academic research.

Main industry concerns regarding the compliance protocol relate to the scope of the compliance measures (declarations and inspections) as well as to the protection of confidential business information. Industry's concerns furthermore include the costs of likely business disruption of extensive inspections and the bureaucracy of dealing with complex and lengthy declaration forms.

Discussions within the Ad Hoc Group of State Parties appear to be very much influenced by the provisions of the Chemical Weapons Convention (CWC). Significant differences are obvious, however, between research or development into and manufacturing of biological and chemical products, respectively. Triggers for declaration as well as compliance measures (inspections) must be carefully analyzed and properly defined. Since it is rather easy to remove essentially all traces following the handling of biological material (as contrasted to chemicals), challenge inspections rather than routine inspections appear to be the most useful tools of compliance control of the BTWC.

Declaration are certainly a key element but they should focus on facilities for high degree of containment (Biosafety Level 3 or 4 only); this would avoid declarations for benign facilities such as fermentation plants for antibiotics or even breweries. Certain techniques (such as recombinant DNA technology) or possession of specific types of equipment should not be singled out and used as a trigger for declarations.

It is suggested to introduce clarification procedures in case of any ambiguities regarding declarations. Such clarifications might comprise informal consultations with the government with clarification visits as ultimo ratio.

Challenge inspections (i.e., short-notice inspections in case of suspected non-compliance) should be sufficient to guarantee the compliance with the Protocol without interfering with the business interest of the industries concerned.

Biotechnology industry welcomes any opportunity to share their experience with the handling of biological material to help design an instrument capable of detecting any misuse of biological material without undue interference with it's legitimate uses.

Meeting U.S. Industry Concerns within a Strong BTWC Compliance Regime
Author: Lynn C. Klotz, Ph. D. Federation of American Scientists Working Group on BW Verification.

Introduction

A BTWC Compliance Regime should provide both significant transparency and deterrence. A strong Compliance Regime requires three components: (1) facility declarations of dual-use capabilities; (2) challenge investigations to examine alleged violations of the Biological Weapons Convention; and (3) non-challenge visits of one or more kinds (e.g., random visits, declaration clarification visits) to ensure that States Parties are fulfilling their obligations under the regime. A Compliance Regime that does not include all three components will be significantly weakened.

From my observations, U.S. industry has a number of legitimate concerns regarding aspects the Compliance Regime under discussion in Geneva. The object of this talk is to examine ways in which U.S. industry's concerns can be addressed within the framework of a strong BTWC Compliance Regime.

A Sampling of U.S. Industry Concerns and Means of Addressing Them

A sampling of industry's concerns as I see them, positions they have taken in response to the concerns, and some ideas on how the concerns may be addressed are discussed below. While the discussion here is necessarily brief, the Federation of American Scientists' web site (fas.org) contains a number of publications that discuss in detail the subjects covered here and additional related subjects.

Concern: Theft of proprietary microorganisms

A single strain of production microorganism may be responsible for hundreds of millions of dollars of product sales. For this reason, industry would prefer to restrict sampling and analysis to final product to prevent theft of live microorganisms. Industry therefore proposes that there be no sampling and analysis allowed during non-challenge visits if such visits are to be a component of the Compliance Regime.

However, sampling and analysis of microorganisms is a good way to confirm compliance and can serve as a significant deterrent to potential proliferators. Modern diagnostic methods that employ, for example, DNA probes or antibodies can be carried out on dead microorganisms, thus protecting against the theft of valuable live microorganisms. While such diagnostic methods need considerable development for BTWC purposes and to satisfy industry's high standards, this is one way in which this industry concern can be addressed.

Concern: Loss of confidential information about processes and manufacturing cost

Because of this concern and a concern over the cost of hosting inspections and visits, U.S. industry has proposed that there be no non-challenge visits and that facility declarations contain only minimal information about the capabilities and activities of the facility.

Managed access, as designed for the Chemical Weapons Convention, is a powerful tool for protecting confidential information. In addition, the CWC has adopted strong confidentiality rules that inspectors must follow. Similar managed access and confidentiality guidelines are expected to be adopted for the BTWC Compliance Regime. Managed access allows the State Party, not the BTWC inspectors, to have the final say as to what information, site-areas, etc. can be made available to inspectors during a facility investigation or visit; therefore, confidential materials and activities can be shielded from inspectors.

U.S. industry is concerned, however, that the U.S. government (who will have ultimate authority and responsibility for compliance) may for political reasons decide to reveal confidential information during a challenge investigation or non-challenge visit. This concern has been further amplified by the unfortunate intrusive visits of a Pfizer facility under the Tri-lateral Agreement among the U.S., Britain, and Russia.

Industry's concerns could be lessened by adopting U.S. implementing legislation that will clearly spell-out the roles of industry and government during investigations and visits. Such industry-responsive US implementing legislation should (1) mandate significant industry participation in preparation of declarations; (2) spell-out roles and responsibilities of government and industry during visits and investigations; and (3) shift decision-making authority from government to industry as much as possible during investigations and visits, recognizing however that the US government, not industry, is the responsible party to the BTWC.

Furthermore, it is possible to design declaration forms to eliminate the need for critical confidential information, and, at the same time, provide enough information to serve as a useful base for inspectors during investigations and visits. Computerized declaration forms with check-off items and with quantitative information provided in ranges (or above or below a threshold value) should go a long way toward protecting confidential information.

Conclusions

While this talk has presented only a few areas of U.S. industry concern and means of addressing those concerns, I believe that answers to all industry's concerns are possible within a strong compliance regime. In this regard, the intense small-group discussions now underway between U.S. industry and U.S. government are encouraging, because from such small-group discussions creative solutions to industry's concerns could emerge. It is my hope that details of the Compliance Regime and U.S implementing legislation will emerge that both support a strong Compliance Regime and at the same time afford significant protection to our valuable industry.

The US Biological Safety Requirements for Facilities Transferring or Receiving Select Agents
Jonathan Y. Richmond, Ph.D., Director, Office of Health and Safety, Centers for Disease Control and Prevention, US

ABSTRACT:

In response to a Congressional mandate in 1997, CDC promulgated a regulation, Additional Requirements for Facilities Transferring or Receiving Select Agents. The select agents were drawn from the Australia List and includes forty or so microorganisms, a dozen toxins, and certain recombinant DNA molecules. Institutions were provided Registration Packages that included a self-assessing laboratory survey form based on the CDC/NIH publication, Biosafety in Microbiological and Biomedical Laboratories. Each registered facility is to be inspected by personnel from the OHS during a three year cycle. To date there are 67 laboratories registered. This presentation will provide a status report on the activities associated with implementing this regulation. CDC is currently working to develop a plan to address the role of Public Health to meet the growing national concerns about bioterrorism.

SLIDES:

Potential Agents of Bioterrorism: - Restrictions on their distribution and use

Interstate Shipping Regulations for Infectious Substances

Regulations

Additional Requirements for Facilities Transferring or Receiving Select Agents : 42 CFR Part 72.6, 1996

Exemptions:

Clinical and diagnostic purposes.
Research labs that already posses any select agent may work with it.

Viruses:

1. Crimean-Congo haemorrhagic fever virus

2. Eastern Equine Encephalitis virus

3. Ebola viruses

4. Equine Morbillivirus

5. Lassa fever virus

6. Marburg virus

7. Rift Valley fever virus

8. South American Haemorrhagic fever viruses (Junin, Machupo, Sabia, Flexal, Guanarito)

9. Tick-borne encephalitis complex viruses

10. Variola major virus (Smallpox virus)

11. Venezuelan Equine Encephalitis virus

12. Viruses causing hantavirus pulmonary syndrome

13. Yellow fever virus

Exemptions -

Vaccine strains
Junin Virus strain candid #1
Rift Valley fever virus strain MP-12
VEE virus strain TC-83
Yellow fever virus strain 17-D

Bacteria

1. Bacillus anthracis

2. Brucella abortus, B. melitensis, B. suis

3. Burkholderia (Pseudomonas) mallei

4. Burkholderia (Pseudomonas) pseudomallei

5. Clostridium botulinum

6. Francisella tularensis

7. Yersinia pestis

Exemptions: Described in Title 9 CFR, Part 78

B. abortus strains 19 and RB51

Rickettsiae
1. Coxiella burnetii

2. Rickettsia prowazekii

3. Rickettsia rickettsii

Fungi

1. Coccidioides immitis

Toxins

1. Abrin

2. Aflatoxins

3. Botulinum *

4. Clostridium perfringens epsilon *

5. Conotoxins

6. Diacetoxyscirpenol

7. Ricin ⁺

8. Saxitoxin

9. Shigatoxin

10. Staphylococcal enterotoxins

11. Tetrodotoxin ⁺

12. T-2

* never exempt except for research

⁺some never exempt except for research

Exemptions -

Toxins for medical use
Toxins inactivated for vaccine use
Or toxin preps for biomedical use at an LD50 for vertebrates 100 ng/kg
National standards for potency testing of USDA-approved vet. vac

Recombinants / Genomic Materials

1. Genetically modified microorganisms or genetic elements from organisms in Appendix A, shown to produce or encode for a factor associated with a disease or toxicosis. (pathogenecity, virulence, &ldots;)

2. Genetically modified microorganisms or genetic elements that contain nucleic acid sequences for any of the toxins listed in Appendix A, or their toxic subunits.

Other Restrictions

The deliberate transfer of a drug resistance trait to microorganisms listed in Appendix A not known to acquire the trait naturally if such acquisition could compromise the use of the drug to control these diseases agents in humans or animals.

Facility Registration

Identify Responsible Facility Official
Prior to transferring or receiving SA
- Completion of application and facility survey (BMBL & 1910.1450)
- Review by CDC/OHS
- Site visit (initially or at least 1/3yr)
- Fee payment (anticipate none after 9/98)
Issuance of registration number

Registration Denial

Facility not or is no longer capable of handling agents at appropriate BSL.
Facility has handled covered agents in a manner contravention of BMBL.
Facility has or intends to use agents in a manner harmful to human health.
Facility does not comply with provisions of the regulation.

Inspections

All EA-101 forms (transfer, receipt) and records [42 CFR 72.1]
Compliance with BMBL & 1910.1450
- practices, procedures, facilities & containment
Handling of select agents, including
- receipt, storage, disposal
- intra-facility transfer

Shipment of SAs

All select agents are to be shipped as "special infectious agents"
triple packaging
- meet DOT requirements
- use a system that tracks packages
- 24 hr telephonic contact capability
- shipper notifies addressee
- addressee notifies shipper & CDC

More Information?

Laboratory Registration / Select Agent Transfer Program

www.cdc.gov/od/ohs/lrsat.htm

Framework Of Regulatory Controls For Human And Animal Pharmaceutical Products
Rudolf Bliem, Tarac Consulting, Vienna, Austria

Aim:

To present the international system of regulatory control of industrial facilities to assure product-related biosafety within the pharmaceutical industry

To show how the system

provides transparency for the authorities
without compromising confidentiality of proprietary information
that distinguishes between proprietary and non-proprietary information
that may act as a model for BTWC.

PHARMACEUTICAL REGULATIONS

Overall Purpose:

To assure product safety for consumers.

Approach:

By assuring product safety and process safety

BASIS FOR REGULATORY EVALUATION AND APPROVAL FOR MARKETING:

A. PRODUCT requirements for clinical safety, effectiveness and quality

Information provided to authorities through

Product License Application

B. MANUFACTURING requirements for facility, equipment, personnel, management, operations, and controls ("GMP regulations")

Information provided to authorities through

Manufacturing License Application or Product License Application

and Pre-Approval Inspection

C. SURVEILLANCE

Information provided through

reporting of:

adverse drug effects

changes to product or manufacturing system

Inspections: periodic (biannual)

PRODUCT AND MANUFACTURING LICENSE APPLICATION

Total amount of information provided: typically 5000 pages

PRODUCT GROUPS COVERED BY THESE REGULATIONS

Blood Products, Vaccines, Toxins, Fermentation Products, Biotech; Chemical Synthetics

THE REGULATORS

Governmental Drug Agencies:

USA. Food and Drug Administration (FDA)

1. Central Offices - Coordination and Product Review and inspections

2. Field - Inspections

EU:

1. European Medicines Evaluation Agency (EMEA) - Overall coordinators

2. Committee for Proprietary Medicinal Products (CPMP) - Product review

3. National Member State Agencies - Inspections

Other: each developed country employs a similar governmental system

Principles of protection (protection of product safety):

Containment (e.g. NIH, G(I)LSP): keep bugs in (risk: cross contamination)

GMP Practice: keep bugs out (risk: product quality damage)

GLP

GMP also encompasses the principles of containment and GLP!

SYSTEM OF REGULATIONS:

Core regulation: GMP Regulations (GLP)

USA: US CFR Title 21 (human, animal pharmaceuticals, (human) medical devices, human and animal diagnostics

EU: 91/356/EEC (human products) and 91/412/EEC (animal products)

Additional Regulatioy: Environmental (e.g. EPA), Food and Chemicals (e.g. USDA), Biotech G(I)LSP

Auxillary regulations and standards: Cleanroom standards, Literature ("state of the art")

Furthermore: ISO 9000, EN 45000, OSHA etc.

Principles of compliance?

International Compliance and recognition and acceptance

What information do they see in practice?

CONFIDENTIALITY

information that is routinely collected by the pharmaceutical companies for the authorities that is not regarded as commercial proprietary information.

