FDA's enforcement arm 'tied behind its back'
record by US Democratic lawmakers has highlighted a plunge in the
number of warning letters the agency has sent to drug manufacturers
since 2000, citing several examples where violations spotted in
site inspections were not followed through.
The investigation found that officials at the FDA headquarters routinely rejected the recommendations of field officers, resulting in fewer enforcement actions.
The number of warning letters issued by the agency for violations of federal requirements has fallen by over 50 per cent, from 1,154 in 2000 to 535 in 2005, a 15-year low according to the report.
Crucially, the decline in enforcement does not appear to be the result of increased compliance by manufacturers since the number of "483 forms," which record the number of violations observed by field inspectors, was higher most of the years between 2000 and 2005.
Nevertheless, the report does not look before 2000 to see if the recent drop in warning letters is part of a long-term trend, eager to point to the close relationship of the Bush Whitehouse to big pharma.
"I was primarily interested in seeing what has happened to FDA enforcement during the Bush administration," House Government Reform Committee ranking member Henry Waxman, the congressman behind the report, told In-PharmaTechnologist.com.
"The time period we studied includes the end of the Clinton administration to the present."
Waxman alleges that political appointees at FDA headquarters set both the tone and written policies of the agency.
He points to the record of Daniel Troy, who President Bush named Chief Counsel of FDA in 2001.
"Before his appointment, Mr Troy had been a lawyer for the tobacco and pharmaceutical industries, aggressively fighting FDA regulation," Waxman said.
"On his arrival, Mr Troy implemented a new policy that all warning letters and notices of violations issued by the agency had to go through him, resulting in serious delays and a dramatic decline in enforcement."
Based on internal FDA documents, the report found 99 cases where drug manufacturing standards where violated and insufficient or no enforcement action was taken.
It cites several examples, including GlaxoSmithKline's facility in Cidra, Puerto Rico, where the agency's field inspectors spotted several violations of current good manufacturing practice (cGMP) between 2002 and 2004, even recommending the site's closure. Yet it was not until 2005 that the FDA censured the drugmaker, but did not impose a fine, shut down the facility or order a recall of the products it was unable to seize, such as the diabetes treatment Avandamet and the antidepressant Paxil.
In another case, FDA field inspectors found significant violations at the Chiron vaccine production plant in Liverpool, England, in June 2003 and recommended the initiation of enforcement action, but their recommendation was rejected, catching the agency by surprise when British regulators closed the facility after discovering sterility problems in some batches of FluVirin vaccine.
There was even an incident where no active ingredient was found in an analgesic and itch cream made by a small unnamed company, but the FDA headquarters, eleven months after field inspectors brought the issue to their attention, decided not to issue a warning letter on the basis that the manufacturer "is a very small operation."
However the FDA has responded strongly to the report, stressing that criminal fines and restitutions resulting from the FDA's enforcement actions alone since 2000 have amounted to more than $2.5bn (€2bn), a figure that exceeds the agency's annual budget.
"FDA enforcement cannot be properly judged by counting the number of actions taken by the agency," David Elder, director of FDA's Office of Enforcement, said in a statement.
"The FDA has increasingly used an enforcement strategy based on efficient risk management principles that focuses on combating the greatest public health risks and maximising our deterrent effect against potential violators."
When a violation of FDA standards is documented during an inspection, the FDA can send out a warning letter, which notifies a firm of violations, requires a written response, and warns that failure to correct the violations can be expected to lead to additional enforcement action.
But the FDA has several options and one of them is to send an untitled letter, which is a significantly less serious step, simply informing a firm of observed violations and not requiring a written response or warning that enforcement action may ensue if violations are not corrected.
The report is expected to have little impact on FDA enforcement, political analysts say, as long as the Republicans control both chambers of the US legislature.
