In the 20 month period before the heparin crisis no Chinese producers were inspected by the FDA and efforts during and since have been hindered by legal and practical challenges.
During the 20-month period before the crisis no Chinese heparin companies were inspected by the US Food and Drug Administration (FDA). In contrast, the FDA conducted 14 inspections of 11 Chinese heparin firms, two of which had been previously visited, during and after the crisis.
Before detection of the contaminant the FDA focused inspections on active pharmaceutical ingredient (API) production facilities, not crude heparin manufacturers. However, both crude and API Chinese heparin firms had never been inspected and the distinction is sometimes unclear.
These findings were published in a report into the FDA’s handling of the heparin crisis by the US Government Accountability Office (GAO). Having spoken to FDA officials and reviewed documents and data the GAO concludes the agency’s response helped protect public health.
Legal and practical challenges
The response was hindered by legal and practical issues the FDA encountered, and continues to face, when trying to inspect overseas facilities. For instance, in two cases Chinese crude heparin consolidators refused to give the FDA full access during limited inspections.
In one of these instances the company refused to let FDA inspectors walk through its laboratory or access its records. Both inspections were classified as ‘no action needed’ and the FDA did not attempt to re-inspect, choosing to focus on API producers supplied by the crude heparin firms.
A December 2007 memorandum of understanding (MOU) between the FDA and Chinese State Food and Drug Administration (SFDA) gives the US agency some leverage. However, the MOU excludes crude material in its definition of a drug, limiting the action the FDA could take.
Resistance from the Chinese government, which denied the contamination originated in China, was also encountered. Although there was collaboration during the crisis a request by the FDA for jurisdiction to conduct a criminal investigation into the source of the contaminant was refused.
Risk of undermining public confidence
Much of the criticism of the FDA in the report focuses on the use of external scientists. To make up for a lack of in-house instrumentation and expertise the FDA worked with external scientists, most of who were paid for their work.
However, a team at Momenta Pharmaceuticals performed work on a voluntary basis. Momenta “dedicated approximately 30 staff members from its analytical and biology groups for periods ranging from a few weeks to three months”, writes the GAO.
At the time Momenta was seeking approval to sell a generic version of heparin-derived Lovenox, prompting the GAO to ask if Momenta’s support “would compromise, or appear to compromise, the agency’s activities, including its activities related to the approval of heparin products”.