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.

Question: If a patient withdraws consent in a clinical study, is the study coordinator/site allowed to contact the patient for return of the study drug to the site even if the participant has not responded to the site via phone calls and a registered letter?

Answer: Every effort should be made to have the subject return the investigational product (IP). If the product is not returned, documentation of your efforts to have the IP returned is important. Sponsors and investigators should have internal standard operating procedures in place to address this issue. It is appropriate for the site/sponsor to contact the subject that has withdrawn from a study to obtain the unused IP.

Under FDA’s regulations, both the sponsor and the investigator have responsibility for accounting for investigational drugs that are shipped for a clinical trial.

During an FDA bioresearch monitoring inspection, FDA investigators review records to determine compliance with FDA’s regulations. This would include compliance with requirements for accounting for IP and compliance with the protocol/investigational plan.

Additionally, FDA regulations require that a sponsor ensure that unused drugs are returned or otherwise disposed of in a way that does not expose humans to risk and that records be maintained as to disposition of all such drugs (21 CFR 312.59). Allowing individual study sites to dispose of unused investigational drugs would not be inappropriate. You as the core pharmacy/sponsor can specify the conditions for such drug disposal or allow the site(s) to follow their own disposal policy if it is acceptable to you.

The individual sites would need to maintain proper documentation regarding the amounts of drug, identifying codes, date of disposal and actual method of disposal and a copy of such documentation would need to be sent to you for your records. While you might not have the resources to monitor actual drug disposal at each study site, review of drug accountability records, which would include such disposal documentation, is usually part of the final study monitoring or closeout visit for each site.

Question: In situations where notification is sent to the IRB before emergency administration of the IP (as the manufacturer requires the notification up front to ship the article), do IRBs also need to obtain documentation within five days after the drug is administered or is the one notification prior to administration sufficient?

Answer: 21 CFR 50.23(a)(3) requires that the documentation be submitted to the IRB within five working days after the use of the IP. However, if there is time for this information to be provided to the IRB before the administration of the IP and the information was sufficient for the IRB’s needs, then there would be no expectation that the information would need to be subsequently submitted to the IRB again.

The exception from informed consent described at 21 CFR 50.23(a) is intended for the situation in which a participant with a life-threatening situation is unexpectedly identified and it is thought they might benefit from the IP but consent cannot be obtained in a timely manner because of the clinical need to use the IP quickly, that is, within the therapeutic window. It is not meant to be a prospectively planned method in which to enroll subjects into a clinical trial and should be used judicially.

Question: ICH E6(R2) section 5.14.5 states that you must maintain sufficient quantities of the IP(s) used in the trials to reconfirm specifications, should this become necessary, and maintain records of batch sample analyses and characteristics. Additionally, it states that, to the extent stability permits, samples should be retained either until the analyses of the trial data are complete or as required by the applicable regulatory requirement(s), whichever represents the longer retention period.

Does this mean we need to maintain records or need to maintain IP samples?

Answer: Under FDA’s regulations, both the sponsor and the investigator have responsibility for accounting for investigational drugs that are shipped for a clinical trial.

Required accountability for a drug used in a clinical trial is the same whether or not the drug is already commercially available. The drug supplied by the sponsor for use in the clinical trial needs to be maintained separately from any purchased for general use at the site. Manufacturers usually allocate a specific lot of the drug for the study so any problems/adverse effects that could possibly be associated with a manufacturing problem can more easily be identified. As far as disposition of the drug, you need to follow the directives in that regard in the study protocol. If no instructions are in the protocol or other documents that are part of the investigational plan, you should ask the sponsor what they want you to do with any drug remaining at the end of the study. Both the sponsor and each clinical trial site is responsible for maintaining detailed accountability for drugs used in a clinical trial.

Please consult your sponsor for specifics on how drug accountability can be maintained at your site. Please remember any study-related documents given to study subjects should be approved by your reviewing IRB. Also, please remember, if you are performing additional procedures for drug accountability, it is best to develop standard operating procedures so that there is consistency among study staff.

For more information on the CenterWatch publication GCP Questions, FDA Answers, click here: https://bit.ly/3ylWOpj.