TWN Briefing Note on Smallpox for WHO Executive Board (January 2013)



Dear friends and colleagues
Re: TWN briefing note on smallpox for WHO Executive Board (January 2013)
Please find below a Third World Network briefing note on the issue of destruction of variola virus (smallpox) stocks. The Executive Board of the World Health Assembly, which is meeting in Geneva (21-29 January 2013), will consider the progress report on this issue.
After contentious discussions at the World Health Assembly (WHA) in 2011, with no agreement reached on setting a new date for destruction of the remaining live variola stocks held in WHO repositories in the US and Russia, the compromise was to postpone the decision until the 67th WHA in 2014. This despite a major health review from a public health perspective finding that there is no essential public health purpose remaining for retention of the virus. Further retention increases biosafety risks, including that of accidental escape from the laboratory.
The briefing note highlights the progress made in antivirals licensure, which should end any further justification for retention of variola virus stocks. It also raises concerns about approval of unnecessary, non-essential research projects involving live variola virus and the stagnation of efforts to improve the oversight of research. Previously, the WHA had to step in to stop experiments on genetic engineering of the variola virus.
It would be important to begin the process of preparation for fixing a destruction date now, in order to adopt a resolution to that effect at the 67th WHA.
With best wishes,
Third World Network
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A Note Prepared by Third World Network for the 132nd WHO Executive Board Session, January 2013
In document EB132/42, the Secretariat presents its update on destruction of variola (smallpox) virus stocks. 
The World Health Assembly’s (WHA) most recent resolution on this matter was 60.1, adopted in 2007.  That year, the majority of WHO Member States, particularly developing countries, felt there was no remaining public health need for retention of the virus stocks and favored fixing a date for virus destruction.
Russia and United States, the two countries hosting WHO Repositories of the virus, joined by some allies, however, were opposed to fixing a date, despite the fact that they have previously agreed to dates in WHA resolutions dating back to the 1990s. In 2007, these countries argued that research remained to be performed.
Resolution 60.1 thus represented a compromise. It called for WHO to perform a “major review” of research involving the smallpox virus stocks, for consideration by the 64th WHA in 2011, with a view to reaching agreement on a date for their destruction.
The WHO presented its major review in two parts, a scientific review and a public health assessment.  The scientific review (WHO/HSE/GAR/BDP/2010.3) was authored primarily by Russian and US virologists employed by the ministries conducting smallpox research. This paper acknowledged that several WHA-authorized research purposes have been satisfied, but had ambiguous conclusions with respect to the need for continued retention of virus for some purposes. 
The public health review (WHO/HSE/GAR/BDP/2010.4) was prepared by an independent and geographically balanced group of public health experts appointed by the Director-General. Called the Advisory Group of Independent Experts to review the smallpox research program (AGIES), this public health review found that there is no essential public health purpose remaining for retention of the virus [1].
At the 64th WHA in 2011, Member States were again unable to reach agreement on a resolution fixing a date for destruction of virus stocks. In lieu of a resolution, a decision was adopted to postpone the discussion until the 67th WHA in 2014. Meanwhile, the Director-General will continue the mandate of the Advisory Committee on Variola Virus Research (ACVVR) and the AGIES.
Little remaining justification for virus retention
In document EB132/42, the Secretariat provides an update on WHA-authorized variola virus research and its oversight in 2012. EB132/42 makes reference to the report of the 14th meeting of the ACVVR, however, this report not been posted to WHO’s website. The report of the 13th meeting (WHO/HSE/GAR/BDP/2011.2), at the end of 2011, is the most recent available.
In the past, the ACVVR has been the subject of controversy due to imbalanced geographic representation and conflicts of interest, with some committee members representing institutions with vested interests in the continuance of research with live variola virus, including attempts to perform genetic engineering experiments. (The ACVVR was notably overridden at the 58th WHA, when the Assembly rejected its approval of variola genetic engineering experiments.)
There are positive and negative developments reflected in EB132/42, both of which should be noted by Member States at the Executive Board.
In 2012, the committee consulted with representatives of two companies developing two different antiviral drugs for variola virus infection [2]. These companies believe their products may be licensed within one year (EB132/42, para 33).  Licensure of these drugs represents extinction of the final remaining WHO-authorized use for variola virus in the view of the AGIES, clearing the final arguable hurdle to fixing a destruction date.
