FDA Clarifies Human Subjects Protection Expectations

A new guidance from the U.S. Food and Drug Administration (FDA) provides welcome direction to sponsors, investigators, and institutional review boards (IRBs) on human subjects protection.

The guidance is one of the agency’s follow-ups to its revisions of the “Common Rule” (Federal Policy for the Protection of Human Research Subjects), which became effective in July 2018. General compliance for the revised Common Rule is mandated to begin in January 2019. The purposes of the Common Rule are to promote “uniformity, understanding, and compliance with human subject protections and to create a uniform body of regulations across federal departments and agencies,” FDA explains in the new guidance.

The requirements contain several new areas of informed consent, including changes relating to the content, organization, and presentation included in the consent form. It also clarifies the process to facilitate a prospective subject’s decision about whether to participate in research. FDA is clarifying the provisions to help sponsors and investigators develop, and IRBs implement, two separate informed consent forms.

The guidance also follows up on earlier FDA rules which allowed IRBs to use expedited review procedures for certain kinds of research involving “no more than minimal risk.” The new guidance includes a list of categories that may qualify for the fast track, while it also makes clear that, as appropriate, IRB reviewers must find that the research on the list involved no more than minimal risk.

EMA: Compliance Guidelines for Clinical Trial Master File Requirements

Is adhering to ICH Good Clinical Practice guidelines enough to ensure compliance?

The European Medicines Agency’s latest guideline says clinical trial master files should also include quality reports and checklists, product certifications and trial-specific computer system guides. These essential documents are not listed as required in ICH Good Clinical Practice guidelines. This guideline includes the following:

• Documentation that would help evaluate the trial’s conduct should be included in the file, whether they were explicitly listed in guidelines or not.

• Both paper and electronic TMF information should be verifiable with an audit trail and should protect subject confidentiality.

• TMF organization should segregate documents held by the sponsor and those held by the investigator, while avoiding duplication (i.e., separating product-development level documents such as training records, SOPs or product brochures, as well as relevant GMP information).

• Clinical master files must be archived for at least 25 years following the end of the clinical trial. For all trials that support a marketing authorization, essential documents must be retained for at least 15 years, or at least 2 years after the last approval. Subject medical files should be retained in accordance with national regulations.

Download the guidance here.