Immunocompetent

Chair's Text for the December WHO Virus Sharing Meeting: Comments and Link

perezoso — Sun, 16 Nov 2008 12:53:42 -0500

WHO has posted the Chair's Text to be considered in December at the next installment of the WHO Pandemic Influenza Preparedness Intergovernmental Meeting (WHO PIP IGM). The meeting name is a mouthful; but all you need to remember is that this is the group that is trying to resolve the virus sharing controversies.

The Chair's lengthy text is exactly that, a text drafted by the Chair of the meeting, and word on the street is that the Australia's Jane Halton actually did do much of the drafting. (Often "Chair's texts" are only nominally written by the Chair.)

Too bad the text doesn't do a better job of plugging gaps in the system and reflecting the proposals of developing countries. A complete listing of problems great and small would probably explode this blog's buffer; but, in short form, here are some of the key problems in Halton's text that will have to be resolved:

• The text's definition of "Pandemic Influenza Preparedness biological materials" (i.e. the viruses and other materials given to the WHO system) is way too narrow. As presently written, the main option has got a lot of verbiage; but it would only protect donor country sovereignty over the materials as submitted (e.g. a throat swab) and not after they'd been worked on. It would not cover, for example, synthesized copies of H5N1 genes. The restricted definition is a non-starter. It will have to be expanded.

• The Chair's system would only cover viruses isolated from human cases of potentially pandemic influenza. Another non-starter. H5N1 candidate human vaccine strains have incorporated not only genes fro humans; but from animals too, and this is likely to continue throughout the prepandemic phase. H5N1 viruses isolated in animals and elsewhere (i.e. environmental samples) will have to be covered, or else the benefit sharing system will not work.

• The text proposes to place the obligation to share benefits from use of the viruses on governments and not on vaccine and pharmaceutical manufacturers. No way, Jose Sanofi. Perhaps governments like the US and in the EU will provide some benefits to developing countries; but a binding obligation to share benefits - like vaccine technologies and an international fund - must be part of the Material Transfer Agreement that companies and other researchers sign when they access PIP materials (i.e. viruses and related materials and data). It's very simple: If companies want access to H5N1 viruses to make and sell vaccines, they're going to have to make contributions to promote access to H5N1 treatments for poorer countries.

• Thre are no major restrictions made on patenting H5N1 viruses and genes. The only restriction the Chair's text would impose would be patents on viral gene sequences. This falls well short of what is needed and will have to be improved. Stopping the patent ripoffs are a requirement for the new system.

• The Chair's system for acquiring and sharing viruses is very leaky and would not stop piracy. Through a variety of means that become apparent on close analysis, in the system proposed it would be possible for companies and other labs to acquire and utilize H5N1 viruses outside the WHO system, and without agreeing to share benefits. These holes, which are many, will need to plugged. If the viruse sharing system isn't airtight, then developing.

• At one point, the text seems to suggest that a "benefit" for developing countries would be for some of their citizens to be used as guinea pigs in vaccine trials. We hope this was a misunderstanding, because it will be patently offensive to many. Being an experimental subject is not a benefit.

• The Chair's text is schizophrenic about the role of the so-called "Essential Regulatory Laboratories" (i.e. the US FDA and its UK and Australian equivalents). It can't seem to decide if the regulatory labs are fully in the WHO system or not, and if they regulate vaccines or if they develop them. Part of the confusion is perhaps understandable. Although it is the function of the WHO Collaborating Centres to develop vaccines, in fact, the US, UK, and Australia seem to have assigned some of the these duties to their regulatory labs. This can no longer fly. The regulatory laboratories are going to have to stick to regulating, not developing vaccines, and if this means that changes have to made in the US/UK/Aus organizational structures, so be it. If the ERL's want to develop vaccines, they are going to have to be treated as vaccine manufacturer.

The text can be found here:

http://www.who.int/gb/pip/e/E_pip3.html

Stay tuned to Immunocompetent for more commentary on the text and issues for the upcoming meeting, which begins in Geneva on December 8th.

Richard Holbrooke and Laurie Garrett are Full of Sh*t

perezoso — Tue, 12 Aug 2008 21:17:46 -0500

Update: 6 September 2008

An Important Note About This Blog Entry

The short essay below was originally written as a Letter to the Editor of the Washington Post, because I believed that it was very important to publicly correct the numerous errors and misperceptions contained in the Holbrooke / Garrett editorial.

