FDA Warning Letter Review Suggests Aggressive Action Needed, Troy Says

The FDA Office of Chief Counsel's review of warning and untitled letters suggests the agency should be taking more aggressive enforcement actions, Chief Counsel Daniel Troy suggested Feb. 21.

"As often as not, our review of letters, thus far, has caused us to ask why the agency isn't being more, rather than less, aggressive," Troy told a Drug Information Association meeting on marketing and compliance in New York.

"Our review has often caused us to ask why the district is proposing a letter instead of a suit."

Troy gave the example of "a proposed letter directed at a very small cosmetic company which made OTC drugs as a very small part of its business. But they didn't comply to [Good Manufacturing Practices] at all. I'm not talking about trying to comply, they didn't comply, there were no GMPs. And they had been warned before."

FDA's Office of Chief Counsel "called the compliance director and asked him, 'Why aren't we going to sue?' These people have no GMPs, we've sent them letters."

"I mention this because I think it's an example of the kind of thing we hope to accomplish in reviewing warning and untitled letters," Troy said.

The dietary supplement industry has long called on FDA to be more aggressive in enforcing the Dietary Supplement Health & Education Act, arguing the agency has not used the tools it has available to act against non-compliant companies.

FDA appears to have taken a firmer stance regarding two warning letters sent to Omni Nutraceuticals and B.F. Ascher. The letters maintained that the combina-tion dietary supplement/OTC drugs they were marketing were actually unapproved drugs (¹ (Also see "B.F. Ascher Halts Supplement/OTC Combo Sales Following FDA Warnings" - Pink Sheet, 18 Feb, 2002.), p. 7).

However, Troy noted the agency is limited by resource and time constraints. "One of the things that I've become incredibly aware of is the unbelievably scarce resources with which we deal at FDA."

Due to these pressures, "we are not going to review every letter with the same comprehensiveness that we review a case that's been sent to us. We can't do that. The agency would grind to a halt."

Instead, the Office of Chief Counsel is taking several steps to streamline the process, and will attempt to prioritize its actions to maximize resources.

"Let's say we send out 1,000 letters a year," Troy said. "There's a [General Accounting Office] report that suggests that 75% of companies comply, for which we thank most of you very much." Of the 250 non-compliers, "we can only bring 50, 75 - if we really ramp up - 75 or 100 cases a year."

"We need to think carefully and strategically about which of the 250 law violators we're going to go after," Troy maintained. "You have to have some process for at least thinking about how you're going to strategically deploy the resources."

The Office of Chief Counsel's review of FDA warning and untitled letters stems from an HHS directive from Deputy Secretary Claude Allen. Under the HHS directive, all letters would need to be cleared by the counsel office prior to issuance (² (Also see "Allen, Azar & Troy: FDA Legal Partners Streamline Enforcement Activity" - Pink Sheet, 17 Dec, 2001.), p. 9). The directive was expected to take effect by the end of February.

The "primary motivation" for the directive, Troy said, was "that FDA was in danger of being perceived as toothless - that too often we would issue...warning letters and not follow them up with lawsuits, even in the case of...flagrant noncompliance."

In addition, HHS "had heard complaints about inconsistencies in warning letters and untitled letters," including concerns that different standards were used across FDA district offices, especially those for GMP issues, Troy said.

"It's frankly not clear that OCC review can eliminate this problem," he noted, "but we may be able to help avoid it, and perhaps...help resolve it if it does arise."

Mounting legal issues with warning and untitled letters were another contributing factor in promulgating the HHS directive. Troy noted that some letters had been "legally problematic."

"Given the legal content of these letters, failing to have anyone at Parklawn review and track them was simply regarded as not good clearance practice," he explained.

Consistency also has been a major concern, he said, both between FDA's centers and within the review divisions. "I do hope and expect that coming out of this will be a more uniform and consistent treatment generally of the many different kinds of letters," he said.

"There has been a lot of inconsistency, in part because you always have tension," Troy maintained. "You want to give people freedom and autonomy to do their jobs and you don't want to have too much centralized management. On the other hand, when you don't have centralized management, you don't have consistency. That is an obvious tension that one needs to work out."

"One of the things that has come out of the implementation of the deputy secretary's warning letter directive is the understanding that different letters have been treated differently," Troy stated.

For example, "there's no one central depository in the agency of all warning and untitled letters," he noted. FDA currently is installing information technology to track, store, retrieve and recall letters.

Another step is establishing categories of letters. "To implement it, we had to try and first define categories and then find ways to track them and treat them. So that's some of what's been going on."

Implementation of the directive has been slow; Troy acknowledged that his office is still trying to manage the paper flow. "We couldn't review every letter that somebody sends out that has any kind of legal consequence at all."

Although there were requests for guidance on the standards that the Office of Chief Counsel would use when reviewing letters and determining the appropriate enforcement action, Troy indicated there would not be a formal codification.

FDA will look for the reasons behind the letter, whether previous letters have been sent and whether a lawsuit should be considered.

Conversely, OCC also will attempt to weed out letters that are not merited. "There may be some that we look at and say that's too out there, that's inconsistent with other things we've said. There may be some cases where we're going to look at whether that's really an issue of regulatory significance," Troy said.

"We can say we want to send this message this year, and we're going to focus our scarce resources in this direction. And that's the kind of thinking that we want to encourage...we want to facilitate more of that kind of thinking," he added.