FDA Inspection Program Under Scrutiny - Pharmaceutical Technology

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FDA Inspection Program Under Scrutiny
Heparin contamination casts a shadow on regulatory oversight of product quality.


Pharmaceutical Technology


Baxter also routinely conducts tests on all incoming APIs. When the company started receiving an unusual volume of adverse-event reports, it began the hunt withFDA for the source of product contamination. Baxter's usual battery of API tests provided no clues. But more sophisticated nuclear magnetic resonance spectroscopy and capillary electrophoresis revealed the presence of a heparin-like substance in API from both Wisconsin and China. FDA hesitated to directly link this contaminant to patient allergic reactions, but offered no other explanations.

FDA officials say that Chinese regulators facilitated broader inspection of the supply chain, which goes beyond the cooperative efforts covered by a memorandum of agreement (MOA) negotiated in Dec. 2007 by US and Chinese officials. The MOA calls for information sharing and regulatory cooperation to facilitate oversight of food, drugs, and medical products. Meanwhile, Chinese SFDA officials insist that they are enforcing regulations on chemicals used in pharmaceutical products. The Chinese authorities also point out that importing countries and companies are ultimately responsible for ensuring product safety and quality.

FDA officials agree that government agencies are not solely responsible for ensuring the quality of APIs. Although FDA inspects many ingredient manufacturers, the agency still relies on pharmaceutical companies to test API quality. This approach is standard overseas, where many foreign regulators leave API oversight entirely to manufacturers.

At a Feb. 2008 conference on FDA enforcement sponsored by the Food and Drug Law Institute, David Elder, director of ORA's Office of Enforcement, emphasized that the finished-product manufacturer must take responsibility for problems with drug quality or safety. Too often, he said, manufacturers blame suppliers for product failures. But he specifically pointed to drug companies in asserting that FDA "will continue to hold them accountable" for such problems.

Additional oversight

Even though an earlier FDA inspection of Changzhou might not have prevented these problems, the inspection error raised questions about how well FDA can track drug manufacturers around the world and ensure that all drug ingredient suppliers fully meet GMPs. Rep. Frank Pallone (D-NJ), chairman of the House Energy and Commerce (EC) Health subcommittee, termed the inspection failure that resulted from confusion over the facility's name an "egregious mistake." It has nothing to do with lack of resources, he stated, but reflects "sloppy work" and "carelessness that seriously jeopardized the health of American patients." The EC panel held a hearing in Nov. 2007 to address FDA's capacity for overseeing the vast increase in drugs and APIs imported from abroad (see "Limited Resources, Expanding Imports Challenge Regulators," Pharmaceutical Technology, Feb. 2008). The heparin debacle provides more fuel for this ongoing investigation.

An important FDA initiative is 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, making it difficult to detect errors and avoid confusion. The FDA Amendments Act of 2007 provides additional funding to build an integrated drug registration and listing system, and FDA's Bioinformatics Board is working to establish uniform tracking of all regulated products and for adverse event reporting in all product areas. FDA hopes to move forward on this program this year, but first the agency must finalize a proposed regulation for modifying current national drug codes to create a common coding system.

The Bush administration recently signaled its support for legislation that would clarify FDA's authority to investigate foreign firms that violate the Food, Drug, and Cosmetic Act. This power is not explicit under current law, which can make it difficult for US regulators to access foreign manufacturing facilities. Although this legal change might help US officials oversee foreign operators, it would do little to address the international difficulties facing FDA and industry.


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