Tainted Drug Imports Set Off Warnings, Not FDA Action (Update1)

Tainted Drug Imports Set Off Warnings, Not FDA Action (Update1)
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May 30 (Bloomberg) -- 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 FDA's 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 Baxter's supplier.

Heparin accounted for about $30 million in annual sales for Baxter, which reported $11.3 billion in revenue last year. Baxter fell 4 cents to $61 at 9:50 a.m. in New York Stock Exchange composite trading after climbing 5.2 percent this year through yesterday.

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 hasn't 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 couldn't provide data from earlier years.

The agency doesn't 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 FDA's associate commissioner for regulatory affairs from 1989 to 1999, who is now retired. ``You couldn't cover it the way you'd like to.''

The agency wasn't 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 there's 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.

Employees' Proposals

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.

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

The tablets didn't 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 FDA's 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 couldn't 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 FDA's ``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 FDA's 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 FDA's 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.

A 1996 memo from the FDA's Forensic Chemistry Center about imported drugs warned that ``we have just scratched the surface of the problem of counterfeit drugs and will need considerable assistance in getting the problem under control.''

Competing priorities, including ensuring the safety of the blood supply and developing AIDS drugs, preoccupied the FDA, said David Kessler, the agency's commissioner from 1990 to 1997.

``There's no doubt that we could have done more,'' said Kessler, now a professor at the University of California, San Francisco, School of Medicine. A group he created to map strategy on imported drugs was disbanded after he left office.

Kessler's successor, Michael Friedman, was traveling and unable to comment, said Roberta Nichols, a spokeswoman for the City of Hope in Duarte, California, in an e-mail. Friedman is president and chief executive officer of the cancer center.

Little Control

In 2000, then-Representative Thomas Bliley of Virginia, the Republican chairman of the House Commerce Committee, wrote in a letter to the FDA that substandard and counterfeit imported drugs were ``silently infiltrating the U.S. health delivery system, and harming the American people.''

Bliley cited deaths that may have been linked to a counterfeit ingredient from China in gentamicin sulfate, an antibiotic to treat infections such as blood poisoning.

The agency's commissioner at the time, Jane Henney, said that while policing drug imports was a priority, agency budget requests were routinely reduced by the White House or Congress.

``At FDA you deal with so many high-profile, priority issues that it is very hard to say that any of them are not worthy,'' said Henney, now a professor at the University of Cincinnati Academic Health Center. ``But you have to look at the approaches within your means to deal with them.''

In 2002, FDA officials presented Lester Crawford, the agency's acting commissioner, with a plan to improve the safety of imported products by performing more inspections overseas and at U.S. borders, according to Hubbard, who helped lead the effort. Much of the plan was shelved, he said.

`No Money'

``People didn't deny that it needed to be fixed,'' Hubbard said. ``But Lester said there was no money. It was early in the Bush administration, and word from above was we're cutting budgets, not increasing.''

Crawford, now senior counsel for the lobbying firm Policy Directions Inc. in Washington, said he didn't remember the presentation. During his tenure, 800 FDA inspectors were added, Crawford said. Funding for the added employees, used mostly to scrutinize food at the border, was later eliminated, according to Hubbard.

Janet Wood***, chief of the FDA's drug division, told a congressional committee this month that ``heparin is a wake-up call'' about the FDA's difficulties in ensuring the quality of imported drug products. The agency plans to upgrade its computer technology to better track imports and the risks they pose, according to Wood***.

The FDA also plans for the first time to permanently station about a dozen employees in China, which has 714 plants registered to ship medications to the U.S., more than any other country, according to the GAO.

Adding $275 Million

FDA Commissioner Andrew von Eschenbach told lawmakers this month the agency needed $275 million added to its budget of more than $2 billion to ensure the safety of drug imports and other products.

The plans are inadequate to protect consumers, said Representative John Dingell, a Michigan Democrat who is chairman of the House Energy and Commerce Committee, which oversees the FDA. Dingell is pushing legislation requiring drugmakers to pay new fees to fund more inspections.

Dingell said he's been urging FDA commissioners for years to do a better job guarding against tainted drug imports.

``We're letting a bunch of bastardly importers or exporters abroad send in this appalling kind of crap that's killing our people, and we're not checking it or correcting it or addressing it at all,'' Dingell said in an interview.

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Civis Romanus Sum
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