of FDA Regulations
1PURPOSE
1.1Guidance about FDA regulations that involve the IRB.
2RELEVANCE (to HSD and the IRB)
2.1Allowable actions. Some actions and determinations allowed under 45 CFR 46 are not allowable under the general FDA regulations (21 CFR 50, 56) governing research. They include:
2.1.1Exempt status as described in 45 CFR 46.101(b), except for some category 6 activities
2.1.2Waiver of consent, or of required elements of consent as allowed by 45 CFR 46.116(c), which is the waiver for federal demonstration and public service projects
2.1.3Waiver of parental permission, or of required elements of parental permission, as allowed by 45 CFR 46.116(c) [federal demonstration and public service projects] and 45 CFR 46.408(c), [“not a reasonable requirement”]
2.1.4Waiver of documentation of consent, as allowed by 45 CFR 46.117(c)
2.1.5Waiver of documentation of parental permission, as allowed by 45 CFR 46.117(c) and 45 CFR 46.408(d)
2.2IRB membership. An IRB member who is a licensed physician must participate in any IRB meeting that is reviewing FDA-regulated research.
2.3IRB registration. Any IRB that reviews FDA-regulated research must be registered as such, with the federal Office of Human Research Protections (OHRP).
2.4Required determinations and actions. Certain IRB determinations and actions are required for some FDA-regulated research but not for any other type of research. Examples include:
2.4.1A risk determination for some types of devices
2.4.2Confirmation of an IND or IDE described by the researcher
2.4.3Communication of certain determinations and actions to the IND or IDE holder
2.5Required elements of consent. Two elements of consent are required for FDA-regulated research but not for other research:
2.5.1A statement describing the possibility that the FDA may inspect the research records
2.5.2A statement (if applicable) about the registration of the research at ClinicalTrials.gov and about the meaning of the registration
2.6Required reporting.Certain IRB determinations and findings about FDA-regulated research must be reported to the FDA: suspension or termination of IRB approval; unanticipated problems; and serious or continuing noncompliance.
2.7Non-research activities required IRB oversight. FDA regulations require IRB involvement in some clinical (non-research) activities. See relevant UW SOPs about these activities:
2.7.1Single patient emergency use of investigational drugs and devices
2.7.2Compassionate use of devices
2.7.3Humanitarian Use Devices (HUDs) used solely for clinical purposes
2.7.4Expanded Access use of investigational drugs and devices
3FDA REGULATIONS THAT INVOLVE THE IRB
3.1FDA regulations that involve the IRB include.
3.1.121 CFR 50, Protection of Human Subjects
3.1.221 CFR 56, Institutional Review Boards
3.1.321 CFR 312, Investigational New Drug Application
3.1.421 CFR 812, Investigational Device Exemptions
3.1.521 CFR 814, Premarket Approval of Medical Devices
3.2Relationship among these FDA regulations. 21 CFR50 and 21 CFR 56 apply to all research that meets the FDA’s definition of non-exempt human subjects research. Other FDA regulations apply only to specific subsets of FDA-regulated research:
3.2.121 CFR 312, research use of an investigational drug.
3.2.221 CFR 812, research use of an investigational device.
3.2.321 CFR 814, any use of a Humanitarian Use Device (HUD).
4DETERMINING WHICH FDA REGULATIONS APPLY (if any)
4.1Final authority. The FDA has the ultimate authority on this issue. In the absence of any FDA opinion on a specific activity, it is UW policy that HSD staff make the determination about the applicability of specific FDA regulations, based on information provided by the researcher.
4.2Determination process.The SOP FDA-Regulated Research describes the process for determining which FDA regulations apply to a specific study.The process relies upon the definitions, criteria, and interpretations provided in:
4.2.1WORKSHEET: Human Subjects Research
4.2.2WORKSHEET: FDA Drugs and the IND Requirement
4.2.3WORKSHEET: FDA Devices and the IDE Requirement
4.3Which activities.Some activities associated with FDA-regulated studies are not considered by the FDA to be part of the study itself. Therefore, those activities are not FDA-regulated.
4.3.1Screening tests and procedures, whennot performed solely for determining study eligibility, are not considered by the FDA to be part of the study.
4.3.2Interviews and questionnairesadministered to subjects are not part of the FDA-regulated research unless they involve the use of the test article, a human subject, and the data will be submitted to (or held for inspection by) the FDA.
4.4Relationship with non-FDA regulations.Some activities are considered part of the research by some regulations but not by others. The UW IRB applies the applicable regulations to the specific activity. When multiple regulations apply to a specific activity, the UW IRB applies the most restrictive rules.
5EXAMPLES of research activities that are not subject to FDA regulations
Activity
Note: This is not intended to be an all-inclusive list.
1 / Medical records review (retrospective or prospective)2 / Use of adrug or medical device when the purpose is to obtain basic physiological information rather than gathering data for submission to (or inspection by) the FDA. Examples:
- Participants will be given a FDA-approved statin drug after consuming citrus juice, and blood samples will be collected during the next 12 hours to examine the effect on statin metabolism. The use of the statin does not make the study subject to FDA regulations.
- A study is designed to look at the relationship between body temperature and self-reported hot flashes. Body temperature will be measured by having the participants swallow a capsule designed by the PI’s lab that measures core temperature during the 10-20 hours that it takes the capsule to pass through the digestive system. The use of the capsule does not make the study subject to FDA regulations.
3 / Use of a drug or device in a study, but the drug or device is not the focus of the study (and data about the itemare not being gathered for submission to (or inspection by) the FDA). Example:
- A study of biomarkers for Alzheimer’s disease will collect cerebrospinal fluid samples from participants. Participants will be provided with aspirin or acetaminophen if they develop a headache due to the spinal tap. The use of the aspirin or acetaminophen does not make the study subject to FDA regulations.
4 / Studies of surgical techniques that are evaluating only a new technique and not the safety or efficacy of FDA-regulated devices that are used during the surgery.
5 / Use of a custom device, if it is not intended to gather data about the device that will be submitted to (or held for) the FDA.
6 / The activity(s) of UW researchers on a non-UW researcher’s FDA-regulated study is limited to:
- Data analysis (whether or not the data are identifiable)
- Discussing a study with potential subjects (but not obtaining consent)
- Pre-screening of records for eligibility determination
- Procedures that will be performed as part of clinical practice and which would be performed exactly the same way regardless of whether the subject is in the study
6REFERENCES
6.1The March 30, 2012 recommendations and analysis of the Secretary’s Advisory Committee on Human Research Protections (SACHRP) about the Applicability of FDA Regulations.
6.2Association for Accreditation of Research Protection Programs (AAHRPP): Accreditation Evaluation Instrument, and Tip Sheets.
6.3Direct communication between HSD and the FDA’s Drug Division.
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