Code of Federal Regulations

Question 1

What regulation(s) does 21 CFR Part 11 cover?

Answer 1

Requirements for electronic records & electronic signatures.

Question 2

What regulation(s) does 21 CFR Part 50 cover?

Answer 2

Requirements & exemptions for informed consent. Subpart D also includes additional provision for children.

Question 3

What regulation(s) does 21 CFR Part 56 cover?

Answer 3

Requirements for institutional review boards (IRBs).

Question 4

Per 21 CFR Part 50, informed consent forms/discussions must include what components?

Answer 4

ICFs must include: purpose of the research study, explanation of the study procedures involved, duration of study participation, explanation of any risks & benefits associated with participation, disclosure of any alternatives, injury info (including who to contact), statement regarding confidentiality & who may have access to study records, & statement explaining it is completely voluntary to participate and they can withdraw participation at any time

Question 5

In what situation is the use of a short form appropriate to obtain consent?

Answer 5

Short forms can be used instead of full ICFs in conjunction with a study summary and oral explanation of the study. A witness must be present during the explanation and also sign the short form and summary page.

Question 6

Per 21 CFR Part 56, how often do IRBs need to submit their registration?

Answer 6

IRBs must initially register with HHS prior to reviewing any protocols, and must renew their registration every 3 years.

Question 7

How many people make up an IRB?

Answer 7

Each IRB must contain at least 5 members, at least 1 of a scientific background, at least 1 of a non-scientific background, & at least 1 member not otherwise affiliated with the institution.

Question 8

If an IRB decides to disband, how soon do they need to communicate this to the FDA?

Answer 8

The IRB desiring to disband must communicate this to the FDA within 30 days.

Question 9

When an IRB experiences a personnel change, they need to notify the FDA within ____ days.

Answer 9

90

Question 10

If an IRB decides to change the types of FDA-regulated products they review, when do they need to notify the FDA of this change?

Answer 10

Within 30 days of the change.

Question 11

What are the additional elements to be included in ICFS (as applicable)?

Answer 11

Depending on the study, these elements may also be needed in ICFs: statement about unknown risks, potential their participation may be terminated by the investigator at any time/for any reason, describe any additional potential costs, statement about whether or not findings will be provided to participants, statement including the approx # of ppts in study, & ClinicalTrials.gov statement

Question 12

If emergency use of a test article is needed prior to obtaining consent, the PI needs to … ?

Answer 12

The PI needs to submit a written notice to the IRB within 5 working days of the emergency use event.

Question 13

Expedited reviews are allowed in what 2 scenarios?

Answer 13

1. When the research is minimal risk and is listed on the FDA Federal Register of types of research meeting requirements of expedited review.
2. When the investigators are submitting minor changes to previously-approved materials during the current approval period (no more than 1 year).

Question 14

When IRBs review research protocols for approval, they specifically look for … ?

Answer 14

Informed consent process, anticipated risks & benefits (risks to subjects must be minimalized), defined selection criteria of subjects (is this representative of the target population?), DSMP (as applicable), & process for subject confidentiality & privacy (as applicable).

Question 15

If an IRB suspends or terminates approval from investigators/institutions when noncompliance is found, what needs to be done?

Answer 15

Per 21 CFR 56, the FDA, investigator, & institutional officials need to be alerted immediately, and research operations for the noncompliant study must cease.

Question 16

How long do IRB records need to be kept?

Answer 16

IRB records for each protocol must be kept for at least 3 years after completion of the research.

Question 17

Per 21 CFR 56, what types of records need to be kept by the IRB?

Answer 17

The IRB must keep: copies of research proposals (and their associated materials), any IRB meeting minutes, names & contact info for all IRB members, all CR records, written procedures of the IRB, all correspondence between the IRB & investigators, & statements of significant findings provided to subjects.

Question 18

If the FDA finds an IRB noncompliant, what happens?

Answer 18

Per 21 CFR 56, the noncompliant IRB will receive a written notice from the IRB, requiring a response, likely with corrective action. If action is not taken/refused, the Commissioner of Food & Drugs can disqualify the IRB, preventing them from reviewing any protocols.

Question 19

What regulation(s) does 21 CFR Part 312 cover?

Answer 19

This regulation covers investigational new drug (IND) applications.

Question 20

Per 21 CFR Part 312, what defines an adverse event (AE)?

Answer 20

An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not the event is directly related to the drug itself

Question 21

Per 21 CFR 312, what is a suspected adverse reaction (SAR)?

Answer 21

An event where there is reasonable assumption (evidence for causal relation) that it was caused by the drug.

Question 22

Per 21 CFR 312, when are events considered life-threatening?

Answer 22

When the investigator determines the event put the subject at risk for death.

Question 23

Per 21 CFR 312, when is an event determined to be serious? (e.g., SAE or SSAR)

Answer 23

Events are considered serious when it is a life-threatening event, results in death, results in persistent or significant incapacity or disability, requires or prolongs inpatient hospitalization, or causes congenital anomaly/birth defect

Question 24

Per 21 CFR 312, when are events considered “unexpected”?

Answer 24

Events are unexpected when they are either 1. not listed in the protocol or IB as a potential risk associated with the drug or 2. the event is not listed at the severity or specificity observed

Question 25

When a sponsor identifies a potential serious risk from a safety report, what needs to be done?

Answer 25

The sponsor must report this to the FDA & all investigators involved within 15 calendar days of receiving the information from the investigator(s) & determining it needs to be reported

Question 26

What form(s) should the sponsor use when reporting events to the FDA?

