Inspections, Compliance, Enforcement, and Criminal Investigations
Review of Human Subject Research
Review of Human Subject Research
|Date Revised: |
April, 12 2005
To establish the policies and procedures ORA employees must follow when submitting human subject research for review to FDA's Institutional Review Board (IRB), the Research Involving Human Subjects Committee (RIHSC).
To assure that all new and current ORA research that involves human subjects complies with the relevant federal regulations (see: 45 CFR 46) and FDA policies and procedures (see http://first.fda.gov/Rihsc/document/RIHSCwrittenproceduresfinal.doc).
FDA has provided assurance to the Department of Health and Human Services (HHS) that all activities related to human subject research will (1) be guided by the ethical principles outlined in the Belmont Report (see References), (2) comply with the Office for Human Research Protection's (OHRP) terms of assurance for protection of human subjects, and (3) comply with HHS regulations for the protection of human research subjects, including provisions of the Federal Policy for the Protection of Human Subjects (45 CFR part 46 subpart A). As part of this assurance, FDA has established policy that, except for those categories of research specifically exempted or waived under the HHS regulations and not otherwise included by FDA policy, all human subject research conducted, supported, or funded in whole or in part by FDA will be reviewed and approved by an IRB established by FDA. The RIHSC is FDA's established IRB.
The scope of activities encompassed by Human Subject Research (HSR) standard operating procedures with in FDA is very broad, and may include scientific, investigatory and research activities involving humans. This Field Management Directive applies to all research involving human subjects conducted by, supported, or funded in whole or in part by the FDA in which ORA employees participate. Approval by the FDA Research Involving Human Subject Committee (RIHSC) is required before any studies are performed for research purposes involving human subjects, clinical data, or any materials (including tissues, serum, cells, and DNA) from any human source, whether specimens are from a known, specified individual or are "de-identified". An exempt status designation must be applied for by the investigator and given by the FDA RIHSC. The only exception is if the materials can be routinely purchased commercially (from a company publicly selling laboratory reagents and supplies).
In general, the only projects which need not be submitted to the RIHSC are those that are entirely part of regulatory responsibilities, or utilize only specimens that are freely available to the public at large (e.g., from commercial sources, public or academic repositories).
Some projects may encompass BOTH regulatory components and those that meet criteria for classification as research as defined in the regulations. If so, research portions of protocol must be submitted to the RIHSC and be approved or designated as "Exempt" before any work is permitted on those portions of the project. If there ANY doubts, concerns, or questions about requirements for a specific protocol, contact the ORA RIHSC Liaison (Lori A. Love. M.D., Ph.D. <firstname.lastname@example.org>) to discuss any issues. Follow-up consultation with the RIHSC Executive Director (Dr. Suzanne Fitzpatrick) may be necessary to determine appropriate procedures and provide critical written documentation of required procedures.
Please see http://first.fda.gov/Rihsc/document/RIHSCwrittenproceduresfinal.doc for complete information on FDA policies and procedures on research involving human subjects. It is the researcher’s responsibilities to know and comply with these regulations and FDA procedures.
Research Involving Human Subjects Committee (RIHSC): FDA's Institutional Review Board (IRB), located in the Office of Science and Health Coordination, FDA. Materials relating to the function and responsibilities of the RIHSC can be found on the Intranet at http://first.fda.gov/rihsc.
ORA liaison to the RIHSC (ORA liaison): The ORA staff member designated by the Associate Commissioner for Regulator Affairs (ACRA) to review any human subject research in which ORA employees participate, or plan to participate, or ORA plans to fund, for possible review by the RIHSC. Lori A. Love. M.D., Ph.D. <email@example.com> (HFC-2) is the current ORA liaison. A list of RIHSC liaisons for all Centers can be found at http://first.fda.gov/rihsc.
ORA lead: The ORA staff member submitting research for review and/or continuing review as an individual or as the designated lead of a group of ORA employees working on the same human subject research. The ORA lead is identified as the FDA sponsor. If the principal investigator is not from FDA, he/she is also listed on the transmittal memorandum to be signed by the ORA liaison.
Human subject: "A living individual about whom an investigator . . . conducting research obtains (1) data through intervention or interaction with an individual, or (2) identifiable private information." (45 CFR 46.102(f))
Research: "A systematic investigation, including research, development, testing and evaluation, designed to develop or contribute to generalizable knowledge." (45 CFR 46.102(d))
Human subject research: Includes, but is not limited to:
- All FDA intramural projects
- All off-site studies, domestic or foreign, including studies with other government
agencies or academic institutions
- All focus group testing or survey research
- All retrospective research involving record reviews
- All research using human biological materials
- All studies using FDA's private database information, either alone or in collaboration with another government agency
- All studies that have IRB approval from other organizations, including approval from other government entities
FDA Internal Standard Operating Procedures for the Research Involving Human Subjects Committee (FDA SOPs): The standard operating procedures that apply to all human subject research conducted, supported, or funded in whole or in part by FDA. A copy of the FDA SOPs can be found at http://first.fda.gov/rihsc.
