The final version of US Prescription Drug User Fee Act (PDUFA) re-authorisation legislation must not include mandatory risk evaluation and mitigation strategies (REMS) for tracking the safety of marketed products, legislators have been told by both industry and a leading advocate for greater patient access to developmental drugs.

REMS strategies currently being proposed in both the House and the Senate PDUFA reauthorisation bills could actually be counter-productive and unworkable, Caroline Loew, senior vice president for scientific and regulatory affairs at the Pharmaceutical Research and Manufacturers of America (PhRMA), warned a hearing held by the House Committee on Energy and Commerce.

These strategies would create a complicated system that could actually impair drug safety oversight, by miring Food and Drug Administration safety officers in unproductive bureaucratic exercises rather than meaningful surveillance activities, said Dr Loew. They would also add significant costs to the drug development process, thus harming innovation and impeding access to life-saving medications, she added.

Steve Walker, co-founder of the Abigail Alliance for Better Access to Developmental Drugs, agreed. REMS are “yet another one-size-fits-all solution that won’t work,” he told the hearing, and pointed out that the FDA already uses its authority to impose Risk Management Plans (RiskMAPs) on drugs at the time of approval. However, he claimed, RiskMAPs have so far proved to be “a mixed bag of prudent controls burdened with unnecessary approval delays and prescribing restrictions, coupled with requirements for highly-unethical post-approval clinical trials,” and have also resulted in major intrusions by the FDA into the practice of medicine. Mandatory REMS would likely evolve quickly into an over-applied defensive mechanism instead of its intended use as a “rational, sober post-marketing monitoring tool,” he forecast.

Industry slams call for FDA oversight of marketing plans

PhRMA’s Dr Loew was particularly unhappy with the legislators’ REMS discussion draft’s “unprecedented” proposal to grant the FDA authority to require companies to supply it with the marketing plans for drugs under review. “It is inappropriate for a regulatory body to be charged with routine review of internal business planning documents,” she said, adding that the FDA has neither the experience nor the resources to review internal market analyses and other components of commercial planning materials on a regular basis.

Moreover, the proposal would essentially give the agency power to review and approve internal company documents but, “absent extraordinary and highly compelling reasons, neither FDA nor any other agency should be charged with the extreme measure of overseeing the internal affairs of the private entities it regulates,” she stressed.

In any case, current law already requires all advertising and promotional materials to be submitted to the FDA, while a new proposal put forward by the agency will create a system for prior review of consumer advertisements. “Nothing further will be gained by creating a new mechanism for agency review of a company’s internal plans,” said Dr Loew.

However, Consumers Union president Jim Guest told the panel that the proposed REMS provisions would give the FDA an effective “tool chest” of authorities to ensure that, when safety issues warrant action, such action can indeed be taken, and without slowing the drug approval process. “Today, the FDA has limited authority to ensure post-market safety studies are actually conducted, or that labels can be changed quickly. Its enforcement tools are either too drastic or too weak. There is no system to regularly monitor a drug’s history over its life cycle, and the adverse events reporting system is ineffective,” he said.

Mr Guest particularly welcomed the REMS discussion draft’s proposal for moratorium on direct-to-consumer advertising. “Despite the lack of truly educational information in DTC advertising, consumers tend to believe the pharmaceutical industry’s message that only the safest and most effective drugs appear in advertisements,” he said, adding: “this is particularly dangerous given the fact that the goal of this advertising is to sell a costly product that can potentially have serious safety risks.”

He also urged legislators to encourage the FDA to require the inclusion of a 1-800-FDA number, where consumers can report adverse reactions, in all DTC and other drug ads. “Currently, most consumers probably have no idea that there is an adverse event reporting system or how to participate in that process,” he commented.

However, said Dr Loew, the proposals to curb DTC ads would violate the First Amendment by interfering with the free flow of truthful and accurate information about prescription drugs. Moreover, as DTC advertising encourages dialogue between physicians and patients and promotes improved compliance with physician-prescribed treatments, such restrictions could reduce or eliminate these public health benefits, particularly with respect to new treatments for patients looking for better options, she warned.

She also criticised the discussion draft’s proposal to give the FDA authority to impose distribution and use restrictions when necessary to assure safety, claiming that this could create significant limitations on patient access to needed medications. And, turning to its plan to require the product’s labeling and any DTC advertising to include a “unique symbol indicating the newly-approved status of the drug or indication” for the first two years after a new drug or indication is approved,

Dr Loew pointed out that the FDA had in fact considered a similar requirement, for a black triangle on new drugs for three years following approval, back in December 2000. However, she reminded the panel that after a five-year public stakeholder process, it had abandoned the idea on the grounds that the triangle would not be universally understood and could be confusing to prescribers. By Lynne Taylor