21 CFR Part 312

Question 1

What does 21 CFR Part 312 cover?

Answer 1

Investigational New Drug Application

Question 2

clinical investigation of a drug product that is lawfully marketed in the US is exempt from the requirements of part 312 if all of the following applies:

Answer 2

1) The investigation is not intended to be reported to the FDA as a well-controlled study in support of a new indication for use nor intended to be used to support any other significant change in the labeling of the drug.
2) If the drug that is undergoing investigation is lawfully marketed as a prescription drug product, the investigation is not intended to support a significant change in the advertising for the product.
3) The investigation does not involve a route of administration or dosage level or use in a patient population or other factor that significantly increases the risks associated with the use of the drug product.
4) Investigation is conducted in compliance w/ the IRB and appropriately consents.
5) Investigation is conducted in compliance with the requirements.

Question 3

What products are exempt from requirements of 312?

Answer 3

1) blood grouping serum
2) reagent red blood cells
3) anti-human globulin.

Question 4

In what setting is a drug exempt from requirements of 312?

Answer 4

drugs intended solely for tests in vitro or in laboratory research animals

Question 5

A clinical investigation involving use of THIS is exempt from the requirements of 312 if the investigation does not otherwise require submission of an IND

Answer 5

Placebo

Question 6

Is an Unlabeled indication of drug/device subject to provisions of 320.31? (Applicability of requirements regarding an “Investigational New Drug Application”)

Answer 6

No, does not apply to the use in the practice of medicine for an unlabeled indication of a new drug product

(320.31 applies to bioavailability studies)

Question 7

Independent ethics committee (IEC)

Answer 7

a review panel that is responsible for ensuring the protection of the rights, safety, and well-being of human subjects involved in a clinical investigation and is adequately constituted to provide assurance of that protection.

Question 8

Investigational new drug

Answer 8

a new drug or biological drug that is used in a clinical investigation.

Question 9

FDA shall provide a written determination within ____ days after receiving IND application

Answer 9

30

Question 10

Grounds for clinical holds on Phase I studies:

Answer 10

unreasonable risk
unqualified investigators
IB is misleading, inaccurate or incomplete
or IND doesn’t contain sufficient information to assess risk to subjects

Question 11

Grounds for clinical holds on Phase II or III studies:

Answer 11

deficient protocol to meet stated objectives

Question 12

When an ongoing study is on a clinical hold can new subjects be enrolled and what happens to subjects currently enrolled and on IP?

Answer 12

no new subjects,

subjects on IP have to stop unless specifically permitted by the FDA

Question 13

Who can appeal the FDA’s decision for a clinical hold?

Answer 13

Sponsor

Question 14

How must the FDA notify the sponsor of a clinical hold on an IP?

Answer 14

Can be imposed by telephone, rapid communication or in writing

Question 15

What is required to resume study after clinical hold on IP?

Answer 15

Cited issues must be resolved and the FDA must notify the sponsor to proceed

Question 16

Under an IND, if no subjects are entered into a study for 2+ years or if all studies under an IND remain on clinical hold for 1 year+, the IND may be placed on “_____”

Answer 16

Inactive status

Question 17

INDs that are “Inactive” for ___+ years may be terminated

Answer 17

5

Question 18

For an IND, how soon should the sponsor report serious unexpected life-threatening safety events to FDA?

Answer 18

7 calendar days.

Question 19

For an IND, how soon should the sponsor report serious unexpected safety events to FDA when not life-threatening?

Answer 19

15 calendar days.

Question 20

For an IND, what form is used for the sponsor reporting serious unexpected safety events?

Answer 20

Form FDA 3500A

Question 21

What does SUSAR stand for?

Answer 21

Suspected unexpected serious adverse reaction

Question 21

For an IND, when do investigators report serious events to sponsors?

Answer 21

As soon as possible (typically stated in protocol). (15 Days)

Question 22

For an IND, when is the annual report is provided to the FDA by the sponsor?

Answer 22

60 calendar days from the anniversary of the IND becoming active.