Any ORA lead who is, or plans to be, involved in human subject research must submit the research for review and/or continuing review, as specified in the FDA SOPs, to the ORA liaison.
The ORA liaison will assess whether the submitted materials on the research are sufficient to allow a review by the ORA liaison and the RIHSC. When sufficient information has been submitted, the ORA liaison will make a recommendation to the RIHSC regarding the extent of the review needed — exemption, expedited review, or full RIHSC review.
Any questions about whether these requirements apply to specific research should be directed to the ORA liaison.
The ORA lead involved in human subject research must complete training in the relevant human subject protection rules and regulations and must receive a certification of completion. The ORA lead can obtain the required training course from the ORA Liasion.
Associate Commissioner for Regulatory Affairs (ACRA)
The ACRA is responsible for designating a liaison to the RIHSC. The ACRA is also responsible for reviewing or delegating the review of proposals and protocols in which ORA staff will participate, with regard to scientific merit, ethical considerations, program relevance, and public responsibility. A list of the Center/Office liaisons can be found at http://first.fda.gov/rihsc.
The ORA liaison will review all materials on ongoing or future human subject research in a timely manner to make an ORA recommendation to the RIHSC on the actions required by the RIHSC for the research proposed — exemption, expedited review, or full RIHSC review. The ORA liaison will consider scientific merit, ethical concerns, program relevance, and public responsibility.
The ORA liaison will determine for ORA whether the research is exempt from RIHSC review and submit that recommendation to the RIHSC to receive a Letter of Exemption, with a copy to the ORA lead who submitted the materials.
If the research is not eligible for exemption, the ORA liaison will determine for ORA the level of review needed by the RIHSC (expedited or full) and submit that recommendation to the RIHSC, with a copy to the ORA lead who submitted the materials.
When the ORA liaison determines that the research needs RIHSC review, the ORA liaison will provide guidance to employees in completing the necessary forms and will forward the completed package of materials to the RIHSC.
The ORA Liaison will maintain records of all human subject research reviewed by the ORAR liaison and the RIHSC, including protocols, letters of exemption, and all relevant documents sent to and received from the RIHSC for a minimum of 3 years after completion of the research.
The ORA Liaison will maintain documentation that ORA leads involved in human subject research have received training in human subject protection rules and regulations for a minimum of 3 years after completion of the research.
Upon request, the ORA Liaison will provide information to any ORA lead on how to receive necessary training in the regulations related to human subject research (http://www.cdrh.fda.gov/staffcol/investigator101.htm).
Any ORA lead who is currently, or plans to be, involved in human subject research must submit materials detailing the research to the ORA liaison, as outlined in the FDA SOPs. The entire protocol (including the face sheet, expedited or exempt status RIHSC forms, if appropriate, protocol, curriculum vitae, relevant consent forms, and any other relevant data) should be sent to the ORA liaison both in hard copy and electronically.
Any ORA lead must submit contracts, task orders, work orders, requests for proposals, requests for grant applications, and any other documents involving human subject research to the ORA liaison prior to their announcement of availability.
An ORA lead applying for a grant for human subject research does not need to send grant applications and other materials detailing the research to the ORA liaison until the grant is funded. The actual human subject portion of the grant cannot begin without review by the ORA liaison and the RIHSC.
An ORA lead who plans or conducts focus group testing or survey research that requires clearance through the Office of Management and Budget (OMB) must submit materials detailing the proposed research to the ORA liaison prior to submission to OMB.
The ORA lead must comply with any provisions for continuing review required by the RIHSC. Continuing review is generally conducted by the RIHSC on an annual basis, although the RIHSC may request early evaluation or updates if it determines the research presents significant physical, social, or ethical risks to subjects.
ORA employees engaged in human subject research as an outside activity through their professional affiliation with an educational or research institution and not as part of their responsibilities as ORA employees are not required to submit the research for review to the RIHSC as long as they are not on official FDA time during this activity or do not use FDA equipment or facilities. However, in such instances, the ORA employee may not represent either verbally or in writing that ORA or FDA participated in the funding, design, performance, or analysis of the study, or refer to his or her ORA or FDA affiliation.
ORA employees participating in professional development activities involving human subject research during official time must submit materials detailing the research to the ORA liaison for review by the RIHSC. Employees engaged in professional development activities involving human subject research with another government agency (e.g., the National Institutes of Health or the Veterans Administration) also must submit materials detailing the research to the ORA liaison. In these cases, the ORA employee should contact the ORA liaison to establish the extent of documentation required. In some instances, a cooperative agreement between the RIHSC and the IRB of the other government agency may be required.
Any ORA lead proposing to use federal funds for human subject research must have completed training in the HHS regulations on human subject protection and must have obtained a certification of completion. ORA leads may obtain training materials to complete this requirement from the ORA Liaison or at http://www.cdrh.fda.gov/staffcol/investigator101.htm.
All ORA employees involved in human subject research must read and be familiar with the FDA SOPs and the Belmont Report.
All ORA employees who seek to publish the results of human subject research must adhere to the policies found in the FDA SOPs (http://first.fda.gov/rihsc), as well as any other relevant ORA policies and procedures.