Tainted drug imports set off warnings US agency didnt heed

May 30 | Updated: May 31 2008, 06:56am hrs
Two Americans died and 15 suffered seizures. The suspected cause: The epilepsy medicine they depended on stopped working because of a counterfeit ingredient from overseas.

The case of the flawed drug, made by a company that no longer exists, began unfolding in 1988. Since then, Food and Drug Administration employees and government investigators have called for stronger policing of imported substances used by U.S. drugmakers.

The agency received a ``wake-up call this year after the deaths of 81 people who took the blood thinner heparin, according to a top FDA official. The drug was contaminated by an ingredient from China. In fact, interviews with 10 former employees revealed that alarms about safety went unheeded for two decades, as imports soared. Documents show that FDA staff members raised concerns in 1988, 1991, 1993, 1996 and 2002.

``It was no surprise, said Carl Nielsen, who retired in 2005 as the FDAs director of import operations and policy, referring to the heparin case. ``Especially when you consider how little FDA oversight there is.

Baxter International Inc. of Deerfield, Illinois, voluntarily recalled its version of heparin beginning in January. The company said the main ingredient, made from pig intestines in China, was contaminated before reaching Baxters supplier.

Heparin accounted for about $30 million in annual sales for Baxter, which reported $11.3 billion in revenue last year. Baxter rose 80 cents, or 1.3 percent, to $61.04 in New York Stock Exchange composite trading yesterday and has climbed 5.2 percent this year.

A 30-Fold Increase

U.S. drug companies turned to ingredients supplied by businesses in China and other countries with lower labor and regulatory costs to save money, said Joe Acker, president of the Synthetic Organic Chemical Manufacturers Association in Washington, a trade group.

The value of imported medicine and drug compounds reached $48.9 billion last year, up more than 30-fold from $1.57 billion in 1990, according to the Census Bureau. U.S. pharmaceutical companies buy about 80 percent of their ingredients abroad, according to the FDA.

Scrutiny of overseas suppliers hasnt kept pace. Regulators reported reviewing 287 inspections in fiscal 1996 and completing 332 in fiscal 2007, according to the Government Accountability Office, the investigative arm of Congress. The FDA couldnt provide data from earlier years.

The agency doesnt know how many Americans have died or become ill from imported drugs, according to Christopher Kelly , an FDA spokesman.

History of Crises

``If there was one thing I would wake up in the middle of the night thinking about, it was imports, said Ron Chesemore , the FDAs associate commissioner for regulatory affairs from 1989 to 1999, who is now retired. ``You couldnt cover it the way youd like to.

The agency wasnt more vigilant because it had too little money and too many competing priorities, said William Hubbard , an FDA associate commissioner for policy and planning for 14 years before he retired in 2005. FDA commissioners, presidential administrations of both parties and Congress all bear responsibility, he said.

``The whole history of the FDA is that theres got to be a crisis before action will occur, Hubbard said.

Examining overseas drugmakers requires permission from governments, a complicated and time-consuming process, according to former FDA employees. Finding inspectors who wanted to take the trips was also difficult, Hubbard said.

A trail of memos and reports shows that FDA employees urged more inspections of overseas drug suppliers, improved computer tracking systems and expanded checks of imported medicine and compounds at U.S. borders. Calls for more inspections abroad date back to FDA documents from 1988 and 1993.

Deaths and Seizures

The generic epilepsy drug linked to deaths and seizures, carbamazepine, was voluntarily recalled in 1988 by Pharmaceutical Basics Inc. of Denver.

The tablets didnt dissolve properly, so patients may have received less than the dose required to control seizures, said Paul Vogel, who was then deputy director of the FDAs generic- drug compliance staff, at a congressional hearing in 1989.

Customs investigators and FDA officials concluded several years later that the defective ingredient came from an unidentified overseas country. The material, from an unapproved source, had been re-labeled to make it appear legitimate, Nielsen said.

Akzo Nobel NV , an Amsterdam-based maker of paints that once owned Pharmaceutical Basics, later dissolved the unit. Company spokesman Tim van der Zanden said he couldnt comment because company records cover only the past 10 years.

Increasing Volume

Deaths and injuries linked to carbamazepine and similar cases ``raised concerns about the FDAs ``ability to ensure the safety and quality of the increasing volume of foreign- produced drugs imported daily into the United States, the GAO found a decade later.

In 1991, Thomas Hooker, then head of the FDAs Baltimore district office, wrote that investigative work on imports ``suggests widespread availability of counterfeit bulk drugs in both human and animal drug industries.

Nielsen, then in the FDAs Office of Criminal Investigations, cited the epilepsy drug case in a 1996 memo that described ``little or no FDA control of bulk drugs coming into this country and ``no ongoing enforcement action to serve as a meaningful deterrence to the trafficking and use of counterfeit or unapproved bulk drugs.

Investigation Sought

His bosses never acted on his request to investigate counterfeiting of ingredients internationally, Nielsen said.