Immunocompetent

More Notes from the WHO PIP IGM

Thu, 11 Dec 2008 08:13:29 -0500

Here we continue notes from the World Health Organization Pandemic Inflluenza Preparedness Intergovernmental Meeting. Refer to the previous post to read: Pretending You are In Charge (WHO), America Insults the Scientists of the Developing World - Or Is It About Patents?, and Japan's Big Bluffer.

US Shenanigans on Distributing Vaccine Seed Strain

Uncle Sam is up to something untoward when it comes to WHO's (pre)pandemic influenza vaccine seed strains. Immuncompetent doesn't know for sure what it is; but he's got a hunch. The issue is the language under discussion that would direct WHO Collaborating Centres to distribute influenza vaccine seed strain.

In addition to providing H5N1 vaccine seed strain to industry (which WHO CC's presently do), most countries want to make sure that the vaccine seed strain is also provided to national influenza centers around the globe or, at least, in the country of origin of the HA gene used in the seed strain.

Although the US professes to be in favor of this, it actually seems to have problems with sharing vaccine seed strains. To wit, it insists on inserting qualifying language into the paragraph saying, in a limiting fashion, that vaccine seed strain should only be distributed "as broadly as possible". (Key words: "as possible".)

Asked what the heck it means by this, the US response was frankly unintelligble. The closest thing to something coherent that it said was the qualification is necessary "because we know there may be some restrictions upon us". Whatever the hell that means.

The US also keeps emphasizing that the recipient lab must have acceptable biosafety facilities and practices. Making this point, the US reminded everyone that "these viruses are highly pathogenic and deadly", so the vaccine seed strain could not be so easily distributed.

What? This is factually incorrect. That's odd, because the US usually gets its technicalities right.

Vaccine seed strains produced by WHO are attenuated (i.e. weakened). They are typically handled at BSL-2 containment. They are not deadly nor highly pathogenic like viruses found in nature because of their lab-adapted genetic backbone and/or altered HA gene. Sadly, the WHO Secretariat did nothing to correct the US - despite WHO having stated less than an hour before that its seed strains are attenuated.

So some biosafety capability (BSL-2) is needed; but the safety requirements are not nearly as stiff as the US claims.

What's up with this American nonsense about "as possible" and "deadly" BSL-2 vaccine viruses?

Immunocompetent thinks the US is looking for a back door in the agreement to raise security and patent issues - to permit it to impose export controls on influenza vaccines (like it presently does for Cuba, North Korea, and some others) and/or patent protections on seed strain (an "additional procedure" that the US has contradictorily argued against). This may be why they don't want a clear obligation to share vaccine seed strain with developing countries. They may want to reserve the right to say no to some countries for political reasons (e.g. Cuba) and to make money for patent holders (an in, it's "not possible" to give you the seed strain because you won't pay royalties).

Immunocompetent could be wrong; but that's our guess...

Even if you don't buy this explanation for Uncle Sam's odd behavior, if you think about it, the US position is pretty retrograde nonetheless. There is really no valid reason to refuse to provide WHO vaccine seed strain to anybody who is able to use it to produce effective vaccines.

Notes from the WHO Pandemic Influenza Preparedness Intergovernmental Meeting

Wed, 10 Dec 2008 07:05:04 -0500

Here are some notes, updated when I feel so moved, from the resumed WHO Pandemic Preparedness Intergovernmental Meeting (WHO PIP IGM). This is the continuation of previous WHO PIP IGM meetings on the topic that is commonly understood to the be the conflict between Indonesia and the US over virus sharing, but which in fact is broader and much more complicated. The meeting reopened on Monday, 8 December and will last until this Friday or Saturday.

This is not a comprehensive report. It's a collection of thoughts about issues, particularly when they are amenable to being dealt with discreetly. A more comprehensive piece will, hopefully, follow.

The mini blog posts here here are:

Pretending You are In Charge (WHO)
America Insults the Scientists of the Developing World - Or Is It About Patents?
Japan's Big Bluffer

Pretending You are In Charge (WHO)

To any careful observer of the WHO Global Influenza Surveillance Network it is clear that labs in the powerful countries - like the US, Japan, UK, and Australia - just do whatever they want with H5N1 samples and call it a WHO activity. They are "WHO labs" in name only. So, for example, the US "WHO" lab in Atlanta just starts some practice - say use of a particular diagnostic - and then the real WHO just acts like it planned this all along.

This "WHO Veneer" is subtly apparent all the time when looking at the GISN's operations (some of the WHO-endorsed labs don't even have the loosest terms of reference). But it must be particularly painful for the pride and credibility of the WHO when its ancillary status breaks out into the open. Like when the real WHO doesn't know the details of how its "own" system operates, which happened in public today.

A controversial class of laboratories "inside" the WHO system are the so-called "Essential Regulatory Laboratories" (ERLs), like the US FDA. These labs are essential for licensing vaccines; but their WHO status is ambiguous. WHO has long said that there are three "essential regulatory laboratories" that should get special global treatment - NIBSC in the UK, the FDA in the US, and TGA in Australia. Nevermind that these labs don't have standardized capabilities and nor uniform responsibilities in the WHO system, never mind that they don't have terms of reference. It shows you how loosey-goosey WHO has been in its so-called "oversight" of the GISN.