(This use in antiviral approvals was considered potentially valid by the AGIES solely due to regulatory reasons. The AGIES also concluded that these reasons could be obviated by regulatory changes, thus retention of the virus was, and is, not strictly essential.)
The licensure of these drugs would signify that all reasons, however slim, that were found by WHO’s public health experts for retention of variola viruses have been exhausted. At last, arguments that variola virus may continue to be retained for valid essential public health purposes (which are enumerated and which are the only purposes authorized by WHA) are expired. Member States should remain alert to any attempt to manufacture new reasons for continued retention of the virus.
Oversight of smallpox research needs to be improved
Despite progress with antiviral drugs, the ACVVR also appears to continue a pattern of contradictory actions.  For example, years ago the committee determined that more than sufficient rapid and accurate diagnostics for variola exist – thus satisfying this particular WHA-authorized research item. Yet the ACVVR has continued to approve new diagnostics-related research using live variola virus. 
The latest available report, from 2011, shows that year was no exception to this obfuscating practice.  In 2011, the ACCVR permitted a new project in the United States using live variola virus for diagnostics-related research, contradicting its own previous conclusion that no more research using live variola virus for diagnostics development is necessary. 
Member States at the Executive Board should express their disapproval of the ACVVR’s practice of permitting new research in areas in which the WHA-authorized research goals have been satisfied.
Transparency of the ACVVR and WHO oversight of variola virus research, which began to improve following the 58th WHA, now appears to be slipping backwards.  The report of the 14th meeting of the ACCVR, which took place in late 2012, has not been made publicly available in a timely fashion prior to the 132nd session of the Executive Board.  Abstracts summarizing approved research, posted on WHO’s website, do not appear to have been updated in years [3]. The membership and operations of the ACCVR’s “scientific subcommittee”, which reviews and approves (and sometimes rejects) proposed research, continue to be shrouded in secrecy.
Thus, at the 132nd Executive Board Meeting, Member States may wish to:
• Note that the progress towards licensure of antiviral drugs may shortly bring to an end any arguably essential public health purpose for retention of variola virus stocks, drawing further importance to reaching agreement on a prompt destruction date at the 67th WHA.
• Underscore the importance of the AGIES, whose mandate has been continued by the Director-General following the 64th WHA, and conclusions of the AGIES in the major review (WHO/HSE/GAR/BDP/2010.4).
• Express concern over ACVVR’s approval of new research projects on elements of the WHA-authorized research program (e.g. diagnostics) whose goals have already been satisfied. Such unnecessary, non-essential projects cannot be permitted to interfere with a consensus to fix a date for virus destruction.
• Express concern about the stagnation of efforts to improve the transparency of the ACVVR, in particular the prompt reporting of its and its scientific subcommittee’s decisions, and to emphasize the committee’s openness in the interim before the 67th WHA.
Justification for the retention of smallpox virus stocks at WHO Repositories in the United States and Russia is thinner than ever before. In theory, the United States, Russia, and allies have never left the WHA’s consensus that the virus stocks will be destroyed. Officially, they are only in disagreement about fixing a destruction date.  This prevarication has now spanned decades.  With the imminent exhaustion of any plausible WHA-authorized reason for retention of virus stocks, it is important to begin the process of preparation for fixing a destruction date now, in order to adopt a resolution to that effect at the 67th WHA.
[1] The only continuing use of variola virus that the AGIES found potentially justified related to US regulations for approval of smallpox antiviral drugs. But the AGIES concluded that this need could be promptly ended by an agreement between regulators and drug developers. It thus presents no obstacle to destruction of the remaining virus stocks. For a comprehensive analysis of these two papers, please see the briefing paper Smallpox Virus Stocks at the 64th WHA: Implementing the Conclusions of the Major Review (2011), available at URL:
[2] We have argued, and continue to maintain, that licensure of antivirals should not be considered an essential public health purpose for retention of variola virus stocks.
The primary means to control any future variola epidemic is by vaccination programmes initiated upon identification of an outbreak. Such programs were the means by which smallpox was eradicated to begin with. Numerous vaccines with proven efficacy exist, and some of these are effective when administered post-exposure.  These utilize the related vaccinia virus, and do not require variola virus for production.
Thus while licensed smallpox antivirals would provide hope for any individuals with access to those medicines and unfortunate enough to develop smallpox disease, when viewed from a broad public health perspective, they are not essential.  Further, antiviral drugs may be developed and tested using orthopoxviruses related to variola and which do not pose such an extreme public health threat if released.
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