David's New Book

Thursday, August 18, 2011

FDA Guidance for Antibiotic Development - A Cautionary Note


As I understand it, the FDA will soon be releasing a series of new Draft Guidance documents for the development of antibiotics.  The subjects that have been under consideration include quite a number as noted below.

Community-acquired bacterial pneumonia – hopefully a modification of the previous draft that will now provide for feasible designs.

Hospital-acquired and ventilator associated bacterial pneumonia – again hopefully a modification of the previous draft that will now provide for feasible designs.

Complicated urinary tract infection (cUTI).

Complicated intraabdominal infection (cIAI).

The utilization of superiority trial designs for antibiotics.

Rumor has it that the FDA will be releasing a number of these new guidance documents over the next six months or so starting in September.  I am writing this blog as a cautionary note.

Since the list of commercially interesting indications for antibiotics in the US has now shrunk to skin infections, intraabdominal infections, urinary tract infections and perhaps infection in neutropenic patients, the above list includes some blockbuster topics. The potential indications for much needed drugs to fight Gram negative bacterial infections are all in the above list.  Hospital-acquired and ventilator associated pneumonia frequently involve Gram negative pathogens, but the development of antibiotics for this indication is no longer feasible in the US (thanks to the FDA). cUTI and cIAI trial designs based on guidance dating back to the 1990s remain feasible for now.  A number of companies, including Cubist, Forest, Astrazeneca and others are targeting these indications for their new Gram negative antibiotics.   If the Draft Guidance documents for cUTI and cIAI require infeasible designs – that will quite simply be the end of antibiotics for Gram negative infections in the US. No more no less. So, before releasing any new Draft Guidance in these indications the FDA needs to get the proposed designs vetted for feasibility by people who actually know what they are doing in this regard.  Given performance on recent guidance documents, we can assume that this does not include the FDA folks.

Who can advise the FDA on feasibility? FNIH? FNIH includes all stakeholders and as such will provide comments written by committee – always challenging and may not be the best representation of  key issues.  Industry?  Clearly those in industry can tell the FDA about feasibility, but they are “biased.” Consultants? We never agree.  In this area, to a certain extent, I sympathize with FDA.  What is required is an FDA insider who can actually make these judgements and parse the advice received by FDA.  Even a key consultant would help – but the FDA seems not to have such a consultant specifically tasked to evaluate trial design feasibility. This key individual or group seems to be entirely missing from the anti-infectives group at FDA. I wonder if that situation can be repaired  . . . .