INSTRUMENTS TO DISTINGUISH

proprietary from non-proprietary information:

FOI-Concept

Internet

Literature

International Recognition

GMPs and Countries (matrix)

International Harmonization Initiatives:

USA, EU, Japan set standards for Product Registration: ICH

Mutual Recognition Agreements:

Agreements between USA/FDA and importers to the USA

Agreements between groups of countries on mutual recognition of inspection standards: PIC, PIC/S

Standards with international impact

Industry Acceptance

Trends

FRAMEWORK OF REGULATORY CONTROLS FOR HUMAN AND ANIMAL PHARMACEUTICAL PRODUCTS

Requirements:

1. for marketed products

Product License + Manufacturing License

2. for development products: the manufacture of investigational products for clinical trials - minimal form of product/manufacturing license

Principle Content of a Product License

Product Data:

Formal application data

Technical Information:

Manufacturing data

Non-clinical (animal) pharmacology, especially safety

Human pharmacology (safety, efficacy, doage) and other clinical Data

Samples, Labels

Means of Authorization: Review by authorities and appointed experts

Principle Content of Manufacturing License

Manufacturing Data:

Organization,

Facility,

Products,

Processes,

Quality Control

Quality Assurance

Special Aspect: Validation

Means of Authorization: Inspection

International activities on Biosafety
Piet van der Meer, Netherlands Ministry of the Environment.

ABSTRACT:

In Agenda 21, the result of the United Nations Conference on Environment andDevelopment (Rio de Janeiro, 1992), Chapter 16 is dedicated to "Environmentallysound management of biotechnology".

Starting point of that chapter is the recognition that - although biotechnology does not offer a panacea and quick fix for all problems - it does offer apotential promise for sustainable development in important areas such asagriculture, health care and environmental protection.

In that Chapter 16 it is furthermore recognized that the community at large can benefit maximally from the potentials of biotechnology only if it is developed and applied judiciously, in order to avoid to the extent possible negative side effects that have diminished the potentials of many new technologies in the past.

In line with these considerations, Chapter 16 of Agenda 21 focuses on 5 programme areas for international cooperation for the development and application ofbiotechnology:

Increasing the availability of food, feed and renewable rawmaterials.
Improving human health.
Enhancing protection of the environment.
Enhancing safety in biotechnology and developing international mechanisms for cooperation.
Establishing enabling mechanisms for the development and the environmentally sound application of biotechnology.

There are two important elements in programme area D on international cooperationon safety in biotechnology: - as there are already many internationally developed methodologies and procedures for safety in biotechnology, duplication of efforts should be avoided as much as possible; - the level to which safety methodologies can be conducive to environmentally sound management of biotechnology at the global level depends on the level of international harmonization and agreement.

Chapter 16 offers a blue print for an effective start on international cooperation. From this blueprint two main elements emerge with regard to international cooperation: -capacity building, among others by sharing knowledge and experience in regional conferences; -international harmonization and agreement.

Capacity building - regional conferences

The first regional conference which was explicitly organized as a follow up of Chapter 16 of Agenda 21, was the "African Regional Conference for International Cooperation on Safety in Biotechnology", October 1993, Harare, Zimbabwe. This conference was followed by a series of similar regional conferences in LatinAmerica, Asia and Central and Eastern Europe, and more regional meetings are planned.

International agreement - biosafety protocol

In December 1995, the second Conference of Parties to the Biodiversity Convention(COP2) decided "to develop, in the field of the safe transfer, handling and use of living modified organisms, a protocol on biosafety, specifically focusing on transboundary movement, of any living modified organism resulting from modern biotechnology that may have adverse effect on the conservation and sustainable use of biological diversity, setting out for consideration, in particular, appropriate procedure for advance informed agreement" (decision II/5).

For this purpose, the COP2 established an Open ended Ad Hoc Working Group (WGBS) under the conference of the Parties. Since its first meeting in July 1996, the WGBS has met four times and the negotiations have reached 'cruising speed'. TheWGBS aims at submitting early 1999 a text for a Protocol on Biosafety in for consideration by the COP.

Capacity building / International agreement - UNEP guidelines

Complementary to the development of a Protocol on Biosafety, UNEP has prepared International Technical Guidelines for Safety in Biotechnology. Such guidelinescan serve two main purposes. Firstly, such guidelines can provide a framework forsafety in biotechnology for the duration of the discussion on the status andmodalities of international agreement. Secondly, after the adoption of such agreement, there will be a number of countries, organizations and companies that would need technical guidance in carrying out the commitments of such agreement.

SLIDES:

BIOSAFETY

WHAT?

WHY?

INTERNATIONAL ACTIVITIES

BIOSAFETY PROTOCOL

BIOSAFETY

SAFETY IN RELATION TO:

- RECOMBINANT DNA

- GENETIC ENGINEERING

- GENETIC MODIFICATION

- GENETIC MANIPULATION

- MODERN BIOTECHNOLOGY

BIOSAFETY: IMPORTANT DATES:

1972 FIRST APPLICATIONS OF RECOMBINANT DNA

"BERG LETTER"

1974 ASILOMAR CONFERENCE

MORATORIUM

1975 SECOND ASILOMAR CONFERENCE

END OF MORATORIUM

1986 OECD RECOMBINANT DNA SAFETY RECOMMENDATIONS

THE UNITED NATIONS CONFERENCE ON ENVIRONMENT AND

DEVELOPMENT

JUNE 1992 (UNCED, RIO DE JANEIRO)

AGENDA 21, CHAPTER 16:

"ENVIRONMENTALLY SOUND MANAGEMENT OF BIOTECHNOLOGY"

AGENDA 21, CHAPTER 16:

"BIOTECHNOLOGY HOLDS A PROMISE FOR SUSTAINABLE DEVELOPMENT

IN THE FIELDS OF:

- AGRICULTURE

- HEALTH CARE

- ENVIRONMENTAL PROTECTION"

"The community at large can benefit maximally from the Potentials of new technology only if its developed and Applied judiciously"

AGENDA 21, CHAPTER 16:

PROGRAMME AREA D: BIOSAFETY

TWO MAIN ELEMENTS:

1) There are already many internationally developed methodologies and procedures for safety in biotechnology

Duplication should be avoided as much as possible;
Sharing knowledge and experience - capacity building

2. The level to which biosafety mechanisms can be conducive to globally environmentally sound management of biotechnology depends on the level of international harmonization and agreement

Biosafety capacity building
Sharing knowledge and experience on a regional basis

IMPORTANT DATES:

* OCTOBER 1993, HARARE, ZIMBABWE

* JUNE, 1994, CARTAGENA, COLOMBIA

* FEBR. 1995, SAN JOSÉ, COSTA RICA

* MARCH 1995, BANGKOK, THAILAND

* SEPT. 1995, KESZTHELY, HUNGARY

* OCT. 1996, SMOLENICE, SLOVAKIA

* AUGUST 1997, BUDAPEST, HUNGARY

* MARCH 1998: UNEP ROE MULTI YEAR PROGRAMME FOR BIOSAFETY

CAPACITY BUILDING IN C&EE

BIOSAFETY - INTERNATIONAL AGREEMENT

PROTOCOL ON BIOSAFETY TO THE CONVENTION ON BIOLOGICAL DIVERSITY

* ARTICLE 8.G CBD: " each contracting party shall, as far as possible and appropriate, establish or maintain means to regulate, manage or control the risks related with the use and release of living modified organisms resulting from biotechnology which are likely to have adverse environmental impacts that could affect the conservation and sustainable use of biological diversity, taking also into account the risks to human health"

CONVENTION ON BIOLOGICAL DIVERSITY ARTICLE 19.3 CBD:

* ARTICLE 19.3 CBD: "the parties shall consider the need for and modalities of a protocol setting out appropriate proce- dures, including, in particular, advance informed agree- ment, in the field of the safe transfer, handling and use of any living modified organism resulting from biotechnology that may have adverse effect on the conservation and sustainable use of biological diversity"

CONVENTION ON BIOLOGICAL DIVERSITY: SECOND CONFERENCE OF THE PARTIES (JAKARTA, DECEMBER 1995):

* DECISION II/5: "to develop, in the field of the safe transfer, handling and use of living modified organisms, a protocol on biosafety, specifically focusing on transboundary movement, of any living modified organism resulting from modern biotechnology that may have adverse effect on the conservation and sustainable use of biological diversity, setting out for conside- ration, in particular, appropriate procedure for advance informed agreement"

PROTOCOL ON BIOSAFETY: IMPORTANT DATES:

OPEN ENDED AD HOC WORKING GROUP (WGBS)

* JULY 1996, ARHUS, DENMARK

* MAY 1997, MONTREAL, CANADA

* OCTOBER 1997, MONTREAL, CANADA

* FEBR. 1998, MONTREAL, CANADA

PLANNED:

* AUGUST 1998: WGBS5

* FEBR. 1999: WGBS6:

ORGANISATION OF WORK WGBS

DIVISION OF WORK - 4 SUB GROUPS:
COORDINATION - BUREAU / CHAIRS
INFORMAL CONTACTS -WORKSHOPS
CONSOLIDATED DOCUMENTS - OPTIONS

PROTOCOL ON BIOSAFETY, CONSOLIDATED TEXT RESULTING FROM THE 4TH MEETING

PREAMBLE

ARTICLE 1 - OBJECTIVES

ARTICLE 1 BIS - GENERAL OBLIGATIONS

ARTICLE 2 - DEFINITIONS

ARTICLE 3A - SCOPE OF THE PROTOCOL

ARTICLE 3B - AIA PROCEDURE

ARTICLE 4 - NOTIFICATION

ARTICLE 5 - RESPONSE TO

ARTICLE 6 - DECISION PROCEDURE FOR AIA

ARTICLE 7 - REVIEW OF DECISIONS [UNDER AIA]

ARTICLE 8 - NOTIFICATION OF TRANSIT

ARTICLE 9 - SIMPLIFIED PROCEDURE

ARTICLE 10 - SUBSEQUENT IMPORTS

ARTICLE 11 - MULTILATERAL, BILATERAL AND REGIONAL AGREEMENTS

ARTICLE 12 - RISK ASSESSMENT

ARTICLE 13 - RISK MANAGEMENT

ARTICLE 14 - MINIMUM NATIONAL STANDARDS

ARTICLE 15/16 - UNINTENTIONAL TRANSBOUNDARY MOVEMENTS/ EMERGENCY MEASURES

ARTICLE 17 - HANDLING, TRANSPORT, PACKAGING AND LABELLING

ARTICLE 18 - COMPETENT AUTHORITY/FOCAL POINT

ARTICLE 19 - INFORMATION SHARING/BIOSAFETY CLEARING-HOUSE/

ARTICLE 20 - CONFIDENTIAL INFORMATION

ARTICLE 21 - CAPACITY-BUILDING

ARTICLE 22 - PUBLIC AWARENESS/PUBLIC PARTICIPATION

ARTICLE 23 - NON-PARTIES

ARTICLE 24 - NON-DISCRIMINATION

ARTICLE 25 - ILLEGAL TRAFFIC /

ARTICLE 26 - SOCIO-ECONOMIC CONSIDERATIONS

ARTICLE 27 - LIABILITY AND COMPENSATION

ARTICLE 28 - FINANCIAL MECHANISM AND RESOURCES

ARTICLE 29 - CONFERENCE OF THE PARTIES

ARTICLE 30 - SUBSIDIARY BODIES AND MECHANISMS

ARTICLE 31 - SECRETARIAT

ARTICLE 33 - RELATIONSHIP WITH THE CONVENTION

ARTICLE 34 - RELATIONSHIP WITH OTHER INTERNATIONAL AGREEMENTS

ARTICLE 35 - MONITORING AND REPORTING /

ARTICLE 35 - BIS - COMPLIANCE

ARTICLE 36 - ASSESSMENT AND REVIEW OF PROCEDURES/ANNEXES]

ARTICLE 37 - SIGNATURE

ARTICLE 40 - ENTRY INTO FORCE

ARTICLE 41 - RESERVATIONS

ARTICLE 42 - WITHDRAWAL

ARTICLE 43 - AUTHENTIC TEXTS

UNEP INTERNATIONAL TECHNICAL GUIDELINES ON SAFETY IN BIOTECHNOLOGY

UNEP GUIDELINES AND BIOSAFETY PROTOCOL ARE COMPLEMENTARY

CONTENTS:

I. INTRODUCTION

II. GENERAL PRINCIPLES

III. RISK ASSESSMENT/MANAGEMENT

IV. NATIONAL/REGIONAL MECHANISMS

V. INTERNATIONAL MECHANISMS

VI. CAPACITY BUILDING

ANNEXES:

1. INFORMATION SOURCES

2. GLOSSARY OF TERMS

3. RISK ASSESSMENT - POINTS TO CONSIDER

4. CONTAINED USE

5. RELEASES

Microbial Pathogens and their Toxins: Methods for Identification and Safe Handling during Biotechnology Operations
Howard S. Tranter, Centre for Applied Microbiology Research, Porton Down, Salisbury, Wilts SP4 0JG, UK.

ABSTRACT

The development and industrial exploitation of hazardous micro-organisms or genetically-modified organisms (GMOs) is not uncommon within the biotechnology and biopharmaceutical industries. Vaccine manufacturers in particular, by the very nature of their business, manipulate microbial pathogens or their products to produce an effective prophylaxis against disease. Other examples include biotherapeutic products such as the botulinum toxin manufactured at CAMR for treatment of muscular dystonias and ricin or diphtheria toxins, the toxic moieties of immunotoxins preparations.

In Europe, key legislation governing work of this type exists in two EC Directives. Those concerned with the Contained use of GMOs (90/219/EEC) and with the Protection of Workers from Risks Related to Exposure to Biological Agents at Work (90/679/EEC). Manufacturing operations typically comprise a series of linked processes, each of which may encompass one or more unit operations ranging from the relatively simple (medium preparation) to the more complex (fermentation, effluent processing). The biosafety risks associated with these processes can be reduced or eliminated by appropriate application of containment principles. The principles include keeping to the lowest practical level any workplace and environmental exposure to physical, chemical or biological agents. This requires safe equipment design and methods of operation and adequate testing and validation of the measures that protect workers from exposure. Validation of effective facility and equipment cleaning procedures may require the development of sensitive test methods for the detection and identification of organism and/or product.

This presentation reviews the use of microbial pathogens in biotechnology including their safe handling during manufacturing operations and methods for their detection and identification. It will address the evidence required by regulatory authorities that such processes are performed safely and within the guidelines of Good Manufacturing Practice indicating that which should be available to inspectors during non-challenge visits under the Biological and Toxin Weapons Convention.

