Department of Health and Human Services Policy for the Protection of Human Research Subjects: Update to the Additional Protections for Specific Populations

<RULE> DEPARTMENT OF HEALTH AND HUMAN SERVICES <CFR>45 CFR Part 46</CFR> <RIN>RIN 0937-AA09</RIN> <SUBJECT>Department of Health and Human Services Policy for the Protection of Human Research Subjects: Update to the Additional Protections for Specific Populations</SUBJECT> <HD SOURCE="HED">AGENCY:</HD> Department of Health and Human Services. <HD SOURCE="HED">ACTION:</HD> Final rule. <SUM> <HD SOURCE="HED">SUMMARY:</HD> In this final rule, the Department of Health and Human Services (HHS) is amending its regulations that govern the protection of human subjects for conformity with 2018 revisions made to the Federal policy for protection of human research subjects (the “Common Rule”), as well as to maintain consistency with the prior version of the Common Rule for research that remains subject to those requirements. Amendments include updating citations that were renumbered, adding updated descriptions of the applicability of exemptions, and correcting a technical error. No substantive amendments are included in this final rule. </SUM> <EFFDATE> <HD SOURCE="HED">DATES:</HD> This final rule is effective October 24, 2024. </EFFDATE> <FURINF> <HD SOURCE="HED">FOR FURTHER INFORMATION CONTACT:</HD> Julie Kaneshiro, Office for Human Research Protections (OHRP), Department of Health and Human Services, 1101 Wootton Parkway, Suite 200, Rockville, MD 20852; telephone: 240-453-8293 or 1-866-447-4777; facsimile: 240-453-8430; email <E T="03">Julie.kaneshiro@hhs.gov.</E> </FURINF> <SUPLINF> <HD SOURCE="HED">SUPPLEMENTARY INFORMATION:</HD> <HD SOURCE="HD1">I. Background</HD> <HD SOURCE="HD2">A. Revision of the Common Rule</HD> The Common Rule, codified by HHS at subpart A of 45 CFR part 46, was revised by a final rule published in the <E T="04">Federal Register</E> on January 19, 2017 (82 FR 7149), and subsequently amended by an interim final rule published in the <E T="04">Federal Register</E> on January 22, 2018 (83 FR 2885), and a final rule published on June 19, 2018 (83 FR 28497). The revised Common Rule is defined in the regulatory text as the “2018 Requirements.” The prior version of the Common Rule, initially promulgated on June 18, 1991 (56 FR 28002), and amended on June 23, 2005 (70 FR 36325), published in the 2016 Code of Federal Regulations and effective October 1, 2017, is defined by the revised Common Rule as the “pre-2018 Requirements.” For brevity, in the regulatory text of subparts B, C, and D, HHS is shortening the full explanation of the “pre-2018 Requirements” to “[t]he pre-2018 Requirements means 45 CFR part 46, subpart A, as revised October 1, 2016” and the “2018 Requirements” to “[t]he 2018 Requirements means 45 CFR part 46, subpart A, as revised October 1, 2018.” The applicability of the pre-2018 or 2018 Requirements is defined by § 46.101(l) of the 2018 Requirements. Importantly, research that was approved under the pre-2018 Requirements may continue to follow that rule for the duration of the study; however, research initiated on or after January 21, 2019, must comply with the 2018 Requirements. The preamble of the January 19, 2017 final rule indicated that, to the extent appropriate, HHS intended to amend the other subparts of the HHS human subjects protection regulations to align with the revisions to the Common Rule codified at subpart A. Through this final rule, HHS is updating subparts B, C, and D to reference both the pre-2018 Requirements and the 2018 Requirements, as appropriate. HHS intends to separately amend subpart E to conform with both the pre-2018 and 2018 Requirements. <HD SOURCE="HD2">B. Subparts B, C, and D Background</HD> Subpart B of 45 CFR part 46, “Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research,” was first promulgated on August 8, 1975. The most recent revision to subpart B was published in the <E T="04">Federal Register</E> on November 13, 2001 (66 FR 56775). On November 16, 1978, the then Department of Health, Education, and Welfare published a final rule promulgating subpart C, “Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects” (43 FR 53652). On January 26, 1981, the Common Rule was first published, which substantially updated subpart A of 45 CFR part 46 (46 FR 8366). As part of this update, HHS also published an amendment to subpart C in which citations were corrected or updated and other technical amendments were made. On March 8, 1983, HHS published the final rule promulgating subpart D, “Additional Protections for Children Involved as Subjects in Research” (43 FR 9814). <HD SOURCE="HD1">II. Amendments to Subparts B, C, and D of 45 CFR Part 46</HD> As described above, HHS is amending subparts B, C, and D for conformity with both the pre-2018 and 2018 Requirements. Through this rule, HHS is: • Adding language to subparts B, C, and D to specify when references to subpart A provisions refer to the pre-2018 Requirements or the 2018 Requirements. • Adding