The system is supposed to be controlled by WHO. But today, in response to a question from Indonesia - and a year after it started declaring in official documents that there were three ERLS - WHO suddenly decided that there is a fourth ERL. This newly-discovered ERL is located in Japan. And what's more, WHO's influenza leaders aren't sure where it is and if it is separate or the same as the WHO Collaborating Center in Japan.

What an embarrasssment. The PIP IGM is supposed to be negotiating the roles and responsibilities of labs the constitute the WHO global influenza surveillance system, which allegedly is oveseen by a functional and vigilant WHO. But WHO doesn't even know its own system very well and, in this case, doesn't even know where one of its allegedly "essential" labs is!

After this embarrassing revelation, I shot the following e-mail to a senior WHO official from North America who was sitting on the dias across the room from me:

"The [Essential Regulatory Labs] and [WHO Collaborating Centers] obviously do whatever the hell they want to do and then you guys get up and pretend that WHO actually knows what is going on and approves of it. What an embarrassment. You guys don't even know where all your labs are nor do you have a clear idea of what they all do"

Sometimes he answers my e-mails. No reply yet; but I'll let you know if I get one.

America Insults the Scientists of the Developing World - Or Is It About Patents?

The American delegation in Geneva seems to take a dim view of the capabilities of developing country influenza scientists. Or is it up to something else when it insults their intelligence?

Although the US says "it is imperative that we have as many viruses from human cases as possible", itself not an unreasonable position (assuming "we" means WHO, and not the Pentagon), the United States of America does not think that the countries that provide those viruses should have a right to see the full characterization data that is generated from them.

Instead, the US just wants to give "summary information" about the virus characterization to the donor country, and it doesn't want to the WHO PIP IGM to try to define what that summary information is (thereby leaving it up to .... you guessed it .... the CDC in Atlanta - acting as a "WHO lab" - to decide what to send).

So, if you are a developing country with H5N1 cases, Uncle Sam insists that you must send all your virsues, but Uncle Sam is unwilling to commit to sending you back the full results of the characterization that is performed on those viruses. What a stinking double standard.

It's gets even "better". The reason why it has a double standard, said the US delegation this morning (Wednesday), is that developing country national influenza centers are too stupid or incapable to understand the output from the CDC's sophisticated science. The data would not, the US condescendingly noted in open working group, be useful for other labs. Chalk another one up for the Bush administration's efforts at international cooperation and understanding.

What's going on? Immunocompetent suspects that the Americans are actually up to something more than insulting other countries. We suspect that they are trying to keep intellectual property rights and even perhaps protecting rights to publish or possible proprietary diagnostic procedures and results. Or CRADAs, perhaps?

And seing that this would NOT be an acceptable reason to keep secrets in the WHO public health system, the rather politically-unpalatable excuse that they've come up with is to say that developing countries are too stupid to understand it anyway. (After all countries aren't sending viruses to CDC so they can be patented.)

The above is just a hunch; but Immunocompetent's hunches are often pretty good. The US is either obfuscating its attempts to acquire intellectual property rights with insults, or it just being insulting out of arrogance. Either way, it's bad.

(The EU, meanwhile, is maintaining pretty much dead silence on this issue and many others, mainly because it really doesn't seem to much care. "We need their virus, they need our vaccine, nobody needs this framework", two EU delegates were heard to emphatically agree outside the room. The EU is on track to easily win the award for being the largest group of countries to make the smallest leadership contribution to these talks.

What can be positively said about the Americans is that if it weren't for Japan and sometimes Canada, the US would be the only rich country that at least has taken care and undertaken serious preparation for these talks. Not necessarily constructive preparations; but at least they've got a plan that they've thought about, which is more than it seems possible to say for many other developed countries.)

Japan's Big Bluffer

Japan has been unusually vocal at this PIP IGM, perhaps in response to its domestic influenza vaccine producers, like Biken. While Immunocompetent has no problem with the usually quiet Japanese talking up a storm, we're not so sure about the quality of their contributions.

The evidence is to be found in how Japan is swerving and dodging. Japan seems to have little purpose but to see what it can get away with in watering down the text. Japan weighs in, for example, to delete language on benefit sharing. Or to complain (inappropriately) about not wanting to see new text.

When confronted with opposition, however, Japan usually beats a hasty retreat. But this certainly doesn't seem to be because Japan is unsure of itself. It is quick to the mike when new items open up, with its watering down usually clearly thought through in advance.

At this PIP IGM, Japan has seemed like a heckler to the process, stirring up little problems where it can, but often with little serious constructive intent behind its proposals.

CDC Statutorily Prohibited from Being a WHO Collaborating Center?

Sat, 06 Dec 2008 13:31:00 -0500

The Centers for Disease Control has a World Health Organization Collaborating Center (WHO CC) for influenza, but it may be unable to fulfill its duty to WHO because US domestic law prevents it from adequately sharing influenza viruses. The law is US export control legislation, and it requires that labs, including CDC, obtain a license from the Department of Commerce before sharing a number of disease agents.

This means that shipments of H5N1 to other countries require a license. For some countries, like Canada, obtaining a license is routine; but for many others, including many WHO Member States, tighter export controls apply. These countries are indicated in a list maintained by the US Department of Commerce called the Commerce Control List Country Chart.

(“CB” type controls generally govern H5 virus exports. These range from “CB1” to "CB3”, with “CB3” being the most restrictive. The exception are the extra "special" countries in the USG's eye, like North Korea or, much less probably, Cuba, who have country-specific - i.e. even more restrictive - export control regimes.)