SLIDES

Examples of Human and Veterinary Bacterial Vaccines Currently Available

Organism

Human Vaccine

Veterinary Vaccine

Cl. botulinum

B. anthracis

Cl. perfringens

Cl. tetani

S. typhi

V. cholerae

Y. pestis

F. tularensis

Br. abortus

Br. melitensis

B. pertussis

C. diphtheriae

Ps. aeruginosa

*Licensed vaccines

Biosafety Regulations

The Organisation for Economic Co-operation and Development (OECD) guidelines were basis for

90/219/EEC Council Directive on the Contained Use of Genetically Modified Micro-organisms
90/220/EEC Council Directive on the Deliberate Release in the Environment of Genetically Modified Organisms
90/679/EEC Council Directive on the Protection of Workers related to Exposure to Biological Agents at Work

UK Legislation & Guidance

Control of substances hazardous to health regulations (COSHH 1988 & 1994)
Genetically modified organisms (contained use) regulations (1992 & 1996)
Genetically modified organisms (deliberate release) regulations (1992 & 1995)

Form part of

Health & Safety at Work Act (1974)
Environmental Protection Act (1990)

Process Step

Operation

Hazard

Raw material

Weighing, mixing,

Generation of allergenic

handling

Dissolving

dusts

Inoculum preparation

Inoculation, fermentation

Generation of aerosols

Bioreactor

Fermentation

Aerosols of reactor

contents, spillages, off gas contamination

Biomass Separation

Centrifugation

Aerosols, spillages

Process Step

Operation

Hazard

Product purification

Homogenisation, blending

Production of aerosols

Centrifugation

Production of aerosols, spillages

Dialysis

Production of aerosols, spillage

Chromatography

Spillages, increasedproduct purity, potency

Product finishing

Blending, filtration

Production of aerosols

filling, freeze, spray drying

Production of aerosols, spillages, generation of dusts

Effluent Handling

Sterilisation, discharge

Discharge of untreated effluent

Levels of Containment

Primary

Immediate physical barrier

Secondary

Provides back up to primary containment in the form of physical enclosure or engineering improvements

Tertiary

Defined operational facility preventing contamination outside the laboratory or production area

Biological

Genetic modification of micro-organisms to restrict their ability to survive or transmit genetic information

Operator

Personal protection in the form of positive/negative pressure respirators or whole body suits

Biosafety Features of P3 225 L fermenter at CAMR

Steam barriers on double 'o' rings seals including supply lines, mechanical seals on stirrer shafts

Piping of condensate lines and pressure relief system to kill tank

Double 'in series' filtered inlet and outlet gases

Elimination of unnecessary pipe joints

Use of welded piping

Hermetically sealed condensate traps

Localised containment of sample valve and probe entry ports

Engineering control measures prior to use or during operation can utilise:

Pressure testing - look for drop in pressure over time

Leak testing - soap solution, helium detectors, sulphur hexaflouride detection

Filter integrity - pressure decay, DOP test

Aerosol measurement - direct air and sampling

Environmental monitoring - air sampling

Safety cabinet testing - pressure testing, volumetric, DOP filter test, electrical checks

Engineering control measures:

Planned and preventative maintenance

Equipment logs, testing results and calibration checks

Operator training

Standardised operating procedures

Manufacturing In Biotechnology: Basic requirements of GMP:

Effective Quality Management

Competent and appropriately trained staff

Suitable premises and manufacturing equipment

Documentation system

Documented, pre-established production processes, fully validated modifications

Independent Quality Control Department, appropriately staffed and equipped

Observance of cGMP by sub-contractors

Systems for customer complaint and product recall

Monitoring of cGMP compliance by self-audit

Potential Bacterial BW Agents

Bacteria

Causative Agent

Routes of transmission

Bacillus anthracis

Organism + Toxin

Skin, wounds, inhalation

Clostridium botulinum

Toxins A-G

ingestion, inhalation

Staphylococcus aureus

Toxins A-H

ingestion, inhalation

Vibrio cholerae

Organism + toxin

ingestion

Yersinia pestis

Organism

zoonotic transmission, inhalation

Francisella tularensis

Organism

Zoonotic transmission, ingestion, inhalation

Screening of Samples for BW Agents

Traditional Culture and/or the following:

Immunoassays

Genetic analysis

Biological assays

Chemical analysis

Chemical analysis could include:

FPLC, HPLC

Gas Chromatography-Mass Spectroscopy

Thin layer chromatography

Peptide sequencing

Sampling for BW Agents

Issues still to be resolved:

Method and equipment validation

Testing of denatured protein, DNA

Inhibitory substances

On site/off site analysis

Confidentiality

Theft of Intellectual Property

Maintaining awareness of developments in biosafety regulations and controls
Otto Doblhoff, European Federation Biotechnology, Working Party "Safety in Biotechnology"

Developments in biosafety regulations and controls can be monitored through special commentaries in scientific journals, the press and most directly by reading the publications issued by regulatory bodies. For the scientific and industrial biotechnology community, it has become increasingly difficult to be aware of all the national and international biosafety regulations, as these range from product safety, operator safety, environmental safety all the way to international transport, quarantine regulations and regulations on a global scale, such as the international biodiversity convention, or the Biological Toxins and Weapons Convention.

The Internet has become the prime source of information in the area of biosafety. An ever increasing number of institutions and national regulatory bodies are maintaining internet resources, with on-line access to many relevant legal documents, manuals and information directed towards the lay public. If used efficiently, these resources can make information accessible from any desktop computer with an internet connection. One of the great dangers of the internet is the vast amount of junk information available. Information should therefore only used from sites with reliable quality. Organizations or individuals, from whom information is procured, should be scrutinized for their reliability, in the same way we have learned to discern the value of other information sources.

Search engines are used to locate information on the net. Giant servers are fed with internet sites and their contents, or scan the net for new sites. Narrowing down searches by using the right keyword is comparable to other computer searches (e.g. scientific computer abstract services). Search engines are not perfect mirrors of all internet resources and in some cases an interesting site will not be listed or can not be found with the appropriate keywords. In many cases finding a quality site, will provide the starting point to other related resources through an world wide web feature called "links". Many sites provide lists of such links, with a short description and the internet address.

The world wide email system facilitates the dialogue between individuals and institutions. Email discussion lists bring together a world wide community of specialists, where answers can be automatically forwarded to all individuals signed up on the particular list. As some individuals are signed up in more than one related discussion list, relevant questions get transferred to these list, thus reaching a far greater audience, than initially envisaged. Very often valuable inputs to complex interdisciplinary issues are made possible through these links.

The presentation will cover the internet resources and pinpoint some of prime information sites.

Some biosafety related sites:

http://www.boku.ac.at/iam/efb/ The European Federation Biotechnology Working Party on Safety in Biotechnology

http://www.eurospider.ch/BATS/ The Swiss Agency for Biosafety Research and

Assessment of Technology Impacts BATS

http://biosafety.ihe.be/EBSA/HomeEBSA.html The European Biological Safety

Association

http://www.biodiv.org/biosafe/ Reports of the open-ended ad hoc working group on biosafety under the convention on biological diversity

http://irptc.unep.ch/biodiv/ United Nations Environment Programme UNEP, contains the UNEP Biosafety guidelines

http://www.orcbs.msu.edu/absa/ The American Biological Safety Association

http://biosafety.ihe.be/ The Belgian Biosafety Server with lots of links

http://www.orcbs.msu.edu/biological/biolsaf.htm Biosafety Information at the

http://www.orcbs.msu.edu/biological/resource.htm Michigan State University with it's excellent collection of manuals and resources

http://www.abc.hu/biosafety.html Biosafety Information at the Hungarian Agricultural Biotechnology Center in cooperation

with the

http://www.who.ch/ World Health Organisation WHO with the

http://www.who.ch/outbreak/outbreak_home.html WHO Outbreak Surveillance

http://binas.unido.org/binas/binas.html the UNIDO Bio Informations Network

and Advisory Service BINAS Web Server

http://base.icgeb.trieste.it/ International Centre for Genetic Engineering and

Biotechnology (ICGEB) in Trieste, with its

http://www.bmwf.gv.at/7forsch/forecht/gtg/pggtech.htm The Austrian Ministry of

Science and Technology with the Austrian Gentechnology law, related EU-guidelines and

it`s on-line application and notification procedure

http://www.cdc.gov/od/ohs/biosfty/biosfty.htm The US Office of Health and

Safety, Centers for Disease Control and Prevention biosafety related publications

http://vm.cfsan.fda.gov/~fsis/eco-con.html The U.S. Department of Agriculture

Food Safety and Inspection Service information on E. coli O157:H7

Some BTWC related sites:

http://www.brad.ac.uk/acad/sbtwc/home.htm The Department of Peace Studies at the University of Bradford

http://fas-www.harvard.edu:80/~hsp/pugwash.html Pugwash Study Group on CBW

http://www.cbiac.apgea.army.mil CBIAC (The Chemical and Biological Defense Information Analysis Center)

http://www.sussex.ac.uk/spru/hsp/ HSP (Harvard Sussex Program) on CBW Armament and Arms Limitation

http://www.sipri.se/projects/chembio.html SIPRI (Stockholm International Peace Research Institute) Chemical and Biological Warfare Project

http://www.stimson.org The Henry L. Stimson Center, Chemical and Biological Weapons Nonproliferation Project

http://www.fas.org/bwc/index.html Biological and Toxin Weapons Working Group, Federation of American Scientists

http://www.asanltr.com/ ASA (Applied Science and Analysis, Inc.) Newsletter

http://www.cdc.gov/od/ohs/biosfty/biosfty.htm CDC'S biosafety documents including the Laboratory Registration Select Agent Transfer Program

http://www.pressroom.com/~cbaci/ Chemical and Biological Arms Control Institute

Discussion list

BIOSAFETY@mitvma.mit.edu

To subscribe, send mail to LISTSERV@LISTSERV.NET, leave the subject field blank and place the following command in the text of your message:

SUBSCRIBE BIOSAFTY your_full_name

Replace 'listname' with the Network-wide ID name...the name in the first column corresponding with the list you would like to subscribe.

Replace 'your_full_name' with your full real name...not your login name. Also it is VERY IMPORTANT to delete any other text in you e-mail message. The only thing that should appear in the message is the above command.

The list server will recognize your email from the email heades automatically.

Search engines:

http://www.altavista.digital.com/

http://www.infoseek.com/

http://www.lycos.com/

http://www.hotbot.com/

http://www.yahoo.com/

APPENDIX

APPENDIX I: The Biological and Toxin Weapons Convention

Convention on the Prohibition of the Development, Production and Stockpilingof Bacteriological (Biological) and Toxin Weapons and on Their Destruction.

Signed at London, Moscow and Washington on 10 April 1972. Entered into force on 26 March 1975 Depositaries: U.K., U.S. and Soviet governments.

The States Parties to this Convention,

Determined to act with a view to achieving effective progress towards generaland complete disarmament, including the prohibition and elimination of alltypes of weapons of mass destruction, and convinced that the prohibitionof the development, production and stockpiling of chemical and bacteriological(biological) weapons and their elimination, through effective measures,will facilitate the achievement of general and complete disarmament understrict and effective international control,

Recognizing the important significance of the Protocol for the Prohibitionof the Use in War of Asphyxiating, Poisonous or Other Gases, and of BacteriologicalMethods of Warfare, signed at Geneva on June 17, 1925, and conscious alsoof the contribution which the said Protocol has already made, and continuesto make, to mitigating the horrors of war,

Reaffirming their adherence to the principles and objectives of that Protocoland calling upon all States to comply strictly with them,

Recalling that the General Assembly of the United Nations has repeatedlycondemned all actions contrary to the principles and objectives of the GenevaProtocol of June 17, 1925,

Desiring to contribute to the strengthening of confidence between peoplesand the general improvement of the international atmosphere,

Desiring also to contribute to the realization of the purposes and principlesof the United Nations,

Convinced of the importance and urgency of eliminating from the arsenalsof States, through effective measures, such dangerous weapons of mass destructionas those using chemical or bacteriological (biological) agents,

Recognizing that an agreement on the prohibition of bacteriological (biological)and toxin weapons represents a first possible step towards the achievementof agreement on effective measures also for the prohibition of the development,production and stockpiling of chemical weapons, and determined to continuenegotiations to that end, Determined for the sake of all mankind, to exclude completely the possibilityof bacteriological (biological) agents and toxins being used as weapons,

Convinced that such use would be repugnant to the conscience of mankindand that no effort should be spared to minimize this risk, Have agreed as follows:

Article I

Each State Party to this Convention undertakes never in any circumstancesto develop, produce, stockpile or otherwise acquire or retain:

(1) Microbial or other biological agents, or toxins whatever their originor method of production, of types and in quantities that have no justificationfor prophylactic, protective or other peaceful purposes;

(2) Weapons, equipment or means of delivery designed to use such agentsor toxins for hostile purposes or in armed conflict.

Article II

Each State Party to this Convention undertakes to destroy, or to divertto peaceful purposes, as soon as possible but not later than nine monthsafter entry into force of the Convention, all agents, toxins, weapons, equipmentand means of delivery specified in article I of the Convention, which arein its possession or under its jurisdiction or control. In implementingthe provisions of this article all necessary safety precautions shall beobserved to protect populations and the environment.

Article III

Each State Party to this Convention undertakes not to transfer to any recipientwhatsoever, directly or indirectly, and not in any way to assist, encourage,or induce any State, group of States or international organizations to manufactureor otherwise acquire any of the agents, toxins, weapons, equipment or meansof delivery specified in article I of this Convention.

Article IV

Each State Party to this Convention shall, in accordance with its constitutionalprocesses, take any necessary measures to prohibit and prevent the development,production, stockpiling, acquisition, or retention of the agents, toxins,weapons, equipment and means of delivery specified in article I of the Convention,within the territory of such State, under its jurisdiction or under itscontrol anywhere.

Article V

The States Parties to this Convention undertake to consult one another andto cooperate in solving any problems which may arise in relation to theobjective of, or in the application of the provisions of, the Convention.Consultation and Cooperation pursuant to this article may also be undertakenthrough appropriate international procedures within the framework of theUnited Nations and in accordance with its Charter.