language to clarify the meaning of “pre-2018 Requirements” and “2018 Requirements.” • Updating language in subparts B, C, and D that explains the applicability of the exemptions to research regulated under each subpart to reflect the additional exemptions allowed by § 46.104(b) of the 2018 Requirements. • Correcting a technical error contained in subpart D. <HD SOURCE="HD2">A. Amendments to Subpart B</HD> In this final rule, HHS makes eight amendments to subpart B, “Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research.” First, 45 CFR 46.201(b) is amended to state that for purposes of this subpart, the pre-2018 Requirements means subpart A as published in the 2016 edition of the Code of Federal Regulations. The version of subpart A referenced in the definition of the term “2018 Requirements” refers to 45 CFR part 46, subpart A, as revised October 1, 2018. Section 46.201(b)(1) is added to provide that research subject to the pre-2018 Requirements may apply the exemptions at § 46.101(b)(1) through (6) of the pre-2018 Requirements, while § 46.201(b)(2) is added to provide that research subject to the 2018 Requirements may apply the exemptions at § 46.104(d)(1) through (8) of the 2018 Requirements. Second, § 46.202 is amended to clarify that the definitions found in § 46.102 of the pre-2018 Requirements or the 2018 Requirements, as applicable, shall be applicable to this subpart. Third, § 46.202(h) is amended to clarify that if a neonate is viable then it may be included in research only to the extent permitted and in accordance with the requirements of subpart A of the pre-2018 Requirements or the 2018 Requirements, as applicable, and subpart D of part 46. Fourth, § 46.204(d) is amended to clarify that the pregnant woman's consent must be obtained in accordance with the informed consent provisions of subpart A of the pre-2018 Requirements or the 2018 Requirements, as applicable. Fifth, § 46.204(e) is amended to state that the consent of the pregnant woman and the father must be obtained in accordance with the informed consent provisions of subpart A of the pre-2018 Requirements or the 2018 Requirements, as applicable, except that the father's consent need not be obtained if he is unable to consent for the reasons stated therein. Sixth, § 46.205(b)(2) is amended to state that the consent of either parent of the neonate or, if neither parent is able to consent because of unavailability, incompetence, or temporary incapacity, the legally effective informed consent of either parent's legally authorized representative is obtained in accord with the pre-2018 Requirements or the 2018 Requirements, as applicable, except that the consent of the father or his legally authorized representative need not be obtained if the pregnancy resulted from rape or incest. Seventh, references in subpart B at § 46.205(c)(5) to subpart A's waiver and alteration of consent provisions are updated to reflect conformity with the pre-2018 Requirements as well as the 2018 Requirements. In order for the citation to be consistent with the section numbering of both the pre-2018 and 2018 Requirements, the prior pinpoint citation to § 46.116(c) and (d) has been modified to instead refer to § 46.116 of both the pre-2018 and 2018 Requirements. Finally, the language of subpart B at § 46.205(d) has been revised to replace the reference to subpart A with reference to the pre-2018 Requirements or the 2018 Requirements, as applicable. <HD SOURCE="HD2">B. Amendments to Subpart C</HD> In this final rule, HHS makes six amendments to subpart C, “Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects.” First, 45 CFR 46.301(c) is revised to provide that the requirements of this subpart are in addition to those imposed under the other subparts, including the 2018 Requirements and the pre-2018 Requirements, as applicable. This section is further revised to provide that the term “pre-2018 Requirements” means subpart A as published in the 2016 edition of the Code of Federal Regulations. The term “2018 Requirements” refers to 45 CFR part 46, subpart A, as revised October 1, 2018. Second, § 46.304 is modified to clarify that in addition to satisfying the requirements in § 46.107 of the pre-2018 Requirements or the 2018 Requirements, as applicable, an institutional review board (IRB), carrying out responsibilities with respect to this subpart, shall also meet the specific requirements further detailed in this section. Third, § 46.306(a) is modified to add the word “nonexempt” in order to clarify that, except for research involving prisoners that qualifies for exemption, research subject to subpart C must involve only a category of research reflected in 45 CFR 46.306(a)(2)(i) through (iv). Fourth, § 46.306(b) is revised to provide that research conducted or supported by DHHS (the Depart ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Preview showing 10k of 38k characters. Full document text is stored and available for version comparison. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━