‘Flexibility’ Sought in IND Safety Assessment
Stakeholders are calling on FDA to build more flexibility into a draft guidance on safety assessment for IND safety reporting. Pharmaceutical Research and Manufacturers of America (PhRMA) says that “there is a need for flexibility in designing systematic safety surveillance approaches, and therefore suggests that FDA revise the guidance to focus more on the design and deployment of a Safety Surveillance Plan rather than the Safety Assessment Committee (SAC).” It sees a surveillance plan as a useful and flexible tool that can help sponsors develop a prospective and systematic approach to safety reporting that is specifically tailored to the complexities of each individual drug development program.
FDA should acknowledge that flexibility in approaches is allowable so long as sponsors comply with specific regulations, PhRMA says. It says it makes such a recommendation in light of the fact that many sponsors currently have in place robust safety assessment procedures and reporting mechanisms.
The Biotechnology Innovation Organization (BIO) says it is concerned about the prescriptive nature of the draft guidance and its emphasis on a SAC. “We are also concerned that FDA may not fully appreciate the time and resources required of sponsors to implement the recommendations within the draft guidance,” it says. The letter calls on FDA to “allow for more flexibility for sponsors in how safety assessments for IND safety reporting are performed.” It says the flexibility should allow for accommodation of product-specific aspects of a development program, as well as the most efficient use of sponsor resources, given pre-existing internal safety monitoring processes and governance.
BIO’s comments also deal with the resources needed to implement the guidance recommendations, lack of harmonization with other regulatory agencies worldwide, and unblinding data.
The Association of Clinical Research Professionals says that while it appreciates the need for aggregate, program-wide safety surveillance on investigational products, the proposed SAC, as defined in the guidance, “raises a number of concerns, red flags, and risks to trial integrity.” It says the proposed new committee appears to duplicate the functions of already-existing study committees, especially the Data Monitoring Committee. “Consider making the SAC optional if the sponsor determines IND safety reports require significant analytic work best handled by a team of experts,” it recommends.
In its comments, Sanofi raises a concern that the draft guidance creates several challenges for a large company conducting multinational studies with obligations to comply with varying global regulations and guidance. It calls on FDA to integrate the draft guidance into a 12/2012 guidance on safety reporting requirements for IND and BA/BE studies, or at least that relevant references to the 2012 guidance be incorporated in this draft. Sanofi says the proposal to unblind serious events for aggregated analysis purposes “is not free of potential impact on the study data and analysis integrity.” It cautions that unblinding safety data for aggregate reports could cause bias due to (1) study adaptations incorporated or (2) interim unblended aggregate report distribution.
Finally, Merck says that the draft “is too prescriptive regarding the composition and role of the proposed SAC. The ongoing review of safety data can and often is performed by established multi-disciplinary cross-functional teams within companies or by an external Data Monitoring Committee (if one exists for the product). For sponsors who already have robust processes for overseeing the safety of an investigational product throughout its clinical trial development program, such alternative approaches should be allowed. It would be resource-intensive and duplicative to develop parallel SACs with the same cross-functional expertise to review unblended data from ongoing clinical studies.”