Article VI

(1) Any State Party to this convention which finds that any other StateParty is acting in breach of obligations deriving from the provisions ofthe Convention may lodge a complaint with the Security Council of the UnitedNations. Such a complaint should include all possible evidence confirmingits validity, as well as a request for its consideration by the SecurityCouncil.

(2) Each State Party to this Convention undertakes to cooperate in carryingout any investigation which the Security Council may initiate, in accordancewith the provisions of the Charter of the United Nations, on the basis ofthe complaint received by the Council. The Security Council shall informthe States Parties to the Convention of the results of the investigation.

Article VII

Each State Party to this Convention undertakes to provide or support assistance,in accordance with the United Nations Charter, to any Party to the Conventionwhich so requests, if the Security Council decides that such Party has beenexposed to danger as a result of violation of the Convention.

Article VIII

Nothing in this Convention shall be interpreted as in any way limiting ordetracting from the obligations assumed by any State under the Protocolfor the Prohibition of the Use in War of Asphyxiating, Poisonous or OtherGases, and of Bacteriological Methods of Warfare, signed at Geneva on June17, 1925.

Article IX

Each State Party to this Convention affirms the recognized objective ofeffective prohibition of chemical weapons and, to this end, undertakes tocontinue negotiations in good faith with a view to reaching early agreementon effective measures for the prohibition of their development, productionand stockpiling and for their destruction, and on appropriate measures concerningequipment and means of delivery specifically designed for the productionor use of chemical agents for weapons purposes.

Article X

(1) The States Parties to this Convention undertake to facilitate, and havethe right to participate in, the fullest possible exchange of equipment,materials and scientific and technological information for the use of bacteriological(biological) agents and toxins for peaceful purposes. Parties to the Conventionin a position to do so shall also cooperate in contributing individuallyor together with other States or international organizations to the furtherdevelopment and application of scientific discoveries in the field of bacteriology(biology) for prevention of disease, or for other peaceful purposes.

(2) This Convention shall be implemented in a manner designed to avoid hamperingthe economic or technological development of States Parties to the Conventionor international cooperation in the field of peaceful bacteriological (biological)activities, including the international exchange of bacteriological (biological)and toxins and equipment for the processing, use or production of bacteriological(biological) agents and toxins for peaceful purposes in accordance withthe provisions of the Convention.

Article XI

Any State Party may propose amendments to this Convention. Amendments shallenter into force for each State Party accepting the amendments upon theiracceptance by a majority of the States Parties to the Convention and thereafterfor each remaining State Party on the date of acceptance by it.

Article XII

Five years after the entry into force of this Convention, or earlier ifit is requested by a majority of Parties to the Convention by submittinga proposal to this effect to the Depositary Governments, a conference ofStates Parties to the Convention shall be held at Geneva, Switzerland, toreview the operation of the Convention, with a view to assuring that thepurposes of the preamble and the provisions of the Convention, includingthe provisions concerning negotiations on chemical weapons, are being realized.Such review shall take into account any new scientific and technologicaldevelopments relevant to the Convention.

Article XIII

(1) This Convention shall be of unlimited duration.

(2) Each State Party to this Convention shall in exercising its nationalsovereignty have the right to withdraw from the Convention if it decidesthat extraordinary events, related to the subject matter of the Convention,have jeopardized the supreme interests of its country. It shall give noticeof such withdrawal to all other States Parties to the Convention and tothe United Nations Security Council three months in advance. Such noticeshall include a statement of the extraordinary events it regards as havingjeopardized its supreme interests.

Article XIV

(1) This Convention shall be open to all States for signature. Any Statewhich does not sign the Convention before its entry into force in accordancewith paragraph (3) of this Article may accede to it at any time.

(2) This Convention shall be subject to ratification by signatory States.Instruments of ratification and instruments of accession shall be depositedwith the Governments of the United States of America, the United Kingdomof Great Britain and Northern Ireland and the Union of Soviet SocialistRepublics, which are hereby designated the Depositary Governments.

(3) This Convention shall enter into force after the deposit of instrumentsof ratification by twenty-two Governments, including the Governments designatedas Depositaries of the Convention.

(4) For States whose instruments of ratification or accession are depositedsubsequent to the entry into force of this Convention, it shall enter intoforce on the date of the deposit of their instruments of ratification oraccession.

(5) The Depositary Governments shall promptly inform all signatory and accedingStates of the date of each signature, the date of deposit or each instrumentof ratification or of accession and the date of entry into force of thisConvention, and of the receipt of other notices.

(6) This Convention shall be registered by the Depositary Governments pursuantto Article 102 of the Charter of the United Nations.

Article XV

This Convention, the English, Russian, French, Spanish and Chinese textsof which are equally authentic, shall be deposited in the archives of theDepositary Governments. Duly certified copies of the Convention shall betransmitted by the Depositary Governments to the Governments of the signatory and acceding states.

APPENDIX II: UNEP Biosafety Guidelines

FOREWORD

It gives me great pleasure to launch this edition of the UNEP International Technical Guidelines for Safety in Biotechnology, adopted by the Global Consultation of Government-designated Experts, hosted by the Government of Egypt in Cairo from 11 to 14 December 1995.

It is gratifying to note that the consensus-building process which resulted in the success of the Global Consultation involved a wide spectrum of stakeholders, all of whom took the opportunity to translate their vision of safety in biotechnology into the spirit and flesh of the Guidelines.

The public and the private sectors (including the biotechnology industry), the Secretariat of the Convention on Biological Diversity, relevant United Nations bodies, intergovernmental and non-governmental organizations, among others, all participated and played their part in the development of these Guidelines (at national, subregional and/or global levels).

More importantly, the consultations were undertaken in full cognizance of, and in total harmony with, the work of the Conference of the Parties to the Convention on Biological Diversity and its various bodies in their efforts to develop a protocol on biosafety. In this regard, great significance attaches to decision II/5 of the second meeting of the Conference of the Parties, held in Jakarta from 6-17 November 1995, which states that, during the development of a protocol on biosafety, internationally agreed guidelines on biosafety - such as the UNEP Guidelines (still in draft form at that time) - may serve as an interim mechanism in various substantive ways. They could facilitate the development of national capacities to assess and manage biotechnology risks, the establishment of adequate information systems; and the development of human resources and relevant expertise pertinent to issues of biosafety at the national and regional levels. The second meeting of the Conference of the Parties further noted in its decision II/5 that the UNEP Guidelines, without prejudice to the development of a protocol, could be used to complement it after its conclusion.

To UNEP, the linkage between the application of the Guidelines and the capacity- building that is essential for their implementation is both obvious and inevitable. Indeed, it is vital and urgent for countries and regions to acquire the various relevant capacities to implement the Guidelines. Neither these Guidelines nor the biosafety protocol currently under development, nor any future international agreement on biosafety will in or of themselves ensure safety in biotechnology development, research and application. Consequently, the national and regional capacity-building programmes that are necessary for the effective implementation of these Guidelines should be formulated and given adequate technical and financial support on a priority basis. Founded on sound scientific principles, their implementation needs to be undertaken with technical competence, logical consistency and judicious urgency.

UNEP has formulated such a programme as part of its 1996-1997 programme of work. It incorporates components and proposals for funding by, among others, the Global Environment Facility (GEF), through which developing countries and countries with economies in transition will receive the technical and financial support to develop and/or strengthen their national biosafety frameworks which will permit the effective implementation of these Guidelines and any future international agreement on biosafety within a harmonized regional and global context.

The development of the national biosafety frameworks called for in the Guidelines will entail technical and financial support to Governments and relevant in-country or regional entities. Such support is essential in order to:

* Establish or strengthen national authorities or national institutional biosafety mechanisms;

* Review national legislative, administrative and policy measures on biosafety;

* Assess and identify priorities in human resources development in biosafety and in the related capacity-building (including infrastructural) requirements in the countries (and their subregions/regions);

* Establish or develop appropriate knowledge bases, infrastructure for information exchange and mechanisms for effecting advance informed agreements;

* Elaborate and implement some national capacity-building programmes for biosafety;

* Stage national training workshops/seminars in risk-assessment and risk-management techniques for support staff, technicians and middle-level cadres;

* Enhance public awareness of biotechnology risks and attendant risk-assessment and risk-management techniques through initiatives involving the community at large, policy makers, legislators, administrators, the private sector and the biotechnology industry;

* Implement in practice and further develop and refine the Guidelines, taking into account emerging issues and new developments in the field of biosafety.

There will, additionally, be need for a thorough, in-depth assessment of the status of safety in biotechnology worldwide. It would encompass the identification of emerging issues and new developments in biosafety and biotechnology and the assessment of existing guidelines, agreements and legislation, as well as related human, institutional and infrastructural capacities. Such a global biosafety assessment exercise would also attempt to provide a realistic scenario of the availability of the financial resources that would need to be mobilized and/or invested to achieve safety in biotechnology research, development and applications, as envisaged within the framework of the Guidelines (or future international agreement on biosafety).

In effecting the foregoing activities to assist in the enormous work at hand or ahead of us in the quest for safe development and application of biotechnology products covered by the Guidelines, strong partnerships are required and envisaged between UNEP, relevant United Nations bodies (such as the United Nations Development Programme (UNDP), the United Nations Industrial Development Organization (UNIDO), the United Nations Educational, Scientific and Cultural Organization (UNESCO), the Food and Agriculture Organization of the United Nations (FAO) and the Commission on Sustainable Development) and the various key players in the biotechnology and biosafety arenas at national, regional and international levels, both individuals as well as organizations and institutions (e.g. the Organisation for Economic Cooperation and Development (OECD), Instituto Interamericano de Cooperacion para la Agricultura (IICA), the African Ministerial Conference on the Environment (AMCEN), the International Centre for Genetic Engineering and Biotechnology and the Stockholm Environment Institute's Biotechnology Advisory Commission (BAC)). The agenda includes the preparation of sector-specific manuals on pertinent biosafety issues and themes; fostering North-South cooperation and collaborative ventures; mobilizing bilateral/ multilateral support and its timely disbursement; and staging national/ regional training workshops, seminars, symposia, etc. to facilitate the practical implementation of the Guidelines by all parties concerned.

I would like to reiterate here that, in executing the above tasks at all levels, we need to adopt a participatory approach, embracing the widest possible spectrum of stakeholders from among the scientific and general community at large, as well as the public and private sectors. Pertinent views and issues (including gender-related issues) should be duly taken into account, building through this process a consensus that incorporates and reflects the involvement, concerns and aspirations of the whole populace.

I hereby wish to present and commend the Guidelines to you all.

Elizabeth Dowdeswell

Executive Director

United Nations Environment Programme

UNEP INTERNATIONAL TECHNICAL GUIDELINES FOR SAFETY IN BIOTECHNOLOGY PREFACE

In Agenda 21, Governments undertook to consider international cooperation on safety in biotechnology. That commitment includes: sharing experience, capacity-building and international agreement on principles for safety.

The Governing Council of UNEP in its decision 18/36 B affirmed the desirability of UNEP contributing to international efforts on biosafety, including the development of international technical guidelines, while avoiding duplication with other international activities currently being undertaken by organizations, in particular the work initiated by the Conference of the Parties to the Convention on Biological Diversity.

The Conference of the Parties to the Convention on Biological Diversity, at its second meeting, taking into account the provisions of Articles 8(g) and 19 (3) of the Convention, decided to develop a protocol on biosafety, specifically focusing on transboundary movement, of any living modified organism resulting from modern biotechnology that may have adverse effect on the conservation and sustainable use of biological diversity, setting out for consideration, in particular, appropriate procedure for advanced informed agreement. It stressed the importance of the urgent finalization of the UNEP International Technical Guidelines on Safety in Biotechnology, which may be used as an interim mechanism during the development and implementation of a protocol without prejudice to the development and conclusion of such a protocol and to complement it after its conclusion.

These technical Guidelines are intended as a contribution to the implementation of Agenda 21 commitments and aim to assist Governments, intergovernmental, private-sector and other organizations in the establishment and maintenance of national capacities to provide for safety in biotechnology, to assist in developing expert human resources and for international exchange of information.

These Guidelines have been developed on the basis of common elements and principles derived from relevant existing regional and international instruments and national regulations and guidelines, and drawing upon experience already gained through their preparation and implementation.

I. INTRODUCTION

1. Agenda 21, adopted at the United Nations Conference on Environment and Development (UNCED) held in Rio de Janeiro in June 1992, in its chapter 16 makes specific provision for the "Environmentally Sound Management of Biotechnology". In the introduction to that chapter it is recognized that, although biotechnology cannot provide solutions to all the fundamental problems of environment and development, it could nevertheless contribute substantially to sustainable development by improvements in food production and feed supply, health care and environmental protection.

2. Chapter 16 of Agenda 21 also recognizes that the community at large can only benefit maximally from biotechnology if it is developed and applied judiciously. It therefore seeks to ensure safety in biotechnology development, application, exchange and transfer through international agreement on principles to be applied on risk assessment and management.

3. The Convention on Biological Diversity also addresses the issue of safety in biotechnology in Articles 8(g) and 19, paragraphs 3 and 4. In Article 8(g) Parties to the Convention are called upon to establish or maintain means to regulate, manage or control the risks associated with the use and release of living modified organisms resulting from biotechnology which are likely to have adverse impacts on the conservation and sustainable use of biological diversity, while in Article 19(3) the Parties are called upon to consider the need for and modalities of a protocol for the safe transfer, handling and use of living modified organisms resulting from biotechnology that may have adverse effect on the conservation and sustainable use of biological diversity. Article 19 (4) states that each Party is obliged directly, or by requiring any natural or legal person under its jurisdiction providing the organisms referred to in paragraph 19 (3), to provide any available information about the use and safety regulations required by that Party in handling such organisms, as well as any available information on the potential adverse impact of the specific organisms concerned to the Party into which those organisms are to be introduced.

