45 CFR 46 Subpart C (Additional Protections for Prisoners in Research)

45 CFR 46 Subpart C (“Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects,” §§46.301-46.306) is the section of the Common Rule that governs HHS-conducted or HHS-funded research in which the subjects are prisoners. It requires the reviewing IRB to include a prisoner or prisoner representative and a non-prison-affiliated majority, and it permits prisoner research only where it fits one of four narrowly defined categories.

Who Counts as a “Prisoner” Under Subpart C (§46.303)

Section 46.303(c) defines “prisoner” as any individual involuntarily confined or detained in a penal institution. The definition is broader than “convicted inmate”: it covers individuals sentenced under criminal or civil statutes, individuals detained pending arraignment, trial, or sentencing, and individuals detained in other facilities under statutes or commitment procedures that provide an alternative to criminal prosecution or incarceration. Subpart C attaches based on this confinement status at the time of the research, not the topic of the study or the setting in which it is conducted.

IRB Composition Requirements (§46.304)

When an IRB reviews research covered by Subpart C, §46.304 imposes two specific membership requirements on top of the ordinary Subpart A membership rules:

• Non-affiliated majority. A majority of the Board, exclusive of prisoner members, must have no association with the prison(s) involved beyond their Board membership.
• Prisoner representative. At least one Board member must be a prisoner, or a prisoner representative with appropriate background and experience to serve in that capacity. Where more than one IRB reviews the same research project, only one of the reviewing Boards needs to satisfy this requirement.

These requirements exist alongside, not instead of, the general Subpart A composition and expertise requirements every IRB must already meet.

Additional IRB Duties (§46.305)

Section 46.305 layers additional review duties onto the IRB beyond its ordinary Subpart A approval criteria. Among the findings an IRB reviewing prisoner research must make: that any possible advantages to the prisoner (such as parole consideration) arising from participation are not of such a magnitude that they impair the prisoner’s ability to weigh the risks of the research against the value of participation in the limited-choice environment of a prison; that risks are commensurate with risks accepted by non-prisoner volunteers; that selection of subjects within the institution is fair and not left to the discretion of correctional staff; and that adequate provision is made for follow-up examination or care where research carries a risk of injury. The IRB must also certify to HHS that the requirements of §§46.303-46.305 have been satisfied for each covered proposal.

Permitted Categories of Research (§46.306)

Even after the composition and duty requirements above are met, §46.306 restricts prisoner research to four permitted categories:

• §46.306(a)(2)(i) — Study of incarceration and criminal behavior. Study of the possible causes, effects, and processes of incarceration and of criminal behavior, provided the study presents no more than minimal risk and no more than inconvenience to the subjects.
• §46.306(a)(2)(ii) — Study of prisons as institutions. Study of prisons as institutional structures, or of prisoners as incarcerated persons, provided the study presents no more than minimal risk and no more than inconvenience to the subjects.
• §46.306(a)(2)(iii) — Conditions particularly affecting prisoners. Research on conditions particularly affecting prisoners as a class (for example, vaccine trials and other research on hepatitis, and research on social or psychological problems such as alcoholism, drug addiction, and criminal behavior). This category may proceed only after the HHS Secretary consults with appropriate experts and publishes notice of intent to approve such research in the Federal Register — a public-notice step none of the other three categories require.
• §46.306(a)(2)(iv) — Research intended to improve subject health. Research on practices, both innovative and accepted, that have the intent and reasonable probability of improving the health or well-being of the individual subject.

Research that does not fit one of these four categories, no matter how favorable its risk/benefit profile otherwise looks, cannot be approved for prisoner subjects under Subpart C.

2024 Technical Update

HHS finalized a rule (Federal Register document 2024-24399), effective October 24, 2024, that amended Subparts B, C, and D of 45 CFR 46 for technical and conforming alignment with the 2018-revised Common Rule — updating cross-references and transition-provision language. HHS’s own characterization is that this update made no substantive change to which populations each subpart covers or to the underlying protections described above.

Frequently Asked Questions

Does Subpart C apply to research conducted before someone was incarcerated?

Subpart C is triggered by a subject’s confinement status, not the study’s origin. A person who is not a prisoner when a study begins but becomes one during the study raises a Subpart C question the IRB must address for that subject’s continued participation; a study that only ever enrolls non-confined individuals, even on a prison-related topic, does not trigger Subpart C at all.

Is a prisoner representative required on every IRB at an institution that sometimes reviews prisoner research?

No. The requirement attaches to the specific IRB review of the covered research, not to the institution’s IRB roster generally, and where more than one Board reviews the same project only one needs a prisoner representative. Institutions that regularly review prisoner research commonly add a standing prisoner representative to a designated IRB or panel to avoid ad hoc recruitment for each protocol.

Can a prisoner research protocol be approved under expedited review?

Subpart C’s additional composition and category requirements do not by themselves forbid expedited review where a protocol otherwise qualifies under Subpart A’s expedited-review categories, but in practice most prisoner research is reviewed at a convened meeting given the §46.305 findings the IRB must document and the coercion/undue-influence concerns inherent in a confined population.

See also: 45 CFR 46 Subpart A, the foundational Common Rule provisions Subpart C builds on; 45 CFR 46 Subpart B and 45 CFR 46 Subpart D, the sibling population-specific subparts; Vulnerable Populations in Research, which situates Subpart C alongside the general §46.111(b) IRB safeguard criterion; and OHRP (Office for Human Research Protections), the HHS office that administers and interprets the Common Rule including Subpart C.