The House Energy and Commerce Subcommittee on Oversight and Investigations during an April 29 hearing simultaneously lauded and criticized FDA's handling of the heparin contaminant safety issue, which the agency now says most likely was the result of intentional actions.

"The heparin case illustrates both the best and the worst of FDA's performance under this administration," committee Senior Investigator David Nelson said during the subcommittee's hearing: "The Heparin Disaster: Chinese Counterfeits and American Failures."

"While FDA may respond quickly to a crisis when the danger to the public health is known, committee staff found that its routinely poor performance as a regulatory agency ... invites catastrophe and may have contributed to the tragic use of contaminated heparin on patients in the United States," Nelson testified.

FDA previously announced it had identified a "very solid mechanistic link" between patients who received heparin contaminated with oversulfated chondroitin sulfate and observed adverse reactions. The agency received 81 reports of death with one or more allergic/hypotensive symptoms in heparin patients from Jan. 1, 2007, to April 13, 2008 (¹ Also see "FDA Pinpoints Culprit In Bad Heparin" - Pink Sheet, 21 April, 2008.).

FDA Center for Drug Evaluation and Research Director Janet Woodcock testified the agency's hypothesis is that the contaminant, a synthetically altered - and inexpensive - compound that mimics heparin in testing, was intentionally added somewhere in the supply chain in China.

"The highest probability is that it was intentional. It's hard to determine how it could have been introduced accidentally," Woodcock said.

Nelson estimated chondroitin sulfate is roughly 100 times less expensive than heparin.

Witness Clive A. Meanwell, CEO of The Medicines Company, in Parsippany, N.J., told the subcommittee that a price spike for pigs in China caused by an epidemic of porcine reproductive and respiratory syndrome, or "blue ear" disease, could have led some to try to sell cheaper alternatives to the pig intestines necessary for heparin, and that the price spike should have raised alarms for companies that manufacture porcine-sourced products.

"One has to ask if this will be a temptation, and I believe common sense shows that it is," Meanwell said.

Two audits, two different findings

The subcommittee investigation also took Baxter International to task for its audit of its heparin active pharmaceutical ingredients supplier Scientific Protein Laboratories and the firm's Changzhou subsidiary.

FDA issued a Form 483 letter to SPL for a number of objectionable practices after inspecting the Changzhou facility, months after Baxter audited the same facility.

Subcommittee members and Nelson, the investigator, expressed doubt the plant could have deteriorated as much as FDA observed between the two inspections.

"Baxter spent one day in the plant. FDA sent two inspectors for five days at the facility. Time alone would suggest what FDA was looking for compared to what Baxter was looking for," Nelson said.

"At best it was incomplete, bordering on failure," Nelson said of Baxter's inspection.

More inspections, more money

Subcommittee Chairman Bart Stupak, D-Mich., asked Woodcock why FDA has not asked for the resources necessary to complete foreign inspections, echoing the conversation from the April 22 hearing with FDA Commissioner Andrew von Eschenbach, where Stupak and Energy and Committee Chairman John Dingell, D-Mich., repeatedly asked the commissioner why he refused to request additional funds (² Also see "FDA Head Faces Grilling Over China’s Heparin" - Pink Sheet, 22 April, 2008.).

Woodcock told Stupak it would cost $225 million to inspect every foreign plant every other year. Stupak quickly noted that Dingell's draft FDA Globalization Act of 2008 would bring in $300 million in registration fees to be used for foreign inspections (³ Also see "U.S. Mulls Registration Fees For Foreign Drug Manufacturers" - Pink Sheet, 14 March, 2008.).

Committee members expressed concern that while FDA has identified 12 firms in the Chinese supply chain that had contaminant in their crude heparin, the agency has only issued an import alert for Changzhou SPL, and members questioned how FDA can ensure the safety of imported heparin API, particularly because the agency does not know exactly how many heparin API manufacturers are exporting to the U.S.

"I'm confident that all heparin coming in is being stopped and inspected," CDER Office of Compliance Director Deborah Autor stressed.

"I find FDA the most trusting organization in the world. You are more trusting than a kindergarten class. I would be embarrassed to testify this way," Dingell said in response.

- Daniel Poppy (d.poppy@elsevier.com)

[Editor's note: This article appears courtesy of ⁴ PharmAsia News, F-D-C Reports' new site for Asian biotech and pharmaceutical news. To register for a 30-day risk free trial, visit www.pharmasianews.com.]

FDA’s Poor Performance “Invites Catastrophe,” House Investigator Says

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