The Pharmaceutical Research and Manufacturers of America is proposing reforms to FDA's safety powers that would allow quicker regulatory actions, but not fundamentally alter the agency's authority.

In written testimony before the House Energy & Commerce Health Subcommittee on June 12, PhRMA Senior VP-Scientific and Regulatory Affairs Caroline Loew, described four areas where the brand-name drug association would support "clarifying" FDA's powers - essentially giving the government an explicit mandate for things it already feels it can ask drug companies to do.

For each of the areas - clinical trial registries, postmarketing studies, labeling changes and restricted distribution - Loew emphasized that the "targeted revisions ... can be accomplished without creating an entirely new bureaucratic maze." Among industry's main concerns with the legislative safety proposals is the increase in formal interactions with FDA that the new authorities would require.

For the most part, the draft House bill toes a stricter line than the Senate version, giving FDA more powers to direct pharmaceutical company activity in order to address potential drug safety concerns (¹ [A#00690240003], p. 7). However, the measure has stalled while members try to work out compromises on which drugs would be subject to the provisions and on language addressing preemption of product liability suits (see chart: "² Negotiations Preempt Subcommittee Markup").

For the federally mandated clinical trial registries and the results database, PhRMA urges that they be limited to "hypothesis-testing trials," commonly defined as Phase II and above, as opposed to the requirement to list all clinical studies in the House bill.

PhRMA also supports giving FDA explicit authority to require postmarketing studies, if, "on the basis of new scientific information obtained after a drug is approved, FDA determines that: (a) the drug may be associated with a significant new risk not listed on the current approved labeling; (b) a postmarketing study is necessary to assess the significant new risk; and (c) the information expected to be obtained from the postmarketing study would make a material contribution to the approved labeling for the drug," Loew said.

"Moreover, the new authority should be limited to significant new risks associated with an approved use of the drug. Although physicians should remain free to prescribe a drug any way they deem appropriate as a legitimate exercise of the practice of medicine, companies should not be required to conduct research on a use they have not, and do not intend to, market."

"Finally, postmarketing studies can be extremely burdensome for sponsors and, in many cases, may be unnecessary to mitigate risks posed by a drug," Loew said. "Sponsors should have the option to take other equally effective but less burdensome actions (e.g., label change) before being ordered to conduct a postmarketing study."

PhRMA's concept for new FDA labeling authority seems to essentially align with the new legislation, although the association stopped short of endorsing the timelines in the bill. PhRMA supports "the creation of an accelerated dispute resolution process for label changes that maintains the ability of the sponsor and FDA to engage in a meaningful scientific dialogue but also places time limitations on such dialogue to ensure that new safety information is included on the approved labeling in a timely manner," Loew said.

For restricted distribution programs, "PhRMA supports clarifying FDA's authority," Loew said. "However, because distribution and use restrictions create significant limitations on patient access to needed medications, they should be imposed only in exceptional circumstances. PhRMA is concerned that providing FDA explicit statutory authority to impose distribution and use restrictions could lead to the routine use of very onerous restrictions that should be reserved for exceptional circumstances."

There are several aspects of the legislation that PhRMA fundamentally opposes, including limits on direct-to-consumer advertising and the "black triangle" on new product labeling.

Perhaps most notably, the brand industry also has deep concerns with another of the central tenets of the new legislation - that, in addition to specific new authorities, FDA needs to be able to impose penalties on companies aside from the "nuclear option" of pulling the drug from the market entirely if a firm does not comply with an agency request.

The bill addresses this concern by allowing FDA to impose civil monetary penalties on firms that violate the federal Food, Drug and Cosmetics Act. While not explicitly opposing fines per se, Loew expressed concern about the size of the fines - which in the House bill could be up to 10 percent of a product's annual sales - and the uncertainty the new power will create.

"These dollar amounts, which could reach tens or even hundreds of millions of dollars, are extraordinary," Loew said. "By contrast, the civil penalties in current law for drug sample diversion are $50,000 for the first two violations in a 10-year period, escalating to $1 million only when [there are] subsequent violations in that period, and there is no reference to annual product sales."

"These extraordinary penalty levels are especially troubling given the broad and subjective nature of many of the requirements of the FFDCA. For example, an adulteration violation can be based on failure to meet 'current good manufacturing practices,' a requirement FDA has asserted is always evolving and that is highly subjective at best."

"Advertising and promotional violations likewise are notoriously subjective. These extraordinary penalties will create perverse incentives regarding enforcement of the FFDCA and may make it difficult or impossible for a company to defend itself with the threat of massive [civil monetary penalties] hanging in the background."

- M. Nielsen Hobbs (n.hobbs@elsevier.com)

PhRMA’s Compromise Offer On Drug Safety Would “Clarify” FDA’s Powers

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