CIDRAP: H1N1, seasonal flu vaccines to be tested together

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Source: http://www.cidrap.umn.edu/cidrap/content/influenza/swineflu/news/jul2209trials.html


H1N1, seasonal flu vaccines to be tested together

Robert Roos * News Editor

Jul 22, 2009 (CIDRAP News) ? Federal health officials today announced plans to launch several clinical trials of pandemic H1N1 vaccines in a race to gather safety and immunogenicity data in time for a possible fall resurgence of the novel virus. In some of the trials, volunteers will receive H1N1 and seasonal flu shots at the same time.

In a news release, the National Institute of Allergy and Infectious Diseases (NIAID) said the trials will be conducted at its eight Vaccine and Treatment Evaluation Units at academic medical centers around the country. The vaccines for the trials are being made by CSL Biotherapies and Sanofi Pasteur.

Federal health officials hope to make the first H1N1 vaccine doses available as early as possible in the fall, possibly October, leaving little time to test them. They are also concerned about the prospect of trying to vaccinate millions of people against H1N1 and seasonal flu at the same time or in a short time frame, though the seasonal vaccine is expected to be available sooner.

"The trials are being conducted in a compressed time frame in a race against the possible autumn resurgence of 2009 H1N1 flu infections that may occur at the same time as seasonal influenza virus strains begin to circulate widely in the Northern Hemisphere," the NIAID said.

It said results from the trials are expected to be available "weeks after the trials begin."

The agency said one set of trials will assess the immune response to one or two 15-microgram (mcg) doses and one or two 30-mcg doses in healthy adults (aged 18 to 64) and elderly people (65 and older). The doses will be given 21 days apart. If early results indicate the vaccines are safe, similar trials in healthy children will be launched.

Another set of trials will look at the safety and immune response in healthy adults and elderly people given the seasonal flu vaccine along with a 15-mcg dose of H1N1 vaccine. The latter vaccine will be given to different sets of volunteers before, after, or at the same time as the seasonal vaccine.

A panel of outside experts will closely review the safety data from the trials "to spot any safety concerns in real time," the NIAID said. The trial results will be used to develop recommendations for different age and risk groups

The NIAID said it collaborated closely with the FDA and the Biomedical Advanced Research and Development Agency to launch the trials quickly while maintaining high standards.

The institutions conducting the trials are

* Baylor College of Medicine, Houston
* Children?s Hospital Medical Center, Cincinnati
* Emory University, Atlanta
* Group Health Cooperative, Seattle
* Saint Louis University, St. Louis
* University of Iowa, Iowa City
* University of Maryland School of Medicine, Baltimore
* Vanderbilt University, Nashville

The NIAID announcement came as the Food and Drug Administration's vaccine advisory committee prepared to meet tomorrow to discuss H1N1 vaccine issues. A briefing document the FDA prepared for the meeting says that decisions about vaccine formulation and use may have to be based on limited or even no clinical trial data.

Because surveillance data may indicate a need to start an H1N1 vaccination campaign before much testing is done, the document states, "We recognize that the regulatory approach needs to be flexible and that policy decisions regarding vaccine formulation and use may have to be based on results from incomplete or smaller clinical studies or even in the absence of clinical data with novel influenza A (H1N1) vaccine."

The document was prepared for the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC).

See also:

Jul 22 NIAID news release
http://www3.niaid.nih.gov/news/newsreleases/2009/VTEU_H1N1.htm

FDA briefing document for VRBPAC meeting

 

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Re: H1N1, seasonal flu vaccines to be tested together

Re: H1N1, seasonal flu vaccines to be tested together

Source: http://www.cidrap.umn.edu/cidrap/content/influenza/swineflu/news/jul2109fda_mws.html


FDA approves seasonal flu vaccines

Robert Roos * News Editor

Jul 21, 2009 (CIDRAP News) ? The Food and Drug Administration (FDA) yesterday announced its approval of seasonal influenza vaccines for this year, the annual step that clears the way for manufacturers to start marketing their vaccines.

