ASAP Process BLOG

The FDA is replacing its current annual reporting requirement for INDs with a more comprehensive and informative FDA Development Safety Update Report (FDA DSUR), which is described in FDA’s ICH guidance for industry: E2F Development Safety Update Report (E2F DSUR).  To be considered, comments on the proposed rule must be submitted by March 9.

The current IND Annual Report was only intended to provide summaries of clinical studies conducted under an IND.  However, simply accumulating and reporting data for a given time period – as required under the current IND annual report – without considering all previously available data from clinical trials and other sources, could delay identification of important risks.

The FDA DSUR is a tool for FDA and sponsors, partnering together, to identify and manage potential risks and to reduce exposure of human participants to unnecessary risks.  It expands the scope of the annual update to include comprehensive information from clinical investigations conducted anywhere in the world and a description of all actions relevant to the safety of the drug by any regulatory authority or by the sponsor.  Note, this only requires sponsors to submit the information that is known to them.  It does not create a requirement for sponsors to seek out unpublished studies.  Also, it does not create a requirement for study teams to unblind ongoing blinded studies, rather, for these studies, numbers could be estimated.

The DSUR provides recommendations with respect to periodic safety reporting during clinical development, offers guidance on providing meaningful information to regulators, and facilitates consistency among sponsors and regulators.  It provides an update on the status of the clinical development program and study results, summarizes current understanding and management of identified and potential risks, and describes new safety findings that could have an impact on the protection of study subjects.  Importantly, it examines whether information obtained during the reporting period aligns with prior knowledge of the safety of the investigational drug.

The comprehensive and detailed safety summary will enable FDA to more efficiently identify and review new safety signal information and will create a more efficient reporting process to FDA and regulatory authorities worldwide.  In addition, it will allow regulatory authorities worldwide to have access to the same data at the same time.  This will help harmonize annual reporting of clinical trials, thus enhancing efficiency and providing regulators, investigators, patients, and industry with valuable, consolidated safety information.

There is one section, in particular, that I would like to draw your attention to…

The overall safety assessment is a concise, integrated evaluation of all new clinical, nonclinical, and epidemiological safety information obtained by the sponsor during the reporting period relative to previous knowledge of the drug.  It is not intended to require a repeat of information presented in previous sections; however, it will require an interpretation of the information and its implications for the IND, and an explanation of how safety information obtained during the reporting period integrates with what was already known about the drug.  Furthermore, it will require a description of the balance between benefits (theoretical or anticipated) and cumulative identified risks related to use of the drug and any changes to the benefit-risk profile.

Meaningful understanding of the evolving safety profile of an investigational drug requires a periodic analysis of all available safety information.  Integrated analysis and a summary of overall safety risks would help increase the usefulness of the safety data and help facilitate efforts to expeditiously identify and assess important safety risks.

One more reason to make sure that your Aggregate Safety Assessment Planning (ASAP) process is firmly in place.