When the Washington Post did not publish the letter, I sent it to a number people and urgently asked them if they would be so kind as to put forward the ideas contained in the letter, given the important international humanitarian interest in reforming the GISN.

I was therefore very grateful when Ambassador Wibisono of Indonesia adapted the essay below and was able to have it published in the Jakarta Post on my behalf. An utmost priority in the debate over influenza virus sharing is widely circulating the powerful arguments for changing the current system, therefore, I again thank Ambassador Wibisono for his willingness to carry this message to a broader public.

------

... and it's time for America to wake up to that fact.

In their badly informed Washington Post op-ed "'Sovereignty' That Risks Global Health" (10 August), Richard Holbrooke and Laurie Garrett make a number of factual mistakes and misleading statements, some of which I will enumerate here.

The existing World Health Organization (WHO) system of sharing influenza viruses, called the Global Influenza Surveillance Network, is radically unjust in that it takes resources from developing countries and provides little in return, and leaves us all more vulnerable to an influenza pandemic. Indonesia and other countries that have taken the initiative to reform the WHO system are taking a laudable and overdue step to improve public health for all.

There is no constituency seeking to create "viral sovereignty". De facto, such sovereignty already exists in international law. Inexplicably, the authors mislead by simply ignoring that fact and, in particular, 20 years of development of the Convention on Biological Diversity which, among other international instruments, recognizes national sovereignty over genetic resources, including microbes. Viruses are, unequivocally, genetic resources subject to national sovereignty, whether Holbrooke and Garrett want to admit it or not.

Holbrooke and Garrett claim that it is "ludicrous" to apply sovereignty to genetic resources that easily cross borders. Their position belies ignorance of both biodiversity and related law and policy. As any farmer, biologist, or duck hunter can tell you, most genetic resources cross borders: birds, plants, insects, microbes, crops, and practically everything else made of DNA (or, as in the case of flu, RNA). This simple biological truth has not stopped sovereignty or international cooperation in biodiversity use and protection. Transboundary biodiversity issues have been discussed and addressed for over two decades by the UN. Holbrooke and Garrett have no apparently clue about this, otherwise they would not have made such an off-base assertion.

They further state that "The WHO has elicited pledges from the world's major drug companies not to exploit international repositories of genetic data for commercial benefit". Such pledges, even if they existed in the form claimed, are contradicted by fact. First of all, a number of companies have lodged US and international patent claims over hundreds of H5N1 genetic sequences - resources that were freely given to WHO by Indonesia and other countries. These resources come from the gene repositories.

Secondly, major pharmaceutical companies have advanced clinical trials underway utilizing Indonesian, Vietnamese, and other viruses in vaccines. One vaccine using a Vietnamese strain is licensed. The companies intend to profit from sales of these vaccines, and Indonesia (and other countries) will receive nothing of the proceeds. The fact of the matter is that industry - large and small - massively benefits from resources of the WHO system, and no commeasurate benefit accrues to Indonesia and other countries who, ironically, are facing the gravest immediate threat from H5N1.

Further, contrary to Holbrooke and Garrett's erroneous suggestion, the revised International Health Regulations do not require viruses to be sent to WHO, and Indonesia has not defied them. The revised regulations mandate sharing of information on disease outbreaks of international importance, and such information continues to be shared. The authors further - and unaccountably - allege that Indonesia has violated "a host of other WHO agreements". What agreements? I have participated in the WHO negotiations on influenza virus sharing, where I have not seen either Holbrooke or Garrett, and I am unaware of any such allegations.

In reality, Indonesia has repeatedly offered to provide more viruses to WHO. Neither Indonesia, nor its Health Minister, are intrinsically opposed to providing viruses. Rather, the stumbling block is an unwillingness of some countries to implement a just Material Transfer Agreement (MTA) to define the rights of parties when viruses are transferred.

The underlying proposition that Garrett and Holbrooke rail against in their callous editorial is that Indonesia and other countries are asking for a reasonable MTA for influenza viruses - one that doesn't rob them - and for an unbiased WHO. The hypocrisy of the US and some other countries is especially palpable when one looks at the typical agreements signed by US institutions for transfer of viruses between themselves. Those agreements are far more restrictive than anything that Indonesia or its allies have proposed for sharing their viruses.