Six manufacturers are making seasonal flu vaccines for the US market this year?five inactivated injectable vaccines and one live attenuated vaccine given as a nasal spray. The FDA recently sent all six companies letters approving their supplemental license applications for this year's version of the vaccine.

The seasonal vaccine targets three influenza subtypes; the specific strains are often changed from year to year as health authorities strive to keep up with the strains in circulation. This year's vaccine contains a different influenza B component than the 2008-09 vaccine. The type A/H1N1 and A/H3N2 components are the same as in last year's version.

The manufacturers must obtain a release from the FDA for each lot of vaccine before they can ship it to distributors. FDA spokeswoman Peper Long said the agency has not yet announced any lot releases.

Donna Cary, a spokeswoman for Sanofi Pasteur, which has been the largest supplier to the US market in recent years, said, "We anticipate we'll begin shipping [vaccine] in August, but it all depends on the timing of lot release from the FDA."

In announcing approval of the seasonal vaccines, the FDA was careful to note that they will not protect against the novel H1N1 virus now circling the globe. The government hopes to have the first doses of vaccine for that virus this fall, possibly in October.

Although the seasonal vaccine will not shield people from the pandemic virus, "it is still important for those Americans for whom it is recommended to receive the seasonal influenza vaccine," the FDA announcement said.

In a question-and-answer bulletin posted yesterday, the Centers for Disease Control and Prevention (CDC) indicated that clinical trials will be conducted to determine if seasonal and novel H1N1 vaccines will be safe and effective if given at the same time, though the seasonal vaccine will be available earlier.

The manufacturers supplying inactivated vaccines this year, and their vaccines, are CSL Limited, Afluria; GlaxoSmithKline (GSK) Biologicals, Fluarix; ID Biomedical Corp. (a dvision of GSK), FluLaval; Novartis Vaccines, Fluvirin; and Sanofi Pasteur, Fluzone. The live vaccine, FluMist, is made by MedImmune Vaccines.

Cary said the B strain this year posed some production problems, but Sanofi was able to meet its production target.

"The new B strain this year is a lower yielding strain," she said. "For Sanofi Pasteur we had taken that into account, and we're bringing to market what we promised we'd bring to market"?50 million doses.

In evaluating seasonal vaccines that involve only a strain change, the FDA inspects vaccine lots and production facilities but does not require new clinical data, said Long. "We test lots and production facilities all along the way, it's one of the most important things we do. But it doesn't require new clinical data every year," which wouldn't be possible to provide in the time available, she said.

See also:

Jul 20 FDA announcement
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm172772.htm

CDC question-and-answer bulletin
http://www.cdc.gov/h1n1flu/vaccination/public/vaccination_qa_pub.htm

Feb 18 CIDRAP News story "FDA panel endorses new B strain for 2009-10 flu vaccine"
http://www.cidrap.umn.edu/cidrap/content/influenza/general/news/feb1809selection.html

 

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Re: H1N1, seasonal flu vaccines to be tested together

Re: H1N1, seasonal flu vaccines to be tested together

Source: http://www.cidrap.umn.edu/cidrap/content/influenza/swineflu/news/jul1709board.html


HHS advisors urge full speed on H1N1 vaccine production

Robert Roos * News Editor

Jul 17, 2009 (CIDRAP News) ? An expert panel that advises the Department of Health and Human Services (HHS) today supported the idea of moving quickly on pandemic H1N1 vaccine production with a goal of having "tens of millions of doses" available in September instead of October.

Discussing vaccine issues during a public teleconference today, the National Biodefense Science Board (NBSB) favored the idea of asking vaccine makers to start the final production steps for their H1N1 vaccines on Aug 15?before the first data from safety and immunogenicity trials will be available.

Last week, HHS Secretary Kathleen Sebelius said it was expected that the first H1N1 doses would be ready for distribution in mid-October. HHS has yet not made a formal decision to go ahead with a vaccination campaign, but Sebelius said the step was likely.

Dr. Robin Robinson, director of HHS's Biomedical Advanced Research and Development Authority (BARDA), told the NBSB that HHS should have some data on the immunogenicity of single-dose H1N1 vaccination in September. If filling and finishing?the final production steps?start on Sep 15, the first doses will become available about Oct 15, he said.