Question 23

True or False: Reactions which are serious but expected are subject to expedited reporting requirements

Answer 23

False. Reactions that are serious but unexpected are subject to expedited reporting.

Question 23

For an IND, when do Investigator’s provide annual report to sponsor?

Answer 23

No time criteria, give to sponsor to submit to FDA.

Question 24

For an IND, when does the Investigator need to submit the final report to the sponsor?

Answer 24

When the study site is finished with the investigation (no specified time constraints).

Question 25

For emergency use of a drug, where immediate use of the product was required and the patient was not able to be consented, how long does the sponsor have to notify the FDA of the use of the product?

Answer 25

5 working days

Question 26

Fatal or life-threatening unexpected adverse drug reactions are required to be reported no later than how many days after first knowledge? What about non-life-threatening unexpected ADRs?

Answer 26

Fatal unexpected ADRs: 7 calendar days after first knowledge

Non-fatal serious unexpected ADRs: 15 calendar days after first knowledge

Question 26

What key data elements should be included in expedited reports for serious adverse drug reactions?

Answer 26

Patient details
Suspected medicinal product
Other treatments patient was receiving
Details of Suspected ADR
Reporter of the event
Sponsor details

Question 26

When is unblinding inappropriate in the case of a fatal or serious adverse event?

Answer 26

If a fatal or serious outcome is the primary efficacy endpoint, the integrity of the clinical investigation may be compromised if the blind is broken. It may be advantageous to reach an agreement with regulatory authority not to unblind and expedite reporting.

Question 26

What is form FDA 3500 used for?

Answer 26

Voluntary reporting of an adverse event.

Question 27

Key Aspects of Pre-clinical studies:

Answer 27

o Help establish boundaries for the safe use of treatment when human testing begins
o Studies designed to evaluate compounds for potential pharmacologic use
o Generally performed in animals
o Evaluate the possibility of long-term, adverse events: onset of cancer, interference with reproduction or the induction of birth defects etc.
o When sufficient data are obtained to warrant study in humans subjects, a sponsor submits an IND

Question 28

Key aspects of Phase 1 studies:

Answer 28

o Small trials with healthy subjects, purpose is to determine pharmacokinetics and maximum tolerated dose
o Conducted to determine the appropriate dose range with regard to safety and toxicity (not to evaluate efficacy)
o Conducted in a limited number (20-80) of health volunteers or patients (cancer, AIDS)
o Many compounds are abandoned in this phase because of safety/toxicity problems

Question 29

Key aspects of Phase II studies:

Answer 29

o Initial demonstration of efficacy in patients, short-term safety information
o Conducted in a relatively limited number (100-300) patients who have the disease
o Often involve hospitalized patients who can be closely monitored
o Many focus on dose-response, dosing schedule, or other issues related to preliminary safety and efficacy
o Takes about 1 to 3 years to complete

Question 30

Key aspects of Phase III studies:

Answer 30

o Use in large numbers of patients, long-term safety data
o Conducted in larger (several hundred to several thousand) and more diverse groups for whom the drug is ultimately intended
o Make comparisons between new treatment and standard therapy or placebo
o Study drug used by practicing physicians in the same manner as it would be used after marketing
o Takes about 2 to 5 years to complete

Question 31

Key aspects of Phase IV studies:

Answer 31

o Post-marketing, continue assessing therapeutic value and monitor less common adverse events

Question 32

True or False. FDA Form 1572 is required for all trials.

Answer 32

False. Form 1572 is required for IND studies but not required for IDE. A generic doctor agreement is all that is required for IDE.

Question 33

What does CAPA stand for?

Answer 33

Corrective and Preventative Action Plans

Question 34

When a sponsor intends to conduct a clinical investigation with an exception from informed consent for emergency research, what must be done?

Answer 34

Sponsor shall submit a separate IND for such investigation.

Question 35

The sponsors request for a regulatory hearing must be made within ___ of the sponsors receipt of fda’s notification of nonacceptance

Answer 35

10 days