10 August 2009

WHO addr= esses Pandemic Flu Vaccine Safety: Studies begin in China, Australia, the UK, Germany, and the USA

An 11-page transc= ript was posted on the World Health Organization (WHO) pandemic flu website after their August 6 press conference lead by Dr. Marie-Paule Kieny, Director of = the Initiative for Vaccine Research at WHO.&nb= sp; Vaccine safety issues were the primary focus, although three points = were covered:

(1) State of Vaccine Developm= ent;

(2) Vaccine safet= y;

(3) When pandemic H1N1 flu vaccines will likely become available.

The complete transcript can be accessed at: www.who.int/mediacentre/pandemic_h1n1_presstranscript_2009_08_06.= pdf

Excerpts from this 11-page transcript are emphasized below:

(1) In terms of pandemic H1N1 vaccine development, Dr. Kieny stated that “In t= erms of clinical trials, we now have seven manufacturers who have started clinic= al trials and these…are going on in at least five countries…China, Aus= tralia, the United Kingdom, Germany, and the U.S.A.”

(2) These initial clinical trials that = began in July should yield data “by the first half of September”. They will tell whether one dose or= two doses are needed in order to induce what is considered to be immunologic protection against the pandemic virus.

(3) In terms o= f vaccine safety, multiple statements were notable, e.g., “There is no vacc= ine that induces zero safety concerns…there will be people who will have = an adverse event. The large majority of these events will not be associated at= all with the vaccine which is given. It will be temporally associated which mea= ns this is something that would have happened anyway but which just by chance = is happening after a person has had a vaccination.”

(4) “For those vaccines where the technology remains exactly the same as for seasonal vaccines, what happens = or the way it is treated, is called a “strain change”...In the USA, for example, the FDA approves a strain change by looking at the quality con= trol dossier that the manufacturer submits and does not require a clinical trial. Therefore, for those pandemic vaccines that will be like a strain change, o= nly it will be H1N1 instead of another seasonal strain, the FDA has decided that they will treat this as a normal strain change and, therefore, the vaccine = will be registered without clinical trials.”

(5) “All manufacturers, of course, will conduct a clinical trial if only to confirm whether one or two doses are needed as I said a few minutes ago.”

(6) “In = Europe the procedure for registration of seasonal influenza vaccine is slightly different. In the sense that the regulatory authority requests every year a small clinical trial of the new seasonal vaccine…”

(7) “Now for pandemic use, there = are a number of vaccines which are not the classical seasonal vaccines. These are= the vaccines which have an addition of an adjuvant. These adjuvant vaccines have been tested extensively at the time when all manufacturers were preparing vaccines for a potential H5N1 pandemic. In view of the potential gravity of= an H5N1 vaccine, the European Regulatory Agency had designed a special process= by which manufacturers would test extensively in clinical trials, prototypes of H5N1 vaccines, including with adjuvants, which submit all the safety data of clinical trials. Immunogenicity to the regulatory agency and obtain what is called a “mock-up registration”. So this is a registration for a prototype.”

(8) “So those manufacturers who d= o have a mock-up dossier can go and present to the EMEA all their documentation fo= r the H1N1 vaccine and as previously agreed already in 2007 with the regulatory authority, obtain registration without clinical trials. But again as I said= for the USA<= /st1:country-region>, all manufacturers will conduct clinical trials and the earliest results of these clinical trials will be available in September.”

(9) Regarding when pandemic flu vacc= ine might first become available, Dr. Kieney stated: “Now the manufacturers have started to submit these dossiers to the regulators and to expect that the regulators will make decisions on these vaccines that will allow use in populations during September when the first authorization may = be in September, and then going into October, when the dossiers are ready and = are submitted by the manufacturers.”

(10) In respons= e to questions from the media at this press conference, Dr. Kieney addressed in = more detail adjuvanted influenza vaccines, based on “more than 40 million doses of adjuvanted flu vaccines have been used in Europe” (i.e., pri= or to the current pandemic H1N1 virus).

(11) In contras= t, in the USA, no adjuvanted influenza vaccines have ever been licensed.=

(12) Similarly,= Dr. Kieney later stated that “As you rightly point out there is no experi= ence with using adjuvanted vaccines on pregnant women…”

(13) Regarding concern about Guillan-Barre Syndrome (GBS) due to a “swine flu vaccine” as was reported with the 1976 USA vaccine, Dr. Kieney state= d: “In addition what we will really look with great scrutiny by all invo= lved in post-marketing surveillance will be what is called Guillanin Barre Syndr= ome, which is a very rare side effect which happens sometimes after vaccination.= It is not something which has been described for seasonal influenza vaccinatio= n. It has been described in one situation which was in the 1976 vaccination against Swine flu in the USA but even there it was a very rare event-30 people died out of 40 million pe= ople immunized. Because of this event, the causes of which are only starting to = be understood and not completely, all the post marketing surveillance will certainly be very wary of this possibility of this Guillan Barre Syndrome a= nd will follow this very closely and a procedure put in place in countries to = be sure that even in low income countries it will be possible to detect this s= ide effect very early.”

(14) Later in t= he conference in response to a question, Dr. Kieney noted that in 1976 flu vaccines “there were very many more impurities” compared with f= lu vaccines today.

In my opinion, this press conference is a good start to addressing the concerns many people in the general public and medical professions, in addition to t= he media, have regarding the safety of pandemic H1N1 influenza vaccines. For example, Dr. Kieney made an excellent point by emphasizing from the beginning that adverse events after vaccination will occur, but that they might be the result of a temporal association, and not actually caused by the pandemic H1N1influenza vaccine.

There are, howeve= r, multiple areas that would be helpful for WHO to address in further detail.<= span style=3D'mso-spacerun:yes'> For example, detailed safety data = should be tabulated and summarized by WHO on the specific adjuvanted influenza vac= cines that Dr. Kieney mentioned have been used in Europe. In addition, the adjuvants t= hat have been most often mentioned as candidate adjuvants for influenza vaccines (e.g., MF-59, and others) should be discussed in detail with regard to their safety profile, both for influenza and non-influenza vaccines. <= /span>

If there are spec= ific past concerns regarding these adjuvants (e.g., MF-59 and others), includ= ing with non-influenza vaccines, whether in Europe, the USA, or anywhere el= se in the world then it is best if WHO address these concerns soon, before pandemic H1N1 vaccines using adjuvants become available, whether in the less-developed or developed world, in the southern or northern hemisphere.<= o:p>

In addition, more specific information regarding the surveillance that will be put into place, apparently worldwide, for Guillain Barre Syndrome, should be provided as so= on as possible. Doing so will hopefully increase trust, and allay fear, on the part of everyone including the general population that may receive the vacc= ine, the media, and global health care communities.

Daniel R. Lucey, MD, MPH

EROne Institutes, Department of Emergency Medicine<= /o:p>

Washingt= on Hospital Center

Adjunct Professor of Microbiology and Immunology

Georgeto= wn University Medical Center, Washington, DC

Website for this posting: www.BePast.org (requires IE)

DRL23@Georgetown.edu