4. In its decision II/5, the second meeting of the Conference of the Parties to the Convention on Biological Diversity, held in Jakarta from

6-17 November 1995, while establishing an open-ended Ad Hoc Working Group to develop a protocol on biosafety, stressed the importance of urgent finalization of the UNEP International Technical Guidelines for Safety in Biotechnology and that these could contribute to the development and implementation of the protocol on biosafety without prejudice to its development or conclusion. Furthermore, the Conference of the Parties noted that such International Technical Guidelines may be used as an interim mechanism during the development of the protocol and to complement it after its conclusion for the purposes of facilitating the development of national capacities to assess and manage risks, establish adequate information systems and develop expert human resources in biotechnology.

5. The contribution that the adoption of safe procedures in biotechnology can make to the successful global development of the technology depends on the extent to which international information exchange, cooperation, harmonization, and agreement can be achieved.

6. The development of new techniques of genetic modification in the early 1970s prompted a thorough discussion on safety in biotechnology which resulted in a number of national and international recommendations, guidelines and legislation. By the mid-1980s, it was widely considered that recombinant DNA techniques could be considered as an extension of conventional genetic procedures and that organisms produced by this technology presented risks that were similar in kind to those posed by any other organism. But, while it was also recognized that the potential benefits of biotechnology were greater because of the new molecular techniques which allowed a greater diversity of genes to be introduced into organisms, the relative lack of experience with such organisms nevertheless indicated that it would be appropriate to develop the technology in a precautionary and judicious manner.

7. Modern biotechnology has now been developed and applied since the early 1970s under contained conditions, and since the mid-1980s for applications in the environment. As recognized by decision II/5 of the second meeting of the Conference of the Parties to the Convention on Biological Diversity, although considerable knowledge has accumulated, significant gaps in knowledge have been identified, specifically in the field of interaction between living modified organisms (LMOs) resulting from modern biotechnology and the environment, taking into account the relatively short period of experience with releases of such organisms, the relatively small number of species and traits used, and the lack of experience in the range of environments, specifically those in centres of origin and genetic diversity. Given the rapid development in the use of this technology and taking into account the knowledge and considerable experience gained with certain types and uses of modern biotechnology, international agreement on safety in biotechnology is now opportune.

8. The status and modalities of such international agreement have been the subject of international discussion. One of the issues under consideration then was whether such agreement should take the form of a legally binding instrument (such as a follow-up to Agenda 21 or a protocol to the Convention on Biological Diversity) or whether it should be voluntary in nature (such as a code of conduct, etc). The Conference of the Parties to the Convention on Biological Diversity, at its second meeting in Jarkata, decided to establish an open-ended Ad Hoc Working Group to develop, in the field of the safe transfer, handling and use of living modified organisms, a protocol on biosafety, specifically focusing on transboundary movement, of any living modified organism resulting from modern biotechnology that may have adverse effect on the conservation and sustainable use of biological diversity, setting out for consideration, in particular, appropriate procedure for advance informed agreement. The negotiation process may take several years to conclude the protocol. Furthermore, upon a binding agreement being adopted, a number of countries and intergovernmental, private-sector and other organizations will need technical guidance of the kind contained in these Guidelines to fulfil their commitments under such an international agreement. These technical Guidelines are intended to provide a common framework for safety in biotechnology at national, regional and international levels, without prejudice, but as a complement, to the development of a biosafety protocol. The Conference of Parties, therefore, stressed the urgent need for rapid finalization of the UNEP International Technical

Guidelines for Safety in Biotechnology which may be used as an interim

mechanism during the development and implementation of a protocol and to complement it after its conclusion (see paragraph 4 above).

9. The Guidelines have been developed on the basis of common elements and principles derived from relevant national, regional and international instruments, regulations and guidelines, and drawing upon experience already gained through their preparation and implementation. The sources taken into consideration are listed in Annex 1.

10. The Guidelines are based on the premise that adequate mechanisms for risk assessment and risk management and capacity-building through - among others - the exchange of information and the use of these Guidelines at national, regional and international levels can contribute significantly to safety in biotechnology.

11. The Guidelines address the human health and environmental safety of all types of applications of biotechnology, from research and development to commercialization of biotechnological products containing or consisting of organisms with novel trait(s). They recognize that before such biotechnological products are placed on the market, they must comply with any specific product requirements, such as food safety, efficacy and quality, but these are not addressed in the Guidelines.

12. The Guidelines can be implemented by using existing structures and measures, or by introducing new ones.

13. To be credible, safety mechanisms need to be based on up-to-date knowledge.

14. Adequate safety mechanisms and international agreement on safety in biotechnology can contribute to the sustainable development of biotechnology and to the international trade in biotechnological products.

15. The adoption of guidelines does not in itself ensure safety. Rather, the guidelines propose mechanisms for evaluating biosafety, identifying measures to manage foreseeable risks and to facilitate processes such as monitoring, research and information exchange, all of which improve the safe application of biotechnology.

16. These technical Guidelines acknowledge the importance of assessing the socio-economic and other impacts of new biotechnologies, but they do not address such issues, which are often considered within the particular national or regional context.

17. Complying with these Guidelines does not override obligations required under existing national, regional or international legal systems.

II. GENERAL PRINCIPLES AND CONSIDERATIONS

18. As with any human activity, the safety of any technological application is achieved by carrying out certain sequential steps, as follows:

(a) Identifying any hazards;

(b) Assessing the risks: if a hazard has been identified, the combined effect of the consequences and the likelihood of the hazard being realized are estimated;

(c) Managing the risks: where indicated by the results of the risk assessment, either by applying adequate management strategies, including designing procedures and methods to minimize risks and their consequences, or by deciding not to proceed. Management strategies should be commensurate with the results of the risk assessment. Therefore, there might be cases where very few, if any, risk management measures will be necessary.

19. In applying this general principle to biotechnology, which involves the use of organisms, risk assessment takes into account the following components and the interactions between these (see also Chapter III):

- The characteristics of the organisms (see Annex 2) involved, including any newly introduced traits;

- The manner in which organisms are to be used, including any management practices applied, such as provision for containment and waste treatment;

- The characteristics of the areas and other organisms that might be affected, i.e. the potential receiving environment, including humans.

20. Risk assessment and risk management can be based in part on knowledge of and experience (i.e. familiarity) with an organism, the intended application and the potential receiving environment. Risk assessment may vary from a very short process to an extensive review, depending on the extent of familiarity. Adequate familiarity does not necessarily imply that an organism is safe, but it means that known management procedures can be applied. A lack of familiarity does not mean that an organism is not safe, but it means that, until sufficient familiarity with such organisms has been acquired, risks associated with such organisms are assessed on a case by case (e.g. variety by variety or strain by strain) basis and in a step-wise manner. As experience and knowledge evolve, risk assessment may serve for a group of organisms for characteristics that are functionally equivalent on a physiological level. Greater knowledge and experience will be required for the exemption of larger groups of organisms. As a consequence, applications with certain groups of organisms may proceed under defined generic conditions, or might be exempted from oversight. The development of such generic approaches of risk assessment or exemption in one country does not necessarily mean that similar generic approaches will be applied in other countries.

21. There is generally less familiarity with the behaviour of organisms whose genetic make-up is unlikely to develop naturally, such as organisms produced by modern genetic modification techniques, than with the behaviour of organisms developed traditionally. This has been the reason why many countries have focused on such organisms and products containing them. In these Guidelines, such organisms are called organisms with novel traits. These Guidelines should allow the benefits of biotechnology to be realized and, at the same time, ensure that concerns about novelty are addressed. Although these Guidelines are directed to organisms with novel traits and products containing such organisms, the general principles for safety are applicable to all organisms.

22. The Guidelines provide assistance for identifying organisms whose characteristics may differ from those of the parent organisms from which they are derived in ways that would suggest additional scrutiny might be appropriate. This may be because they produce substances which are not found in the species concerned, or because there are new environmental or other risks associated with the new characteristic.

23. Experience with environmental releases to date suggests that the risks associated with organisms with novel traits, much of which has concerned well- known agricultural crop plants in well-known agricultural environments, will in most cases be the same in kind as those associated with the parent organisms, and can be dealt with satisfactorily by comparable mechanisms. It is generally anticipated that, in most cases, there will be low environmental risk from introducing into a similar environment such well-known crop plants after they have been modified by altering or adding only one or a few genes, especially when compared with the risks of introducing entirely new or alien species.

24. Monitoring can contribute significantly to gaining knowledge and experience with the use of organisms with novel traits. Monitoring may vary from a very simple observation to an extensive research programme. Monitoring can be carried out by the user and/or by an independent authority, organization or body and is often used to verify the assumptions made in a risk assessment and should be used to evaluate whether the risk-management measures used are appropriate and effective.

25. Once adequate risk-management strategies have been formulated, the effectiveness of those strategies depends partially on the user. Therefore, the primary responsibility for the safe use or transfer of organisms with novel traits lies with the user. Consequently, users should be well informed, competent and well aware of their responsibility.

26. An organism with novel traits which is considered to be harmless in one region might be potentially harmful in another region which offers different environmental conditions. Therefore, there is a need for the exchange and supply of scientific information in cases where organisms with novel traits are intended to be released into new environments and when transfer of such organisms across national boundaries is being considered, particularly in those cases in which organisms with novel traits are intended to be released in the environment.

27. In cases in which organisms with novel traits are to be transferred to their centres of origin, there is a need to pay particular attention to risk assessment and risk management, because of possible effects on related species that are present, to ensure adequate protection of genetic resources and biological diversity.

III. ASSESSMENT AND MANAGEMENT OF RISKS

28. An assessment of the risks to human health and the environment associated with the use of organisms with novel traits is based on consideration of the following key parameters, when applicable:

(i) The characteristics relating to the organism with novel traits, taking into account:

- the recipient/parental or host organism;

- the relevant information on the donor organism and the vector used;

- the insert and the encoded trait;

- the centre of origin, when known.

(ii) The intended use, i.e. the specific application of the contained use or deliberate release or placing on the market, including the intended scale and any management procedures and waste treatment;

(iii) The potential receiving environment.

Forecasting models could be developed in the future that may aid in these assessments.

29. Examples of the points to consider in risk assessment are given in Annex 3. These points should be used to arrive at a judgement concerning the consequences and likelihood of hazards occurring which could cause harm to human health and/or the environment and the effectiveness of proposed management strategies to minimize the risk. The severity of harm might depend on the extent to which and the period over which other organisms and their ecosystems or their components are affected.

30. If the risk assessment at first shows that the level of risk of the intended use is not acceptable, additional risk-management measures are to be taken and assessed until the risks have been minimized to an acceptable level. If the risk cannot be minimized in this way, it might be concluded that the intended operation should not proceed, or a risk/benefit analysis might be carried out to determine whether a higher level of risk is acceptable and whether the intended operation should proceed.

31. The type of risk management to be applied depends on the organism with novel traits and the particular application. For contained uses, the degree of containment achieved depends primarily on the type of physical barriers and the application of appropriate work procedures. In the case of controlled releases, different types of barriers, such as biological, chemical, physical or temporal barriers can be used to minimize or limit the dissemination and impacts of organisms with novel traits and/or to provide genetic isolation, if required. Different risk-management practices may be applied, depending on the scale of the proposed release and its duration. Examples are given in Annex 5.

32. International databases are important sources of information for risk assessment and risk management, because they provide detailed knowledge of and experience gained with organisms with novel traits and aid in the development of models. They provide a contact from which further information could usually be obtained. Countries should be encouraged to provide information on access to their own databases. Countries, organizations and companies should be encouraged to contribute to and coordinate the development and maintenance of regional and international databases such as those listed in Annex 6. Databases should be regularly updated and, whenever possible, interlinked and made available for users.

IV. PROVIDING FOR SAFETY: MECHANISMS AT NATIONAL AND REGIONAL LEVEL

33. To implement adequate risk assessment and risk management, countries would need to establish or designate or strengthen national and/or regional authorities/national institutional mechanisms for oversight and/or control of the use of organisms with novel traits. The authority or mechanism should have, or have access to, relevant scientific and technical knowledge and experience.

34. Effective oversight mechanisms require that: a risk assessment has been done; or the organism has been exempted from oversight on the basis of experience and knowledge; relevant users supply to the authority/national institutional mechanism all required relevant information or appropriate references; users record the outcome of relevant activities and inform the authority/national institutional mechanism of the outcome when required. In particular, they should provide relevant information if there is an unexpected or adverse effect on human health or environmental impact during, or as a result of, the notified use.

35. To fulfil their responsibilities efficiently and effectively, authorities/national institutional mechanisms need adequate capacities which should help to avoid any delay in making decisions.

36. For organisms with novel traits requiring evaluation, an authority/national institutional mechanism should determine who is responsible for preparing and reviewing risk assessments and proposed risk management. It might consider local review to be appropriate; it might conduct the review itself; it may establish a multidisciplinary body, consisting of scientific experts; or it may choose to use a combination of particular expertise from inside and outside the country or region.

37. Mechanisms for oversight and/or control can include prior notification to the authority/national institutional mechanism of contained use facilities and certain contained uses and releases of organisms with novel traits, and the marketing of products containing or consisting of organisms with novel traits. If prior notification of activities under oversight is required, such notification may or may not require a positive decision from the authority/national institutional mechanism before the notified use can proceed.

38. As set out in Agenda 21 and relevant provisions of the Convention on Biological Diversity, authorities/national institutional mechanisms are responsible for encouraging public participation by allowing access to information on which decisions are based, whilst respecting confidential commercial information. This should allow for local knowledge and circumstances to be taken into account in risk assessments. Users are encouraged to enter into dialogue with their staff/personnel as well as with the general public and workers about their activities. Examples of mechanisms for informing the public are provided in Annex 7.

39. The responsibility for establishing and/or implementing appropriate mechanisms providing for safety lies with countries and/or regions.

V. PROVIDING FOR SAFETY: MECHANISMS AT INTERNATIONAL LEVEL USING INFORMATION SUPPLY AND EXCHANGE

40. Countries would need to establish or designate focal points responsible for the international exchange of information. This might be the authorities responsible for oversight. Countries are encouraged to cooperate with existing international agencies, organizations, mechanisms and regional networks (see Annex 6) for the dissemination of biosafety-related information. Countries and organizations should agree to protect confidential commercial information. The content of such information, however, needs to be discussed between the specific country and company or organization in order that the country can make a decision.