To make vaccine available in mid-September, filling and finishing would have to start Aug 15, Robinson said. "Certainly the department, including FDA, is seriously considering how this can be done," he said.

Board member Patrick J. Scannon, MD, PhD, said, "There was a considerable sense of urgency that came out of the June meeting because of the possibility that a new wave of H1N1 could come back to us by September. I think that's what's driving this line of questions." He was referring to a June meeting of the board's Pandemic Influenza Working Group, whose report from that meeting was discussed at today's conference.

Robinson said that about 60 million to 80 million doses could be made available starting in September if the decision were made to go ahead with final production steps Aug 15. He said Aug 15 is a "reasonable date" when vaccine makers could start those steps, as they are currently still producing their seasonal flu vaccines.

At this point no one knows if 15 micrograms (mcg) of vaccine antigen, the standard amount used for each flu subtype in seasonal vaccines, will be enough to generate a protective immune response with H1N1 vaccines.

"The FDA is considering if the vaccine could be at the standard dose based on the many years" of using 15 mcg, said Robinson.

Board member Andrew T. Pavia, MD, suggested that the vaccine could be bottled at a concentration of 15 mcg of antigen per 0.5 milliliter (mL) of solution. If trial data later showed a need for a greater dose, it could be doubled by administering 1 mL instead of 0.5 mL, he said.

Pavia said his sense was that the risk in moving ahead "is relatively small compared with the upside of committing at least a portion of the 60 million doses to fill and finish."

Board member John Grabenstein, RPh, PhD, counseled against picking a specific number of doses to produce by September, since the number of people targeted for early vaccination is not yet known. "Our role is to decide whether we want some product by mid-September," he said.

After further discussion, the group agreed to recommend that HHS "set a goal of having several tens of millions of doses available by Sep 15." The vaccine would not contain an adjuvant.

In briefing the board early in today's session, Robinson said HHS has contracted for 193 million doses of vaccine so far, assuming 15 mcg per dose. After 2.5 weeks of production, manufacturers have made 18 million doses worth of bulk vaccine, he said.

HHS has ordered 119 million doses of two different adjuvants, MF59 and ASO3, he reported.

Commenting on reports of low yields of vaccines, which are grown in eggs, Robinson said yields are actually right in line with what HHS had expected from experience with H5N1 vaccines: about 1.4 doses per egg. However, he said the H1N1 vaccine virus apparently contains less hemagglutinin (the antigen) than seasonal strains and is a little harder to purify.

The story is the opposite with the live attenuated H1N1 vaccine being made by MedImmune, Robinson reported. Instead of low yields, the company is getting surprisingly high yields.

"They've already actually made a super virus seed that's actually producing 2 logs titer higher than you'd normally see," he said. "That means there's going to be more bulk product available than we can actually fill."

He said HHS will look for other vendors to help package the extra product, adding, "We may be able to have more live attenuated vaccine than anticipated earlier, so that's good news."

In other comments, Robinson said:

* HHS wants to increase the proportion of zanamivir (Relenza) in the national stockpile relative to oseltamivir (Tamiflu), in light of a few recent instances of H1N1 resistance to the latter. The current split is 80% oseltamivir and 20% zanamivir; the agency would like to move to 50-50, but that will take time.
* HHS is considering issuing an emergency use authorization for peramivir, an antiviral drug that is in phase 3 clinical trials but not yet licensed. "It's under consideration whether we should have some of that drug available for individuals in desperate need," he said.

See also:

NSBS teleconference information
http://www.hhs.gov/aspr/conferences/nbsb/090717-nbsb-meeting.html

Full report of June meeting of NBSB pandemic working group
http://www.hhs.gov/aspr/conferences/nbsb/nbsb-h1n1forum-sum-090617.pdf

Executive summary of June meeting report
http://www.hhs.gov/aspr/conferences/nbsb/panflu-wg-execrpt-090717.pdf

NBSB home page
http://www.hhs.gov/aspr/omsph/nbsb/

NBSB members
http://www.dhhs.gov/aspr/omsph/nbsb/members.html