Export controls have been sharply criticized by developing countries for being arbitrary and political, and for contradicting technology transfer obligations in international agreements.

The US Department of Commerce has authority to simply deny shipment of H5N1 virus to other countries, even if the virus was given to the WHO Collaborating Center at CDC by a National Influenza Center in another country. In other cases, the US Department of Commerce may insist that foreign labs comply with US-style security rules or that they even to try prove to the US government that they are not a security threat to the United States.

US domestically legislated procedures to obtain H5N1 are contained the Select Agent Rule. They include submitting the fingerprints and biographical data of researchers to the Federal Bureau of Investigation (FBI), periodic laboratory security inspections (ironically conducted by CDC itself), and a large number of mandatory physical security measures and procedures.

Other restrictions on H5N1 viruses under US law include a prohibition on foreign recipients of H5N1 viruses from US labs from transferring them to others. So, for example, if the WHO CC at the Centers for Disease Control is able to send an H5N1 virus to a foreign National Influenza Centre for research purposes, the CDC may require the NIC to not transfer that virus to anyone else, even another WHO network laboratory.

Such strict domestic legislation may be sensible in the US because of its severe domestic bioterrorism threat (for example, the 2001 anthrax letters that were produced at US government lab and sent by a US government scientist), however, they may interfere with the ability of the Centers for Disease Control to effectively function as a WHO Collaborating Center for Influenza and to abide by its WHO Terms of Reference, which require sharing H5 viruses internationally.

The WHO Pandemic Preparedness Intergovernmental Meeting (PIP IGM) should be careful to avoid allowing national legislation to stand in the way of WHO-approved virus sharing by WHO Collaborating Centers. Therefore the PIP IGM should ensure that WHO Collaborating Centers for influenza are not located in where domestic legislation conflicts with the Collaborating Center’s responsibilities to WHO Member States.

In the specific case of the United States, WHO Member States should seek a public assurance from the US government that the WHO CC at the Centers for Disease Control will provide H5N1 viruses and vaccine seed strains to all Member States with a WHO-recognized laboratory, without the imposition of any delays, denials, or additional requirements due to export controls or other national legislation.

WHO, NAMRU-2, and Indonesia According to the US Pacific Command

Tue, 02 Dec 2008 09:41:35 -0500

Stashed away in a somewhat obscure corner of the .mil webzone are an interesting set of H5N1 reports. Prepared about every week by the US Pacific Command (PACOM) and the Australian Army's Land Headquarters (LHQ), the reports summarize recent developments with H5N1 with an interesting twist. Who they are prepared for isn't clear; but Immunocompetent thinks they look like a slide that goes into scheduled briefing for higher-ups somewhere on the military food chain, probably at the Office of the US Secretary of Defense, on whose website the files can be found.

We have some choice extracts below; but there's plenty more interesting reading that you can download. (And if the OSD "disappears" this information off its website, we have a complete archival copy.)

The reports, marked "unclassified", provide abbreviated updates H5N1 cases worldwide; but they are more interesting for what they select as newsworthy H5N1 politics.

Recently, PACOM has been very interested in the NAMRU-2 negotiation and the WHO PIP IGM, and the reports have included information not public elsewhere. For instance, details on conversations between WHO staff and US government representatives, and on the (apparently failed) bilaterals between Indonesia and the US. (These were facilitated by Australia.)

The reports, at least recent ones, appear to be prepared by Air Force Lt. Colonel Peter Breed, who was recently listed as the PACOM's Chief of Force Health Protection. PACOM is headquartered in Hawaii.

There is no direct publicly-accessible URL to see a listing of these reports (it appears to be only available to people in the .mil and .gov domains). Instead, if you have construct a Google search that will hit them. This search works pretty well.

In short, the reports offer an interesting view into Bird Flu According to The Pentagon. And they show just how closely the US (and Australian) military are following H5N1 issues. Here are some recent extracts:

31 October 2008:
CEO of Indonesia’s National Committee for Avian Influenza and Pandemic Control (KOMNAS), reportedly told French officials that the “successful” GOI-USG negotiations,” facilitated by Australia, could lead to an end of the sample-sharing impasse at December’s WHO Intergovernmental Meeting.

24 October 2008:
Indonesia: Legal proceedings against the USG and WHO brought in April 2008, alleging responsibility for the death of an Indonesian from H5N1 have again been postponed. As a result of internal debate, the court further postponed a decision regarding the proceedings until perhaps mid-December.

26 September 2008:
Indonesia: (1) NAMRU-2 laboratory will be temporarily shut down because it offers "little benefit" to Indonesia said the GOI’s MOH. Negotiations between the USG and GOI are ongoing. U.S. HHS Secretary said Indonesia's refusal to share its samples of the H5N1 virus with the rest of the world has spilled into the NAMRU talks. (2) USDEL in Manila reported in conference calls September 21 and 22 that the two delegations, in discussions facilitated by Australia, made progress in reviewing a U.S.-drafted notional materials transfer agreement (MTA) text, as well as a text on Terms of Reference (TORs) for the WHO influenza surveillance network provided by Indonesia

19 September 2008:
Indonesia: The next round of consultations involving Indonesia, the U.S., and the WHO Intergovernmental Meeting Chair (Australia) on sample and benefit sharing is scheduled for September 21-22 in Manila. USG will draft a human influenza virus model Materials Transfer Agreement for discussion in Manila.

