21 CFR Part 312

Question 1

Primary purpose of IND

Answer 1

If a drug is used in a clinical investigation to gather data for FDA marketing approval or labeling changes, an IND application is required.

Question 2

Secondary purpose of IND

Answer 2

Process gets put in place to ensure proper testing, monitoring, protecting pt’s safety and generating reliable data on the drug’s safety and efficacy.

Question 3

In what cases is it justified to charge pt’s for IND.

Answer 3

-Evidence that drug has potential clinical benefits that demonstrates significant advantage over competitors
- Trial is not possible without charge due to cost

Question 4

Phase 1

Answer 4

-may be conducted in pts or normal subjects
-designed to determine the metabolism and pharma actions of the drug in humans
-test early side effects
-initial evidence of effectiveness
-(N=20-80)

Usually requires the shortest interval of reports, annual too infreqeunt

Question 5

Phase 2

Answer 5

-Controlled studies to evaluate effectiveness of the drug for a particular indication or diseases that fall under study objectives
-ascertain the common short-term side/effects/risk
(n<several hundreds)

Question 6

Phase 3

Answer 6

Expanded controlled + uncontrolled trials intended to capture the overall benefit-risk relationship
-provide foundation for physician labeling
-(n=several thousands)

Question 7

FDA assessment of Phase 1 is for

Answer 7

safety of drug

Question 8

FDA assessment of Phase 2 + Phase 3

Answer 8

intended to cultivate an assessment of the scientific quality of the investigation and likelihood that the investigators will yield data capable for marketing approval

Question 9

FDA assessment of Phase 4

Answer 9

concurrent with marketing approval

Question 10

FDA’s primary objective when reviewing an IND

Answer 10

1. Assure the safety and rights of subjects
2. For P2 + P3 assure that the quality of the investigation (and its assessment qualities) of the drug is adequate to permit an evaluation of its efficacy and safety and meeting the standards of marketing approval)

Question 11

Essentials of IND submission

Answer 11

1. Cover sheet
2. Table of contents
3. Intro statement/general investigational plan
4. Investigators brochure
5. Protocols
6. chemistry, manufacturing and control information
7. Pharmacology and drug disposition
8. previous human experience with IND
9. Add info
10. Relevant info

Question 12

COVER SHEET

Answer 12

Form 1571
-Sponsor info
-Clinical phases
-Compliance commitments
monitoring + safety
-CRO info
Signature (signed by sponsor or auth reps_ and if outside US co-signed by US based official

Question 13

Investigator’s Brochure

Answer 13

Title Page
Drug description
Effects summary
Pharmacokinetics
Toxicology
Safety and Efficacy
Marketing Exp
Previous Studies
Risks + Monitoring

Question 13

Under 21 CFR Part 312.44, what action may the FDA take if a sponsor fails to correct deficiencies in an IND application?

A. The FDA may issue a warning letter but will allow the study to continue.
B. The FDA may place the IND on clinical hold until the deficiencies are corrected.
C. The FDA may immediately withdraw the study and require all participants to stop participation.
D. The FDA may terminate the IND and require the sponsor to submit a new application.

Answer 13

B

Question 14

What are the investigator responsibilities under 21 CFR 312?

Answer 14

• ensuring study is conducted according to protocol
  -protecting the rights, safety and welfare of subject
  -obtaining ICF

Question 15

What does 21 CFR 312 require investigators to maintain?

Answer 15

-they need to keep adequate/accurate records of drug disposition, subject case histories (CRFs) and ensure records are available for FDA inspection

Question 16

What are investigators responsibility regarding AEs?

Answer 16

-report to sponsor ASAP, and write detailed written report

Question 17

What is the responsibility of the investigator regarding IRB oversite?

Answer 17

the investigator must ensure the IRB has approved the study BEFORE starting the study activities, while also reporting any significant changes or new risks –> IRB

Question 18

What actions must an investigator take if they discontinue participation in a clinical study?

Answer 18

they must permit FDA inspection of their records, and explain why the study was discontinued if applicable.

Question 19

Under 21 CFR 312.55, what must an investigator do if they discover an unexpected serious adverse event during the clinical trial?
A. Immediately notify the FDA and sponsor, and provide a written report within 15 days.
B. Stop the trial and notify the IRB only.
C. Wait until the end of the trial to report the adverse event.
D. Inform the FDA only at the end of the trial.

Answer 19

A

Question 20

Under 21 CFR 312.37, what should a sponsor do if they wish to discontinue the clinical investigation?
A. Notify the FDA and all participating investigators, and submit a final report.
B. Immediately destroy all investigational drugs and inform the public.
C. Request an extension from the FDA and continue the study.
D. Submit a new IND application for a modified study.

Answer 20

A

Question 21

Under 21 CFR 312.56, what must a sponsor do if there is a significant new finding during the clinical investigation that may affect the risk/benefit assessment?
A. Submit an amendment to the IND within 30 days.
B. Immediately stop the clinical trial and submit a final report.
C. Inform the FDA and all investigators, and submit a new IND application.
D. Provide an interim report at the end of the year.

Answer 21

A

Question 22

What is the sponsor’s primary responsibility

Answer 22

ensuring the clinical trial is properly designed, conducted, monitored, and evaluated in compliance with the IND regulations

Question 23

What must a sponsor do if sig new safety information arises during a clinical trial

Answer 23

sponsor must promptly review the safety information, amend the IND as necessary, notify the FDA and inform all investigators of new findings.

Question 24

What is sponsor’s role in monitoring the clinical trial?

Answer 24

Sponsor is responsible for selecting qualified investigators providing them with the necessary information, and ensuring proper monitoring of the study’s progress.

Question 25

How should sponsor handle safety information?

Answer 25

the sponsor must ensure that new safety information, especially unexpected risks is communicated to FDA and investigators promptly

Question 26

What must a sponsor submit annually?

Answer 26

they must submit an annual report to the FDA that includes a summary of the study’s progress, safety information and any amendments to the protocol

Question 27

what is the IRB’s role in a clinical trial?

Answer 27

responsible for reviewing and approving the study to ensure that the rights and welfare of the human subjects are protected.

Question 28

what must the IRB do if new risks emerge during the clinical trial?

Answer 28

review any new risks or changes in the study, ensure that the risks remain minimized and the ICF are updated.

Question 29

How does the IRB contribute to FDA inspections?

Answer 29

IRB must maintain all relevant records to ensure they are available for FDA inspection, including study protocols, ICFs and meeting minutes.

Question 30

what must the IRB consider when reviewing the risk-benefit ratio of a study

Answer 30

ensure risks are minimized and reasonable in relation to the potential benefits.