The move to reform the WHO Global Influenza Surveillance Network is neither self-destructive nor anti-Western. Holbrooke and Garrett's lashing out against Indonesia is uninformed about the pertinent policy and law related to genes and sovereignty, and callous toward the concerns of developing countries trying to better protect their own citizens from a pandemic. In their blindness to the obvious injustices of the WHO system, Garrett and Holbrooke recklessly dismiss a very important, and potentially very positive - but delicate - negotiation underway to make the multilateral system more fair and equitable.

It's time for the US and its allies to stop hurling abuse at Indonesia and to acknowledge the need to reform the virus sharing system so that developing countries receive tangible benefits for their participation. Indonesia and other developing countries have put concrete and detailed proposals on the table for negotiation in Geneva. The real danger to public health is not sovereignty that is already a reality; but that these proposals are not discussed and implemented, leaving us with a dysfunctional global influenza surveillance system.

Material Transfer Agreement Hypocrisy

perezoso — Mon, 11 Aug 2008 17:41:42 -0500

One of the things that's got a lot of the Cro-Mag Indonesia bashers up in arms is that Jakarta is asking the US (and other countries) to sign reasonable Material Transfer Agreements for influenza viruses, in the context of an unbiased WHO system.

Wow, how radical and anti-American. Not.

The hypocrisy of the Bush administration's resistance to a decent MTA for flu virus transfers is especially palpable when one looks at the typical MTAs signed by US institutions for transfer of flu viruses and flu-related genetic materials between themselves.

To show that hypocrisy, I chased down some actual MTAs signed by US institutions for transfer of research materials containing flu strains and genes originally from the WHO GISN. Here is a brief introduction to those MTAs, written with TWN, and a link to PDFs of actual influenza Material Transfer Agreements that you can see for yourself.

Third World Network
The Sunshine Project

November 2007

INFORMATIONAL HANDOUT

Intergovernmental Meeting on Pandemic Influenza Preparedness: Sharing of influenza viruses and access to vaccines and other benefits

Material Transfer Agreements for Influenza Viruses and Genes Some Examples of Recent Standard Practice in the United States

Since the May 2007 World Health Assembly, which prompted international discussion of sharing of influenza viruses, some developed countries have been reluctant to discuss development of Material Transfer Agreements (MTAs) applicable to the provision of influenza viruses and clinical specimens to WHO Collaborating Centres, as well as for international agreement on MTA terms for transfers from the WHO Centres to third parties. Some have even objected to use of the term MTA at all. Perhaps developed countries hope that providers of H5N1 genetic resources will continue to transfer their viruses with no strings attached, which has led to a wave of patent claims on viruses and their parts.

Contrary to the suggestion of the some North countries, detailed MTAs for the transfer of influenza viruses and their pieces are, in fact, standard practice in the United States and other developed countries. Some standard MTAs are extremely restrictive with respect to the uses permitted to the virus recipient, for example, banning transfers to third parties and granting no rights to the recipient apart from those expressly authorized in the document.

Behind this cover sheet are six recent Material Transfer Agreements between US influenza research centers. They illustrate the kinds of terms and conditions that are already typically placed upon virus transfer.They are:

• MTAs between the US Centers for Disease Control, AstraZeneca (MedImmune), University of Wisconsin, and the University of Texas at Austin, for influenza materials and reverse genetics systems, November 2004 and January 2005;

• MTA between St. Jude Children’s Research Hospital and the University of Texas Medical Branch, also protecting interests of AstraZeneca (MedImmune), for plasmids encoding Chinese and Vietnamese H5N1 strains, November 2006.

• MTA and Letter of Transfer Agreement between the University of Georgia and BEI Resources, a US government contractor that manages microbial collections, for proteins produced by Thai and Vietnamese influenza isolates, September 2006.

It is not necessary delve into the fine detail of the attached documents to understand our point. In fact, these MTAs treat intellectual property in ways that make these agreements inappropriate to consider for use in a WHO system. It is sufficient to review the paperwork and identify the severity and types of stipulations, and the conditions and procedures used.

If it is standard practice in a country like the US for influenza viruses to be transferred under such heavily elaborated and frequently very restrictive terms, why have developed countries claimed that it is too onerous to develop material transfer agreements to govern the exchange of influenza viruses between donor countries and a WHO network?

Is it because a well-designed MTA would be too difficult to develop, or is it because rich countries want to continue to get viruses with no strings attached so that they may be freely appropriated?