Exchange of general information

41. Countries are encouraged to participate in the exchange of general information about national biosafety mechanisms; generic research of value to risk assessments and risk management; and approvals given for the marketing of products containing or consisting of organisms with novel traits. This last category of information will be of particular importance for living products of modern biotechnology placed on the international market. Countries, organizations and companies will wish to be aware of which countries have adopted measures similar to those set down in these Guidelines to facilitate the exchange of mutually acceptable data and assessments. This form of information exchange can be carried out through direct information exchange, as well as through the creation of an international register or database.

Supply of information when the use of organisms with novel traits

could affect human health in, or the environment

of, another country

42. The use of an organism with novel trait(s) might in some cases affect other countries. For organisms representing a possible impact or threat due to transboundary movements, the following two points should be followed:

- The potentially affected country should be given notice of the intended use and the opportunity to state whether particular measures will be needed to protect its interests, in particular its biodiversity;

- The potentially affected country should be informed immediately in the event of an adverse effect of the use of a organism with novel traits which could affect it.

43. The information supplied would include the identity, the relevant characteristics and numbers/volumes of the organisms with novel traits involved and any available information regarding the handling of the organisms and information related to risk assessment and risk management.

Supply of information related to transboundary transfer of

organisms with novel traits

44. Organisms with novel traits have been and will be transferred from one country to another for research and development purposes and for placing on the market. A person or organization intending to transfer organisms with novel traits to a country will need to comply with the safety mechanisms in that country. However, it is recognized that not all countries are at present able to implement safety mechanisms fully. For such countries, the following paragraphs offer a scheme for information exchange involving a range of mechanisms, from the provision of information from one user to another, to "advance informed agreement" for certain cases. They are aimed at those countries in order to enable them to achieve safety in biotechnology and to make informed decisions.

45. The key to this scheme is that, depending on the characteristics of the organism with novel traits and of the intended use, a user intending to transfer such organisms from one country to another must provide relevant information to the user or appropriate focal point(s) in the receiving country. This request for information transfer would still apply even if the organism has been exempted from oversight in the supplying country. Information could, in some cases, be supplied together with the transferred organisms with novel traits and, in other cases, in advance of the transfer (see paragraph 46 below). The provision of information prior to transfer involves a mechanism of "advance informed agreement", i.e. the transfer of organisms with novel traits to another country first requires the agreement of the receiving country.

46. Under this scheme, whether the relevant information would have to be supplied with, or in advance of, the transfer of organisms with novel traits depends on the intended subsequent use of these organisms, as follows:

- The provision of information to the intended user together with the transfer of organisms with novel traits would be appropriate in cases when such organisms are to be used in containment (e.g. research and development or storage in collections). In general, the information provided should be sufficient to enable the receiving country to undertake a risk assessment. In the case of transfer only for subsequent storage in collections, the identity and possible hazards of the organism with the novel traits would suffice, together with relevant information on appropriate storage procedures.

- The provision of information to the focal point in the receiving country before the transfer of the organisms with novel traits and under advance informed agreement would be appropriate in cases where such organisms to be transferred are intended for subsequent release into the environment (such as in field trials) or are intended to be placed on the market, unless the receiving country has indicated, based on the familiarity or the characteristics of the organisms with novel traits, that no advance informed agreement is required.

- Contained use of certain organisms with novel traits on an industrial scale would in some cases use some organisms in such quantities that they may have adverse effect on human health and the environment if they are released by routine or accident. Transfer of such organisms with novel traits could for these reasons be covered by this advance informed agreement procedure.

47. Examples of the information to be supplied, at the request of the receiving country, prior to the intended transfer of organisms with novel traits in these cases would include:

- name and address of exporting user;

- name and address of receiving user;

- origin, name and taxonomic status of recipient organism;

- description of traits introduced or modified and characteristics of the organism;

- summary of the assessment of risks to human health and the environment;

- intended dates of transfer;

- number of organisms to be transferred or volume of culture and physical form;

- any relevant requirements to ensure safe handling, storage, subsequent transport and use;

- methods for safe disposal and suitable procedures in case of accidents;

- intended use of the organism;

- information on relevant previous releases.

48. Recognizing that some organisms with novel traits will be traded internationally as commodities, there is a limitation in the extent to which information can be provided to an importer about the presence of organisms with novel traits in that commodity. Implementation of the guidelines would, however, assist focal points in obtaining knowledge of the types of traits that have been approved in exporting countries.

49. When information is supplied before transfer, the appropriate focal point in the receiving country should advise the person or organization intending to transfer the organisms with novel traits of the specific information required. After making a decision about the transfer, the appropriate focal point in the receiving country should indicate to the person or organization transferring such organisms and the intended recipient any conditions that might be imposed on the transfer and subsequent use.

50. National focal points should indicate to other focal points and to any international register or database created for this purpose their particular information requirements for cases in which advance informed agreement applies.

51. National focal points approached by other national focal points, authorities/national institutional mechanisms or international bodies for information about organisms with novel traits and their uses, or for advice, are encouraged to provide as full a response as possible. Regional groups are encouraged to make arrangements for routine reciprocal exchanges of information about current activities involving the use of organisms with novel traits. Exchanges can be arranged in a variety of ways, such as between different regional groups, on either a regular or an ad hoc basis. National databases may be useful to provide information to other national databases or focal points.

52. In order to maintain safety levels during transport and transit, organisms with novel traits should be packed and labelled adequately. Packaging and labelling requirements should be commensurate with the level of risk involved. In order to maintain safety during transit and transport, existing international recommendations, agreements and conventions on transport should be taken into account.

VI. CAPACITY-BUILDING

53. These Technical Guidelines have been developed under the clear recognition that:

- The implementation of these Guidelines depends on the availability of human resources (in terms of quantity and quality) and financial resources, information, and/or institutional and infrastructural capacities at the national, regional and international levels;

- Such resources and capacities are currently either not available or are not adequate in a number of countries at various levels.

54. Capacity-building is one of the prime elements which will facilitate effective implementation of the Technical Guidelines. Capacity-building is the strengthening and/or development of human resources and institutional capacities. It involves the transfer of know-how, the development of appropriate facilities, training in sciences related to safety in biotechnology and in the use of risk-assessment and risk-management techniques (see Annex 3).

In this regard, countries, organizations, the private sector and biotechnology industry are called upon to contribute actively to capacity-building at the local, national, regional and international levels.

55. Capacity-building should aim to ensure:

- That countries develop and strengthen their endogenous capacities to facilitate the implementation of these Technical Guidelines;

- That nations and countries involved in the development, use, release or production of organisms with novel traits are aware of any risks associated with their work and have the means to assess and manage risks;

- That Governments are able to achieve safety when certain organisms with novel traits (see Chapter V) are to be transferred into and/or to be used in their countries;

- That the safe development, transfer and application of biotechnology be enhanced by the development and/or strengthening of appropriate policies, facilities (including adequate information systems) and training in sciences related to biosafety and biotechnology, including training in risk-assessment and risk-management techniques and procedures for biosafety.

56. In drawing up programmes directed at capacity-building, Governments and international agencies providing technical and financial assistance to other countries should consider the expressed need of those countries to increase awareness of, expertise in and facilities and resources for assessing and managing risks associated with the use of organisms with novel traits.

57. Those conducting studies or developing products involving organisms with novel traits in countries which have not yet been able to implement safety mechanisms should assist in training at the local and national level in the safe handling and use of such organisms in cooperation with the concerned Governments.

58. Regional and international cooperation and coordination are key factors of the implementation of these Guidelines. Countries, organizations and companies are encouraged to contribute actively to the sharing of experience, through appropriate means.

59. National and international organizations are encouraged to draw up and/or provide directories/databases of individuals (such as scientists, administrators, policy makers and legislators) and organizations that can help in reviewing risk-assessments and risk-management strategies and in providing detailed guidance on mechanisms for national and regional controls.

Annex 1: SOURCES CONSULTED IN PREPARATION OF THESE GUIDELINES AND OTHER RELEVANT SOURCES

Sources consulted include:

- UNCED, 1992, Agenda 21, Chapter 16: Environmentally Sound Management of Biotechnology.

- UNCED 1992, Research Paper No: 55 In our Land; EARTH SUMMIT '92.

- OECD recombinanant DNA recommendations (1986).

- OECD Safety considerations in Biotechnology (1993): Scale up of crop plants.

- IICA guidelines for the release into the environment of genetically modified organisms;

- Convention on Biological Diversity;

- Report of the Expert Panel IV Established to Follow-up on the Convention on Biological Diversity;

- The UNIDO Voluntary Code of Conduct for the Release of Organisms into the Environment;

- European Community Directives on the Contained Use of Genetically Modified Microorganisms and the Deliberate Release into the Environment of Genetically Modified Organisms;

- UNEP London Guidelines for the Exchange of Information on Chemicals in International Trade;

- The FAO Code of Conduct on the Distribution and Use of Pesticides;

- The FAO draft Code of Conduct for plant biotechnology as it affects the conservation and utilization of plant genetic resources;

- International Plant Protection Convention.

National regulations, UN transportation regulations, and European Community Directives on Workers' Protection, among others, were also consulted.

Annex 2: GLOSSARY OF TERMS USED IN THESE GUIDELINES

1. Capacity-building: It is the strengthening and/or development of human resources and institutional capacities.

2. Contained use: Any operation involving organisms which are controlled by physical barriers or a combination of physical and/or chemical and/or biological barriers which limit their contact with, or their impacts on, the potentially receiving environment, which includes humans.

3. Controlled release: Deliberate release of organisms where risk management measures are applied.

4. Containment: Prevention of the spread of organisms outside the facilities which may be achieved by physical containment (the use of good work practices, equipment and installation design) and/or biological containment (the use of organisms which have reduced ability to survive or reproduce in the environment).

5. Containment level: The degree of physical containment which depends on the design of the facility, the equipment installed and the procedures used.

6. Deliberate release: Any use of organisms that is not a contained use.

7. Donor: The organism from which genetic material is derived for insertion into or combination with another organism.

8. Centre of origin of diversity: The place or region where the source of diversity is located.

9. Familiarity: Knowledge and experience with an organism, the intended application and the potential receiving environment (see paragraph 20).

10. Genetic modification: Modern biotechnology used to alter genetic material of living cells or organisms in order to make them capable of producing new substances or performing new functions.

11. Hazard: The potential of an organism to cause harm to human health and/or the environment.

12. Host: An organism in which the genetic material is altered by modification of a part of its own genetic material and/or insertion of foreign genetic material.

13. Organism: Any entity able to replicate its own genetic material including viruses.

14. Organisms with novel traits: Organisms produced by genetic modification and whose resultant genetic make-up is unlikely to occur

in nature. These do not include organisms obtained by conventional techniques and traditional breeding methods.

15. Oversight: A system for addressing questions of potential risk through guidelines, regulations or other structures.

16. Parents: Organisms from which an organism with novel trait(s) is derived.

17. Pathogen: An organism that can cause disease.

18. Potential receiving environment: An ecosystem or habitat, including humans and animals, which is likely to come in contact with a released organism.

19. Risk: The combination of the magnitude of the consequences of a hazard, if it occurs, and the likelihood that the consequences will occur.

20. Risk assessment: The measures to estimate what harm might be caused, how likely it would be to occur and the scale of the estimated damage.

21. Risk management: The measures to ensure that the production and handling of an organism are safe.

22. Users: Any persons, institutions or organizations (including companies) responsible for the development, production, testing, marketing and distribution of organisms with novel traits. Any member of the general public who purchases and/or uses an organism is not a user in the meaning of these Guidelines, unless specific conditions are attached to its use.

23. Vector: An organism or object used to transfer genetic material from a donor organism to a recipient organism.

Annex 3: RISK ASSESSMENT: EXAMPLES OF POINTS TO CONSIDER, AS APPROPRIATE

Risk assessment is based on the characteristics of the organism, the introduced trait, the characteristics of the intended use, the receiving environment, and the interaction between these. Knowledge of and experience with any and all of these provide familiarity which plays an important role in risk assessment. A relatively low degree of familiarity may be compensated for by appropriate risk-management practices. Familiarity can be increased as a result of a trial or experiment. This increased familiarity can then form a basis for future risk assessment.

Risk assessment is typically a routine and ongoing component of research and development, and testing of organisms with novel traits. It can range from a routine ad hoc judgement by the researcher to adherence to a formalized assessment.

Risk assessment requires a range of expertise which should be reflected in the competence and experience of those carrying out the assessment in a scientifically sound manner.

The different fields of expertise needed for scientifically sound risk assessment may include, as appropriate:

* Nucleic acid technology * Plant biology/botany

* Molecular genetics * Veterinary science

* Population genetics * Agronomy

* Marine biology * Forestry

* Ecology * Pathology

* Taxonomy * Epidemiology

* Microbiology * Process technology

* Virology * Biochemistry

* Zoology * Toxicology

* Entomology

This list is provided as a guide to the major fields of expertise which may be required and is not intended to be comprehensive. Not all of these are likely to be relevant in each case and, as knowledge and technology advance, other fields of expertise will be important in risk assessment.

The objective of risk assessment is to answer questions related to:

* Identifying any hazards: what are the hazards, if any?

* Assessing the risks: if a hazard has been identified, what is the combined effect of the consequences and the likelihood of the hazard being realized? Can these be estimated?

* Managing the risks: To what extent can the risks be managed? Where indicated by the results of the risk assessment, either by applying adequate management strategies, including designing procedures and methods to minimize risks and their consequences, or by deciding not to proceed. Management strategies should be commensurate with the results of the risk assessment

* How do any identified risks compare with the risks that would be posed by the use, instead, of an organism not covered by these guidelines, if this is possible, or with risks that might be posed by doing nothing.

The impacts to be considered include those on human health, agricultural production, other organisms and the quality of the environment.

Full regard should be paid to the experience gained and to the relevant literature and consultation with available experts and public authorities.

