Tom Harkin
A consent decree of permanent injunction filed Wednesday by the U.S. Department of Justice against an India-based generic drug company highlighted many of the pharmaceutical safety challenges outlined during a September 2011 hearing held by U.S. Sen. Tom Harkin.
The DOJ, which was acting on behalf of the U.S. Food and Drug Administration, filed the consent decree in the U.S. District Court of Maryland. Named were generic drug manufacturer Ranbaxy Laboratories, Ltd., a subsidiary named Ranbaxy Inc., headquartered in Princeton, N.J. and several company officers.
A total of four plants — three in India (Paonta Sahib, Batamandi and Dewas) and a wholly owned subsidiary Ohm Laboratories in Gloversville, N.Y. — will be required to comply with detailed data integrity provisions before the FDA will resume reviewing drug applications containing data or other information from the plants.
According to information released this evening by the DOJ:
Specifically, Ranbaxy must:
(1) hire a third party expert to conduct a thorough internal review at the facilities and audit applications containing data from the affected facilities;
(2) implement procedures and controls sufficient to ensure data integrity in the company’s drug applications; and
(3) withdraw any applications found to contain untrue statements of material fact and/or a pattern or practice of data irregularities that could affect approval of the application.
In addition, the consent decree prevents Ranbaxy from manufacturing drugs for introduction to the U.S. market and for the President’s Emergency Plan for AIDS Relief (PEPFAR) Program at the Paonta Sahib, Batamandi, Dewas, and Gloversville facilities until drugs can be manufactured at such facilities in compliance with U.S. manufacturing quality standards.
“Because this company continued to violate current good manufacturing practice regulations and falsify information on drug applications, the FDA took these actions in an effort to protect consumers,” said Dara Corrigan, FDA associate commissioner for regulatory affairs. “The FDA continues to be committed to protecting consumers from potentially unsafe products that may be offered on the market.”
As the public learned last fall during a hearing convened by Harkin, who leads the Senate Health, Education, Labor and Pensions Committee, the number of drug products taken by Americans and manufactured at foreign establishments has more than doubled since 2002 (PDF). China and India have held the greatest share of that growth.
Allan Coukell, director of medical programs for The Pew Charitable Trusts, noted in his testimony before the HELP Committee that an Indian manufacturer was cited by the FDA in 2008 for “alleged falsification of stability testing records and use of active ingredients made at unapproved sites.” That manufacturer was Ranbaxy, which has had its three India facilities on FDA import alert since that time. It has also since closed the Gloversville facility.
Government officials are offering assurances that no drugs from the affected plants are currently being distributed in the U.S. market; and the agreement reached between the government and Ranbaxy, pending court approval, includes monetary penalties — capped at $10 million a year — if products from the plant are found in American markets. Additional penalties exist for each day the company violates the law or the agreement at the facilities, and for making false statements on FDA applications.
“The safety of our medicines has a profound effect on the health and security of our country, and we must have confidence that our system of oversight is up to the task of protecting our families,” Harkin said during an opening statement at the hearing.
“In today’s increasingly global economy, most of the key ingredients used in the drugs prescribed by American doctors and consumed by American families are produced overseas. About 80 percent of the active ingredients found in U.S. pharmaceutical products come from abroad, as do about 40 percent of finished drugs. This trend is projected to continue and increase, with more and more of our medicine cabinets being stocked with products from countries like India and China with less robust regulatory systems than our own.”
On Nov. 30, 2011, Ranbaxy was given approval to manufacture one of the two available generic drugs for cholesterol-lowering Lipitor (the most widely sold pharmaceutical in history, generating roughly $11 billion per year for patent holder Pfizer). During the first full week in December that the generics were available, according to the Associated Press, nearly 60 percent of sales went to the generics (one of which has partnered with Pfizer). Throughout the remainder of the month, the generic options picked up an additional 4 percent of sales.
The report adds that it was “because [of] long-standing manufacturing issues at some Ranbaxy factories,” the FDA held off until the night of Nov. 30 — the day the Pfizer patent expired — to grant permission for Ranbaxy to market its generic in the U.S. The company currently manufactures the drug (atorvastatin) in a New Brunswick, N.J. factory that is not a part of the consent decree filed Wednesday.
Although it is unlikely that the agreement will result in a shortage of the Lipitor generic, Ranbaxy has agreed to relinquish any 180-day marketing exclusivity that it might have for three other pending generic drug applications. It will also relinquish any 180-day marketing exclusivity that it may have for several additional generic drug applications if it fails to meet certain decree requirements by specified dates. The FDA has also reserved the right to add additional Ranbaxy facilities to the decree if substandard conditions exist or data integrity is compromised.
“The profound interests at stake are highlighted for us by tragic examples of American patients who have taken adulterated drug products, such as the 150 U.S. patients who died in 2007 after taking contaminated Heparin. These appalling examples remind us that the need for vigilance is high and the costs of failure are staggering. Parents in my state of Iowa shouldn’t have to worry that the medicine they give their sick children is substandard or contaminated,” said Harkin.
