Institutional Review Board (IRB) Written Procedures: Guidance for Institutions and IRBs

Comments and suggestions regarding this draft document should be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register.

Submit comments on paper, disk, or CD-ROM by mail/hand delivery/courier to:

Office for Human Research Protections
Division of Policy and Assurances
1101 Wootton Parkway, Suite 200
Rockville, MD 20852

Food and Drug Administration
Division of Dockets Management (HFA-305)
5630 Fishers Lane, Room 1061
Rockville, MD 20852

August 2016

Additional copies are available from:

Division of Policy and Assurances
Office for Human Research Protections
1101 Wootton Parkway, Suite 200
Rockville, MD 20852
(Tel) 240-453-6900 or 866-447-4777
(Fax) 301-402-2071
http://www.hhs.gov/ohrp/newsroom/rfc/index.html

For questions on the content of this guidance, contact the Office for Human Research Protections or the Office of Good Clinical Practice at the address/phone number listed above.

U.S. Department of Health and Human Services
Office for Human Research Protections
Food and Drug Administration

Table of Contents

Guidance for Institutional Review Boards (IRBs)

IRB Written Procedures

This draft guidance, when finalized, will represent the Office for Human Research Protections’ (OHRP’s) and the Food and Drug Administration’s (FDA’s) current thinking on this topic. This guidance does not create or confer any rights for or on any person and does not operate to bind OHRP, FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the appropriate OHRP or FDA staff responsible for implementing this guidance. If you cannot identify the appropriate OHRP or FDA staff, call the appropriate number listed on the second title page of this guidance.

I. INTRODUCTION

This draft guidance has been prepared jointly by the Department of Health and Human Services (HHS’s) Office for Human Research Protections (OHRP) and the Food and Drug Administration (FDA). This guidance is intended for institutional review boards (IRBs) and institutions responsible for review and oversight of human subject research under the HHS or FDA regulations, or both.

This joint draft guidance is intended to assist IRB administrators, IRB chairpersons, and other institutional officials responsible for preparing and maintaining written procedures for the IRB. The guidance provides an IRB Written Procedures Checklist that incorporates the HHS and FDA regulatory requirements for IRB written procedures and additional topics that we recommend including in written procedures. When finalized, this document will supersede OHRP’s July 1, 2011 “Guidance on Written IRB Procedures”[1] and FDA’s 1998 “Appendix H: A Self-Evaluation Checklist for IRBs,”[2] (formerly part of FDA’s Information Sheet Guidance for IRBs, Clinical Investigators, and Sponsors).

OHRP’s and FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidance describes OHRP’s and FDA’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in OHRP and FDA guidance documents means that something is suggested or recommended, but not required.

II. BACKGROUND

OHRP and FDA frequently receive requests for clarification regarding the scope and content of IRB written procedures. We recognize that procedures may vary among institutions and IRBs due to differences in the type of research studies reviewed by the IRB, institutional policy or administrative practices, number of IRBs at the institution, affiliation with an institution, and local and state laws and regulations. In order to provide guidance on the appropriate content of written procedures, while taking into account these variations, we created an IRB Written Procedures Checklist (see section IV) to assist IRBs in preparing and maintaining detailed written procedures suitable for their institutions. NOTE: IRB written procedures do not need to follow the order of the items presented in the Checklist and may be integrated to avoid redundancy.

III. DISCUSSION

IRBs that are subject to both the HHS and FDA regulations in Titles 45 (45 CFR Part 46), and 21 (21 CFR Parts 50 and 56), respectively, must comply with the requirements for IRB written procedures in both sets of regulations. The HHS and the FDA regulations[3] require that IRBs follow written procedures for the following specific functions:

• Conducting initial and continuing review of research;
• Reporting findings and actions to the investigator and the institution;
• Determining which projects require review more often than annually;
• Determining which projects need verification from sources other than the investigator that no material changes have occurred since previous IRB review;
• Ensuring prompt reporting to the IRB of proposed changes in a research activity, and ensuring that changes in approved research, during the period for which IRB approval has already been given, may not be initiated without IRB review and approval except where necessary to eliminate apparent immediate hazards to the human subjects;
• Ensuring prompt reporting to the IRB, appropriate institutional officials, any department or agency head and OHRP for research conducted or supported by HHS, and the FDA for FDA-regulated research of:
  • Any unanticipated problems involving risks to human subjects or others;
  • Any instance of serious or continuing noncompliance with the applicable HHS and FDA regulations or the requirements or determinations of the IRB;
  • Any suspension or termination of IRB approval.

