FDA has finalized its November 2018 proposal to provide the agency with the authority to permit an exception from informed consent requirements when the proposed clinical testing poses no more than minimal risk to the human subject and includes appropriate safeguards to protect the rights, safety, and welfare of the human subject. The final rule adds Section 50.22, “Exception from informed consent requirements for minimal risk clinical investigations” to CFR Part 50, which permits an additional exception from the general requirements of informed consent for certain FDA-regulated clinical investigations when:

• The investigation involves no more than minimal risk to the subjects;

• The investigation could not practicably be carried out without the requested waiver or alteration;

• If the clinical investigation involves using identifiable private information or identifiable biospecimens, the clinical investigation could not practicably be carried out without using such information or biospecimens in an identifiable format (see discussion below);

• The waiver or alteration will not adversely affect the rights and welfare of the subjects; and,

• Whenever appropriate, the subjects or legally authorized representatives will be provided with additional pertinent information after participation.

In a press release announcing the latest final rule, FDA Commissioner Robert M. Califf, M.D., praised how the rule “will enable minimal risk research that would not be practicable to conduct otherwise,” including “studies comparing the effectiveness of approved products to determine which option works best for certain patients.”

Changes in the final rule

Though the final rule largely mirrors the proposed rule, FDA made minor organizational and editorial changes to the regulation that aim to increase clarity and consistency with the regulatory text of the revised Federal Policy for the Protection of Human Subjects, known as the “Common Rule.” For example, the final rule simplifies the regulatory text to make explicitly clear (in 21 USC § 312.60) that it is the investigator who is responsible for obtaining the informed consent of each human subject to whom the drug is administered in accordance with Part 50.

FDA also made the minor editorial change to the text “or that waives,” such that it now reads “or may waive.” As previously intended, the regulation permits the IRB responsible for the review, approval, and continuing review of the clinical investigation to approve an informed consent procedure that does not include or that alters some or all of the elements of informed consent in § 50.25(a) and (b) of FDA's current regulations, or to waive the requirement to obtain informed consent, provided that the IRB finds and documents five criteria under § 50.22(a) through (e).

In addition, based on comments received on the proposed rule, FDA added a criterion at § 50.22(c) that states that if the clinical investigation involves using identifiable private information or identifiable biospecimens, the clinical investigation could not practicably be carried out without using such information or biospecimens in an identifiable format. This fifth criterion was previously incorporated by FDA in its July 2017 guidance “IRB Waiver or Alteration of Informed Consent for Clinical Investigations Involving No More Than Minimal Risk to Human Subjects,” which FDA intends to withdraw after the final regulations become effective.  Note that if identifiable information and/or biospecimens will be used, an IRB waiver of authorization under the Health Insurance Portability and Accountability Act (“HIPAA”) may also be necessary to the extent HIPAA applies.

Last, in adding § 50.22(e), FDA adopts the criterion that was proposed at § 50.22(d) and adds “or legally authorized representatives” to the criterion. This means that whenever appropriate, the subjects or legally authorized representatives will be provided with additional pertinent information after participation.

Separate single IRB and human subject research regulations proposals

This most recent rule does not affect FDA’s separate September 2022 proposed rules that aim to clarify inconsistencies between FDA’s human subject protection regulations and the Common Rule, and that would promulgate a single IRB requirement under FDA’s regulatory authority. We summarized those proposals online here, and FDA has yet to indicate in HHS’ regulatory agenda any timeline for finalization of those rules.

Last year, however, FDA finalized nine-year-old draft guidance on informed consent for sponsors, institutions, IRBs, and investigators; we summarized that final guidance online here. Taken together, these efforts show increasing regulatory focus on human subject protection issues and on FDA / HHS coordination.

Next steps

The final rule is effective January 22, 2024.