Enhancing Drug Safety - Pharmaceutical Technology

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Enhancing Drug Safety
User-fee legislation will require more testing and data disclosure to prevent unsafe drug use.


Pharmaceutical Technology


A central provision of this broader FDA reform legislation gives FDA added authority to require a Risk Evaluation and Mitigation Strategy (REMS) from companies when the regulators decide that a formal approach is needed to manage prescribing. The legislators initially wanted to require a REMS for all new drugs, but they agreed with manufacturers that such a broad mandate could waste time and resources if applied to well-understood, low-risk products. The REMS process creates "a complicated and bureaucratic safety and oversight system that may not be workable in practice," advised Caroline Loew, senior vice-president at the Pharmaceutical Research and Manufacturers of America, in testimony before the House Energy and Commerce Committee in June.

For those drugs that raise increased safety concerns, manufacturers may submit a REMS plan in a new or supplemental application, or FDA may require such a process based on new safety signals or other information that raises concerns about the safety of a drug already on the market. A REMS would evaluate the need to:

  • Conduct additional postapproval studies and clinical trials to assess a specific safety signal
  • Require labeling changes to disclose new safety concerns
  • Prepare and distribute a medication guide or patient package insert
  • Develop a communication plan for disseminating additional healthcare information to healthcare professionals
  • Seek FDA prereview of advertising and marketing materials to ensure that ads describe risks appropriately and fairly
  • Limit drug prescribing and distribution.

FDA may determine that certain treatments should be prescribed only by health professionals that have special training or expertise and only for certain patients. Distribution similarly could be limited to select wholesalers and pharmacists. Such limited-access programs also may require additional laboratory testing, patient monitoring, and patient enrollment in a registry.

Increasing disclosure

In addition to establishing a REMS for certain products, the legislation enhances FDA authority to implement new oversight and disclosure policies for all drugs. Some of these policies are described below.

Speedy labeling changes. Congress strengthens FDA authority to require manufacturers to make certain labeling changes that reflect new safety information. Under current policy, discussions between sponsors and FDA about the need to revise a product label may take months, or even years. The legislation sets timeframes for negotiating such changes, including the need for black-box warnings and additional information about warnings, contraindications, precautions, or adverse reactions. The negotiating process also includes provisions for sponsors to challenge a requested labeling change and for resolving such disputes. But if FDA insists on a certain change, it will have more power to compel manufacturer compliance.

Timely completion of postapproval studies. FDA currently may request additional clinical trials and analysis following approval of a new drug, but the agency lacks authority to levy fines and other penalties on companies that fail to complete these studies as expected. Long timeframes for completing postapproval studies have frequently been a source of controversy. Sponsors claim that many studies that seem reasonable when a new product is approved for market later appear inappropriate, and many projects have trouble enrolling patients in trials after a drug becomes widely available. But FDA staffers and patient advocates believe that manufacturers often put postapproval studies on the back burner.

The new policy calls for postapproval study options to be discussed earlier in the approval process to ensure that agreements are realistic and address important issues. FDA also can request more postapproval studies after a drug is on the market. Manufacturers will have to propose timetables for completing studies, report periodically on their progress, and explain why they cannot meet set goals if problems arise.

More information about active clinical trials. To better inform patients of opportunities to participate in clinical trials, sponsors will have to submit more information about ongoing clinical trials to the clinicaltrials.gov/ website. The legislation extends the registration requirement to all regulated drugs and beefs up registration listings to include a long list of specific trial information, including whether there is an expanded access program for a not-yet-approved treatment. Congress emphasizes that the registration system should make it easy for patients to search for trials based on disease or condition, trial location, and other factors, and that listings should be updated frequently.


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