Mark A. DeSorbo
WASHINGTON, DCalthough it has managed to hand down some of the stiffest fines in history to drug makers employing shoddy production practices, the U.S. Food and Drug Administration (FDA) is struggling to reaffirm its authority and quash suggestions that it caters to the pharmaceutical industry.
Over the last 18 months, the FDA has issued steep fines, including one to Abbott Laboratories (Abbott Park, IL) for $100 million, suspended manufacturing operations and issued sharp warnings to some of the world's major pharmaceutical companies. The issues vary from technical to contamination to failure to validate procedures, but the FDA's action reflects that such violations pose risks to consumers.
At the same time, however, the agency has come under fire for the manner and speed with which the agency approves new drugs. The approval process is partially funded by drug makers who pay “user fees,” but the enforcement division does not receive any such funds and has few resources, namely inspectors.
Last year, the FDA approved 27 medicines that have active ingredients never before sold in the United States. The agency also took an average of 17.6 months to approve experimental drugs, compared with only 12.6 months for the 35 it approved in 1999.
The number of inspections last year, however, fell by 14 percent, to 5,518 reviews of facilities where drugs and vaccines are manufactured, according to FDA spokesperson Crystal Rice. The FDA's policy calls for inspections of manufacturing plants every two years; however, it has been unable to meet this goal due to the increasing number of facilities, a lack of inspectors and budgetary constraints.
“The FDA is concentrating on cases with a bigger impact, which includes plants with the most risky products, companies that have shown a pattern of noncompliance and plants where firms manufacture newly approved drugs,” she adds.
FDA will not be ignored
James G. Dickinson, editor and publisher of Dickinson's FDA Review (Camp Hill, PA) says the FDA has been making a very deliberate effort to reverse a perception that the agency has “lost its teeth and is too heavily oriented in approvals.”
“The suggestion has certainly been raised, and although that's been the case, things are changing,” he says, adding that a budget proposed by President Bush will be far more helpful to the FDA than any of the budgets that Bill Clinton introduced. “We have seen, in recent months, a major crackdown on some of the major drug manufacturers.”
Targets for the FDA crackdown include:
- Abbott Laboratories, fined a record $100 million for serious deficiencies in the production of medical diagnostics and screening devices and for ignoring FDA warning letters for six years;
- American Home Products, fined $30 million for failing to meet government standards at two plants producing vaccines for flu and childhood diseases and for ignoring repeated FDA warnings;
- Schering-Plough, faces large FDA fines, lawsuits by investors and delays in government approvals for repeatedly flunking inspections over a three-year period at plants in New Jersey and Puerto Rico.
The FDA has also issued warning letters to Swiss drug maker Hoffman-LaRoche, Genetech Inc. (San Francisco) and Eli Lily Corp. (Indianapolis).
cGMPs: A priority or an afterthought?
Depending on which analyst you talk to, the pharmaceutical industry is or is not concerned with current good manufacturing practices (cGMPs).
Jami Rubin, a pharmaceutical industry analyst with Morgan Stanley Dean Witter (New York City), says manufacturing has never been a primary concern to the industry.
“Research comes first, marketing second and manufacturing third,” she told The Star-Ledger of New Jersey. “Some of the companies have under-invested in manufacturing. That was the case with Schering-Plough, and now they are getting their eyes punched out.”
Marc Goodman, another pharmaceutical research analyst for Morgan Stanley Dean Witter, says, drug makers are most concerned with manufacturing and that issues in the process are most often the result of personnel cutbacks.
“Manufacturing is critical to them. If they don't have FDA approval, they can't sell the drugs, so they need to make sure they do the right thing,” he says. “Sometimes companies, over time, overlook things. Sometimes it's cut backs in personnel. It's not like the companies are ignoring the FDA, although every now and then you get a company that blatantly disregards regulations.”
Dickinson agrees with Rubin, saying Schering-Plough and Abbott, did tend to minimize the importance of manufacturing practices. “Good manufacturing practices have low visibility in the board room,” he adds.
When contacted by CleanRooms magazine, officials at Schering-Plough, Abbott Labs, Genetech and Hoffman-LaRoche did not return telephone calls.
Doug Petkus, a spokesperson for Wyeth-Ayerst Laboratories, the pharmaceutical division of American Home Products, refused to comment on whether or not the company minimized the importance of cGMPs as analysts suggested.
He did say that the company has an ongoing dialogue with the FDA, and a list of improper manufacturing conditions at the Marietta, PA, and Pearl River, NY, plants from the agency is being addressed.
“We are under a consent decree for those two facilities. The issues are cGMPs, the largest of which deal with process, and we are working with the FDA to address the issues,” Petkus says. “We are moving ahead and meeting timelines with the ultimate goal of resolving all outstanding issues.”
As for the $30 million fine, Petkus adds that it is indeed a significant amount of money, but “it's not material to the long-term health of the company.”
Dickinson says the FDA's message will not be received over night, but the agency's stance is obvious.
“It will take a while to sink in, but the message is clear. The FDA is willing to hold up drug approvals and [the agency] is prepared to litigate,” he says. “Many consider warning letters to be a gentle wrap on the knuckles, but make no mistake, there is a new day dawning, and companies that have been taking things for granted will be in for a shock.”