For most clinical trials, compliance with ICH GCP is sufficient for U.S. FDA acceptance. However, sponsors conducting global trials should be aware of key differences between IRB and IEC requirements and consult the FDA when necessary.
Two notable exceptions require special attention [1]:
- Differences in IRB/IEC membership and operations requirements
- Stricter FDA rules on informed consent in certain cases
Ethics committee membership and operations requirements
For studies conducted outside the U.S. under an IND, sponsors typically rely on an EC that follows GCP. However, IECs may not fully meet all IRB requirements under 21 CFR Part 56. If a foreign study follows ICH GCP instead of FDA’s IRB regulations, the FDA may grant a waiver allowing an IEC to substitute for an IRB. This ensures that global trials conducted under ICH GCP can still be accepted by the FDA.
The table below summarizes key differences in IRB and IEC membership requirements.
| Requirement | FDA (21 CFR 56.107) [2] | ICH GCP (R2) | ICH GCP (R3) [3] |
|---|---|---|---|
| Minimum number of members | At least five members. | At least five members. | At least five members. |
| Diversity of members | Members must have varying backgrounds to ensure complete and adequate research review. Consideration must be given to race, gender, cultural backgrounds, and community attitudes. | IRB/IEC should have a reasonable number of members with collective qualifications and experience to review science, medical aspects, and ethics. | IRB/IEC should have a reasonable number of members with collective qualifications and experience to review science, medical aspects, and ethics. |
| Scientific and non-scientific representation | Must include at least one member whose primary concerns are in scientific areas and one member in non-scientific areas. | Must include at least one member whose primary area of interest is nonscientific. | Must include at least one member whose primary area of interest is not in medical sciences. |
| Independence from institution | Must include at least one member who is not affiliated with the institution and not related to anyone affiliated. | Must include at least one member who is independent of the institution/trial site. | Must include at least one member who is independent of the institution/investigator site. |
| Gender balance | IRB cannot be composed entirely of men or women, but selection cannot be based on gender. | No specific requirement. | No specific requirement. |
| Professional diversity | IRB cannot consist entirely of one profession. | No specific requirement. | No specific requirement. |
| Conflict of interest | A member with a conflict of interest cannot participate in the review except to provide information. | Only IRB/IEC members who are independent of the investigator and sponsor should vote/provide opinions. | Only IRB/IEC members who are independent of the investigator and sponsor should vote/provide opinions. |
| Consultants / non-members | The IRB may invite specialized consultants, but they cannot vote. | The IRB/IEC may invite non-members with expertise to assist in the review. | The IRB/IEC may invite non-members with expertise to assist in the review. |
| Decision-making and quorum | No explicit quorum requirement, but decisions must be made with sufficient expertise and diversity. | Decisions must be made at announced meetings with a quorum as per written procedures. | Decisions must be made at announced meetings with a quorum as per documented procedures. |
| Investigator participation | Investigators cannot participate in IRB review of their own projects, except to provide information. | Investigators may provide information but cannot participate in deliberations or voting. | Investigators, investigator site staff, and sponsors may provide information but cannot participate in decision-making or voting. |
| Operating procedures | No explicit mention. | IRB/IEC must follow written operating procedures and maintain records of activities. | IRB/IEC must follow documented operating procedures and maintain records of activities. |
Overall, FDA 21 CFR 56.107 is stricter on diversity and independence requirements, while ICH GCP (R3) refines and clarifies GCP (R2) with more precise wording and additional transparency in investigator participation.
Informed consent requirements
The FDA has stricter informed consent regulations than ICH GCP, particularly in emergency research and pediatric clinical trials.
- Under 21 CFR 50.24, the FDA permits exceptions to informed consent only in life-threatening emergency research and under stricter conditions than ICH GCP, which provides less specific guidance on handling such cases.
- Similarly, under 21 CFR Part 50, Subpart D, the FDA imposes additional protections for children involved in research, going beyond the general guidelines set by ICH GCP.
See also
Another relevant pages
Links to this page
References and notes
- ↑ FDA, June 2010, Information sheet: Frequently Asked Questions – Statement of Investigator (Form FDA 1572), Guidance for Sponsors, Clinical Investigators, and IRBs, https://www.fda.gov/regulatory-information/search-fda-guidance-documents/frequently-asked-questions-statement-investigator-form-fda-1572 Accessed Feb 2025
- ↑ 21 CFR Part 56, https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-56 Accessed Feb 2025
- ↑ ICH, 2025, ICH Harmonised Guideline: Guideline for Good Clinical Practice E6(R3), https://database.ich.org/sites/default/files/ICH_E6(R3)_Step4_FinalGuideline_2025_0106.pdf Accessed Feb 2025
External links