  HHS and FDA regulations[4] do not provide additional detail on the content of IRB written procedures, which gives IRBs the flexibility to establish procedures best suited to their own operations.

  Developing robust IRB written procedures involves a comprehensive and critical assessment of the IRB’s responsibilities, functions, operations, and organizational structure. IRB written procedures should be sufficiently detailed so that IRB members and administrative staff understand how to carry out their duties consistently and effectively in ways that ensure that the rights and welfare of subjects are protected, and that the IRB operates in compliance with the regulations. When preparing IRB written procedures, IRBs should identify who carries out specific duties by reference to position title (e.g., IRB Administrator) rather than by employee name in order to avoid the need to update written procedures if an employee’s duties change or there are changes in IRB staff.

  IRBs should consider making their written procedures available to investigators to ensure investigators are aware of the IRB’s requirements, and to facilitate investigator compliance with IRB requirements. Step-by-step operational details in written procedures also help regulators[5] understand how the IRB operates and fulfills its regulatory responsibilities. OHRP and FDA have observed that some IRB written procedures simply reiterate the regulations, which is an approach that does not provide sufficient detail about the IRBs’ operations necessary to meet the regulatory requirements for written procedures.

  Both OHRP and FDA have a range of guidance documents[6] that cover a variety of topics that may be useful to IRB administrators, IRB chairpersons, and other institutional officials when preparing written procedures for the IRB. For example, guidance on IRB continuing review of research[7] speaks to key considerations for the IRB at the time of continuing review and offers suggestions about written procedures specific to continuing review. These key considerations and suggestions should be incorporated into the IRB written procedures and used to differentiate procedures followed by the IRB at the time of continuing review from procedures followed by the IRB at the time of initial review.

  The IRB Written Procedures Checklist is designed to prompt a thorough evaluation of procedures essential for ensuring the protection of human research subjects. The IRB’s written procedures should be reviewed on a regular basis and updated as necessary to ensure they reflect the IRB’s current processes. When IRBs develop and follow clear written procedures, we believe there is a greater likelihood that the rights and welfare of human subjects are protected.

  IV. IRB WRITTEN PROCEDURES CHECKLIST

  The IRB Written Procedures Checklist included below identifies the HHS and FDA regulatory requirements and recommendations for IRB written procedures. The regulatory requirements are denoted in the Checklist as headers to sections I, II, III and IV. The Checklist also includes recommendations on topics to cover in written procedures to ensure an adequate description of IRB functions and operations. For example, if an IRB reviews studies involving children as subjects, the IRB should have written procedures that describe how the IRB ensures the review of such research is in accordance with the regulatory requirements for the additional protections for children (45 CFR Part 46 Subpart D, or 21 CFR Part 50 Subpart D). For this reason, the Checklist also includes footnotes that cross-reference relevant regulations, which we recommend IRBs consider addressing in written procedures.

  Although written procedures for items in the Checklist may not be required by the regulations (e.g., administrative support staff duties), such items are appropriate to consider when developing an IRB’s comprehensive written procedures.

  The amount and nature of the detail included in IRB written procedures may vary across IRBs and not all of the topics listed in the Checklist may be applicable to all IRBs. The institution and the IRB may also determine that, based on the unique aspects of the research reviewed by the IRB, additional topics not included in the Checklist should be included in their IRB written procedures (e.g., written procedures related to how the IRB interacts with an Institutional Biosafety Committee, or a Radioactive Drug Research Committee).

  Finally, we note that several of the activities described below in the Checklist are required by the regulations but the HHS and FDA regulations do not explicitly require that an IRB establish and maintain a written procedure for conducting the activity. However, we recommend IRBs consider addressing these activities in the written procedures.

  IRB WRITTEN PROCEDURES CHECKLIST

  Check yes if the IRB has a written procedure on this topic and no if it does not.