November 2024 SOCRA Source Journal - Journal - Page 9
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505(o) of the FD&C Act to
assess a serious risk.
The clinical investigation
has signi昀椀cant potential
for serious risk to human
subjects.
The clinical investigation
involves asking subjects
to forgo or delay effective
treatment that is known to
decrease long-term mortality
or irreversible morbidity.
FDA has other con昀椀dential
or proprietary information
not available to an IRB
that affects the assessment
of whether the informed
consent form adequately
addresses risks.
After reviewing the consent
materials, if the FDA review
divisions have speci昀椀c
concerns about the adequacy
or compliance of the consent
materials with 21 CFR part 50,
details about these concerns
normally will be conveyed to
the sponsor in writing. In rare
circumstances, FDA may 昀椀nd a
consent form to be misleading,
inaccurate, or incomplete in
a way that makes informed
consent inadequate and
noncompliant with 21 CFR part
50 to the extent that subjects
would be exposed to an
unreasonable and signi昀椀cant risk
of illness or injury. In these cases,
FDA may require that speci昀椀c
revisions be made to address
the concern(s) before the clinical
investigation can proceed (21
CFR 312.42).
2. Investigational Medical
Devices
For clinical investigations of
medical devices for which an
IDE application is required
to be submitted to FDA, the
sponsor must include in the
application copies of all forms
and informational materials that
will be provided to subjects to
obtain informed consent (21
CFR 812.20(b)(11)). FDA reviews
the consent form to ensure that
it conforms to the requirements
of 21 CFR part 50. After review,
FDA may send the sponsor
a letter citing de昀椀ciencies
regarding the consent form
(21 CFR 812.30(a) and (b)(4)).
The clinical investigation may
not begin until the sponsor has
corrected these de昀椀ciencies
(21 CFR 812.30(a) and 812.42).
In the event an IRB requires
substantive changes to the
informed consent document
after IDE approval, i.e., changes
that affect the rights, safety,
or welfare of the subjects, the
sponsor must submit the revised
informed consent document to
FDA for its review and approval
prior to implementing the
changes to the document (see
21 CFR 812.35(a)).
References
64 See section IV.A.4 for guidance regarding identi昀椀cation of the most up-to-date version of the informed consent form.
65 See FDA’s “Guidance for Industry Investigator Responsibilities – Protecting the Rights, Safety, and Welfare of Study
Subjects” at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigator-responsibilitiesprotecting-rights-safety-and-welfare-study-subjects.
66 See the HHS guidance document, “Financial Relationships and Interests in Research Involving Human Subjects:
Guidance for Human Subject Protection,” available at https://www.hhs.gov/ohrp/regulations-and-policy/guidance/昀椀nancialcon昀氀ict-of-interest/index.html#.
67 See “Guidance for Industry, Using a Centralized IRB Review Process in Multicenter Clinical Trials,” available at
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/using-centralized-irb-review-processmulticenter-clinical-trials.
68 See 21 CFR 812.35(a).
69 The 2018 Common Rule requires that any institution located in the United States that is engaged in cooperative research
conducted or supported by a Federal Department or Agency must rely upon approval by a single IRB for that portion of the
research that is conducted in the United States, unless the research is not subject to the provision (45 CFR 46.114(b)).
The compliance date for research subject to this provision was January 20, 2020. On September 28, 2022, FDA issued a
proposed rule to harmonize with this requirement to the extent practicable and consistent with statutory provisions (see
https://www.federalregister.gov/documents/2022/09/28/2022-21089/institutional-review-boards-cooperative-research).
The January 19, 2017, 昀椀nal rule revising the Common Rule is available at https://www.hhs.gov/ohrp/regulations-and-policy/
regulations/昀椀nalized-revisions-common-rule/index.html.
70 See “Guidance for Industry: Investigator Responsibilities – Protecting the Rights, Safety, and Welfare of Study Subjects,”
available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigator-responsibilitiesprotecting-rights-safety-and-welfare-study-subjects.
71 For the purposes of this document, unless otherwise speci昀椀ed, all references to “drugs” or “drug products” include
human drug products and biological products that are also drugs.
SOCRA SOURCE © November 2024
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