FDA Struggles with Risk Management and Drug Safety - Pharmaceutical Technology

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FDA Struggles with Risk Management and Drug Safety
Weighing the pros and cons of REMS for bringing risky products to market.

Pharmaceutical Technology
Volume 34, Issue 9, pp. 26-32

Promoting competition

An added challenge is whether REMS programs erect barriers to generic-drug development and marketing. There is general agreement that generic and innovator products should use a shared risk-management system to avoid unnecessary multiple approaches. Achieving that goal, however, raises questions about who controls the risk program and how costs should be shared—both for REMS developed for drugs before generic competition begins, and for those that are modified after generic competition starts.

FDAAA specifies that a REMS should not prevent generic drugs from entering the market and includes provisions that provide considerable relief for generic-drug makers during REMS implementation. FDAAA requires FDA, rather than generic-drug firms, to operate REMS communication plans for generic drugs, primarily to avoid creating multiple educational and information programs for providers. Generic-drug firms, unlike brand companies, are not required to assess the effectiveness of REMS programs.

But generic-drug manufacturers complain of innovator tactics that can slow down market authorization. Brand manufacturers, they claim, cite limited distribution systems imposed by highly restrictive REMS programs as an excuse for denying the release of products for bioequivalence testing needed to develop generic versions of a drug. Health plans and payers fear similar tactics by developers of follow-on biologics, which generally involve more risky therapies that likely will be subject to restrictive REMS requirements.

Restricted distribution programs also thwart open competition by preventing capable specialty pharmacies from dispensing certain drugs, according to Kaiser Permanente. The health plan has its own in-house pharmacy operation with specialty pharmacy services, and says that having to purchase a drug through an outside distributor adds to costs and delays access to drugs.

More collaboration

Added support for REMS and other postmarketing drug-safety programs, such as the proposed safety initiative for long-acting opioids, could come from FDA's Safe Use initiative. The agency launched Safe Use last November to encourage agency collaboration with healthcare providers, patient groups and other government agencies on programs to promote the safe use of medical products. FDA aims to identify drugs associated with potential harm and to devise plans to work with hospitals, doctors, nurses, patient groups, and others on ways to mitigate these risks. These programs could involve distributing information to consumers and improving packaging and dosing devices.

In some situations, however, FDA's hands are tied. The agency has authority to regulate drug manufacturers, but cannot regulate health professionals or the practice of medicine. The agency, therefore, cannot require a medical society to add certain information on a new drug to a medical education program or mandate that physicians take a certain educational program.

Consequently, FDA must impose REMS requirements on regulated companies, even though such action may put the agency in the awkward position of requiring manufacturers to "influence healthcare," Woodcock pointed out. Many healthcare providers and payers are leery of manufacturer involvement in continuing medical-education programs and reject many pharmaceutical-funded initiatives as overly promotional. These concerns will continue to shape REMS programs and efforts to ensure the safe use of drugs throughout the healthcare system.

Voluntary REMS are not enough

In July, FDA asked two advisory committees to weigh its proposal for preventing the misuse and abuse of long-acting opioid painkillers. The response reveals just how difficult it is for the agency to find a comfortable middle ground between ensuring the safe use of risky products and maintaining patient access to needed therapy. Despite more than a year of collaborative efforts by manufacturers and consultations with stakeholders, the members of the Anesthetic and Life Support and Drug Safety and Risk Management Advisory Committees voted overwhelmingly (25 to 10) to reject FDA’s proposed classwide REMS plan, which relies on a voluntary educational program for prescribers to curb illegal use of these drugs. The practitioners and academics on the panels said that FDA’s plan was too weak and unlikely to to stop unsafe use of these potentially dangerous products. Instead, they urged a much tougher approach, with mandatory training for prescribers linked to an assessment of competencies and licensure. They also called for extending the program to immediate-release opioid products, which some panel members consider just as dangerous as the long-acting drugs.

FDA officials said they lack the authority and resources to adopt these recommendations. The agency previously has mandated the training of health professionals, but for much smaller product classes involving far fewer practitioners, explained John Jenkins, director of CDER’s Office of New Drugs. More than 700,000 providers are authorized to prescribe long-acting opioids to some 4 million patients, and a mandatory educational program could place a large burden on the healthcare system. Broadening the REMS to all opioids would only compound the problem.

One option is to link prescribing of opioids to the federal Drug Enforcement Agency (DEA) registration system, which oversees the prescribing and dispensing of controlled substances. Such a move would require legislation that links training on opioids use to obtaining a DEA prescriber-registration number. FDA still may launch its voluntary opioid REMS while waiting for Congress to act. Alternatively, the agency could ask manufacturers to devise a new program that limits opioid prescribing to providers who complete mandated training and are listed in a registry of qualifying physicians. The goal still would be a single educational and registration system, designed by brand and generic-drug manufacturers that hopefully would continue to work together.

Jill Wechsler is Pharmaceutical Technology's Washington editor, 7715 Rocton Ave., Chevy Chase, MD 20815, tel. 301.656.4634,


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