SOCRA - Society of Clinical Research Associates FDA Regulations and Compliance Questions and Answers 1 — Questions and Answers
Question 1: According to 21 CFR 312, an investigator is required to report a serious adverse event (SAE) to the sponsor:
- Within 24 hours of becoming aware of the event.
- Immediately, regardless of whether it is considered drug-related. (Correct answer)
- Within 7 calendar days if it is unexpected and life-threatening.
- Only after confirming the event is directly caused by the investigational product.
Correct answer: Immediately, regardless of whether it is considered drug-related.
FDA regulation 21 CFR 312.64(b) requires investigators to immediately report any serious adverse event to the sponsor, whether or not the investigator considers the event to be drug-related. The sponsor then has specific timelines to report to the FDA, but the initial responsibility of the investigator is immediate notification to the sponsor.
Question 2: A clinical investigator conducting a study under an IND is required by 21 CFR 54 to disclose certain financial interests to the study sponsor. This disclosure must be updated:
- Only at the beginning of the study.
- Annually at the time of the continuing review.
- During the study and for one year after completion. (Correct answer)
- Only if the financial interest exceeds $50,000.
Correct answer: During the study and for one year after completion.
According to 21 CFR 54.4(b), clinical investigators must provide the sponsor with accurate financial information and update this information if any relevant changes occur during the clinical study and for one year following its completion. This ensures that any potential for bias due to financial interests is monitored throughout the study and for a period after.
Question 3: Which of the following is a primary responsibility of an Institutional Review Board (IRB) as defined by FDA regulations?
- To ensure the scientific validity and design of the research protocol.
- To approve or disapprove research and ensure the protection of the rights and welfare of human subjects. (Correct answer)
- To monitor the investigational product's manufacturing process for quality control.
- To negotiate the clinical trial agreement and budget with the sponsor.
Correct answer: To approve or disapprove research and ensure the protection of the rights and welfare of human subjects.
FDA regulations (21 CFR Part 56) establish that the primary purpose and authority of an IRB is to review, approve, require modifications to, or disapprove biomedical research involving human subjects. This role is critical to protect the rights, safety, and welfare of the participants.
Question 4: A site is preparing for a clinical trial involving an investigational new drug. The Principal Investigator (PI) must sign the FDA Form 1572. By signing this form, what is the PI committing to?
- Guaranteeing a minimum number of subjects will be enrolled at the site.
- Personally conducting every study-related procedure for all enrolled subjects.
- Assuming full financial responsibility for any subject injuries.
- Complying with FDA regulations for the conduct of a clinical investigation and personally supervising the study. (Correct answer)
Correct answer: Complying with FDA regulations for the conduct of a clinical investigation and personally supervising the study.
The FDA Form 1572 is a legally binding agreement between the investigator and the sponsor. By signing it, the investigator commits to personally conduct or supervise the investigation, follow the protocol, and comply with all pertinent FDA regulations for the conduct of clinical trials, as outlined in 21 CFR 312.
Question 5: Under what circumstances may an FDA-regulated clinical investigation be initiated without a signed informed consent form from the subject?
- When the study involves no more than minimal risk.
- When the subject is a minor and a parent has provided verbal permission.
- In a life-threatening situation where specific conditions under 21 CFR 50.23 are met. (Correct answer)
- If the Institutional Review Board (IRB) provides a blanket waiver for all subjects in the study.
Correct answer: In a life-threatening situation where specific conditions under 21 CFR 50.23 are met.
FDA regulations under 21 CFR 50.23 allow for an exception from the general requirements of informed consent in life-threatening situations when the subject cannot provide consent, time is not sufficient to obtain consent from a legal representative, and both the investigator and a non-participating physician certify these conditions in writing.
Question 6: Which of the following must be submitted to the FDA to obtain an exemption to ship an unapproved drug across state lines for a clinical investigation?
- A marketing application (NDA or BLA).
- An Investigational New Drug Application (IND). (Correct answer)
- An Institutional Review Board (IRB) approval letter.
- A signed Form FDA 483.
Correct answer: An Investigational New Drug Application (IND).
An Investigational New Drug Application (IND) is the mechanism through which a sponsor requests an exemption from the federal law that prohibits the shipment of unapproved drugs in interstate commerce. The IND allows the lawful shipment of the investigational drug for the purpose of conducting clinical investigations.
SOCRA - Society of Clinical Research Associates FDA Regulations and Compliance Questions and Answers 1
According to 21 CFR 312, an investigator is required to report a serious adverse event (SAE) to the sponsor: