MSU HRPP Manual Section 2-4
2-4, International Conference on Harmonization Good Clinical Practice E6
Good Clinical Practice
Good clinical practice provides standards for the conduct of all aspects of a clinical investigation, including the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting. Clinical trials regulated by the U.S. Food and Drug Administration (FDA) are required to adhere to applicable FDA regulations, including those regulations that imply good clinical practices, e.g. 21 CFR 11, 50, 54, 56, 58, 310, 312, 812, 814.
International Conference on Harmonization’s (ICH) Guidance for Industry E6 Good Clinical Practice (GCP)
The International Conference on Harmonization’s (ICH) Guidance for Industry E6 Good Clinical Practice (GCP): Consolidated Guidance provides a unified, international standard for the conduct of clinical trials involving human subjects. The FDA utilizes ICH-GCP as guidance for GCP. Clinical trials that follow ICH-GCP E6 guidance are conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with GCP and applicable regulatory criteria.
The ICH GCP E6(R3) guideline was amended in 2025 with Annex 1 adopted at the international level. The E6(R3) Guidance is more flexible, adaptable with the main goal being to promote a risk-proportionate approach and foster a culture of quality that supports and strengthens clinical trials. This guidance may also be applicable to other interventional clinical trials of investigational products that may or may not be intended to support marketing authorization applications in accordance with local requirements.
The ICH GCP E6(R2) guideline was amended in 2016 with an integrated Addendum.
Because not all sponsors have transitioned to ICH-GCP E6(R3), compliance with E6(R2) is permitted if the sponsor continues to follow ICH-GCP E6(R2).
Applicability of ICH GCP E6 (R2) or (R3)
A sponsor of a clinical investigation (e.g., multi-site clinical trials, international clinical trials) may require ICH-GCP E6(R2) compliance. In those instances, the Compliance office will review the research plan submitted to identify aspects that may be inconsistent with ICH-GCP E6(R2) and provide the information to the investigator and/or the Institutional Review Board as appropriate. Such review will include evaluation by the reviewing IRB of the adequacy of the available information in the protocol to support the proposed research study and include a review that proposed research is scientifically sound and answers the proposed questions. See HRPP Manual 6-2-A, Minimization of Risks: Sound Research Design. If an investigator in the research contract agrees to conduct an investigation in full compliance with the investigator obligations under ICH-GCP E6(R2), any ICH-GCP review conducted by the Compliance office will be done using the complete set of ICH-GCP(R2) requirements.
A sponsor of a clinical investigation may require ICH-GCP E6(R3)compliance. In those instances, the Compliance office will review the research plan submitted to identify aspects that may be inconsistent with ICH-GCP and provide the information to the investigator and/or the Institutional Review Board (IRB) as appropriate.
Investigator Considerations for ICH GCP E6(R2) or ICH GCP E6(R3)
If an investigator in the research contract agrees to conduct an investigation in full compliance with the investigator obligations under ICH-GCP, any ICH-GCP review conducted by the Compliance office will be done using the complete set of ICH-GCP requirements. Prior to a participant’s participation in the trial, the investigator should ensure that the written informed consent form is signed and personally dated by the participant or by the participant's legally authorized representative, and by the investigator or delegated investigator site staff who conducted the informed consent discussion.
IRB Considerations for ICH GCP E6(R3)
ICH GCP E6(R3) review will include evaluation by the reviewing IRB of the adequacy of the available information in the protocol to support the proposed research study and include a review that proposed research is scientifically sound and answers the proposed questions. The scientific goal and purpose should be carefully considered so as not to unnecessarily exclude particular participant populations. See HRPP Manual 6-2-A “Minimization of Risks: Sound Research Design.”
When reviewing a study that is required to comply with ICH-GCP E6(R3), the IRB will consider the following ICH GCP E6(R3) guidelines:
1.1 Submission and Communication
For the submission to or communication with the IRB/Independent Ethics Committee (IEC), in most regions where there is also a requirement to make a submission to the relevant regulatory authority, these may be combined in a single submission in accordance with applicable regulatory requirements. Submissions and communications with the IRB/IEC and regulatory authorities are made in some regions by the investigator/institution and by the sponsor in other regions in accordance with applicable regulatory requirements.
1.2 Responsibilities
1.2.1 The purpose of an IRB/IEC is to safeguard the rights, safety and well-being of all trial participants. Appropriate consideration should be given to trials that intend to recruit vulnerable participants.
1.2.2 The IRB/IEC should review the following information, where applicable:
(a) Protocol and amendments;
(b) Informed consent material(s), assent material(s), where applicable, and any updates, including the description of the process for how informed consent and assent is to be obtained;
(c) Investigator’s Brochure or current scientific information, such as a basic product information brochure (e.g., Summary of Product Characteristics (SmPC), package leaflet or labelling), as appropriate, including their updates;
(d) Other trial-related information to be provided to the trial participant(s), including a description of the media through which such information will be provided;
(e) Advertisement for participant recruitment (if used) and information on the recruitment process;
(f) Plans to compensate participants (if any);
(g) Ongoing updates to safety information;
(h) Investigator’s current curriculum vitae and/or other documentation evidencing qualifications;
(i) Any other documents that the IRB/IEC may need to fulfil its responsibilities.
1.2.3 The IRB/IEC should review a proposed clinical trial within a reasonable time and document its reviews, clearly identifying the trial, the documents reviewed and the dates for the following:
(a) Approval/favourable opinion;
(b) Modifications required prior to its approval/favourable opinion;
(c) Disapproval/negative opinion;
(d) Termination/suspension of any prior approval/favourable opinion.
1.2.4 The IRB/IEC should conduct continuing review of each ongoing trial at intervals appropriate to the degree of risk to participants.
1.2.5 The IRB/IEC may request more information than is outlined in section 2.8.11 be given to participants when, in the judgement of the IRB/IEC, the additional information would add meaningfully to the protection of the rights, safety and/or well-being of the participants.
1.2.6 Where the protocol indicates that prior consent of the trial participant or the participant’s legally acceptable representative is not possible (see section 2.8.8), the IRB/IEC should determine that the proposed protocol and/or other document(s) adequately address relevant ethical concerns and meet applicable regulatory requirements for such trials (e.g., in emergency situations).
1.2.7 If minors are to be included in a trial, the IRB/IEC should review the assent information considering the age, maturity and psychological state of the minor population intended to be enrolled, as well as applicable regulatory requirements.
1.2.8 If the trial participants are compensated for their participation in the trial, the IRB/IEC should review both the amount and method of payment to participants to assure that neither presents problems of coercion or undue influence on the trial participants. Payments to a participant should be timely, prorated and not wholly contingent on completion of the trial by the participant. Reasonable reimbursement of expenses incurred by participants, such as for travel and lodging, is not coercive
1.2.9 The IRB/IEC should ensure that information regarding payment to participants, including the methods, amounts and schedule of payment to trial participants, is set forth in the informed consent materials and any other information to be provided to participants.
1.3 Composition, Functions and Operations
1.3.1 The IRB/IEC should consist of a reasonable number of members who collectively have the qualifications and experience to review and evaluate the science, medical aspects and ethics of the proposed trial. It is recommended that the IRB/IEC should include:
(a) At least five members;
(b) At least one member whose primary area of interest is not in medical sciences;
(c) At least one member who is independent of the institution/investigator site.
Only those IRB/IEC members who are independent of the investigator and the sponsor of the trial should vote/provide an opinion. A list of IRB/IEC members and their qualifications should be maintained.
1.3.2 The IRB/IEC should perform its functions according to documented operating procedures, should maintain records of its activities and minutes of its meetings, and should comply with GCP and with the applicable regulatory requirement(s).
1.3.3 An IRB/IEC should make its decisions at announced meetings at which at least a quorum, as stipulated in its documented operating procedures, is present. Alternative processes may be applicable for expedited review (see section 1.4.5).
1.3.4 Only members who participate in the IRB/IEC review and discussion should vote/provide their opinion and/or advice.
1.3.5 The investigator, investigator site staff and/or sponsor, where appropriate, may provide information on any aspect of the trial but should not participate in the decision making of the IRB/IEC or in the vote/opinion of the IRB/IEC.
1.3.6 An IRB/IEC may invite non-members with expertise in special areas for assistance.
1.4 Procedures
The IRB/IEC should establish, document and follow its procedures, which should include:
1.4.1 Determining its composition (names and qualifications of the members) and the authority under which it is established;
1.4.2 Scheduling, notifying its members of and conducting its meetings;
1.4.3 Conducting initial and continuing review of trials;
1.4.4 Determining the frequency of continuing review, as appropriate;
1.4.5 Providing, according to the applicable regulatory requirements, expedited review and approval/favourable opinion of minor change(s) in ongoing trials that have the approval/favourable opinion of the IRB/IEC;
1.4.6 Specifying that no participant should be enrolled in a trial before the IRB/IEC issues its documented approval/favourable opinion of the trial;
1.4.7 Specifying that no deviations from or changes to the protocol should be initiated without prior documented IRB/IEC approval/favourable opinion of an appropriate protocol amendment except when necessary to eliminate immediate hazards to the participants or, in accordance with applicable regulatory requirements, when the change(s) involves only logistical or administrative aspects of the trial;
1.4.8 Specifying that the investigator/institution should promptly report to the IRB/IEC (see section 1.1):
(a) Deviations from the protocol to eliminate immediate hazards to the trial participants (see sections 1.4.7, 2.5.4 and 2.5.5);
(b) Changes increasing the risk to participants and/or significantly affecting the conduct of the trial (see section 2.4.6);
(c) All suspected unexpected serious adverse reactions (SUSARs) in accordance with applicable regulatory requirements;
(d) New information that may adversely affect the safety of the participants or the conduct of the trial.
1.4.9 Ensuring that the IRB/IEC (see section 1.1) promptly notifies in writing (paper or electronically) the investigator/institution or sponsor concerning:
(a) Its trial-related decisions/opinions;
(b) The reasons for its decisions/opinions;
(c) Procedures for appeal of its decisions/opinions.
1.5 Records
1.5.1 The IRB/IEC should retain all relevant records (e.g., documented procedures, membership lists, lists of occupations/affiliations of members, submitted documents, minutes of meetings and correspondence) in accordance with applicable regulatory requirements and make them available upon request from the regulatory authority(ies).
1.5.2 The IRB/IEC may be asked by investigators, sponsors or regulatory authorities to provide its documented procedures and membership lists.
Compliance Office
The Compliance office or the IRB will bring any issues of concern to the attention of the investigator, who may in turn ask for clarification from the sponsor. A standard form will be completed to document the ICH-GCP review.
This policy and procedure supersedes those previously drafted.
Approved By: Vice President of Research and Graduate Studies, 7-19-2011. Revision 1 approved by Assistant VP Regulatory Affairs on 11-20-2015. Revision 2 approved by Assistant VP Regulatory Affairs on 4-3-2018. Revision 3 approved by Assistant VP Regulatory Affairs on 11-15-2021. Revision 4 approved by Associate VP Research Regulatory Support on 11-28-2025. Revision 5 approved by Associate VP Research Regulatory Support on 4-26-2026.