Answer 26

Preferred option is FDA Form 3500A; can also use CIOMS 1 Form or write a narrative explaining the event.

Question 27

When an event is determined to be life-threatening or results in death, the sponsor needs to report to the FDA with ___ calendar days of receiving notice.

Answer 27

7 calendar days

Question 28

Sponsors must submit a summary report to the FDA within 60 days of the anniversary date of the IND going into effect. This includes …

Answer 28

Individual site summaries (how sites are doing with drug), overall summary of reportable events, & any anticipated protocol or IB changes

Question 29

A ______ can withdraw an IND at any time, but must notify the FDA & all clinical investigations must cease. If the withdrawal is due to a safety concern, the sponsor must notify the ____, all _____, and all ____ immediately.

Answer 29

Sponsor, FDA, investigators involved, IRBs involved

Question 30

The sponsor must report any event (or findings) to the FDA that …

Answer 30

is considered both serious & unexpected, includes findings from other studies (animal & in-vitro too) that suggest increased risk to humans, or any increase in a specific SSAR/SAE

Question 31

What is a phase 1 trial?

Answer 31

Initial introduction of the drug for human use; primary objective is to assess safety and side effects

Question 32

What is a phase 2 trial?

Answer 32

Primary objective is to assess how effective the drug is at fixing/helping the medical condition being studied

Question 33

What is a phase 3 trial?

Answer 33

This is conducted after preliminary effectiveness and safety has been established. Results from trial can provide an adequate basis for physician labeling.

Question 34

Products that are under an effective IND are exempt from ____ and ___.

Answer 34

premarketing approval requirements, shipping restrictions

Question 35

Sponsors CAN charge investigators for use of a drug under an IND, with written authorization from the FDA, if …

Answer 35

Charging is essential to conduct the trial, there is evidence that clinical benefit from the drug may pose an advantage over other drugs already on the market, or if they can demonstrate the data obtained in the trial is essential to establishing effectiveness of the drug for the specified medical condition.

Question 36

If an IND has been on inactive status for ___ years, or if the FDA finds any noncompliance, serious safety issues, etc. from the sponsor and/or study sites, the FDA will ____ the IND and submit written notice to the sponsor inviting correction or explanation within ____ days.

Answer 36

5+, terminate, 30

Question 37

If no subjects are enrolled into an IND investigation for at least ___ years, or if any clinical investigations under the IND have been on clinical hold for at least ___ years, the FDA may deem the IND ____.

Answer 37

2, 1, inactive

Question 38

What are pre-NDA meetings?

Answer 38

These are meetings between FDA & sponsor at the end of phase 3 trials that are ready to market the drug that was being tested.

Question 39

When preparing for “end-of-Phase 2” meetings or pre-NDA meetings with the FDA, what does the sponsor need to prepare?

Answer 39

The sponsor should submit materials demonstrating feasibility of moving from Phase 2 –> Phase 3, or Phase 3 –> market (whichever is applicable), including info about safety, effectiveness, & future plans for the next steps. Materials should be submitted to FDA no later than 1 month prior to the meeting(s).

Question 40

Per 21 CFR 312, what are sponsors responsible for? (hint: there are 5 responsibilities listed)

Answer 40

1. selecting qualified investigators & providing them with the proper materials (including IB) to conduct the study
2. monitor sites & ensure approved protocols/GIPs are being followed, in line with HSR regulations
3. maintaining effective IND status
4. informing investigators & FDA of any safety reports & new findings about the drug
5. gathering unused study drug at the end of an investigation (or ensuring proper disposal)

Question 41

Per 21 CFR 312, the sponsor may transfer their responsibilities to a _______, with written notice to the FDA.

Answer 41

contracted research organization (CRO)

Question 42

Prior to activating an investigator site, what must the sponsor (or CRO) obtain from the investigator?

Answer 42

Investigator must provide updated CV, FDA 1572 form, clinical protocols, & financial disclosure information (COIs).

Question 43

If an investigation must be discontinued due to a safety concern, the sponsor must notify the FDA & all investigators involved with _____ working days of making the decision.

Answer 43

5 (preferably asap)

Question 44

The sponsor must keep records of all IP shipment notifications & receipts, site financial records, & reserve samples of IP for at least _____ after the investigation has ended/marketing has been approved.

Answer 44

2 years

Question 45

Per 21 CFR 312, what are investigators responsible for? (hint: there are 9 responsibilities listed)

Answer 45

1. ensuring investigation is conducted according to approved GIP, protocol, & HSR regulations
2. protecting the rights, safety, & welfare of study subjects
3. obtaining informed consent from study subjects
4. maintaining site control of study drug
5. keep records of drug disposition & case histories for all study subjects for at least 2 years after investigation/market
6. submit progress reports to sponsor
7. submit SAE/SSAR reports to IRB & sponsor immediately
8. submit financial disclosure reports to sponsor
9. work with an IRB & do not conduct any unapproved procedures

Question 46

When investigational drugs are intended to treat life-threatening or severely debilitating conditions, regulations are often more _____ and risks/side effects may be ______.

Answer 46

flexible, higher

Question 47

Phase ___ trials are sometimes conducted concurrently with marketing process to further evaluate side effects & drug effectiveness, & testing out different doses.

Answer 47

4

Question 48

In requesting an IND for expanded access, what form must be submitted with the application?

Answer 48

FDA Form 1571

Question 49

What regulation(s) does 21 CFR Part 812 cover?

Answer 49

Investigational device exemptions (IDEs)

Question 50

An approved IDE application means … ?

Answer 50

The device may be shipped, exempt from premarket approval & performance standards, for clinical investigational use.