FDA seeks comment on post-market drug safety plans

The US Food and Drug Administration (FDA) DA has published draft guidance describing plans on how to handle serious drug safety issues with marketed drugs, which is now open for comment.

The guidance is intended to lay out a framework for the agency's response to post-marketing safety issues including serious adverse events, product quality issues and medication errors, with a ranking system to help prioritise each issue according to its level of risk.

The FDA has been criticised in a string medical journal articles in the last 18 months for not monitoring its own adverse event reporting (AER) database effectively enough and failing to communicate safety issues in a timely and effective way to healthcare professionals and the public.

For example, a study published in Medical Care in January concluded that while some FDA drug risk communications had immediate and strong impact, many had either delayed or had no impact on healthcare utilisation or health behaviours.

Similar conclusions were drawn by articles published in Archives of Internal Medicine and the Journal of the American Medical Association in 2011.

The FDA's Center for Drug Evaluation and Research (CDER) maintains that it has been refining its procedures for handling safety issues for some time, for example launching a centralised tracking system in 2007 called DARRTS (Document Archiving, Reporting, and Regulatory Tracking System) to help manage information about safety issues.

Since the introduction of DARRTS, about 1,000 tracked safety issues (TSIs) have been entered into the database, says the draft guidance document.

"Although all of these issues are considered significant, all 1,000 TSIs are not, in fact, of the same urgency," it says. "Without sufficient resources to manage all TSIs equally, FDA has been prioritising them on a case-by-case basis, but without an agreed-to priority framework."

Three levels
The new guidance aims to remedy that situation with the establishment of a means of prioritising TSIs according to risk with three levels: priority, standard or emergency. Those deemed to be priority or emergency will be most closely monitored, with clear timelines for decision-making.

Once a TSI is logged, FDA staff will undertake a hazard assessment looking at issues such as the nature of the safety issue, the size of the population exposed to the drug and the likelihood that patients will be harmed by it.

The assessment will then move on to various modulating factors, such as whether there are therapeutic alternatives available, if the drug is used in a supervised setting and/or whether the population at risk of the safety issue is vulnerable.

Among the mechanisms used to manage the TSIs are label changes, risk evaluation and mitigation strategies (REMS), and withdrawal of the drug, either voluntarily or via removal of its marketing approval.

The FDA is now seeking comments on the proposal and says it hopes to begin implementing it within the next year.

• The FDA has the draft guidance available for download