12 September 2008:
(2) MOH recently claimed that developed countries are creating new viruses that are meant to infect people in poorer nations in order to help drug companies sell more vaccines.

...

WHO Assistant Director-General David Heymann spoke with Special Rep Lange today about the November Intergovernmental Meeting on Pandemic Influenza Preparedness. Based on his conversations, Heymann expects that developing countries will seek recognition of some kind of “viral sovereignty" and will agree to continue sharing human influenza virus samples only in return for “sustainable” benefits (i.e., some system by which developing country access to benefits, such as vaccine stockpiles, is guaranteed over the long term).

29 August 2008
India/Bangladesh: The bird flu virus, that caused India's worst AI outbreak, has been found to be "a lot similar" to the one in that cause havoc in Bangladesh. However, we can't say that Bangladesh was the cause of the outbreak. Sources said India complained to FAO and OIE about Bangladesh's slack handling to contain the virus, putting at risk India's internal security.

Indonesia: GOI authorities are now reporting possible human AI cases to the WHO within 24 hours in compliance with the International Health Regulations. WHO does not report Indonesian cases until the GOI MOH announces them, on a monthly basis. However, if there are international public health risks, WHO will report it with or without GOI permission.

18 July 2008:
Indonesia: A WHO official confirmed to Embassy Jakarta on 16 July that the GOI had reported a new, confirmed human AI fatality: a 38-year old male resident of Tangerang municipality died on 10 July. A WHO representative told Embassy Jakarta that Health Minister Supari had assured him that Indonesia would comply with the Health Regulations by notifying WHO of fatalities.

11 July 2008:
Indonesia:(1) MOA “temporarily”bans import of U.S. poultry. Poultry “treated to inactivate the avian influenza virus”is exempt, if it can pass a “risk analysis”and is approved by MOA. (2) Australian Authorities have sought clarification of Indonesia’s policy on reporting human cases of avian influenza to the WHO. A senior Australian official has said that Indonesia’s management of avian influenza is severely deficient.

3 July 2008
Indonesia: GOI and USG plan to meet in Australia, 25-28 July 08, to discuss next steps toward resolving sample sharing issue.

20 June 2008:
Reporting of these 2 cases demonstrates that Minister Supari is somewhat cooperate with WHO, but reporting not done within 24hr International Health Regulation requirement agreed to by the 193 member states of WHO.

22 May 2008:
Indonesia:(1) Virus sequence (genome) sharing with pubic database but no actual virus isolate sharing & proposed pay-for-virus system unacceptable to WHO.

29 February 2008:
Indonesia:Clarification on last week’s sample shipping report: US CDC confirms 15 samples, all came from 2 cases, a mother/daughtboth still alive; samples received without MTA or other restriction

18 January 2008:
GoI has reached tentative deal with Iran to co-produce bird flu vaccines, MoH says Iran has an advanced pharmaceutical industry, capable of producing bird flu vaccines using Indonesian virus.

WHO, the Pentagon, and Influenza Collections

Tue, 02 Dec 2008 09:19:50 -0500

A flu article recently written for SUNS...

US military flu virus collection parallels WHO virus system

Bogota, 26 Nov (Edward Hammond*) -- A large and rapidly growing global US military virus collection system parallels the World Health Organization's Global Influenza Surveillance Network (WHO GISN) but does not entirely share its public health purposes.

The US military system is a source of viruses for the WHO GISN; but it does not give most of its virus collections to WHO. It does keep all the lab specimens and viruses it collects for its own use.

Wider knowledge of the extent of the US military virus collection system and its ambiguous relationship to the WHO GISN system will raise important questions for the WHO Pandemic Influenza Preparedness Inter-Governmental Meeting (PIP IGM), which will convene in Geneva the second week of December.

The extent of the Pentagon's quiet but large virus collecting and its relationships with the WHO GISN will surprise many. For example, the Pentagon claims credit for having collected several important influenza viruses that were subsequently selected by WHO for use in seasonal and H5N1 pre-pandemic vaccines from 2000 through the present, including viruses from Panama, Peru, Nepal, Malaysia, and Indonesia.

Some developed countries, including the United States, have insisted that developing countries only share influenza viruses with the WHO GISN and not bilaterally with others. Yet, contradictorily, the United States has a
massive military influenza virus collection program, but only provides a very small percentage of the materials that it collects to the WHO.

It is unclear if and how viruses collected by the US military in other countries would be covered by a WHO GISN material transfer agreement because they are obtained and transferred outside what is now-understood to be the WHO system.

If one WHO Member State unilaterally amasses influenza viruses without full participation in the WHO access and benefit sharing system there is strong potential for the WHO system to be undermined.

Also undefined is the legal status of a virus received by the WHO system; but not from an approved lab of its country of origin - a situation that now frequently occurs due to the activities of the US military virus collection system.

The US military system is active globally, including at least 56 countries where it is collecting influenza viruses (as of 2007). The system pulls in clinical specimens and locally isolated viruses that are shipped to the
United States. It provides some of these viruses to the WHO GISN network, mainly through the US Centres for Disease Control (CDC), a WHO Collaborating Centre in Atlanta, Georgia (and part of the US health ministry), but keeps all specimens and viruses for its own purposes.

