The FDA’s Office of Good Clinical Practice responds to inquiries on a variety of trial-related subjects, providing answers on the agency’s official regulations as well as best practices. The following is a selection of questions and answers excerpted from the CenterWatch publication, GCP Questions, FDA Answers.
For a drug (or biologic) under an IND that is manufactured outside of the U.S. and shipped directly to investigators in the U.S., must a specific release process be followed by the sponsor? Must corresponding documentation accompany the shipment?
Any shipment of the study drug must be properly documented and must assure that control of the study drug is maintained. Generally, the details of how the study drug is handled are spelled out in the study protocol. If the protocol does not address how the drug is shipped from the research pharmacy to the site, you should discuss this with the study sponsor and obtain agreement on the method to be used. Please note that a protocol amendment may be needed. Additionally, the reviewing IRB(s) should review and approve the change as the IRB(s) may also have concerns about an investigator’s ability to control access to the study drug and account for supplies of the study drug.
FDA’s regulations do not specifically address methods for shipping the study drug but do address documentation of shipment of the study drug and, for example, would include information such as the lot number or other identification of the product transferred, the dates, the means of shipment and the sites involved. Both the research pharmacy and satellite site will need to maintain documentation.
When should a clinical investigator’s noncompliance with GCPs be reported to the FDA?
The FDA’s expectation is that clinical investigators, sub-investigators and study staff will be knowledgeable about good clinical practice, including human subject protection, data integrity, recordkeeping, etc.
Regulations in 21 CFR 312.53 require that sponsors choose investigators qualified by training and experience and that investigators commit themselves to personally conduct or supervise the investigation.
Additionally, FDA would expect physicians who are clinical investigators to follow state and local laws regarding medical licensure and medical practice requirements in addition to sponsor requirements.
The FDA follows up on allegations of clinical investigator misconduct submitted by any party (e.g., sponsor, IRB, study subject, nurse coordinator, family member of study subject or other individual who may be in a position to know of the alleged wrongdoing). If necessary, FDA will issue an inspection assignment of the investigator’s site.
Such assignments may include studies that are conducted under an FDA application for research (e.g., Investigational New Drug Application, Investigational Device Exemption, Investigational New Animal Drug Application, as well as non-U.S. sites or studies that are not conducted under an FDA application for research.
Additionally, please note that if a sponsor is aware of investigator noncompliance and unable to secure compliance, the sponsor is to discontinue shipment of the investigational article to the investigator and terminate his/her participation in the investigation. The regulations governing drug and device investigations vary in how they address FDA notification, although both regulations indicate that FDA notification is required. For drug studies under 21 CFR 312, the regulation states: “A sponsor who discovers that an investigator is not complying with the signed agreement (Form FDA-1572), the general investigational plan or the requirements of this part or other applicable parts shall promptly either secure compliance or discontinue shipments of the investigational new drug to the investigator and end the investigator’s participation in the investigation. If the investigator’s participation in the investigation is ended, the sponsor shall require that the investigator dispose of or return the investigational drug and shall notify FDA.”
Serious noncompliance that risks the health, safety and welfare of research subjects should be reported as soon as possible.
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