CDER releases policy for handling newly identified safety signals

The US Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) last week issued a new manual of policies and procedures (MAPP) explaining its internal process for identifying, evaluating and resolving newly identified safety signals (NISS) for marketed drugs.
 
FDA says the MAPP is meant to provide a “high level” overview of how and when communication related to newly identified safety issues is transmitted between different offices and disciplines within CDER. The MAPP applies to safety signals related to approved drugs and biologics, marketed yet unapproved drugs, over-the-counter monograph products, compounded drugs and medical gases.
 
FDA explains that NISS are serious adverse events, medication errors or adverse events that suggest therapeutic inequivalence or quality issues that warrant further investigation. NISS also include quality issues that “could negatively affect public health or the benefit-risk profile of a product; and cannot be resolved through existing routine processes,” such as recalls or inspection findings.
 
Within the MAPP, FDA lays out a three-phase process for evaluating and managing NISS and explains staff responsibilities during each phase. The MAPP also sets timeframes for evaluating NISS based on the level of risk identified: six months for important potential risks and 12 months for potential risks. If a NISS is categorized as an emergency, CDER leadership is tasked with setting an evaluation timeframe.
 
During the pre-evaluation phase, the signal identifier is tasked with determining whether a potential safety signal is a NISS and triaging the NISS for further evaluation.
 
At the evaluation phase, a safety lead is named to manage the evaluation and make a recommendation to the signatory authority that will ultimately make a final decision on the NISS. During the evaluation phase, the NISS team will determine the risk of the safety signal, whether regulatory or compliance actions are necessary and whether a drug safety communication or drug alert is warranted.
 
The MAPP also calls for staff to “be transparent to industry and the public about CDER’s postmarket safety work,” and provides instructions for notifying application holders and manufacturers during the NISS evaluation.
 
When a NISS moves to the action phase, the signatory authority is tasked with coordinating the implementation of any actions identified during the evaluation. Once complete, the outcome is documented and the NISS is closed out with instructions for future monitoring if necessary or a switch to routine pharmacovigilance and surveillance.
 
FDA