The size and capacity of the US military program is dramatically expanding and has more than doubled in recent years. In 2005, it was active in 30 countries and included three BSL-3 labs and a total sample processing capacity of 9,000 specimens per year. By 2007, the network was active in 65 countries and included eight BSL-3 labs and the capacity to process 18,000 samples annually.

The network is named the US Department of Defense Global Emerging Infections Surveillance & Response System ("DoD-GEIS"). A DoD-GEIS program called the US Department of Defense Worldwide Influenza Surveillance Program focuses specifically on flu viruses.

The military network has "sentinel" sites around the globe, reported by US military sources to include 128 or more locations. These are installations where US military personnel are based, as well as collaborating non-military sites that collect samples from US personnel and local civilian populations.

In 2006-2007, the system collected influenza viruses from developing countries including:

-- Americas: Belize, Guatemala, Honduras, El Salvador, Nicaragua, Venezuela, Colombia, Ecuador, Peru, Bolivia, Paraguay, and Argentina.

-- Africa: Morocco, Libya, Egypt, Eritrea, Djibouti, Sudan, Uganda, Kenya, Burundi, Gambia, Ghana, Nigeria, and Cameroon.

-- Middle East: Turkey, Jordan, Iraq, and Oman.

-- Central/South Asia: Azerbaijan, Kazakhstan, Uzbekistan, Mongolia, Afghanistan, Pakistan, India, Nepal, and Bangladesh.

-- Southeast Asia/Oceania: Myanmar, Thailand, Vietnam, Laos, Cambodia, Philippines, Indonesia, Papua New Guinea, and Solomon Islands.

A US Air Force lab at Brooks City Base in San Antonio, Texas coordinates the system. In 2006 and 2007, its systemwide budget was over $40 million per year. In the 2006-2007 flu year, the Texas lab alone processed 5,810 specimens from persons across the globe suspected to have respiratory infections. Of these, 2,444 tested positive for a respiratory virus, including 1121 positive for influenza virus. According to the US Department of Defense (DOD), "All original specimens are archived and kept for requests from [Department of Defense] partners or the CDC."

Another lab at a US Navy facility in San Diego, California processes an unknown number of additional samples. Of note, the Navy lab systematically isolates flu viruses from military personnel who become infected during port
visits. Using this unusual collection method, in 2007, it isolated seasonal influenza viruses from countries including Indonesia, Papua New Guinea, and the Solomon Islands after US Navy ships docked there and US sailors became infected while ashore.

Including the Navy lab and other facilities (see below), the military system handled an overall total of approximately 8,000 influenza and other viral cultures in 2007. Of these, only a small percentage are given to CDC. In 2006, this number was 120 viral isolates (about 1.5%), meaning that over 98% of the viruses collected by the US military program do not enter the WHO system.

In addition to the CDC, collected viruses (especially H5N1 viruses) are provided to US Army Medical Research Institute of Infectious Diseases (USAMRIID) at Fort Detrick in Frederick, Maryland. USAMRIID is the historical home of the US offensive biological weapons program (terminated in 1969), and is presently the headquarters of the US military's biological defense effort. Drawing on viruses collected by the US military and WHO sources, as of 2007, USAMRIID maintained a collection of thirty different H5N1 strains plus many other flu types that it uses in research and provides to other US military labs.

According to the program, the primary purpose of the virus collection system is to ensure US military readiness: "The principal objective is to enable the rapid discovery of novel strain mutations that could trigger a pandemic and to monitor these strains for their ability to transmit and to cause disease... the priority of the DoD is to maintain readiness and protect the health of service-members and beneficiaries, the contributions from the [San Antonio-based] surveillance program also benefit the greater global health community."

Five overseas laboratories operated by the US Department of Defense act as regional coordination centres for the collection effort. The five labs are:

-- Naval Medical Research Unit No. 2 (NAMRU-2) in Jakarta, Indonesia.
-- Naval Medical Research Unit No. 3 (NAMRU-3) in Cairo, Egypt.
-- Naval Medical Research Centre Detachment (NMRCD) in Lima, Peru.
-- Armed Forces Research Institute of Medical Sciences (AFRIMS) in Bangkok, Thailand.
-- United States Army Medical Research Unit-Kenya (USAMRU-K) in Nairobi, Kenya.

With the exception of NAMRU-2, which was recently closed by the Indonesian government, each of the above labs works not only in the country in which it is located; but also in nearby countries, where laboratory and personnel
detachments are sometimes placed.

NMRCD operates a high containment (BSL-3) lab in Peru, and coordinates virus collections in several South and Central American countries and, for example, has staff in Guatemala. In 2007, it reported that it is seeking to
expand virus surveillance efforts in Ecuador, Bolivia, Paraguay, and Uruguay.

AFRIMS in Bangkok operates a BSL-3 lab and, in addition to work in Thailand, maintains a facility in Nepal and collects samples from other countries in the region. In total in 2007, AFRIMS collected over 1,000 respiratory
samples from seven countries in Southeast and South Asia.

NAMRU-3 in Cairo has at least BSL-3 capability and collects human and animal influenza viruses. It is a WHO GISN H5 reference lab, submitting viruses both to other US government labs as well as WHO labs. NAMRU-3 maintains
activities in many African, Middle Eastern, and Asian countries, from Ghana eastward all the way to Pakistan.