The level of risk can be minimized either by applying risk-management strategies or by deciding not to proceed with the intended use of the organism with novel traits.

The information required for a scientifically sound risk assessment could include the following, depending on the organism, the application and the receiving environment, as appropriate; in some instances, providing a scientifically convincing rationale as to why particular data are not relevant may be helpful:

INFORMATION RELATING TO THE ORGANISM WITH NOVEL TRAITS:

Characteristics of the organism from which the organism with novel traits is derived:

The relevant biological, physiological and genetic and environmental characteristics of the recipient/parental/host organism include, as appropriate:

* the name and identity of the organism;

* Pathogenicity, toxicity and allergenicity (in the case of micro-organisms, it should be noted that there are internationally accepted classification lists for human pathogens. Similar lists exist at national level for plant and animal pathogens);

* the natural habitat and the geographic origin of the organism, its distribution and its role in the environment;

* mechanisms by which the organism survives, multiplies and disseminates in the environment;

* means for transfer of genetic material to other organisms.

Characteristics of the organism(s) from which nucleic acids are obtained (the donor):

The relevant characteristics include, in particular, pathogenicity, toxicity and allergenicity.

Characteristics of the vector:

* identity, origin, natural habitat, and the relevant safety characteristics of the vector;

* the frequency at which the vector is mobilized or can transfer itself to other organisms;

* factors which would influence the ability of the vector to become established in other hosts.

Characteristics of the inserted nucleic acid (the insert):

* functions coded by the inserted nucleic acid, including any residual vector;

* information on the expression of the inserted nucleic acid and the activity of the gene product(s).

Characteristics of the organism with novel traits:

The organism with novel traits should be compared with the organism from which it is derived, examining, where relevant, the following points:

* pathogenecity, toxicity and allergenicity to humans and other organisms (in the case of micro-organisms it should be noted that there are internationally accepted classification lists for human pathogens. Similar lists exist at national level for plant and animal pathogens);

* survival, persistence, competitive abilities and dissemination in the environment or other relevant interactions;

* capacity to transfer genetic material and the ways in which this might occur;

* methods for detecting the organism in the environment and for detecting the transfer of the donated nucleic acid;

* functions which might affect its ecological range;

* characterization of the product(s) of the inserted gene(s) and, where appropriate, the stability of the modification.

INFORMATION RELATING TO THE INTENDED USE

The amount of information required will vary with the characteristics of the organism and use, frequency and the scale of the intended use.

For contained uses, this can include:

* number or volume of organisms to be used;

* scale of the operation;

* proposed containment measures, including verification of their functioning;

* training and supervision of personnel carrying out the work;

* plans for waste management;

* plans for safety of the health of personnel;

* plans for handling accidents and unexpected events;

* relevant information from previous uses.

For deliberate releases, this can include:

* purpose and scale of the release;

* geographical description and location of the release;

* proximity to residences and human activities;

* method and frequency of release;

* training and supervision of personnel carrying out the work;

* likelihood of transboundary movement;

* time and duration of the release;

* expected environmental conditions during the release;

* proposed risk-management measures including verification of their functioning;

* subsequent treatment of the site and plans for waste management;

* plans for handling accidents and unexpected events/disasters;

* relevant information from any previous releases.

CHARACTERISTICS OF THE POTENTIAL RECEIVING ENVIRONMENT

The potential for an organism to cause harm is related to the environments into which it may be released and its interaction with other organisms. Relevant information can include:

* the geographical location of the site, the identity and any special features of the receiving environments that expose them to damage;

* the proximity of the site to humans and to significant biota;

* any flora, fauna and ecosystems that could be affected by the release, including keystone, rare, endangered or endemic species, potential competitive species and non-target organisms;

* the potential of any organism in the potential receiving environment to receive genes from the released organism.

Annex 4: EXAMPLES OF RISK-MANAGEMENT MEASURES FOR CONTAINED APPLICATIONS

Details of risk-management procedures are available in guidelines and regulations available from many countries and organizations.

Annex 5: EXAMPLES OF RISK-MANAGEMENT MEASURES FOR CONTROLLED RELEASES

Risk management is employed during the development and evaluation of an organism in a systematic fashion, for example from the laboratory, through stages of field testing, to commercialization. The number and forms of these stages are not fixed, but depend on the outcome of risk assessment at the different stages. Progression through the appropriate developmental stages, in order to gain knowledge, generally entails a reduction in control and possibly in monitoring, while often increasing in scale.

Appropriate risk management measures for releases will vary considerably from case to case. They will be determined by the risk assessment, the organisms involved and the way that they will be released. In addition to general precautions to control releases, risk management measures often focus on the control of the dissemination of the released organisms and control of the gene flow from the released organisms.

The type of risk-management measures to be employed should be commensurate with the risks identified. Therefore, there might be cases where very few, if any, risk-management measures will be necessary. Consequently, not all of the examples given below are likely to be relevant for any given controlled release.

Examples of risk-management measures for controlled releases include:

General precautions

- Appropriate information and training is provided for those involved in handling the organisms;

- Monitoring procedures are applied in such a way that appropriate measures can be taken in case of unexpected effects during or after the release;

- The dissemination of the released organisms and/or gene flow from the released organisms are controlled;

- Controlling access to the release site.

For plants

- Applying reproductive isolation, by:

* spatial separation;

* temporal separation: use of plants that will flower either earlier or later than plants of nearby reproductively compatible species;

* biological prevention of flowering (e.g. by omitting vernalisation);

* removal of the male or female reproductive structures;

* bagging of flowers;

* making use of sterility.

- Controlling the persistence or dispersal of reproductive structures such as propagules or seeds.

- Destroying volunteer plants after harvest; control of volunteers may be necessary during longer periods, depending on the species.

For animals

- Confining by appropriate means such as fences, filters, islands, ponds;

- Applying reproductive isolation by using sterile animals;

- Isolation from feral animals of the same species.

- Controlling the persistence or dispersal of reproductive structures such as larvae or eggs.

For micro-organisms

- Using organisms with impaired ability to grow or persist in the environment;

- Minimizing gene transfer by:

* using organisms that do not contain known self-transmissible mobilizable or transposable genetic elements;

* ensuring that introduced traits are stably located on the chromosome.

These measures will often not be applicable once an organism with novel traits, such as a modified crop plant, is at the stage of being marketed as a product if, as a result of testing during research and development, it has been shown that the risks are acceptably low.

Annex 6: DATABASES

Computerized and other forms of databases are important elements of a systematic approach to safety in biotechnology and to the process of wider international cooperation. Different types of databases have been established or are in the final stages of preparation and others are under consideration or in early stages of development. In order to contribute positively to the safe use and development of biotechnology, it is important that databases be harmonized wherever possible, that they be made as readily accessible to as many users as possible, and that they be kept up to date. Information in databases should be validated appropriately.

There are databases covering regulation, introductions or releases, microbiology, molecular biology, cell lines and hybridomas, sequence data, bibliography and general biotechnology information. Information is less widely available in systematic form on the wide variety and vast number of crop plants modified by plant breeding techniques.

Major databases include:

- The World Data Centre's Directory to Culture Collections of Micro-organisms;

- National and regional microbial strain databases (MiCIS, MINE in Europe);

- Hybridoma Data Base;

- Immunoclone Database;

- Interlab Animal Cell Database;

- Sequences databases (EMBL, Seqnet, Can/Snd, Gen Bank);

- Botanic databases (ILDIS);

- Taxonomic databases (Biosis, ICECC);

- Plasmids/vectors/gene libraries (NIH Repository of Human DNA Probes);

- Bibliographic databases (Datastar, Dialogue);

- General biotechnology databases (Bioindustry Association databases, BIKE, BIOREP);

- Biotechnology Information Knot for Europe of GBF in Germany;

- Biotrack: on the Use and Release of Organisms (OECD);

- IRRO: Information Resource for the Release of Organisms to the Environment.

- BINAS: Biosafety Information Network and Advisory Service.

Some of these are linked through the internationally sponsored information and communications network, the Microbial Strain Data Network (MSDN).

Note: This Annex will be further expanded in the future to include databases related to agronomy, ecology, taxonomy, etc.

Annex 7: POSSIBLE MECHANISMS FOR PROVIDING INFORMATION TO THE PUBLIC

Examples of methods for communicating with the public include:

- Establishing a register of information about work with organisms with novel traits, whether in containment or in deliberate releases into the environment. Such a register should provide for appropriate safeguards for commercially sensitive information; a summary of risk assessments; evaluations by the authorities or any relevant advisory committees;

- Giving interested groups the opportunity to comment on proposals to work with organisms with novel traits, possibly on the basis of a register of information as outlined above;

- Publishing a newsletter outlining the kind of work that is being carried out with organisms with novel traits, its purpose, and the controls under which it is taking place;

- Encouraging those intending to release organisms with novel traits into the environment to inform local people, through public meetings, advertisements in local newspapers, or other appropriate means;

- Encouraging dialogue between companies and academic institutions working with organisms with novel traits and public interest groups;

- Electronic billboarding;

- Making use of radio and television;

- Providing information about products;

- Any other means appropriate within the local context.

APPENDIX III: Summary statements on special topics compiled by experts at the symposium

Export Licensing Measures

Article III of the BWC obliges the States Parties not to transfer to any recipient what so ever, directly or indirectly, and not in any way to assist, encourage, or induce any States, group of States or international organizations to manufacture or otherwise acquire any of the agents, toxins, weapons, equipment or means of delivery specified in article I of the Convention.

This is a legally binding obligation. A number of countries have implemented national export licensing measures as an effective means of implementing these obligations and to avoid the possibility of the inadvertent supply of any item which could be used in a BW program.

Export licenses are not bans. They operate to deter proliferation by monitoring trade of relevant materials, and provide authority to stop a sale in the infrequent cases where a prospective export is likely to contribute to a BW program. It is also in the interest of industry and research institutes to ensure that such firms and institutes are not inadvertently supplying pathogens and dual-use equipment for use in the production of BW.

Visits

One of the political concerns:

To cater the need for an element of deterrence apart from investigations. Investigations are politically sensitive to initiate and as a result are not expected to be performed on a frequent basis.

A gap between declarations and investigations would enable proliferaters to develop BW behind the safe screen of a declared facility.

This is why visits, especially the so called random visits, are essential to an effective protocol.

The risk of a random visit would make life difficult and more costly for a proliferator.
The proliterator would face the choice to continue the BW production at a declared site and be ready for a good cover up if a visit takes place, or, more likely, move production to a not declared facility.

Both options would create obstacles for the proliferator.

If the proliferator makes the choice to continue production at a declared facility a good cover story is needed. Even a very non intrusive visit would be able to detect inconsistencies in the picture given by the facility.

If the proliferator makes the choice to move to a non-declared facility, this facility would either not be the most suitable (in order to avoid the requirement to declare the facility), or risk raising suspicion since it, with the activities going on and the capacity of the facility, should have been declared.

Misunderstanding:

The visiting team is not directly searching for non-compliance, but is to verify that the company is doing what it says it is doing. This means that the visiting team is looking at the skills, procedures, capacities etc. to see if these are the normal for example for a vaccine producer.

How industry concerns are addressed:

- The company have the right to deny access to sensitive information

- The company will have the support from government representatives

- Limited time (2 days) spent at the facility

- Limited number of inspectors (4).

- Professional inspectors

- No sampling

THURSDAY
08:30 - 10:00	Registration
10:00-10:15	Opening Ceremony

10:15 - 10:45	Biological and toxin weapons: Introduction and overview Dr. Brad Roberts, Institute for Defense Analyses, Washington,DC, USA ( Editor, "Biological Weapons: Weapons of the Future")

10:45 - 11:15	The Biological and Toxin Weapons Convention- A historic and political perspective Willy Kempel, Ministry of Foreign Affairs, Austria

11:15 - 11:45	UNSCOM : Lessons for Biological Arms Control arising from the experience of the UN Special Commission on Iraq (UNSCOM) Johannes Rath, UNSCOM Chief Inspector, University Vienna, Austria

11:45 - 12:15	The current status of the Geneva negotiations on the protocol to strengthen the BTWC Tibor Toth, Chairman Ad Hoc Groupof the States Parties to the BTWC, Hungary

12:15 - 14:00	Lunch and Tutorial: Biosafety information on the Internet

14:00 - 14:30	The Chemical Weapons Convention (CWC) verification regime: Implications for Biotechnology Julian Perry Robinson, Director Havard Sussex Program on CBW Armament and Arms Limitation, Science Policy Research Unit, University of Sussex - Lecture was held by Graham S. Pearson

14:30 - 15:15	The likely practical aspects of the strengthened BWTC protocol Graham S. Pearson, Visiting Professor of International Security, University of Bradford, former Director General and Chief Executive of the UK Chemical and Biological Defence Establishment at Porton Down

15:15 - 15:45	Coffee Break

15:45 - 16:30	Plenary Discussion - Introductory Statements
	Implications for biotechnology Malcolm Dando, Professor of International Security, Department of Peace Studies, University of Bradford, UK

	Implications for academic R&D O. Doblhoff-Dier, Chairman WP Safety in Biotechnology of the European Federation Biotechnology, Inst. for Applied Microbiology, Austria

	Implications for industrial operations Helmut Bachmayer, Cooporate Biosafety, Novartis

	Meeting U.S. Industry Concerns within a Strong BTWC Compliance Regime Lynn C. Klotz, Ph. D. Federation of American Scientists Working Group on BW Verification

16: 30 - 17:00	Plenary discussion

FRIDAY

09:00 - 09:30	Comparison of the strengthened BTWC protocol with other regulatory systems Rudolf Bliem, Tarac Consulting, Consultant for the Bioindustries specializing on FDA and European approvals

09:30 - 10:00	The EC Biosafety Regulations David Bosworth, European Commission, Brussels

10:00 - 10:30	The US Biological Safety and Requirements for Facilities Transferring or Receiving Select Agents Jonathan Y. Richmond, Director, Office of Health and Safety, Centers for Disease Control and Prevention,

