Illustration: Roger Schillerstrom
In an effort to prevent future heparin-type safety importation problems, lawmakers have drafted new legislation that would grant the US Food and Drug Administration (FDA) hundreds of millions in additional annual appropriations and user fees to strengthen the foreign drugs inspection program. But FDA officials, cognizant that big bucks carry big expectations and quick fixes are often transitory, remain cautious.
“The world is changing and our ability to assure the quality of the drug supply is becoming diminished, and we all need to recognize that,” said Dr. Janet Woodcock, MD, director of FDA’s Center for Drug Evaluation and Research. “And I think heparin is a wake-up call that we are not as able as we were to assure that quality,” she told the House Energy and Commerce Subcommittee on Health in May, 2008. “We are in the process of reviewing the discussion draft in detail and we look forward to working with you on this legislation.”
Since late last year, batches of the blood-thinner heparin manufactured in China have been found to be contaminated with over-sulfated chondroitin sulfate. The contaminant thus far has been linked to more than 80 deaths and 785 severe allergic reactions in the US and has affected patients in 10 other countries.
Suspicion centers around an active pharmaceutical ingredient (API) manufactured for Baxter International Inc. at a plant in China. The facility, Changzhou SPL, is a joint venture with Scientific Protein Laboratories LLC of Waunakee, Wisc. It is one of hundreds or perhaps thousands of largely unregulated plants in China that produce finished drugs and APIs for export to the US and other countries. Chinese authorities, while acknowledging never having inspected the plant, insist the contamination occurred outside their country.
Under current law, the FDA is required to inspect US drug manufacturers at least every two years for current good manufacturing practices (cGMP), but is not required to similarly inspect foreign manufacturing plants that export products to the US. Nearly 80% of all APIs used by US drug manufacturers are imported, mainly from China and India, and 40% of all finished drugs come from facilities around the world, including developing nations where fake and counterfeit drug products are most prevalent.
House Democrats led by Rep. John Dingell (D-Mich.), chairman of the Energy and Commerce Committee, have drafted legislation to grant FDA new enforcement powers. The draft measure, the “Food and Drug Administration Globalization Act of 2008,” would give the agency hundreds of millions of dollars in new funding to support biannual inspections of overseas plants. It would require all manufacturing facilities, foreign and domestic, to register and pay annual fees to the FDA. It would also require drug and biologics manufacturers to test their products for contaminants.
“The FDA must amplify its international presence if it is to have the hope of keeping up,” noted committee member Rep. Henry Waxman (D-Calif.). “FDA will need a serious infusion of resources and multiple new authorities to do the job we all expect it to do.”
The agency has budgeted only $11 million this year and $13 million next year for foreign inspections. An April, 2008 report by the Government Accountability Office (GAO), the investigative arm of Congress, said FDA would need about $70 million annually to inspect overseas plants, with those in China alone costing about $15 million.
Woodcock told the panel the FDA needed an additional $225 million to inspect each of the 3,300 or so foreign facilities believed to be manufacturing drugs and APIs for the US market every two years. But she said FDA needed “at least $20 million this year, and for many upcoming years” to fix the agency’s “obsolete” information technology infrastructure. “There’s no use in building new systems for imports if we can’t run them on our infrastructure,” Woodcock said.
She also disagreed with several provisions of the draft legislation, including the requirement to inspect every foreign facility biannually. “Any legislation should allow flexibility for FDA to set requirements and priorities based on scientific risk assessments,” Woodcock said. If a facility adds a product that is similar to those it already manufactures, the risks should be less than those posed by adding a totally new or different product. “We believe it would be best for FDA to have its flexibility preserved to put our resources, whatever they are, against the highest risks,” she said.
Major players agree
Woodcock also expressed concerns over industry user fees, noting they would be appropriate only if narrowly targeted. In a rare display of unanimity, representatives of the three major industry trade groups—the Pharmaceutical Research and Manufacturers of America (PhRMA), the Generic Pharmaceutical Association (GPhA), and the Biotechnology Industry Organization (BIO)—largely concurred.
“PhRMA agrees with the committee that the rate of FDA foreign inspections should be increased and recommends that FDA utilize a risk-based approach to prioritize such inspections,” said Lori Reilly, PhRMA vice president for policy and research.
New user fees “should not duplicate existing registration and establishment fees, and should be specifically allocated to supporting FDA’s drug and biologic inspection programs and not used to subsidize the inspections of other regulated parties’ establishments,” urged BIO President Jim Greenwood. Speaking on behalf of the GPhA, Christine Mundkur, chief executive of generics manufacturer Barr Laboratories Inc., said new user fees must be directed to inspecting foreign facilities, “where there is an immediate and significant need for resources to address the larger issues that are providing the momentum for this legislation.” In return, she added, FDA must be held to performance goals.
Reflecting the views of some consumer groups, Rep. Joe Barton (R-TX), ranking member of the full Energy and Commerce Committee, cautioned that additional user fees could make the FDA too dependent on industry. “It might be better to authorize out of the general revenue as opposed to becoming more and more dependent on user fees,” Barton said.
But Rep. Frank Pallone Jr. (D-N.J.), chairman of the health subcommittee, was grateful for industry’s support. “I’m pleased that the industry, pharmaceutical companies, biologic companies and generic companies have been so far willing to cooperate and assist in our endeavors,” he said.
Also in early May, FDA Commissioner Andrew C. von Eschenbach asked Congress for an immediate infusion of $275 million, including $100 million for medical products and drug safety, $40 million to modernize its science and work force, and $10 million to upgrade facilities. Sen. Herb Kohl, (D-Wis.) has sponsored a measure that would provide FDA an additional $275 million this year—part of an emergency supplemental appropriations bill largely intended to finance the war in Iraq.
About the Author
Contributing editor Ted Agres, MBA, is a veteran science writer in Washington, DC. He writes frequently about the policy, politics, and business aspects of life sciences.
This article was published in Drug Discovery & Development magazine: Vol. 11, No. 6, June, 2008, pp. 10-12.
Filed Under: Drug Discovery