Overarching findings
Finding 1. Since the PIP Framework Secretariat is not mentioned in the PIP Framework (PIP FW) document, or a definition included under 4.4, the role/status of the PIP Secretariat should be explained in any revision of the PIP FW document. In particular, the role/status of the PIP Secretariat should be described in relation to its assistance to the Advisory Group and its relationship to the GIP and GISRS which are the foundation upon which the trust-based PIP FW is built. Concerns have been raised about the potential disconnect between the PIP Secretariat and GIP/GISRS in the proposed structure of the new WHO Health Emergencies Programme.
Difficulties which the GISAID Initiative has experienced in developing dialogue with the PIP Secretariat (and the Advisory Group) exemplify a lack of transparency and openness with some key stakeholders, engendering a lack of trust in contrast to that enjoyed by GISAID with GISRS and the GIP. While raised on numerous occasions, this problem has never been responded to in a satisfactory manner that would indicate the concerns raised are actually addressed.
This situation has been exacerbated by continual deviation in numerous reports, including from the TEWG and TWG, from the precise use of clear and definitive language and terminology in the PIP FW, and more specifically the introduction of confusion regarding the choice MS have in the way they share GSD. Furthermore, the implication in the TWG report and the most recent Advisory Group report that there is an intention to establish an alternative GSD sharing mechanism is of great concern. Misrepresentation, apparently intentional, by the PIP Secretariat of the extent of use of the GISAID sharing mechanism by GISRS laboratories has become quite apparent and inexcusable, given incontrovertible data indicating that the GISAID mechanism is preferentially utilized by GISRS.
Ensuring the relevance of the PIP Framework
Finding 5. As repeatedly pointed out by the German Government, the GISAID sharing mechanism addresses such a concern regarding GSD, in that its ensures the chain of custody of GSD, guaranteed by the German Government as host of its EpiFlu™ database, and is one reason this mechanism has been adopted preferentially by GISRS laboratories.
Expanding the Framework to seasonal influenza
It should be remembered that agreement to the PIP FW was only possible by the exclusion of seasonal influenza viruses, given the likely complications and potential disadvantages to the well-established operational GISRS sharing and benefit system, and to avoid confusion between epidemic seasonal influenza and the special health emergency of an influenza pandemic.
Virus sharing
Overview
Finding 1. In considering what constitutes ‘adequate’ sharing of IVPPs, it should be acknowledged, as under ‘Virus-sharing metrics’, that information from sharing of viruses and GSD are complementary and that there is a stark contrast between the promptness and levels of sharing GSD and viruses.
Finding 4. In relation to “at no cost to Member States”, the members of the Review Group will be well aware that many, if not most, MS have and continue to contribute significantly in providing funding and human resources for NICs, CCs, ERLs and/or H5 Ref labs, i.e. the institutional components of GISRS, as well as other resources important to the collaborative enterprise.
Genetic Sequence Data
Finding 1. It would be helpful to provide some statistics on the sharing of IVPP GSD, as for viruses, especially in view of the comments under “Virus-sharing metrics”. We request that this information be obtained and reported by the Advisory Group, in view of its importance under the PIP FW, and usefulness (as acknowledged under Virus-sharing metrics), for example, “to provide pandemic surveillance and risk assessment and early warning information – to all countries” (PIP FW 6.0.2 (1), benefit sharing system).
In relation to the PIP FW as a “trust-based system”, GISAID was established, three years before the PIP FW was adopted, through a collaboration of GISRS, MS and experts in transparent information (content/data) sharing to promote trust through transparency of use and users of data. It has since been highly successful, not only being adopted by GISRS and securing the confidence of MS, but has become increasing widely recognized (within and outside influenza) as an effective sharing mechanism, as evidenced by over 6,500 active users and influenza data from well over 800 institutions worldwide, a substantial amount of which is publicly accessible nowhere else.
We agree with the necessity for greater clarity and, especially, on what must be achieved in the context of the FW document. In this regard, it would be helpful to distinguish between the actual sharing of GSD and the ‘handling’ of GSD in relation to its use for development of commercial products under the FW. Unfortunately, documents from the Advisory Group/PIP Secretariat and reports from the TEWG and TWG have not provided an accurate portrayal of the procedures adopted and used to share GSD, within and beyond GISRS. This has led to confusion and a lack of appreciation of the characteristics of the sharing mechanisms, relative to the principles of the FW and those governing the sharing of viruses/PIP BM. For example the GISAID sharing mechanism encompasses principles 5, 9 and 11 of the FW, emphasizing the importance of collaboration and benefit sharing in the true spirit of the FW.
