1	Human Specimen Repositories Requirements of FDA Regs. 21 CFR Parts 50 & 56 ISBER Human Subjects Workshop May 11, 2006 Sally A. Hojvat, Ph.D. Director of Microbiology Devices FDA/CDRH/OIVD/DMD sally.hojvat@fda.hhs.gov
2	FDA Human Research Protection Regulations 21 CFR Part 50: Informed consent and limited emergency exceptions 21 CFR Part 56: IRB Review Apply to all clinical investigations regulated by FDA
3	Comparing the FDA and HHS Protection of Human Subjects Regulations Overall Objective: FDA: title 21 CFR Parts 50&56 Protects the rights, safety and welfare of subjects involved in clinical investigations involving products regulated by FDA HHS: title 45 CFR Part 46 Subpart A Protects the rights and welfare of human subjects involved in research conducted or supported by HHS
4	Definition Clinical Investigation/Research FDA Any experiment involving a test article and one or more human subjects that: Must meet requirements for prior submission to FDA or Results of experiments intended to be submitted to FDA as part of application for research or marketing permission (21 CFR 812.3 (p)) HHS Systematic investigation, including research development, testing and evaluation, designed to develop or contribute to general knowledge
5	Definition Human Subject FDA Human who participates in research either as a recipient of the test article or as a control. A healthy human or a patient Subject is an individual on whom or on whose specimen an investigational device is used HHS A living individual that an investigator conducting research obtains data from through intervention or interaction; or obtains identifiable/ private information
6	Definition Minimal Risk FDA & HHS Risks of harm anticipated in research no greater than encountered in daily life or routine physical or psychological examinations or tests
7	IRB Review FDA requires IRB review and approval for any clinical investigation that must meet the requirements of prior submission to FDA HHS request IRB review for all research involving human subjects conducted, supported or otherwise subject to regulation by any Federal Dept. or Agency. It contains several waiver exemptions
8	Expedited IRB Review FDA & HHS Yes, if risks to subject is no more than minimal HHS Minor changes to approved research
9	Informed Consent FDA / HHS Requirement to obtain informed consent of subject or legally authorized representative Exemptions to requirement differ
10	Exemptions to Requirements for Informed Consent FDA Limited to emergency, life threatening situations, military operations Needs independent physician opinion Emergency research
11	Identifiable Information FDA Individually Identifiable information not defined or taken into consideration HHS Exempts some types of research if subject cannot be identified
12	"Confusion by IRB'" Confusion by IRB' s on applicability of which regulations cover “low-risk” device investigation meeting criteria for exemption from most IDE regulations (21 CFR 812.2 (c)(3)) FDA’s “Critical Path” initiative (3/2004) focused concern on unnecessary obstacles to medical product development Use of leftover specimens identified as obstacle
13	Guidance for Sponsors, IRBs, Clinical Investigators and FDA Staff 4/25/2006 “Guidance on Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable.”
14	Human Subject Protection Principles Maintained Results of investigational test not communicated to subject No new medical risks posed to subject from the time when leftover or banked specimen collected Not identifiable specimen mitigates privacy risks
15	Enforcement Discretion Proposed FDA intends to exercise enforcement discretion, under certain circumstances, with respect to requiring informed consent when human specimens are used in FDA-regulated IVD Device investigations Guidance, not a change in the regulation (21 CFR Part 50)
16	Enforcement Discretion: Applicable in what Circumstances? Investigation meets the IDE exemption criteria at 21 CFR 812.2 (c)(3) The study uses leftover specimens – remnants from routine clinical care or analysis that would have been discarded or; Repository specimens – leftover or previously collected for other unrelated research purpose Specimens may be coded but not individually identifiable by the investigator, sponsor, or any individual directly associated with the study
17	Enforcement Discretion: Applicable in what Circumstances? (Cont.) Specimen may be accompanied by clinical information if source not identifiable to anyone associated with study Individuals caring for patients are different from those conducting the study Supplier of specimen has established policies and procedures to prevent release of identifiable information Study protocol must be reviewed by an IRB (21 CFR Part 56)
18	What type of records should be kept for these studies? Sponsor should Maintain written documentation regarding circumstances described in the guidance (section 4) Ensure specimen provider has written documentation regarding subject non identifiability Consider if sufficient clinical information about subject available to support a device pre market clearance/approval
19	IRB Role Check documentation regarding circumstances described in guidance (section 4) IRB review should pay attention to privacy, confidentially, and whether potential for information from study influencing patient management
20	FDA Information – Websites http://www.fda.gov/oc/gcp/default-htm Regulations and FDA information sheets http://www.fda.gov/cdrh/oivd/guidance/1588.html Guidance on Informed Consent for IVD studies using leftover non-identifiable specimen http://www.fda.gov/cber/tissue/docs Human cells, tissues and cellular and tissue-based product