WHO Influenza Preparedness Report Shows Companies Not Fulfilling Obligations

The World Health Organization Pandemic Influenza Preparedness (PIP) Framework is at risk due to some companies not fulfilling their obligations, a new WHO report says.

The PIP Framework Advisory Group held a meeting in October and released its report on the meeting a few days ago. The report underlines issues such as some companies not following requirements under the framework, threatening the sustainability of its funding. The group also worked on influenza product development and how to define if some synthetic products should be covered by the framework.

The WHO PIP Framework Advisory Group met from 21-24 October.

The meeting report is available here [pdf].

The PIP Framework was developed by WHO member states and became effective on 24 May 2011 when it was adopted by the 64th World Health Assembly. The framework serves two purposes, according to the WHO. It ensures that countries share influenza viruses with human pandemic potential (IVPP) with the WHO-coordinated network of laboratories called GISRS (Global Influenza Surveillance and Response System). It also provides that benefits derived from the sharing of those viruses will be shared with all countries in need.

Benefits can be realised according to six different options, listed in the annex of the PIP Framework, as part as the standard material transfer agreement 2 (SMTA-2), which refers to agreements outside the GISRS. Those benefits include donation to WHO of vaccines, treatment courses of antiviral medicine, and provision of vaccines and treatments at affordable prices to the WHO.

As part of the agreement, an annual cash partnership contribution to WHO is also expected to be paid by influenza vaccine, diagnostic and pharmaceutical manufacturers who use the GISRS.

Genetic Sequence Data, Biosynthetic Technologies

Genetic sequence data (GSD) is the order of nucleotides found in a molecule of DNA or RNA. According to the WHO, they contain the genetic information that determines the biological characteristics of an organism or a virus.

A Technical Expert Working Group (TEWG) was appointed to assess the scientific, technical, operational and intellectual property implications of using IVPP GSD “rather than physical materials for influenza research and vaccine production, including how the transfer of such data could be monitored.”

The TEWG included five members of the Advisory Group, and eight experts including academics, and the private sector. The list of TEWG members is found on page 22 of the TEWG report [pdf].

According to the report of the TEWG, several laboratories are now able to synthesise influenza candidate vaccine viruses, and influenza virus proteins or antibodies using only genetic sequence data.

For example, Novartis “very recently announced positive phase I clinical trial results for a synthetic H7N9 vaccine using a sequence shared by the Chinese Center for Disease Control, which is a WHO Collaborating Centre for Reference and Research on Influenza,” the report said.

According to the report, “there are different perspectives on whether [GSD] are included in the definition of the PIP biological material.” The report however notes that “While at present GSD is not expressly mentioned in the definition of PIP biological materials, the TEWG agreed that GSD falls within the PIP Framework … and that the spirit of the Framework and the importance of maintaining equal footing for the sharing of viruses and benefits derived therefrom, must be kept in mind in considering issues related to the handling of GSD for H5N1 and other influenza viruses with pandemic potential.”

In order to ensure the integrity of the PIP Framework regarding GSD, the TEWG suggested that mechanisms to ensure the monitoring and/or tracing of the use of GSD should be considered.

“In the absence of such mechanisms, and given the options open by the use of GSD for the development of vaccines, the attainment of essential objectives of the PIP Framework may be systematically frustrated. On the other hand however, it is essential that such mechanisms do not slow down the sharing of genetic sequence data,” the TEWG report said. It noted that an increasing number of vaccine manufacturers are using GSD as an alternative to conventional whole virus approaches, “making it possible to more rapidly develop vaccines.”

GSD IP, Traceability Issues

According to the TEWG report, “Whether GSD or products of GSD can be subject to intellectual property protections is dependent on the laws of the country in which the intellectual property rights are sought and will therefore vary between WHO Member States.”

In most jurisdictions, the report noted, “influenza GSD would not be considered patentable subject matter.” But it added: “However, innovations from the development of influenza-related products could be protected if the patentability requirements, as applied in the countries where protection is sought, are met. This may lead to a complex IP environment for vaccines and other products using GSD and synthetic DNA.”

The TEWG further explains that GSD of PIP biological material can also be generated by non-GISRS laboratories which “may sequence this material and distribute the sequences to third parties,” through publication of by depositing them in databases, for example. That distribution would escape WHO’s knowledge, and the sharing of this material will be difficult to monitor, the report says.