It states that in 2007, "From Egypt, 141 human specimens were received for influenza A/H5N1 reference testing, and 26 specimens tested positive for H5N1. H5 reference testing was performed on 459 animal specimens, with 92 positive for H5N1 from Afghanistan, Egypt, and Ghana." From these H5N1 isolates, MANRU-3 deposited HA gene sequence information for 74 strains in GenBank.

USAMRU-K in Nairobi collects virus samples from hospitals and Kenyan military facilities and says that it is developing collection capabilities through universities in Uganda and Cameroon and the Nigerian defense ministry. Flu viruses it collects are provided to the CDC and the US military.

Until the Indonesian government closed it, NAMRU-2 in Jakarta played a similar role, including coordinating US laboratory detachments in Indonesia, Cambodia and Laos. In 2007, it says that it collected and tested more than 4,500 respiratory samples in Indonesia alone. It is unclear what will happen to NAMRU-2's activities outside of Indonesia now that the Jakarta laboratory has been closed.

Other US military BSL-3 labs in the network are located in Germany and South Korea. The DoD-GEIS network also collaborates with the US Defense Threat Reduction Agency (DTRA), although the exact nature of the collaboration has
not been publicly described.

Despite the Pentagon's claims that it has frequently contributed to WHO vaccine strain selections, none of the negotiating texts or background documents made available by WHO in the course of the Pandemic Influenza
Preparedness Inter-Governmental Meeting have discussed the large US virus collection system that parallels the GISN, much less explained the relationships between the two.

Nevertheless, the purpose of the US military system does not wholly coincide with WHO's public health ends, and its activities at times do not appear to be compatible with most proposals for a revised WHO GISN virus and benefit
sharing system.

The massive US military virus collection system, which parallels the WHO system yet does not currently operate under the same rules, creates an additional complication for diplomats seeking an agreement on virus and
benefit sharing. Its extent and different purposes than the WHO system may also be of concern to some countries, particularly because WHO system virus sharing is for public health and not military purposes.

Efforts should be made to ensure that all virus collection and transfers take place within the WHO system, using a WHO material transfer agreement, and that virus collections for purposes other than public health not be permitted.

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

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.

Swiss-American Venture Claims Blood of Vietnamese H5N1 Survivors (and Much More!)

Mon, 06 Oct 2008 13:06:37 -0500

Think antibodies might be useful to prevent or treat bird flu? Better get out your checkbook, because a company based in San Francisco says it owns all H5N1 antibodies, including all human (and some animal) antibodies against the critical HA gene of the H5N1 "bird flu" virus. The claims are made in an international patent application published on September 18th.

But wait, it gets even more disgusting: The company also specifically claims DNA (and amino acids) taken from at least 3 Vietnamese survivors of H5N1. The DNA, which encodes antibodies, is contained in human cell lines established from the victims' blood.

If granted, the patent application could have profound effects in limiting research on antibody treatments against the potentially pandemic H5N1 type of influenza. It could also earn its owners huge profits from the blood of 3 (or 4) Vietnamese persons who were nearly killed by the virus. Who exactly wants to profit? Well, one of the would-be owners of H5N1 antibodies and pieces of Vietnamese people is none other than a co-founder of Chiron and former Director of Novartis. Sadly, there is no remedial ethics class to which to send these perverted patent applicants.

The patent application (WO2008110937) was published on 18 September 2008. It was submitted by HuMabs LLC, a relatively unknown company in California. HuMabs is owned, however, by Synergenics, a private venture capital-type firm financed and led by William Rutter. A prominent figure in biotechnology, Rutter is known for co-founding the company Chiron and as a former Director of Switzerland-based life science giant Novartis.

The scientific lead of HuMabs, and the sole inventor indicated on the patent application, is immunologist Antonio Lanzavecchia, an Italian researcher who leads the Institute for Research in Biomedicine (IRB) located in Bellinzona, Switzerland.

The blood samples were collected in late 2004 and early 2005 at the Hospital for Tropical Diseases (HTD) in Ho Chi Minh City, Vietnam. Some details have been published about the H5N1 victims whose blood was used.

Two were men, 22 and 23 years old when infected. They were hospitalized 7 and 3.5 weeks, respectively. A third victim was a 26-year-old woman whose hospitalization was relatively short, at ten days. It is from her blood that the most promising antibody, called FLD21.140, was isolated. There is no published information about the 4th blood donor.

The collections were part of a research program sponsored by the UK's Wellcome Trust and conducted by Oxford University scientists, who maintain a Wellcome-sponsored research centre at the Hospital. The Oxford scientists say they obtained informed consent from the Vietnamese H5N1 victims, who were treated at the Hospital.

The blood samples were sent to US and Swiss researchers collaborating with the Oxford team at the US National Institutes of Health (NIH) and the IRB in Switzerland.

In research with mice, antibodies extracted from the blood samples proved highly effective against Vietnamese-type (Clade 1) H5N1 viruses and partially effective against other (Clade 2) H5N1 types. The antibodies target the HA (hemagglutinin) gene of the influenza virus, preventing or inhibiting infection.

In parallel, the Wellcome Trust public relations department facilitated media access to the Oxford team in Vietnam, and a feature article about the research appeared in the Times (London) in October 2006.

