Michelle Keyvani Blog #1

Name of Guidance:
Process for Handling Referrals to FDA Under 21 CFR 50.54 - Additional Safeguards for Children in Clinical Investigations

Status of Guidance:
Final Guidance released December 2006
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm127605.pdf

Target Audience:
Clinical investigators, Institutional Review Boards (IRBs), and sponsors

Laws and Regulations Referenced:
21 CFR 50.54
45 CFR Part 46, Subpart D
45 CFR 46.407
21 CFR Part 50, Subpart D (Subpart D); (See 66 FR 20598)
21 CFR 50.51, 50.52 or 50.53
21 CFR 50.1 and 56.101
CFR 50.55

Summary:
This guidance was created to help clinical investigators, IRBs, sponsors, and other interested parties understand the Food and Drug Administration's (FDA's) process, procedures, and final decisions in regards to clinical investigations that include children as subjects and that have been referred to FDA for review under 21 CFR 50.54.

Rationale:
If an IRB believes that a clinical investigation involving children as subjects does not meet the requirements of 21 CFR 50.51, 50.52 or 50.53, the clinical investigation may still proceed if:

• The IRB provides proof that the clinical investigation presents an opportunity to prevent or alleviate a serious problem affecting the children; and
• The Commissioner of Food and Drugs determines either: a) The clinical investigation does satisfy 21 CFR 50.51, 50.52 or 50.53, or b) The following 3 conditions described in 21 CFR 50.54 are met:

1. The clinical investigation may provide further understanding, prevention, or alleviation of a serious problem affecting the children.
2. The clinical investigation is conducted ethically; and
3. Appropriate soliciting of assent from both children and parents or guardians are made as set forth in 50.55.

Resulting Recommendations:

Public participation is encouraged as such the FDA would like public comment regarding the accepted referral's proposed investigation. The public would have access to review the following materials: the referral documents sent by the IRB, related agency correspondence, public comments on the referral, the transcripts of both the Subcommittee meeting and the PAC meeting, and the final determination of the Commissioner regarding the referral under 21 CFR 50.54. These materials will be available through FDA's Division of Dockets Management or through FDA's Division of Freedom of Information. In addition, the Subcommittee and PAC meetings will be open to the public.

For Clinical Investigators, IRBs and Sponsors - Documents to Include in the Referral:

• IRB's explanation as to why the clinical investigation does not meet the requirements of 21 CFR 50.51, 50.52, or 50.53.
• The research protocol and if applicable, the Investigational New Drug application (IND) or Investigational Device Exemption (IDE).
• All informed consent documents; and
• Any other informative documents (IRB minutes, correspondence between the IRB and the investigator, product labeling, and the investigator's brochure).

When the FDA receives the referral it determines whether the protocol is FDA-regulated and notifies the IRB its determination in approximately 2 weeks.

The Office of Pediatric Therapeutics (OPT) projects the referral process will take approximately six months to complete.

Impact:

"In FDA-regulated clinical investigations involving children, the agency makes every effort to protect the rights, safety, and welfare of those children. In addition, the agency strives to achieve the basic goals of adherence to sound ethical principles, transparency through public and expert input, efficiency, timeliness, clarity, and consistency. FDA believes that these goals are best served by having a clear, efficient, and comprehensive process for referrals by IRBs under 21 CFR 50.54."