Regulatory Focus™ > News Articles > Post-FDAAA, Regulators Move to Adapt to Changing Risk Models

Post-FDAAA, Regulators Move to Adapt to Changing Risk Models

Posted 01 June 2012 | By Alexander Gaffney, RAC 

With all the attention given to the US Food and Drug Administration's (FDA) approval process, it can sometimes be easy to forget an equal amount of its time is spent on postmarketing issues related, in part, to product safety. Two components of assuring a product's safety involve adverse event reporting (AER) and risk management plans, both of which were the focus of a presentation given at Harvard Medical School in early May 2012.

In his presentation, Dr. Gerald Dal Pan, FDA's Acting Director of the Office of Surveillance and Epidemiology (OSE) at the Center for Drug Evaluation and Research (CDER), provided an update regarding recent postmarketing risk analysis trends at the agency and where the agency is headed in the future.

Adverse Event Reporting

Dal Pan noted FDA is overseeing a growing volume of dispensed medical products. In 2001, FDA oversaw a total of three billion dispensed prescriptions from outpatient retail pharmacies. By 2011, that number had increased to 3.6 billion dispensed prescriptions.

Historically, said Dal Pan, "individual case safety reports were the main source of drug safety information," and these reports were primarily about rare but major events resulting from drug or toxin exposure.

As time has gone on this situation has changed dramatically. Large databases, not people, now regularly scour large volumes of data and are able to detect far more subtle adverse event reactions which may be substantially more common in the general population.

As a result of the simultaneous trends of increasing prescriptions and adverse event tracking technologies, FDA has seen a dramatic rise in the number of adverse event reports brought to its attention. In 2001 the agency saw approximately 200,000 adverse event reports, of which roughly half were expedited reports sent through an FDA web system. By 2011, FDA was receiving nearly 800,000 adverse event reports each year, of which approximately 2/3rds were expedited adverse event reports.

To increase the quality of the reports, FDA has been looking at passive reporting systems requiring less human interaction to file a report. A report could be generated through an automated system, for instance, if a physician stops prescribing a medication due to an adverse reaction. The report would already contain the patient's file history and information, and would only require more information about the specific adverse event.

The approach, used briefly in a pilot program known as the ADE Spontaneous Triggered Electronic Reporting System, or ASTER, had a number of flaws preventing it from being widely implemented, said Dal Pan. These problems included the ability to obtain demographic and "other easily derived objective data" from the reports and missing data. Nevertheless, the "approach is feasible and needs to be refined to improve report quality," concluded Dal Pan.

Risk Management

FDA has also been looking to reduce the total of adverse events experienced by the public through a range of risk management strategies.

One of the most visible strategies is its use of Risk Evaluation and Mitigation Strategies (REMS) plans, which were implemented under the terms of the Food and Drug Administration Amendments Act of 2007 (FDAAA). FDA has issued approximately 201 REMS plans since the authorization of FDAAA, and FDA has become increasingly nuanced about how and when it mandates the plans.

Instead of a plan to restrict access to medication, for instance, FDA might approve the use of a Medication Guide to educate consumers about the safe use of a product without requiring a full REMS plan. This is a significant divergence from previous iterations of FDA policy, explained Dal Pan. The agency formerly required all new Medication Guides as an element of a REMS program.

Of the 201 approved REMS plans, 125 have been Medication Guide-only REMS, 36 have elements to assure safe use, and 40 have a communication plan as their main mode of action. Some of these REMS plans have changed after their initial approval, with some losing the REMS plan altogether, and others being down-graded to less restrictive REMS plans.

Del Pan said the agency is continuing to refine its approach to risk management plans, and to expect further changes in the future.


Read more:

FDA - Emerging Regulatory Changes in Post-Approval Safety and Risk Management


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