David's New Book

Tuesday, March 6, 2012

Antibiotics, FDA and PDUFA

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The Prescription Drug User Fee Act (fondly known as PDUFA) is apparently up for renewal by our do-nothing congress.  This act, created in 1992, was designed to provide FDA funding from sponsors to accelerate the review process for drug approval applications by allowing the FDA to hire additional personnel and to acquire other necessary resources. The Infectious Diseases Society of America has led a charge that now includes 50 other societies to support the passage of PDUFA while insuring that incentives are provided for anti-infective therapeutic and diagnostic R&D.  But their letter is so tepid and vague as to be unclear as to their goals for congress other than including consideration of antibiotic and diagnostic R&D in reauthorization of PDUFA.  Our top 10 goals should be regulatory reform at the FDA such that the FDA is prohibited from requiring clinically or logistically infeasible designs in draft guidance documents.  The guidances for virtually every indication that have emerged since 2003 fit this description and include the following indications – acute otitis media, acute bacterial sinusitis, acute bacterial exacerbations of COPD, community acquired bacteria pneumonia (CABP), hospital acquired and ventilator associated pneumonia, and, most recently, complicated urinary tract infection.  The guidance for acute bacterial skin and skin structure infection trials requires designs that are feasible but with endpoints that are clinically irrelevant.  The CABP guidance is both infeasible and irrelevant. In the case of the so called mild, self limited infections like AOM, ABS and ABECOPD – no one has even discussed these with FDA as far as I know and there are certainly no new antibiotics being studied in these indications. The CABP guidance is now in its fifth year of discussion and we still don’t have a feasible way forward. Hospital acquired pneumonia is our area of greatest medical need and that guidance is completely infeasible.

The FDA has taken to issuing draft guidance documents and then waiting for the world to explode with critical commentary before getting around to the real business of feasibility.  This re-evaluation then takes years to complete.   This has got to stop. 

I am now thoroughly convinced that the FDA’s perseveration around non-inferiority trial design has nothing at all to do with science – either regulatory (whatever that is) or otherwise.  It is entirely based on politics.  They fear another Ketek scandal and investigations by folks like Grassley and Markey. Tom Fleming is probably still on the advisory committee because of his links to these congressmen.

So – I would ask the IDSA to send a different letter.  It should ask congress to withhold PDUFA authorization until the anti-infectives group at the FDA is reformed such that they would be required to have draft guidance documents reviewed for feasibility before release by people who know what they are doing in this regard.  This requirement would clearly let most of the folks on the FDA staff and even the AIDAC out of the picture.  An independent group would be necessary for such vetting.

Such regulatory reform is THE ONLY way forward.  No incentives in the world will help our pipeline if there is no regulatory way to approval for new antibiotics.

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