Finding 2. Once again the dilemma as to “the lack of agreement as to what should be traced” in part reflects the lack of acceptance of features of the GISAID sharing mechanism that are already in place as specific components of a pragmatic solution to sharing IVPP GSD under the FW.
“Tracking of access to GSD or commercial products developed using GSD“ represent complementary approaches and should not be seen as mutually exclusive, and should be employed in the collaborative spirit of the trust-based FW.
“Progress -- made by the Advisory Group” has been hampered by the omission of the fact of the existence of an effective GSD sharing mechanism, its acceptance by GISRS and contributions to the PIP FW. What is clearly missing is an assessment of existing GSD sharing mechanisms that addresses each and every aspect of the sharing of GSD under the PIP FW.
Finding 3. While it may be true that “monitoring all access to GSD may not be feasible”, the GISAID sharing mechanism has become the accepted means for the responsible timely sharing of IVPP GSD, nearly all IVPP GSD having been submitted to its EpiFlu™ database. As Germany has repeatedly stated, this provides a means of monitoring access to all IVPP GSD in the EpiFlu™ database Germany hosts (complemented with data which has eventually been published in public-domain databases), as well as alerting users to obligations under the FW.
While it is easier to share GSD, the concerns about “fairness and equity in benefit sharing” and “free-riders” also apply to sharing of viruses. Unauthorized access to and unlawful use of GSD is no different to such treatment of biological material (BM). Furthermore, use of an animal/avian equivalent of the ‘human’ virus or its GSD, not covered by the PIP FW, provides an easy way (to free-riders) of circumventing obligations under the FW. It would prove counter-productive to employ too strict a regimen that would encourage such a response, and which in itself may be seen as contrary to the spirit of GISRS and the consensual nature of the trust-based PIP FW.
Why would the PIP FW Secretariat be any more responsible for monitoring access to GSD, than viruses in the IVTM? Would this not be a responsibility of the GIP/GISRS, rather than the PIP Secretariat whose role is to support the Advisory Group? This would need to be handled in a manner consistent with the collaborative ethos of GISRS so as to encourage compliance with the FW and not to discourage research and development. It should be noted that GISAID, because of the conditions attached to the use of the GSD, effectively brokered the rapid collaborative development of a synthetic vaccine candidate H7N9 virus in April 2013, at a time when the PIP Secretariat declined any responsibility for advising on obligations attached to the use of H7N9 GSD under the PIP FW. A heavy-handed approach by the PIP Secretariat, especially if not under the wing of GIP, might undermine not only the spirit of the FW, but also its potential sustainability.
While agreement may be forthcoming regarding “Monitoring use in commercial end-products” as the basis for WHO to impose, retrospectively, obligations on the use of GSD of IVPP, it is not clear that this approach could be applied to GSD that are made available for any use without any conditions, such as data placed in the public-domain, or that are not included under IVPP GSD. What would the legally enforceable basis be for such an approach?
Finding 4. Such considerations appear very premature.
Finding 5. While we agree with the comments, the statement: “since GSD cannot always be substituted for physical materials” is unclear, as is the reference to “specificities of GSD”.
We understand that the reference to ‘Article 6’ should read ‘Section 4.1’. An amendment might include a ‘definition’ of material developed and produced based on GSD and its relation to PIP BM. It may be helpful to indicate that GSD is shared freely (and falls under 6.0.2 (1)) and could not be accommodated under the IVTM or SMTA2, but that the GISAID Database Access Agreement encompasses the equivalent of the SMTA1.
Benefit sharing
Standard Material Transfer Agreement 2 (SMTA2)
Findings 2 and 4. Established models do exist in other walks of life which cover considerations that “In practice, a delicate balance needs to be maintained with the companies that are not facilitating completion of the negotiations“ and that “Some Member States have queried whether the labour-intensive process of signing SMTA2s with small and medium companies is worth the resources required given the relatively modest additional volume of vaccines and other products secured.” in relation to fairness and equity.
Finding 5. To what extent has the PIP Secretariat enlisted the assistance of expert partners in GISRS in “assessing the introduction of laboratory and surveillance training”?
Governance
Findings 1 and 2. While commitment is not in question, the functioning of the governance structure in overseeing certain aspects of the PIP FW have given serious cause for concern.
The PIP FW clearly describes the intended governance of this “trust-based system”, with the Advisory Group as an “independent expert body” to provide the Director-General with “evidence-based reporting, assessment and recommendations regarding the functioning of the Framework”, including monitoring of the components of GISRS (NICs, CCs, H5 Ref labs, ERLs), with information provided by the WHO Secretariat, presumably the GIP, and other independent sources, and that “the Director-General will make available the necessary human and financial resources to support the work of the Advisory group”, presumably the PIP Secretariat (Annex 3, Advisory Group TORs).