LINK TO DONWLOAD THE MTAS: http://www.sunshine-project.org/flu/MTA_Handout.pdf

Quick Sketch of a New Global Virus Sharing System

perezoso — Mon, 11 Aug 2008 16:36:23 -0500

Back when I ran the Sunshine Project, and with the help of Third World Network, I wrote a brief item describing how the WHO Global Influenza Surveillance Network could be reformed. We distributed this at a meeting of the WHO Pandemic Influenza Preparedness Intergovernmental Meeting (WHO PIP IGM). (Yes, it's a mouthful.)

The jist of the following nearly year-old article is still about right. I should have given more attention to sequence data, with the rapid rise of synthetic biology; but it's there in rudimentary form. Take a gander at this short piece if you want to know what some of us are thinking about for a New Global System.

Third World Network
The Sunshine Project

INFORMATIONAL HANDOUT

November 2007

Intergovernmental Meeting on Pandemic Influenza Preparedness: Sharing of influenza viruses and access to vaccines and other benefits

A Quick Sketch of a New Global System for Sharing of Influenza Viruses

In the interest of public health and access to affordable medicines, a new international system is needed for the sharing of influenza viruses. The purpose of this short paper is to describe, in simple terms, the basic principles and methods of operation of such a system, without delving into great detail about problems with the present system. Here some important underlying concepts for the new Global System are presented, followed by a practical description of how it would operate.

In this document, viruses are understood to include sequences, virus genes and proteins (and subunits of both), as well as materials specifically derived therefrom, such as antibodies and complementary DNAs (and genetic constructs encoding the same).

The Global System must not allow patenting of influenza viruses. A fundamental problem currently is that transfer of viruses into the system is resulting in piracy of influenza viruses by companies and other labs, and even by some WHO Collaborating Centres themselves. These patents are ethically unacceptable and ignore the rights of donor countries and influenza victims. They will result in economic and social injustices including more expensive and less accessible treatments. Therefore, all transfers of biological materials and data into and out of the WHO system, including publication of sequence data, shall be with the legal stipulation that these items shall not be subjected to intellectual property claims.

The Global System must respect national sovereignty over influenza viruses. Sovereignty over genetic resources found within a country’s borders is established in international law and most prominently enshrined in the Convention on Biological Diversity.(1) Sovereignty should not be confused with ownership. Respecting sovereignty does not mean that a government owns influenza viruses occurring within its borders, rather, it means that the government has rights in determining how they are used. These rights must be preserved and applied when the viruses are transferred into and out of the Global System.

Specifically, in the new Global System, sovereignty means that governments must grant their prior informed consent to uses of the viruses that they contribute. For key functions such as surveillance and development of vaccine seed strains, this prior informed consent can be pre-negotiated and applied in the form of an agreement like those already routinely used for transfer of biological research materials. For other purposes, including commercial ones, it may be necessary to specifically request consent from the donating country.

The Global System must require the commitment of all participants to the fair and equitable sharing of benefits that arise from influenza virus research. The Global System must provide real, tangible benefits to participating countries, particularly developing countries, who receive next to nothing in return of participating in the current system. This would be the best way to avoid frustration with the system, which in turn could lead instead to mainly bilateral arrangements. The precise benefits will vary depending upon the situation, however, under the umbrella of the New Global System, for developing countries they may include: (1) free access to and assistance with vaccine production such as equipment and know-how (e.g. cell culture systems and adjuvants), (2) vaccine stockpiles under WHO physical control which would be distributed on the basis of public health needs, (3) free or discounted set-asides of a percentage of prepandemic and pandemic vaccine production lots; (4) free or discounted access to other influenza medicines, and (5) commitments of non-enforcement of influenza-related intellectual property rights. How would a New Global System operate? As a practical matter, there would be a number of major changes from the current system for sharing influenza viruses. These include:

Rewriting the terms of reference between WHO and the Collaborating Centres and enforcing them. Current WHO Collaborating Centres are governed by loose and unenforced arrangements. Because of intense commercial interest in influenza viruses and actual and potential conflicts of interest at some Centres, the terms of reference must be radically revamped. In particular, WHO itself will assume responsibility for virus use and transfers, meaning that in these areas, the Centres will no longer have any latitude to do as they see fit. In those matters, they will act only on behalf of WHO and only as specifically authorized in the new Terms of Reference. This means that transfers of virus into and out of the Centres will effectively be governed by the terms of agreement between donor countries and WHO and not ad hoc or peculiar arrangements, or lack of arrangements, between the Centres and donor countries.

