Sick Process

Saturday, January 30, 1999

The U.S. Food and Drug Administration likes to claim that it is the world’s “gold standard” in the field of overseeing drug development. But it isn’t. The FDA suffers by comparison to its pan-European counterpart, the European Agency for the Evaluation of Medicinal Products (EMEA), using a variety of subjective and objective criteria.

The FDA is the most omnipresent regulatory agency in the United States. It has responsibility for more than $1 trillion of consumer products annually. These include everything from drugs, vaccines, cardiac pacemakers, and X-ray machines to toothbrushes, condoms, and artificial sweeteners. The FDA likes to tout its standards as the most difficult to meet in the world (implying that the products it has approved are the safest).

The FDA’s regulatory zeal, however, has a dark side. The agency has constantly sought out new mandates and promulgated new requirements, regardless of the costs to patients and the various affected industries. According to the 1996–97 annual report of the Tufts University Center for the Study of Drug Development, since the 1960s the total time required for drug development—from synthesis in the laboratory to the patient’s bedside—has almost doubled, from 8.1 years to 15.2 years. From 1990 to 1993 alone, the average cost of bringing a single drug to market increased from $359 million to $500 million, the highest price tag in the world.

Europe, in effect, has two ways of approving drugs—and the competition spurs efficiency.

However, there is an alternative way of regulating drugs, namely, that operated by the EMEA. Headquartered in London, and established in 1995, the EMEA is lean, efficient, surprisingly unbureaucratic, and remarkably well regarded by the drug industry. The EMEA coordinates the scientific resources made available by European nations’ individual drug regulatory agencies (each of which is analogous to the U.S. FDA). It can call on a network of more than 2,100 European experts who perform the actual evaluations. Under European law, the EMEA’s procedures are compulsory for biotechnology but optional for other new products.

The essence of the agency’s success is that it is in direct competition with the regulation provided by national agencies—and competition spurs efficiency. Europe, in effect, has two ways of approving new drugs. The first is a decentralized procedure, based on the principle of “mutual recognition of national authorizations,” or reciprocity. This provides for the extension of one nation’s marketing approval to one or more other members of the European Union. The second is a centralized procedure, whereby applications are submitted directly to the EMEA. At the conclusion of a 210-day period of scientific evaluation by the scientific committee, which consists of several experts drawn from the EMEA’s stable of reviewers throughout Europe, its opinion is transmitted to the European Commission. After an additional 90 days, the commission issues a single-market authorization that applies to the whole European Union.

The coexistence of these two systems provides a measure of competition. Another less obvious competitive aspect of European drug evaluation is that the EMEA is able to choose reviewers from a large pool. Those who are incompetent, excessively slow, or adversarial are unlikely to be selected to evaluate future products. At the FDA, by contrast, reviews are performed in-house, civil service rules prevent anyone from being fired, and agency managers have to make do with what they have.

The EMEA is a new institution, with nothing like the record of the FDA. Hence comparisons between the two must of necessity be preliminary. All the same, there are comparable figures available. The recent data that illustrate how differently the agencies are perceived by their corporate “clients” are striking. A 1997 survey of the interactions between drug companies and the FDA conducted by researchers at the University of California, San Diego, revealed that in 78 percent of companies, poor “clarity of data requests” from the agency had “impeded or stopped” their products. In 62 percent, personnel turnover at the FDA had had that effect. In 40 percent, limitations in the FDA reviewers’ “technical knowledge” had stopped or impeded the progress of a product. At the same time, an anonymous survey by the EMEA of its own applicants found that 33 percent were very satisfied, while 61 percent were satisfied and 6 percent dissatisfied.

Moreover, the EMEA’s mean processing time for marketing applications received in 1997 was 207 days. In stark contrast, the FDA required approximately 460 days for the marketing approvals that were announced in 1997. The FDA is, in fact, even slower than the comparison suggests. The agency intentionally reports data in this way to make its numbers appear more favorable. That is, the reporting only of approvals announced in 1997 tends to minimize the statistical effects of applications that were received in that year (or even earlier years) but languished unapproved.

The regulatory philosophies of the EMEA and FDA could hardly be more different. The EMEA says it focuses narrowly on performing “high quality evaluation of medicinal products,” monitoring product safety, offering advice on research and development programs, and providing “useful and clear information to users and health professionals.” It tries to be client-friendly and carefully tracks and publicizes performance indicators.

The FDA, by contrast, is oriented toward compliance and comports itself like a police agency (it has gun-toting inspectors). The FDA commonly treats drug companies like adversaries and constantly pushes the regulatory envelope, seeking to expand the agency’s mandate, purview, and budget. Recently, for example, the FDA published a draft guidance document aimed at regulating “medical product promotion” among health care providers and professionals. This new action would extend the agency’s regulatory authority to any “relationships” it deems promotional that occur between different members of the health care profession. Not only is this a giant step beyond the FDA’s legal authority, but the wording of the proposal is so deliberately vague that it could shut down vital communication among health care professionals and patients.

Last year, the European agency’s mean time for processing marketing applications was 207 days. The FDA’s mean time? More than twice as long.

The FDA may be the only regulatory game in town as far as the United States is concerned, but it is not the only one in the world. There are well-established, effective, and less expensive mechanisms for the evaluation, approval, and monitoring of new drugs, of which the EMEA is a notable example.

The conundrum of selecting oversight systems that would better protect the public health lies, therefore, not in finding sound alternatives to an imperious, obstructive FDA. They already exist. The problem lies in finding the political will to apply them.