The foreseen increase of the use of sequence-based diagnostics will lead to an increase of genetic sequencing data generated with no involvement of the GISRS, the TEWG said. That generated influenza GSD “may be indistinguishable from GSD generated using PIP biological materials.” That would blur attempts to determine whether influenza GSD used to produce vaccines has originated in GISRS activities.

A number of potential mechanisms could be developed to monitor the use of GSD, such as processes related to influenza-related products, for example, regulatory approval files and patent applications, as well as technical mechanisms to trace or monitor downloading of GSD from databases, the TEWG noted.

The best process for resolution of issues related to handling genetic sequence data under the PIP Framework was discussed by the Advisory Group in October.

According to a source at the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA), which attended the Advisory Group meeting, IFPMA and the Biotechnology Industry Organization jointly said that no particular action should be taken at this time. “The Framework adequately addresses the current state of technology,” he told Intellectual Property Watch.

Generally, companies that develop or manufacture vaccines using GSD still need physical samples of influenza vaccines with human pandemic potential for further developments, he said. “BIO and IFPMA suggest that we address new technologies as part of the 2016 revision,” he said.

Advisory Group to Identify System

According to the Advisory Group report, a technical consultation was held with six database representatives to continue the gathering of technical information. The representatives provided information on topics such as their establishments, content, data access, use and transfer policies, monitoring and enforcement policies.

The Advisory Group observed that most databases have an open access policy, and they are “in general” able to identify the provenance of information that is uploaded, but they find it difficult to trace the transfer of data.

The Advisory Group said in the report that closer collaboration regarding open sharing of influenza GSD among the different databases is desirable. The report also noted that databases agreed to discuss how to better collaborate with each other to improve the sharing of GSD from influenza viruses.

In the report, the Advisory Group also remarked that options for identifying GSD that originate from the WHO GISRS other than monitoring databases should be “feasible, efficient and create legal certainty.” The monitoring of end-products generated through the use of GSD was discussed as a potential option, according to the report.

The Advisory Group proposed to identify the optimal characteristics of a system for the handling of influenza vaccines GSD under the PIP Framework in 2015. This would include consideration of data sharing systems, ease of access to data and sustainability and security of the system.

On systems to monitor the use of influenza vaccines in end-products, the Advisory Group “will consult with GISRS laboratories, databases and industry and other stakeholders.”

The results of this work “will be available to the Secretariat for integration into the 2016 review of the Framework.” The next PIP Advisory Group Meeting is foreseen to take place from 13-17 April.

Partnership Contribution, Some Companies Dragging Feet

According to the Advisory Group report, as a result of the WHO secretariat’s efforts to improve the process to collect the 2014 partnership contribution, there was an increase both in the number of entities contacted in 2014 compared to 2013, and in the number of contributors identified.

For 2014, 56 companies were identified, according to the report, 31 of which had not yet sent back their “Band Selection Form (BSF)”, which allows WHO to apply a formula and determine how much each contributor will pay into the partnership contribution.

“The BSF requires an entity to calculate its average annual influenza product sales over four years and to use that figure to place itself into one of 23 sales bands,” according to the report.

The Advisory Group advised the WHO director general to individually thank companies that have paid their 2013 contribution and “consider publicly acknowledging them,” so as to encourage other companies that have not met their obligations yet.

The PIP secretariat “should continue its efforts to obtain PC [partnership contribution] payments,” and “Member States should be invited to encourage, as appropriate, companies located in their country to fulfil their obligations under the PC.”

Paragraph 6.14.3 of the PIP Framework (under 6.14 – Sustainable and innovative financing mechanisms) states that, “Influenza vaccine, diagnostic and pharmaceutical manufacturers, using the WHO GISRS, will make an annual partnership contribution to WHO for improving global pandemic influenza preparedness and response.”

Civil society is worried that industry is trying to move away from their partnership contribution commitments, and have concerns that less contribution would deprive the WHO from resources much needed to face epidemics, according to a source. The source also underlined the fact that the partnership contribution is mandatory.

But industry may have a different view. The IFPMA source said, “IFPMA and BIO believe it is most important that the PC remain both voluntary and equitable.”

 

Image Credits: Flickr – Sanofi Pasteur