FDA changes policy to offer more clarity on drug reviews

The Food and Drug Administration (FDA) on Wednesday announced a significant change in how it responds to drug applications, abandoning long-used bureaucratic language in order to better communicate where it stands on new medicines.

The new policy has been in the works for 11 years, and though at first blush it may appear to be mere semantics, the FDA believes it is responding to serious concerns from drug makers and its own internal anxieties about how the public interprets its actions.

At issue is just what “approvable” or “not approvable” really mean. The FDA says such nomenclature has been sending the wrong message to drug companies, Wall Street and the general public. As of Aug. 11, it will no longer use the terms in its communication with drug makers.

Instead, the FDA will issue “complete response” letters for any drug it deems not yet ready for the market. As with the other letters, the FDA will spell out what drug companies would have to do to obtain approval.

Under the old policy, when a pharmaceutical company submitted a new drug application to the FDA, the agency reviewed the material and issued one of three basic responses to the firm.

If the FDA determined the medicine to be safe and effective, the drug would be approved, and if it determined definitely it was not, it would be rejected.

More often, the decision was less final. If the FDA thought the drug appeared mostly ready for the market but needed more information before it could make a decision, the company would receive what was known as an “approvable” letter. If, however, the FDA did not think the application demonstrated that the drug should be made available, the agency would deliver a “not approvable” letter.

But the problem with that approach, explained John Jenkins, the director of the FDA’s Office of New Drugs, is that investors and the public often misunderstood what those letters meant. “It led to a lot of confusion [among people] trying to decipher what was the FDA thinking,” he said.

“Approvable has been misconstrued as a guarantee for approval in the short term” and not approvable was misinterpreted as meaning the drug could never be approved, Jenkins said. In fact, the opposite could be true in either case, depending on what additional information the drug companies provided after receiving the letter.

Wall Street analysts and the news media would regularly say that a new medicine had received “conditional” or “tentative” approval when the FDA did not intend to signal anything of the sort, Jenkins said.

Out of concern for how those misinterpretations might have affected Wall Street or patients awaiting news of new treatments, the numbers of the two different types of letters would fluctuate from year to year based on subjective judgments made by FDA reviews, Jenkins conceded. “We started seeing some creep,” he said.

“A ‘complete response’ letter removes some of that subjectivity about whether [a drug is] approvable or not approvable,” Jenkins said.

Investors might not like the change, though, Jenkins acknowledged. “They’re not going to be able to read the tea leaves, because there aren’t any tea leaves,” he said.

The pharmaceutical industry welcomed the development. “That certainty is important because manufacturers and patients want to know when drugs will be approved,” said Jeffrey Francer, the assistant general counsel for the Pharmaceutical Research and Manufacturers of America . “The terminology change really, I think, reflects accuracy,” he said.

Drug makers’ practical dealings with the FDA on new drug applications will not change much, though, Francer said. “The letters themselves will be very similar,” he said.

Based on recommendations from the FDA and the drug industry, Congress enacted this change in terminology in 1997. The FDA made the change the following year for biological drug applications but did not issue a proposed rule for traditional pharmaceuticals until 2004. The agency published the final rule Wednesday. The process for making federal regulations is time-consuming, Jenkins said, and conceded, “This probably wasn’t the agency’s highest priority for rulemaking.”