Washington Editor

WASHINGTON - The FDA lacks the resources to ensure that medications made overseas are safe, witnesses told Congress Thursday.

Many drugs and biologics marketed in the U.S. are manufactured in foreign countries. In fact, about 80 percent of the active pharmaceutical ingredients in U.S. medications are produced overseas, most prevalently in India and China. Yet only 7 percent of foreign drug and biologic manufacturing facilities are inspected annually by the FDA, according to congressional investigators.

While regulators are required to inspect U.S. manufacturing sites every two years, there is no law dictating how often the FDA must inspect foreign drug facilities, said Marcia Crosse, director of health care for the Government Accountability Office, the investigative arm of Congress. The FDA only has the resources to inspect foreign manufacturers about once every 13 years, she told the House Energy and Commerce Subcommittee on Oversight and Investigations at a hearing Thursday.

In addition, Crosse told lawmakers, the FDA's effectiveness in managing the foreign drug inspection process is hindered by weaknesses in the agency's databases used to track overseas manufacturers.

One of the agency's databases indicates that there are about 3,000 foreign establishments currently registered to market drugs in the U.S., while another indicates that about 6,800 foreign firms are importing drugs, Crosse said. She noted that the two databases, which were never designed for the purpose of tracking foreign facility inspections, cannot exchange information.

Unlike domestic inspections where inspectors arrive at manufacturing sites unannounced to ensure quality processes are ongoing, the FDA informs foreign manufacturers in advance of visits, giving those overseas firms time to hide any problems. The agency also relies on a volunteer process for its inspectors to travel overseas, many of whom do not speak the language of the country they are visiting and, therefore, must rely on representatives of the foreign firm to interpret for them.

The "FDA continues to use 20th-century tools and resources to address 21st-century regulatory challenges," said Subcommittee Chairman Rep. Bart Stupak (D-Mich.), and many of those testifying at Thursday's hearing noted that most of the same concerns about the FDA's foreign inspection process are the same as those discussed at a congressional hearing in 2000 and reported by the GAO in 1998.

"It's like déjà vu all over again," asserted Energy and Commerce Committee Chairman Rep. John Dingell (D-Mich.), though he noted that there had been "one slight change" related to the FDA's foreign inspection process since the 2000 congressional hearing.

"Unfortunately, it is a change for the worse," he said. Despite a dramatic increase in recent years of imported drug products, the resources devoted by the FDA to foreign inspections have declined.

The number of FDA personnel assigned to foreign inspections dropped from 149 in 2002 to 102 in fiscal year 2008.

The agency's budget for foreign inspections decreased from $16.7 million in 2002 to $16 million in fiscal year 2008.

Stupak noted that pharmaceutical imports from India, which has a little more than 400 drug and biologic manufacturing facilities, have increased 2,400 percent from 1996 to 2006, "making it the fastest growing drug importer." China, which has more than 700 manufacturing sites, has doubled its pharmaceutical exports to the U.S. over the past five years, he added.

However, Stupak said, while China has considerably more manufacturers than India, FDA devoted only 4 percent of its foreign inspection resources to China in the past year but allocated 22 percent to India.

Rep. Ed Whitfield (R-Ky.) noted that the FDA conducted only 13 inspections of manufacturers in China this past year, the same number of inspections conducted in the UK, which has only 169 manufacturing sites.

Carl R. Nielsen, former director of the FDA's Division of Import Operations and Policy, told lawmakers that the current paradigm for inspections of foreign drug manufacturing facilities "is grossly inadequate, is held together by bailing wire and is incapable of determining or verifying the safety and efficacy of most imported drug products."

Not only are financial and human resources "woefully inadequate," he contended, "the current FDA organization is not designed and funded to adequately oversee the foreign industry, to effectively manage and administer the related programs and to ensure the delivery of safe and effective imported drug products into the United States through secure supply chains." The FDA, he said, needs to "revamp" its entire organizational structure.

"There is no cheap fix," Nielsen declared. "That is part of the price of a global economy."

Stupak noted that he and Dingell introduced legislation designed to provide the FDA with more resources for its foreign inspection process. Lawmakers, he added, also have provided bipartisan input to drug regulators "delineating certain changes to the program that could be enacted almost immediately."

FDA Commissioner Andrew von Eschenbach said the agency was working "aggressively" to make changes to its foreign inspection process and to fix its database problems.

Excluding Elderly Patients?

The FDA drug approval process fails to ensure the safety and effectiveness of drugs for seniors, congressional investigators said in a recent report.

While drugmakers generally include elderly participants in trials and report safety and efficacy data for that population, in a number of cases examined, investigators found that drug trials excluded participants on the basis of age and restricted the participation of seniors.

A GAO report released on Oct. 29 said failing to include sufficient numbers of elderly patients in clinical drug trials may make it less likely that safety concerns and effectiveness outcomes unique to that population will be detected during the studies.

Seniors 65 years or older use drugs at a higher rate than younger persons and are more likely than younger adults to experience complications when taking some prescription drugs, GAO stated. And, in guidance documents for industry, the FDA recommended that drug and biologic makers include elderly persons in clinical drug trials. FDA regulations require that the drug sponsors report clinical drug trial data for new drug applications (NDAs) by age.

However, investigators noted, the agency does not direct its internal medical review officers to report whether sufficient numbers of elderly persons participated in NDA clinical drug trials to assess the safety and effectiveness of a drug for seniors.

"Seniors use more drugs than any other age group, but they are not getting enough attention in the drug approval process," noted Rep. Henry Waxman (D-Calif.), who, along with Sen. Edward Kennedy (D-Mass.), called for the GAO investigation.