Cures Law Requires FDA, HHS to Harmonize Regs

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By Jeannie Baumann

Any discrepancies in how the FDA and the HHS regulate human subject research must be resolved over the next three years under a new requirement in the 21st Century Cures law.

The biomedical innovation law, which President Barack Obama signed Dec. 13 (Pub. L. No. 114-255), seeks to spur development and approval of new drugs and devices to get them to patients more quickly.

While much of the conversation on Cures focused on the billions of dollars in new research money, lawmakers also aimed to remove administrative burdens so scientists can spend more time on their research and less time on paperwork. Any provisions related to that goal will have a clear impact on research administrators, institutional review boards and anyone who is responsible for complying with research participant protection requirements.

Section 3023 of the Cures law, Protection of Human Research Subjects, directs the Department of Health and Human Services to harmonize “to the extent practicable and consistent with other statutory provisions” any differences in the human subject regulations between the Common Rule (45 C.F.R. 46), which is administered by the HHS Office for Human Research Protections, and the Food and Drug Administration‘s regulations (21 C.F.R. 50, 56, 312 and 812). The requirement is a move to “simplify and facilitate compliance by researchers with applicable regulations for the protection of human subjects in research,” the law said.

The HHS has until Dec. 13, 2019—three years from Cures’ enactment date—to complete this harmonization process, with a progress report due within two years of enactment. But in many ways, this section of Cures simply codifies steps the two agencies have taken for years. The FDA and the OHRP are releasing an increasing number of joint guidance documents, including the Dec. 14 one on electronic informed consent. The OHRP’s advisory panel also has focused on this area through a harmonization subcommittee it established more than six years ago.

Impact of Common Rule Changes

The Common Rule also could look very different between now and the next three years as it is undergoing its first-ever rewrite. Proposed revisions in the 519-page proposed rule include substantial changes to the regulation of biospecimens, provisions to encourage use of a single IRB to review multisite studies and changes to informed consent requirements.

“What will be harmonized will of course depend on the outcome of the Common Rule revisions,” Heather H. Pierce, senior director of science policy and regulatory counsel for the Association of American Medical Colleges, told Bloomberg BNA on Dec. 8. “If the Common Rule is substantially revised and implemented, the FDA regulations would need to be revised substantially as well.”

There are a few notable differences between the FDA regulations and the Common Rule, Pierce said, including the scope, definitions and rules on waiving informed consent. “Some of the differences are because of the interpretation of the relevant statute and would be harder to make identical,” she said.

Mark Barnes, a research attorney with Ropes & Gray LLP , said Dec. 8 the most important harmonization would be to add a process for waiving informed consent in the FDA regulations.

Regulatory Differences

According to an FDA table comparing the two sets of regulations, the FDA section on IRB review of research (21 C.F.R. §56.109) is virtually identical to the OHRP’s (45 C.F.R. §46.109), with the following exceptions:

  •  FDA regulations don’t include the Common Rule criteria in 45 C.F.R. §46.117 for waiving the requirement for a signed consent form. Those provisions aren’t in the FDA’s regulations because the “FDA does not regulate research in which the only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality.”
  •  The FDA’s regulations (21 C.F.R. §§56.109(c) and (e)) contain additional language related to the agency’s emergency research rule; the HHS published identical criteria “for emergency research in a Secretarial announcement of waiver of the applicability of 45 CFR 46.”
The FDA has a provision (21 C.F.R. §56.105) allowing it to waive any of the IRB requirements contained in its regulations, including the requirement for IRB review, for specific research activities or for classes of research activities. There is no comparable provision under the Common Rule, the FDA said.

Gary L. Chadwick, senior consultant with HRP Consulting Group, who previously held leadership positions at both the FDA and the OHRP, noted the FDA already has agreed to harmonize its regulations with any Common Rule changes ( 09 LSLR, 10/30/15 ). But if a final revised Common Rule never gets published, these “could be empty words or supportive words.” “In a wild dream scenario, it could mean doing away with [human subject protection sections] 50 and 56,” referring to FDA regulations, “in favor of adopting special provisions into the Common Rule that account for the FDA’s regulation of medical products,” Chadwick said. But the percent chance if this happening is “less than 0.0000001" percent, he wrote in a Dec. 9 e-mail.

IRB Provisions

Cures mentions IRBs several times throughout the nearly thousand-page law. Most notably, the enacted version appears to pull back on a mandate to require a single IRB for multisite studies. This requirement appeared in a 2015 version of the bill that passed the House, but wasn’t in the enacted version. The Cures law Section 3023 says that research subject to the FDA or the HHS’s human subject rules “may use” joint or shared review, or rely on an independent IRB, another institution’s IRB or “use similar arrangements to avoid duplication of effort.”“It means that the [Cures] revisions should expedite and make easier the voluntary use of central IRBs,” Barnes said. Pierce expressed similar thoughts. “I read that language as a directive to remove regulatory barriers to using single IRB, but not a mandate itself or additional authority to HHS to impose a mandate,” she said.But even though it’s not a statutory requirement through Cures, the National Institutes of Health has moved forward with a single IRB requirement as a condition of receiving grant funds, and the proposed Common Rule revisions include a similar requirement.

Separately, in creating a new mechanism to expedite review of breakthrough devices—similar to a pathway that already exists for drugs—the regulations require the FDA to “assign staff to be available within a reasonable time to address questions by institutional review committees concerning the conditions and clinical testing requirements applicable to the investigational use of the device.”

Cures also frees up multisite device studies to move to a single IRB review model by striking the requirements for a local IRB in the device regulations under Section 3056 of the law. Under a separate section on pregnant and lactating women (Section 2041), Cures directs the HHS to “consider any appropriate criteria to be used by institutional review boards and individuals reviewing grant proposals for excluding pregnant women or lactating women as a study population requiring additional protections from participating in human subject research.”

To contact the reporter on this story: Jeannie Baumann in Washington at

To contact the editor responsible for this story: Randy Kubetin at

For More Information

A summary of the 21st Century Cures sections is at

An FDA chart outlining the differences between the regulations is at

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