Pharma wants FDA’s IND reporting rule better aligned with ICH E2F

Pharmaceutical industry stakeholders urged the US Food and Drug Administration (FDA) to better align its investigational new drug application (IND) annual reporting proposal with the International Council’s for Harmonization’s (ICH) E2F guidance on development safety update report (DSUR), especially with regard to the cut-off date for submitting annual reports.
 
These comments are in response to FDA’s proposed rule issued in December 2022 outlining changes to the current annual reporting requirements under 21 CFR 312.22 for investigational new drug applications (INDs) to better harmonize the format and content for periodic safety reporting during clinical trials with the ICH E2F guideline, which was adopted in 2010.
 
FDA received 16 comments on the guideline from major industry groups such as the Pharmaceutical Research and Manufacturers of America (PhRMA) and the Consumer Healthcare Products Association (CHPA), as well as pharmaceutical companies, hospitals, and research centers. The deadline for commenting was 9 March.
 
Most of the comments expressed broad support for the guideline and endorsed FDA’s efforts to harmonize the proposal with the international guideline. Yet many said the agency did not go far enough in its alignment efforts.
 
PhRMA said it “strongly supports FDA’s efforts through the proposed rule to replace current investigational new drug application (IND) reporting requirements with an annual FDA development safety update report (DSUR).”
 
EMD Serono, Merck KGaA’s US and Canadian arm, concurred. The company said it “strongly supports the proposed rule to replace the Agency’s current annual reporting requirement for investigational new drug applications (INDs) under 21 CFR 312.33 with a new requirement: the annual FDA development safety update report (FDA DSUR).”
 
The Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard (MRCT Center) said the proposed rule “will likely increase the burden of annual reporting for Investigational New Drug (IND) sponsors that are not currently submitting DSUR reports (e.g., biotechnology companies),” yet asserted that “the increased burden is more than offset by the expected, potentially significant, safety benefits.”
 
Comments want alignment on data lock points

Most respondents requested greater alignment with the ICH guideline on the definition of a cutoff date, or a data lock point, for submitting annual reports.
 
FDA’s proposed rule defines the data lock point as one calendar day before the anniversary of the date the IND went into effect and proposes that sponsors submit the annual FDA DSUR to FDA not later than 60 calendar days after the data lock point.
 
Yet the ICH E2F guideline defines the data lock as the Development International Birth Date (DIBD) as the start of the annual period for the DSUR, or the date the sponsor received its first authorization to conduct a clinical trial in a country. The start of the annual reporting period for the DSUR is the month and date of the DIBD.
 
EMD Serono said it “strongly recommends that the choice of Data Lock Point follows ICH E2F and remains globally harmonized. Using the ICH E2F definition will reduce the need for sponsors to request waivers to align the data lock point or the need to submit abbreviated or overlapping DSURs.”
 
The MRCT Center said it would like to see the data lock point changed as well, stating that “the reasons for selecting a definition that differs from the DIBD are unclear.”
 
Samsung Bioepis similarly requested that the data lock point be aligned with ICH to “relieve the additional burden on sponsors to submit multiple waiver requests on the change of data lock point if they are to be consistent with other global regulatory documents.”
 
CHPA also weighed in with its opposition. “Given a scenario that a member (sponsor) already prepares the European Union (EU) DSUR for the active ingredient with a data lock point (for example, June 30), which is different than the ideal data-lock point of the FDA DSUR (1 calendar day before the anniversary of the date the IND went into effect (for example November 18), CHPA requests that manufacturers be allowed to submit the same EU DSUR (with a data lock point of June 30) to the Agency.”
 
PhRMA also requested that the report’s executive summary be changed to require sponsors only list the number of countries where the drug has been approved, and not list the country or regions where the drug has been approved for marketing. This would align with the ICH E2F guideline.
 
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