Protocol Deviations for Clinical Investigations of Drugs, Biological Products, and Devices; Guidance for Industry - Draft Guidance

A Clinical Operations Lead at a global CRO supports the draft guidance but requests specific clarifications regarding the definition of "immediate hazards to human subjects." The commenter argues that hazards preventable by stopping or not initiating the use of an investigational product should not be classified as "immediate" to ensure proper protocol amendments and IRB approvals.

The Association of Clinical Research Organizations (ACRO) supports the FDA's draft guidance on protocol deviations but requests specific modifications to improve clarity and international alignment. They argue that certain terminology in the draft creates confusion with EU and UK standards, potentially leading to over-reporting, and they advocate for a more risk-based, harmonized approach.

Boehringer Ingelheim Pharmaceuticals, Inc. provides specific technical comments and proposed revisions to the draft guidance on protocol deviations for clinical investigations. The company seeks to clarify reporting timeframes, the distinction between safety and data integrity issues, and the classification of deviations at the site versus participant level.

Otsuka Pharmaceutical Development & Commercialization, Inc. expresses appreciation for the FDA's efforts in creating guidance for protocol deviations in clinical investigations. They provide a specific technical suggestion to clarify reporting requirements for the Study Data Tabulation Model.

The commenter suggests that the draft guidance should more clearly specify that deviations occurring at the study level or due to protocol omissions should be reported by the sponsor rather than individual sites. They argue that sites lack the necessary information to provide meaningful root cause analyses for such issues and request more nuanced reporting requirements for minor deviations.

Dr. Bo E. H. Saxberg, representing DDO Strategic Services, LLC, supports the draft guidance and suggests a more nuanced classification system for protocol deviations. He proposes a 2x2 categorization based on importance and predictability (Expected vs. Unexpected) to better align with modern industrial process control and risk-based monitoring.

The National Center for Health Research, a nonprofit public health think tank, supports the draft guidance but argues that it needs to be even more specific and objective to ensure the integrity of clinical research results. They urge the FDA to provide clear instructions on deviations that could bias data, such as those affecting blinding and randomization, rather than loosening requirements.

PhRMA, representing leading biopharmaceutical research companies, supports the FDA's draft guidance on protocol deviations but requests several specific revisions. They argue for better alignment with International Council for Harmonisation (ICH) guidelines, a shift in focus from reporting "all" deviations to "all important" deviations, and clarifications on reporting timelines and data standards.

EMD Serono, the healthcare business of Merck KGaA, supports the draft guidance but proposes several specific refinements to improve clarity and practical implementation. They suggest narrowing the definition of "protocol" to avoid excessive reporting, clarifying the role of investigators, and recommending a separate, structured monitoring approach for protocol deviations related to safety events.