10:30 - 11:00	Coffee break

11:00 - 11:30	The Biosafety Regulations in the fromer Eastern Block Contries George Tzotzos, UNIDO Biotechnology Network and Advisory Service, Vienna

11:30 - 12:00	The Convention on Biological Diversity: Possible implications of the International Biosafety / Advance Informed Agreement Protocol Mr P J Van der Meer, Ministry of Housing, Spatial Planning and the Environment, The Netherlands

12:00 - 13:45	Lunch and Tutorial: Biosafety information on the Internet

13:45 -14:30	Biotechnology Controls: What are the technical requirements? Protective equipment and containment validation, documentation, storage and access control, identification of pathogens and pathogenic characteristics Howard Tranter, CAMR, UK

14:30 - 15:00	Maintaining awareness of developments in biosafety regulations and controls O. Doblhoff

15:00 - 15:45	Closing Statement and Discussion: International harmonisation of biosafety protocols

Issue	Geneva negotiations	UNSCOM - IRAQ
impact of National Interests sovereignity aspect sensitive areas confidentiality necessity for compromises	MULTILATERAL TREATY	"DURING WAR" UNSCR
confidence building measurements integrated approach with other organisations	LONG TERM STRATEGY	SHORT TERM STRATEGY, IMMEDIATE NEED TO ACT
future vs. past orientation dynamic vs. stable system	PREVENTION	ELIMINATION-DESTRUCTION (PREVENTION, UNSCR 715)

Elements of control regime	For Schedule 1 chemicals	For Schedule 2 chemicals	For Schedule 3 chemicals	For unscheduled discrete organic chemicals
Production limit	No more than 1000 kg of all types may be held by a state-party	None specified, but all production must be for, and in quantities consistent with, purposes not prohibited under the Convention
Data reporting (initial and annual)	Yes: detailed information on production, use, import and export	Yes: for each one, aggregate national data on production, use, import and export	Yes: for each one, aggregate national data on production, import and export	No, except for plant specific data (as with the scheduled chemicals)
Inspection of facilities producing more than threshold quantities	Yes: highly stringent and augmented with instrumented monitoring	Yes	Yes: less stringent	Not until EIF+3 yrs, if then approved by the Conference of the States Parties
Export control	Exports permitted only to states parties, with advance notification of OPCW	End-use certification required until EIF+3 yrs, after which exports permitted only to states parties	End-use certification required; and possibility of other measures after EIF+ 5 yrs	None specified

CWC element	Information to be declared by each state party	Deadline
VerAx VII.9-10 VerAx VIII.9-10	Each plant site where there is plant that has produced Schedule 2 or 3 chemicals for chemical-weapons purposes at any time since 1 January 1946	By entry into force (EIF) + 30 days
VerAx VI.17-20	Location and details of all facilities approved for production of more than 0.1 kg/yr of Schedule 1 chemicals for research, medical or pharmaceutical purposes. Annual declarations also required: of prior-year production, consumption, storage and transfer, and of projected next-year production.	By EIF + 30 days By year-end + 90 d & year-start - 90 d
VerAx VII.1-2	Aggregate national data on the production, processing, consumption, import and export of Schedule 2 chemicals, for each such chemical during the previous calendar year. Declaration to be repeated annually.	By EIF + 30 days By year-end + 90 d
VerAx VIII.1-2	Aggregate national data on the production, import and export of Schedule 3 chemicals, for each such chemical Declaration to be repeated annually.	By EIF + 30 days By year-end + 90 d
VerAx VII.3-8	Each plant site where Schedule 2 chemicals have recently been, or will next year be, produced, processed or consumed in amounts exceeding 1 ton/yr (or less for three of the chemicals: see Table 3), with details. Annual declarations also required, both of prior-year and of projected next-year activities.	By EIF + 30 days By year-end + 90 d & year-start - 60 d
VerAx VIII.3-8	Each plant site where Schedule 3 chemicals have been or will be produced in amounts exceeding 30 ton/yr, with details. Annual declarations also required, both of prior-year and of projected next-year activities.	By EIF + 30 days By year-end + 90 d & year-start - 60 d
VerAx IX.1-6	For unscheduled discrete organic chemicals, each plant site where more than 200 tons were synthesized during the previous year, unless the chemicals contain P, S or F, in which case the threshold is 30 tons, or unless the chemicals are exclusively explosives or hydrocarbons. The list of sites is to be updated annually.	By EIF + 30 days By yr-start + 90 d

Facility type	Number of inspectable facilities anticipated by OPCW PrepCom	Routine inspection regime
		Facility agreement	Annual production threshold		Continuous monitoring	Notice of inspection	Duration of inspection	Access during inspection	Frequency of inspection
			for reporting	for inspection
CWSF	33 (and 40 for oacw)	Mandatory	[not applicable]		On-site instruments	initial: 72 hrs other: 48 hrs	As agreed	Automatic to declared facilities	Not specified in the CWC
CWPF	43	Mandatory	[not applicable]		On-site instruments	initial: 72 hrs other: 24 hrs	As agreed	Automatic to declared cw	Upto 4 per year
CWDF	4	Mandatory	[not applicable]		On-site instruments and inspectors		As agreed	Automatic to all parts of declared facilities	Not specified in the CWC
Schedule 1 facilities	ca 75	Mandatory	0.01 kg	0.01 kg	On-site instruments		As agreed	Automatic to declared facilities	Not specified in the CWC
Schedule 2 facilities	More than 300	Mandatory unless waived by both sides	bz: 1 kg amiton: 0.1 t pfib: 0.1 t Others: 1 t	10 kg 1 t 1 t 10 t	No	48 hrs	96 hrs	Automatic to plant site and to specified areas within declared plants; beyond that, as agreed	Upto 2 per year per plant site
Schedule 3 facilities	ca 400	Optional	30 t	200 t	No	120 hrs	24 hrs		Upto 2 per year per plant site, with limit on combined total
UDOC facilities	More than 5000	Optional	PSF: 30 t Others: 200 t	200 t 200 t	No	120 hrs	24 hrs	Automatic to plant site; managed, to declared plants

Facilities	Number of facilities	Frequency of visits	Visits per year
Biological defence	40	0.5/year	20
Past BW facilities	20	0.5/year	10
Random visits	2500	< 2/year	20 -- 70
Clarification visits	2500	as necessary	20 -- 0
Voluntary visits	160	on request	30 -- 0

Article X Measure	Benefits to States Parties
Promotional Assistance in setting up National Authorities and in implementing the BTWC Protocol	Enhanced world-wide confidence in the implementation of the BTWC Protocol (and thus of the Convention) by all States Parties
Assistance to national elements of WHO, FAO and OIE Surveillance Networks	Improved national, regional and international surveillance of outbreaks of disease enabling counters to outbreaks to be rapidly instituted Information from the WHO, FAO and OIE Surveillance Networks will be important for the effective operation of the BTWC Organisation in its oversight of the implementation of the BTWC Protocol
Regulatory Regulatory frameworks for dangerous pathogens, toxins and living modified organisms	Improved public confidence that such materials are only being used for controlled and permitted purposes Contribute to ensuring that such materials are not available for terrorist purposes
Regulatory pharmaceutical inspectorates and licences	Improved assurance of safety for humans and animals receiving the medicinal/veterinary products Promotion of trade in pharmaceuticals Enhanced confidence that pharmaceutical production facilities are only being used to produce licensed permitted products

CWC Verification Regime	Draft BTWC Protocol
Mandatory declarations of relevant facilities	Mandatory declarations of relevant facilities
Routine inspections under facility agreements	Non-challenge visits to confirm declarations
Challenge inspections	Facility & Field Investigations
Confidentiality Annex	Confidentiality Annex
National Authorities	National Authorities
Implementing including penal legislation	Implementing including penal legislation

Organism	Human Vaccine	Veterinary Vaccine
Cl. botulinum
B. anthracis
Cl. perfringens
Cl. tetani
S. typhi
V. cholerae
Y. pestis
F. tularensis
Br. abortus
Br. melitensis
B. pertussis
C. diphtheriae
Ps. aeruginosa

*Licensed vaccines

Process Step	Operation	Hazard
Raw material	Weighing, mixing,	Generation of allergenic
handling	Dissolving	dusts
Inoculum preparation	Inoculation, fermentation	Generation of aerosols
Bioreactor	Fermentation	Aerosols of reactor
	contents, spillages, off gas contamination
Biomass Separation	Centrifugation	Aerosols, spillages
Process Step	Operation	Hazard
Product purification	Homogenisation, blending	Production of aerosols
	Centrifugation	Production of aerosols, spillages
	Dialysis	Production of aerosols, spillage
	Chromatography	Spillages, increasedproduct purity, potency
Product finishing	Blending, filtration	Production of aerosols
	filling, freeze, spray drying	Production of aerosols, spillages, generation of dusts
Effluent Handling	Sterilisation, discharge	Discharge of untreated effluent

Primary	Immediate physical barrier
Secondary	Provides back up to primary containment in the form of physical enclosure or engineering improvements
Tertiary	Defined operational facility preventing contamination outside the laboratory or production area
Biological	Genetic modification of micro-organisms to restrict their ability to survive or transmit genetic information
Operator	Personal protection in the form of positive/negative pressure respirators or whole body suits

Bacteria	Causative Agent	Routes of transmission
Bacillus anthracis	Organism + Toxin	Skin, wounds, inhalation
Clostridium botulinum	Toxins A-G	ingestion, inhalation
Staphylococcus aureus	Toxins A-H	ingestion, inhalation
Vibrio cholerae	Organism + toxin	ingestion
Yersinia pestis	Organism	zoonotic transmission, inhalation
Francisella tularensis	Organism	Zoonotic transmission, ingestion, inhalation

Program

Biological and toxin weapons: Introduction and overview Brad Roberts, Institute for Defense Analyses, Washington,DC, USA

The Biological and Toxin Weapons Convention: A historic and political perspective Willy Kempel, Ministry of Foreign Affairs, Austria

UNSCOM: Lessons for Biological Arms Control arising from the experience of the UN Special Commission on Iraq (UNSCOM) Johannes Rath, UNSCOM Chief Inspector, University Vienna, Austria, Jochen Bürgel, FOCUS MC, Austria

The Chemical Weapons Convention (CWC) verification regime: Implications for Biotechnology Julian Perry Robinson, Director Havard Sussex Program on CBW Armament and Arms Limitation, Science Policy Research Unit, University of Sussex

Implications of a strengthened biological and toxin weapons convention for the biotechnology and pharmaceutical industry Professor Malcolm Dando, University of Bradford, UK

Possible implications for R&D Otto Doblhoff, Chairman Working Party "Safety in Biotechnology" of the European Federation Biotechnology

Industry Position on a Compliance Protocol to the BTWC Prof. Dr. Helmut Bachmayer, Head of Corporate Biosafety, Novartis International Basel

Meeting U.S. Industry Concerns within a Strong BTWC Compliance Regime Author: Lynn C. Klotz, Ph. D. Federation of American Scientists Working Group on BW Verification.

The US Biological Safety Requirements for Facilities Transferring or Receiving Select Agents Jonathan Y. Richmond, Ph.D., Director, Office of Health and Safety, Centers for Disease Control and Prevention, US

Framework Of Regulatory Controls For Human And Animal Pharmaceutical Products Rudolf Bliem, Tarac Consulting, Vienna, Austria

International activities on Biosafety Piet van der Meer, Netherlands Ministry of the Environment.

Microbial Pathogens and their Toxins: Methods for Identification and Safe Handling during Biotechnology Operations Howard S. Tranter, Centre for Applied Microbiology Research, Porton Down, Salisbury, Wilts SP4 0JG, UK.

Maintaining awareness of developments in biosafety regulations and controls Otto Doblhoff, European Federation Biotechnology, Working Party "Safety in Biotechnology"

APPENDIX I: The Biological and Toxin Weapons Convention

APPENDIX II: UNEP Biosafety Guidelines

APPENDIX III: Summary statements on special topics compiled by experts at the symposium

Export Licensing Measures

Visits

Biological and toxin weapons: Introduction and overview
Brad Roberts, Institute for Defense Analyses, Washington,DC, USA

The Biological and Toxin Weapons Convention: A historic and political perspective
Willy Kempel, Ministry of Foreign Affairs, Austria

UNSCOM: Lessons for Biological Arms Control arising from the experience of the UN Special Commission on Iraq (UNSCOM)
Johannes Rath, UNSCOM Chief Inspector, University Vienna, Austria, Jochen Bürgel, FOCUS MC, Austria

The Chemical Weapons Convention (CWC) verification regime: Implications for Biotechnology
Julian Perry Robinson, Director Havard Sussex Program on CBW Armament and Arms Limitation, Science Policy Research Unit, University of Sussex

Implications of a strengthened biological and toxin weapons convention for the biotechnology and pharmaceutical industry
Professor Malcolm Dando, University of Bradford, UK

Possible implications for R&D
Otto Doblhoff, Chairman Working Party "Safety in Biotechnology" of the European Federation Biotechnology

Industry Position on a Compliance Protocol to the BTWC
Prof. Dr. Helmut Bachmayer, Head of Corporate Biosafety, Novartis International Basel

Meeting U.S. Industry Concerns within a Strong BTWC Compliance Regime
Author: Lynn C. Klotz, Ph. D. Federation of American Scientists Working Group on BW Verification.

The US Biological Safety Requirements for Facilities Transferring or Receiving Select Agents
Jonathan Y. Richmond, Ph.D., Director, Office of Health and Safety, Centers for Disease Control and Prevention, US

Framework Of Regulatory Controls For Human And Animal Pharmaceutical Products
Rudolf Bliem, Tarac Consulting, Vienna, Austria

International activities on Biosafety
Piet van der Meer, Netherlands Ministry of the Environment.

Microbial Pathogens and their Toxins: Methods for Identification and Safe Handling during Biotechnology Operations
Howard S. Tranter, Centre for Applied Microbiology Research, Porton Down, Salisbury, Wilts SP4 0JG, UK.

Maintaining awareness of developments in biosafety regulations and controls
Otto Doblhoff, European Federation Biotechnology, Working Party "Safety in Biotechnology"