The lack of consultation with the WHO CCs (Finding 7) and the dominant role assumed by the legal personnel of the PIP Secretariat in all aspects of the implementation of the PIP FW would appear to be contrary not only to the intended governance structure perceived by MS, but also to the consensual spirit of a trust-based system?
The dominance of the PIP Secretariat in drafting, editing and final decisions on content of reports of Working Groups and the Advisory Group has become evident in communication with and criticisms by members of the Groups. This explains the consistent portrayal of choice in sharing of GSD in the ambiguous language “GISAID and Genbank or similar databases” (e.g. Annex 5, guiding principle 9, which should be altered in any revision of the PIP FW document), rather than the definitive language “public-domain or public-access databases such as Genbank and GISAID respectively” (5.2.2), culminating in the recommendation of the Advisory Group to the Director-General for redundancy in deposition of IVPP GSD in more than one database, diametrically opposed to the clear principle in the PIP FW in providing MS a choice in how they share GSD with the public, as reiterated by Professor Ampofo, who stated quite emphatically, as the former Chairman of the Advisory Group , during a recent interview the RG had with Dr Alan Hay, that “the discussions were trying to be in line with the PIP Framework which says that Member States can use GISAID or Genbank for depositing GSD”. Such clarity in understanding by Professor Ampofo (incidentally also by ADG Dr Keiji Fukuda in October 2011, Principle Legal Officer Steven Solomon in October 2014, and clearly manifest in the behaviour of MS) emphatically contradicts a categorical statement by Ms Anne Huvos in May 2013, that the PIP FW requires submission of IVPP GSD to both GISAID and GenBank, and the language used since in a least a dozen instances, in TORs, reports or instructions given to Members serving on the Advisory Group, the Review Group, or the TWEG or TWG.
Concerns about the independence of the Advisory Group and the lack of objectivity and impartiality of the PIP Secretariat are reflected in our comments on Reports and correspondence with the Advisory Group and PIP Secretariat, to which no response or clarification was ever received.
Finding 3. With respect to the need for the TWG in particular, why did the Advisory Group not, at least initially, acquire a clear understanding of the workings of GISRS, as regards sharing of GSD, from the GIP and the WHO CCs, given their key role in collating available information on the genetic and phenotypic properties of seasonal influenza viruses and those with pandemic potential? Thus, while the TEWG and TWG were established to gain insight into the use and sharing of GSD, it is not evident that the Advisory Group made best use of consultation with GIP or components of GISRS, especially the WHO CCs, in gaining a clear understanding of the practicalities involved in the operational functioning of GISRS in relation to the acquisition, sharing and use of GSD, or of the adoption of the GISAID sharing mechanism by GISRS laboratories, matters relevant to their annual reports to the Director-General.
Finding 5. “Advisory Group recommendations to the PIP Secretariat and the Director-General”. Such a statement emphasizes the importance of clearly defining the role of the PIP Secretariat, in the absence of a definition under 4.4 of the PIP FW – to serve the Advisory Group, as in its TORs or vice versa. Was the PIP Secretariat created as a special (necessary) additional tier of governance?
Finding 6. GISAID’s experience is quite the opposite. In each and every instance when GISAID has written to the Advisory Group, the PIP Secretariat, and even to the Assistant Direct-General, GISAID has received no response addressing the issues raised.
Finding 7. It should be clarified which ‘WHO Secretariat’ provides the information the Advisory Group obtains for its monitoring of “the institutional components of the Framework”, in reporting on the necessary technical capacities and operational functioning of WHO GISRS, etc (Annex 3, 1.2 and 2). Is it the GIP Secretariat or the PIP Secretariat?
Finding 8. Was it really in the interests of the Review Group to include the former Chair and Vice-Chair of the Advisory Group as regards the independence of the Review Group? Is it really also appropriate for the Review Group’s Secretariat to report to the Team Lead, Ms Anne Huvos, of the PIP Secretariat? It is unclear to us how this arrangement can support independence with respect to the review of the implementation of the PIP FW and recommendations to improve activities in the future.
Finding 9. The statement in the PIP FW refers only to support of the work of the Advisory Group. Presumably that support is provided by the PIP Secretariat. As mentioned elsewhere, the remit and responsibilities of the PIP Secretariat should be explained, in revisions to the FW document, and justified in relation to the resources required/provided.
