FDA's Inspection Program Under Scrutiny - The heparin safety crisis puts a spotlight on manufacturing processes and regulatory oversight - BioPharm International


FDA's Inspection Program Under Scrutiny
The heparin safety crisis puts a spotlight on manufacturing processes and regulatory oversight

BioPharm International
Volume 21, Issue 4


FDA's inspection failure has raised questions about how well FDA can track drug manufacturers around the world and ensure that all ingredients fully meet GMPs. Rep. Frank Pallone (D-NJ), chairman of the House energy and commerce health subcommittee (E&C), said that the heparin case reflects "carelessness that seriously jeopardized the health of American patients." The House Energy and Commerce committee held a hearing last November to address FDA's capacity for overseeing the vast increase in drugs and APIs imported from abroad, and the heparin debacle provides added fuel for its investigation.

The SPL inspection also has generated questions about the adequacy of FDA's preapproval inspection (PAI) program for drugs and biologics. In a letter to FDA Commissioner Andrew von Eschenbach in February, Reps John Dingell (D-MI) and Bart Stupak (D-MI) of the E&C oversight and investigations subcommittee suggested that FDA might be "abandoning its preapproval inspection requirement" for medical products. The legislators said they assumed that FDA has to "approve each step of drug manufacturing, including all ingredient sources" to approve a drug for market. If that is not the case, Stupak added, Congress may be looking for legislative changes that would "prohibit the marketing of any drug from a plant that has not been properly inspected."

FDA officials explain that the agency has to ensure that all marketed drugs comply with GMPs and meet quality standards, but an on-site field inspection is only one way to verify regulatory compliance. If a manufacturer has a good GMP compliance history, and the product under review is relatively low risk, FDA may forego a PAI for a new or altered product from a plant that has been inspected within two years.

A statutory requirement that FDA conduct a PAI for every new drug coming to market would undermine the agency's efforts over the last decade to eliminate redundant inspections and better target its depleted field force to the most critical products and facilities. Throughout the 1990s, FDA conducted more than a thousand PAIs annually, but this volume became unsustainable as agency resources for field inspections became increasingly tight. The downward trend accelerated in recent years as FDA moved to modernize and streamline its oversight of drug manufacturing under its GMPs for the 21st-century initiative. FDA staffers now specify only a limited number of new drugs that would regularly warrant a PAI and leave it to field inspectors to use their discretion in expanding the list.

FDA is developing an important initiative to establish an electronic system for registering all drug manufacturing and labeling facilities and for listing all regulated products. The agency's current tracking system is not integrated with other FDA databases, generating confusion and errors. FDA's Bioinformatics Board is working to establish one system for tracking all regulated products and for adverse event reporting in all product areas. FDA hopes to move forward on this program this year, but the agency first has to finalize a proposed regulation for modifying current national drug codes in order to create a common coding system.

A larger issue is to what extent regulatory authorities are responsible for ensuring the quality of APIs. Although FDA inspects many API producers, the agency still relies on pharmaceutical and biotech companies to test the ingredient quality. This approach is standard overseas, where many foreign regulators leave this task entirely to manufacturers.

The finished product manufacturer has to take responsibility for problems with drug quality or safety, according to David Elder, director of ORA's Office of Enforcement. Too often, he said at a recent compliance conference, manufacturers want to blame suppliers for product failures. However, he specifically pointed to pharmaceutical companies in asserting that FDA "will continue to hold them accountable" for such problems.

Jill Wechsler is BioPharm International's Washington editor, Chevy Chase,MD,301.656.4634,

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