PhRMA, AdvaMed weigh in on safety reporting draft guidance

Regulatory NewsRegulatory News | 08 December 2021 |  By 

Two industry trade associations and a pharmaceutical company are asking for some adjustments and clarification on the US Food and Drug Administration’s (FDA’s) draft guidance on safety reporting or investigational drugs and devices. The comment period on the guidance closed at the end of November.
FDA’s draft guidance includes details of how the agency believes investigators should report serious and non-serious adverse events in investigational new drug application (IND) studies and investigational device exemption (IDE) studies, including unanticipated problems with “risk to human subjects or others” and “unanticipated adverse device effects” in IND and IDE studies, respectively. (RELATED: FDA drafts safety reporting guidance for drug and device investigators, Regulatory Focus 1 October 2021)
Comments from PhRMA
In their comments to FDA, the Pharmaceutical Research and Manufacturers of America (PhRMA) mostly agreed with the agency’s overview of investigator responsibilities. PhRMA noted that sponsors are “generally better positioned” in IND studies to make decisions on whether severe adverse events (SAEs) can be attributed to a suspected adverse reaction based on their level of involvement with the drug’s mechanism of action and each participants’ medical history.
PhRMA did suggest one change to FDA’s section on the responsibility of investigators to review safety reports. “Considering the importance of the investigator’s role in assessing the safety of the investigational product and reviewing safety reports, PhRMA suggests the discussion on the investigator’s responsibility to review safety reports be placed in its own dedicated section of the draft guidance,” they wrote.
Comments from AstraZeneca
Commenting on the FDA’s section in investigator responsibilities in IND studies, AstraZeneca wrote that the safety reporting data structure should now contain clear guidance on investigational reporting of drugs and devices under an IND, and asked if device data should be included in that reporting structure.
AstraZeneca also questioned the number of days FDA laid out for investigators to report an unanticipated device effect (UADE) in a study. “Considering that a UADE could be a life-threatening or fatal event, a window of 10 days for the investigator to report to the sponsor after first learning of the effect seems unduly long and potentially places study participants at unnecessary risk as the sponsor may not be able to act with the required urgency to address the problem if not notified immediately,” the company wrote. “In contrast, SAEs from IND studies must be reported to the sponsor within 1 calendar day.”
Comments from AdvaMed
The Advanced Medical Technology Association (AdvaMed) provided several broad suggestions to FDA’s draft guidance. AdvaMed first suggested the agency expand the guidance title to include both investigators and industry stakeholders to “facilitate compliance with the recommendations.”
In general, AdvaMed questioned whether the guidance applied in the case of a retrospective real-world evidence (RWE) investigations, rather than IDE studies alone. “The proposed draft guidance appears to be narrowly scoped towards IDE studies only, but many device manufacturers are leveraging RWE and other retrospective data to allow for claims expansion in a least burdensome approach,” AdvaMed said. “The guidance should specify whether RWE investigations are in or out of scope of the current guidance and if not provide recommendations for how to handle discovery of UADEs for these different study types.”
Another recommendation from AdvaMed was to expand the devices portion of the definition section of the guidance to include causality. When attributing a serious adverse event to an unanticipated adverse effect of a device, “positive causality should be provided by either the investigator or the sponsor because the relationship of the serious adverse device effect can be incorrectly attributed to the device by confounding factors. Additionally, to avoid either over- or under-reporting, clearer grounds for assigning causality should be provided,” they wrote.
While a discussion on causality exists in the section of the guidance outlining investigator reporting to sponsors for IND studies, “the guidance would be considerably stronger and more useful if a discussion on causality were added to the UADE section,” AdvaMed wrote.
Comments on draft guidance



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