In general, movements of viruses will be covered by Material Transfer Agreements.Presently, no such agreements are executed between donor countries and WHO Collaborating Centres meaning that, in effect, the viruses are a no-strings-attached gift from developing countries to the Centres, for the Centres to treat as they see fit. As benefits have not been shared and this practice has led to piracy, this unacceptable situation must be changed, and WHO must no longer tolerate, endorse or encourage it.

Material Transfer Agreements under the New Global System could be of three general types – 1) those from a country of origin to a WHO Collaborating Centre, 2) those of virus seed stock from a WHO Collaborating Centre to a vaccine manufacturer, and 3) all other transfers. The first two transfer types can largely or even completely be governed by pre-negotiated terms elaborated in a standard form.

Such Material Transfer Agreements are not onerous and are by no means unprecedented. In fact, similar MTAs are already the norm for transfers of biological research materials in developed countries. In many cases, MTAs already commonly used for influenza virus transfers between Northern institutions are more restrictive than those likely to emerge under a New Global System.

In the case of a standard MTA between the country of origin to a WHO Collaborating Centre (acting on behalf of WHO), the main purpose is to authorize the Collaborating Centre to perform its important responsibilities (such as identification and characterization of the strain) set forth in the Centre’s Terms of Reference and to preserve national sovereignty over the virus. /Such MTAs will make stipulations and preserve sovereignty in the event of transfers to third parties beyond the Centre that, in most cases, will require execution of a new MTA between the third party and the country of origin. In some cases, for example transfers between Centres and reference labs, or for research by a third party contracted to a Collaborating Centre for research in accordance with the Centre’s WHO Terms of Reference, there may be latitude for transfer for those purposes under the first MTA.

In the case of a standard MTA between WHO and a vaccine manufacturer for transfer of vaccine seed strain, the main purpose is for the vaccine manufacturer to obtain authorization from the country / countries of origin of the seed strain virus and for the manufacturer to make commitments for benefit sharing as pre-negotiated under the umbrella of the New Global System (as described at the top of page 2). This MTA will enable the manufacturer to use the seed strain for vaccine production or further development for vaccine production and will bind the manufacturer to fair and equitable sharing of benefits.

In the case of other transfers, prior informed consent of the donor country will be required, and execution of a new MTA with the country of origin will be necessary if requested by the donor. These include transfers of viruses that are not vaccine seed strain to companies, and use of virus by the Centres in ways not specifically authorized by the Terms of Reference. Because these transfers may be to very different kinds of institutions for widely varying purposes, no complete single set of terms may be applicable. WHO, governments, scientists, and NGOs should discuss these transfers with a view to establishing standard procedures and boilerplate MTA language, which perhaps may evolve into standard MTAs in the future. Importantly, setting final definition of terms of some of these types of transfers aside for the time being will not prevent establishment of a New Global System.

WHO Collaborating Centres and other entities will renounce influenza-related intellectual property claims as a condition of their participation in the New Global System. These include claims on viruses, genes, sequences, proteins, and their use in human and animal vaccines and diagnostics. This will ensure the availability of the system’s resources and outputs for public health uses. In the current system, some Collaborating Centres have made patent claims or argue that they should be made "defensively". "Defensive" patenting is not a solution, it is a symptom of the problem of privatization. Instead of worsening the condition by increasing the amount of patenting, the New Global System should renounce it, and seek to inoculate its resources and products from such claims.

Access to New Global System sequence data will not be impeded, and subject to the first MTA can be made available online. Important conditions will include that all data be available to all persons, and that all who access it must agree not to sell or make any type of proprietary claim to it or for its use. Models of these types of systems can be found for software and other media and these can be adapted for use with New Global System sequence information.

Virus transfers will be comprehensively tracked by WHO, which will maintain a database of them as it will be advised of all such transfers by virtue of its revised relationships with the Collaborating Centres. This data should be available to Member States and the public.
Donor countries will have certain other research-related rights, including those of immediate material return and provision of characterization data, other research results and publications.

Footnote: (1) It has been suggested by some that influenza viruses do not fall under the Biodiversity Convention because they are a potentially harmful type of genetic resource that humans seek to control. This is not only an incorrect assessment of the language of that treaty, in fact, the operations of the Global System and influenza research are very clearly aligned with the intent of the CBD. The collection, obtaining, distribution, and preservation of influenza diversity is a core purpose of the Global System, as that diversity is critical to treating influenza. The fact that governments value such diversity and its preservation is illustrated by the extreme lengths that have been resorted to in order to recreate the 1918 influenza virus.