Comments on new FDA rules for expedited development of pandemic influenza vaccines

I'm a bit behind on the blog, having spent most of the last four weeks on the road, battling a norovirus (Yuck.  Don't get this bug  Hey Ralph, where the hell is my vaccine?), doing my taxes, and buckling down in the lab trying to get devices fabricated.  Cool progress on the later, which, alas, has to be disclosed to the University, written up for publication, and a patent application filed before I can discuss it here.  Harrumph.

A great deal has transpired on the influenza front, including news that the current H5N1 vaccine is as useless (NY Times) as predicted, which means that the need for alternative vaccine technologies is now even greater (more on this in a forthcoming post).  But I will start with the FDA's new draft guidelines on accelerated licensing of influenza vaccines, which I briefly addressed at the beginning of March.  The suggested guidelines were officially announced a few days later.  What follows is my take after a quick once over.

Here is how the document (PDF warning) starts off:

This document is intended to provide to you, sponsors of pandemic influenza vaccines, guidance on clinical development approaches to facilitate and expedite the licensure of influenza vaccines for the prevention of disease caused by pandemic influenza viruses.  The approaches apply to "split virus" and whole virus inactivated pandemic vaccines propagated in embryonated chicken eggs, and are also applicable to cell-culture derived, recombinant hemagglutinin-based protein, and adjuvanted pandemic influenza vaccines.  We, FDA, also address live attenuated influenza vaccines. This document does not address influenza vaccines that do not contain a hemagglutinin component.  Current U.S. licensed influenza vaccines are trivalent vaccines approved for the prevention of seasonal influenza illness.  Two classes of vaccines are licensed, "split virus" trivalent inactivated vaccines and a live attenuated trivalent vaccine. (pg. 1)

Beginning on page 2, by the way, is a short and very nice introduction to the biology and history of pandemic influenza viruses.

Here are some interesting quotes from the press release:

The FDA provides manufacturers with clear guidance on developing and submitting clinical data to show safety and effectiveness for new vaccines.  Consistent with the aims of FDA's Critical Path Initiative to get products to market more quickly and to advance the development and use of new technologies, these documents outline specific approaches that vaccine developers may follow.

...In issuing this advice, FDA aims to facilitate manufacturers in increasing the number of doses to ensure that enough influenza vaccine is available to vaccinate each person in the at-risk population. Having additional diversity in our vaccine supply helps enhance the capacity to produce more doses of influenza vaccine and contributes to the nation's pandemic preparedness.

...The release of these guidances is part of the comprehensive effort that FDA is undertaking to work with manufacturers to facilitate the development of vaccines.  Other examples include a recent CBER advisory committee meeting to discuss novel approaches to develop influenza vaccine such as using cell technology rather than eggs, frequent interactions with vaccine manufacturers to provide both scientific and regulatory guidance, as well as CBER's preparation of material for testing the potency of new vaccines, which are made available to manufacturers.

All in all, an exceptionally conservative document, given the magnitude of the problem we are facing.  The recommendations should do very nicely in all circumstances save the emergence of an actual pandemic.

The main problem I have with this announcement is that it appears to be geared towards easing the way for approval and use of particular technologies -- namely vaccine production by cell-culture, split virus vaccines, and specific recombinant protein vaccines -- rather than defining engineering and immunological goals that any given technology should meet to be approved.  For example, PowderMed's DNA vaccine does not appear to fit into the new guidelines, despite arguments the company is likely to make that injecting a plasmid coding for the hemagglutinin is equivalent to injecting the protein itself.  I hope I am wrong about this, because DNA vaccines look to be the only technology that can be used to respond on short time scales to rapidly spreading diseases.

No doubt I will return to this issue as the rules are discussed and developed.