The Times author highlighted a charming 11-year-old girl who beat the odds and survived H5N1 and noted, with no apparent irony, that "H5N1 patients are often the rural poor, with no phone and little contact with doctors", and that several of the H5N1 victims interviewed were suffering ongoing financial crises as a result of their hospitalization. Nothing was stated in the article about patents and profits.

In May 2007, the HTD/Oxford/NIH/IRB team jointly published the mouse experiments, which were portrayed as a significant step forward in H5N1 research. The Wellcome Trust simultaneously put out a press release on 29 May 2007. A footnote to the press release stated "Worldwide rights to the antibody technology have been licensed to HuMabs, LLC, a US-based business with offices in Bellinzona."

Sixteen months later, in September 2008, the HuMabs/Lanzavecchia patent application was published by the World Intellectual Property Organization (WIPO). The application claims not only DNA from the 4 Vietnamese victims that encodes 11 specific antibodies, it goes much further.

It specifically claims that HuMabs has invented the DNA and amino acids of ANY human monoclonal antibody against ANY H5N1 strain including all monoclonal antibodies that target the HA gene. The patent application claims many variants of these antibodies, including any that has the same "complementarity determining regions" ("CDRs"). CDRs are short amino acids that help target the virus and fight infection.

With respect to Clade 2 H5N1 viruses, the patent application claims any antibody that can neutralize them -- animal or human, mono or polyclonal.

The patent application raises ethical questions for several reasons. It claims the DNA of H5N1 victims as property, potentially enabling profit from the sale of parts and products of the human body.

This concern is amplified by particulars of this case, specifically, the disparities between the reportedly poor Vietnamese H5N1 victims, and the privileged European scientist and wealthy US venture capitalist who are making the property claims. Details of the consent forms signed by the Vietnamese victims and what, if any, additional agreements exist have not been made public.

In addition, antibody treatments are generally expensive and difficult to reliably produce, formulate, and distribute, raising questions about who will have access to the treatment (if it works), particularly in the event of a pandemic.

Many developing countries, and particularly poor citizens thereof, already are unable to access H5N1 treatments due to high costs. Even if HuMabs attempts to make its high-tech treatment available, it may not be possible to produce this in the quantity and at the price necessary for it to be useful to most of the world's population.

Finally, there is the startling breadth of the patent claims -- to any H5N1 human monoclonal antibody. It amounts to a general patent claim on part of the human body -- any person's body.

Any person infected with H5N1 or who receives H5N1 vaccines will produce H5N1 antibodies. Thus, HuMab's patent claims DNA and natural products of all humans who have the misfortune of being exposed to H5N1 or the benefit of being vaccinated.

This patent application is the latest in a string of aggressive H5N1 claims by companies and government laboratories in the United States and Europe. These applications heighten concerns raised by developing countries that the present international system for sharing of influenza viruses (the Global Influenza Surveillance Network, under the World Health Organisation) is unfair, and that the benefits of influenza research should be shared fairly and equitably.

A WHO Intergovernmental Meeting on Pandemic Influenza Preparedness (PIP IGM) will reconvene in Geneva in November to continue negotiations on the reform of the WHO's Global Influenza Surveillance Network (GISN) which has been criticized for allowing the viruses and other samples it collects for public health to be used for purposes of private profit.

Unaffordable is What Happens When Flu Treatments are Patented

Mon, 29 Sep 2008 09:43:23 -0500

This isn't the really interesting news I promised the other day (that's still being vetted elsewhere); but it's pretty darn telling.

(Above: What it would cost different regions to stockpile Tamiflu under Roche's plan.)

Roche and Glaxo, with their flu antivirals Tamiflu and Relenza (respectively), are offering us a little preview of what's going to happen with pandemic vaccines (and other biologicals) if the patent trend continues unabated. What happens, in a phrase, is that the rich get treated and the poor get dead.

Today's news brings an item about Roche and Glaxo's hawking of their drugs to corporations for private stockpiles. Think of it as a sort of pandemic "health insurance", mega-corporation style. According to this report, the pharma giants are hoping to convince corporations to buy a pandemic drug stockpile for their employees for $6 per person (course) per year (Tamiflu) or $37 per course (Relenza).(I'm going to put the vulgarity of determining who gets antivirals on the basis of their employer - as opposed to need - aside for this post and focus on the economics.)

AP quotes pathetic, should-be-indicted-by-history-for-their-abject-failure-and-subservience-to-business, US authorities as encouraging this, saying "Private stockpiles (would) improve the ability to achieve the national pandemic response goals of mitigating disease, suffering and death, and minimizing impacts on the economy and functioning of society." Whatever happened to public health in the US?

Let's take Roche's Tamiflu stockpile program as the example (because its terms are more clearly stated than Glaxo's).

Six bucks a year, for the wealthy, doesn't sound like too much. But when you start looking around the world, it is apparent that this expense would take an enormous bite out of public drug budgets in developing countries. In the case of Sub-Saharan Africa, already being crushed by AIDS, buying a Tamiflu stockpile at the corporate "discount" rate would consume nearly all of the public drug budget, leaving little for everything else - like AIDS drugs, simple antibiotics and painkillers and other essential medicines.

