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Acceptance of Clinical Data to Support Medical Device Applications and Submissions

This guidance clarifies FDA's requirements for accepting clinical data from investigations conducted both within and outside the United States (OUS) to support medical device applications and submissions. It focuses on ensuring data quality, integrity, and human subject protection through Good Clinical Practice (GCP) compliance.

What You Need to Know? 👇

What are the key GCP requirements for accepting OUS clinical data in medical device submissions?

FDA requires OUS clinical investigations to follow Good Clinical Practice (GCP) standards, including independent ethics committee review/approval, informed consent from subjects, and submission of supporting information per 21 CFR 812.28 to demonstrate data credibility and subject protection.

When did the new clinical data acceptance requirements become effective?

The rule became effective February 21, 2019 (one year after publication). It applies to clinical investigations that enrolled their first subject on or after this effective date, providing sponsors time to adjust procedures.

What supporting information must be submitted for significant risk device investigations conducted outside the US?

All twelve elements under 21 CFR 812.28(b) must be submitted, including investigator qualifications, facility descriptions, detailed protocol summaries, device information, IEC details, informed consent processes, monitoring descriptions, and investigator training documentation.

Can sponsors request waivers from GCP requirements for OUS clinical investigations?

Yes, sponsors may request waivers under 21 CFR 812.28(c) by explaining why compliance is unnecessary/impossible, describing alternative approaches, or providing other justification. FDA evaluates requests case-by-case considering public health interests.

How does FDA handle clinical investigations that don’t fully conform to GCP standards?

Sponsors must either request a waiver or provide a statement explaining non-conformance reasons and steps taken to ensure data credibility and subject protection. FDA reviews these explanations when determining data reliability.

What records must sponsors maintain for OUS clinical investigations supporting device applications?

Sponsors must retain all required records for at least 2 years after FDA’s decision on the marketing application/submission, or 2 years after IDE termination/completion, and make them available for FDA inspection upon request.


What You Need to Do 👇

  1. Assess if clinical investigations comply with GCP requirements
  2. Document IEC review and approval process
  3. Maintain records of informed consent procedures
  4. Prepare detailed descriptions of research facilities and investigator qualifications
  5. Implement monitoring procedures to ensure protocol compliance
  6. Consider waiver requests if unable to meet specific requirements
  7. Ensure proper documentation retention for at least 2 years
  8. Review implementation timeline and plan accordingly for new studies
  9. Evaluate multi-center studies for compliance with local requirements
  10. Prepare statements regarding GCP compliance for submissions

Key Considerations

Clinical testing

  • Clinical investigations must be conducted in accordance with GCP
  • For OUS studies, sponsors must demonstrate data adequacy under FDA standards
  • Multi-center studies must comply with local requirements for each site

Safety

  • Protection of human subjects’ rights, safety and well-being must be ensured
  • Independent Ethics Committee (IEC) review and approval required
  • Informed consent must be obtained from subjects
  • Continuing review by IEC required during the study

Other considerations

  • Documentation of investigator qualifications required
  • Description of research facilities needed
  • Monitoring procedures must be described
  • Records must be maintained for at least 2 years after FDA decision
  • Waiver requests possible for specific requirements if justified
  • Implementation effective one year after publication

Relevant Guidances 🔗

  • ISO 14155:2011: Clinical Investigation of Medical Devices for Human Subjects - Good Clinical Practice
  • ICH E6: Good Clinical Practice: Consolidated Guideline

Original guidance

  • Acceptance of Clinical Data to Support Medical Device Applications and Submissions
  • HTML / PDF
  • Issue date: 2018-02-21
  • Last changed date: 2023-08-10
  • Status: FINAL
  • Official FDA topics: Medical Devices, Good Clinical Practice (GCP), Premarket, Biologics, Investigational Device Exemption (IDE)
  • ReguVirta ID: 026a8cd78d5e0418eb327cf80d8db7e7
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