Even in comparatively wealthy Mexico and Chile, it is unlikely that the state could afford Roche's patent monopoly-backed fees. According to June 2008 OECD figures, Mexican annual per capita public expenditure on pharmaceuticals is US $28. Thus, $6 per capita per year funded by the state would represent an outlay of 21.4% of the entire annual national public expenditure on pharmaceuticals - only for Tamiflu. And Tamiflu is, frankly, not even a very good insurance policy against H5N1. In Chile, total annual per capita spending on pharmaceuticals is reportedly US $81.4. Buying into Roche's scheme would represent an annual cost of 7.4% of ALL (public and private) money spent on pharmaceuticals in the country. In addition, set this against a current expenditure on flu antivirals that is likely close to nil.

But Mexico and Chile are "good" case scenarios. South Africa has "the largest and best developed pharmaceutical market in Africa", yet total annual per capita expenditure on pharmaceuticals (in 2005) was US $63.5. Thus $6 per person per year would represent nearly 10% of all spending on all drugs in the country, pubic and private, and quite likely a very large percentage of the key public budget. (Try convincing a landless farmer or a squatter on the urban periphery to set aside $6 per family member per year for a private pandemic preparedness plan. Hint: It ain't gonna happen.)

But the starkest evidence of how unaffordable the big pharma intellectual property-intensive flu drug model is for developing countries comes when one compares WHO's data on 2007 median per capita annual public drug expenditures (see here, PDF download) against Roche's Tamiflu stockpile fees. I've added the Roche stockpile calculation. Read it and weep:

This is just a preview of what is going to happen with (pre)pandemic vaccines as the patent claws dig deeper into H5N1 vaccines and, indeed, the virus itself. This is a big reason why the debate over virus sharing and reform of the Globlal Influenza Surrveillance Network is so important. Restoring the integrity of the GISN offers at least some hope of making vaccines and other treatments available to far more of the world's population than the Roche-Glaxo model can possibly serve.

Stay Tuned for Interesting News

Thu, 25 Sep 2008 08:14:11 -0500

As others in flubloggia have noted, I am not the most frequent blogger. But when I do write, I aim for quality.

At the moment, there are two very interesting developments in the world of H5N1 patents that I'm slaving away at analyzing and writing up for your perusal.

Check back soon for a full writeup.

And by the way, this blog has a listserv. If you'd like to join the flu listserver, please visit:

http://lists.sunshine-project.org/lists/info/flu

Thanks and see you soon.

H5N1 Related Patent Activity: An Updated Overview

Tue, 23 Sep 2008 10:39:26 -0500

Although some, like US and European governments, would like to pretend it isn't happening, it's no secret that there has been a huge increase in international patent applications claiming bits and pieces of H5N1 viruses and related vaccines and other treatments.

The overall trends can be monitored by searching on PatentScope, a free international patent application database published by the World Intellectual Property Organization (WIPO). If you are new to patents, it might be intimidating at first - patent talk is not plain English - but with a bit of experimentation, searching PatentScope is something anyone can learn to do.

There are three such searches that I have been monitoring for nearly two years now. The results aren't pretty, and they are getting worse. The tidal wave of H5N1 patent claims shows no signs of abating, and is on track in 2008 to meet or exceed 2007, which was already the biggest year of such patent claims on record.

The trend is clear: An emerging "patent thicket" threatens to impair H5N1 research and make vaccines and other treatments unaffordable. But don't count on the US or European governments doing anything about this - they're still in denial mode.

The first search is a simple query of the International Patent Classification for influenza vaccines (PCT Class A61K 39/145). This search includes seasonal and animal vaccines. Here's the result (click on the image to enlarge):

In 2007, there were 54 patent publications on influenza vaccines. (Patent applications are published months or even years after they are actually filed) In 2008, to date, 33 new patent applications have appeared. Over 36% of all applications since 1983 for influenza vaccines (118 of 326) have been published since 1 January 2006. If this isn't a hug increase in patent claims, what is?

The second search is a bit more specific. It is a search of the same patent class, except restricting the results to those applications that contain the term "H5N1" in the patent claims (a specific and most important part of the application). Understand that you can still patent an H5N1 vaccine without specifically mentioning H5N1 in the claims (e.g. a vaccine against all influenza A types); but the appearance of H5N1 in the claims gives some potential indication of the intent of the applicant:

Here an interesting thing to immediately note is that although H5N1 first appeared in 1997, there was only one patent application matching the search until 2006. There is recent dramatic growth in H5N1-related claims. In 2006 there were five claims, followed by eleven in 2007, and seven in 2008 to date. US and EU companies account for nearly all applications (see below).

The third search broadens the horizon beyond vaccines. It includes vaccines, medicines, diagnostics, genes, and pieces thereof wherein the term H5N1 appears in the claims. (Geeks: PCT Classifications A61K/P, C07H/K, C12N/Q, G01N.) Here again, there is a tremendous spike in patent claims:

The amazing thing here is that between 1983 and September 2008, 102 total matching patent applications were published, and of these applications, 83 were published after 1 Jan 2007. That is, more than 80% of the matching patent applications over the last nearly 25 years have appeared in the last 18 months.

And where do these patent applications come from? Hint: It's not the Indonesians that are making proprietary claims over H5N1 viruses, it's the Americans and Europeans. A whopping 53% of these patent applications originate the US, and most of the rest come from Europe. What little is left over primarily comes from Australia, Japan, and Singapore.

The results here speak for themselves. Developing countries like Indonesia are not the people trying to privatize H5N1. In fact, the real culprits of ownership claims over Bird Flu are the companies and government labs of Europe and North America.