CFR 21 Part 812

Question 1

What does 45 CFR Part 812 cover

Answer 1

Investigational Device Exemptions

Question 2

What is a significant risk device?

Answer 2

A device that:
1) is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject;
2) Is purported or represented to be for a use in supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject.
3) is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject
4) Otherwise presented a potential for serious risk to the health safety, or welfare of a subject.

Question 3

Transitional Device

Answer 3

Transitional device means a device subject to section 520(l) of the act, that is, a device that FDA considered to be a new drug or an antibiotic drug before May 28, 1976.
Any device that was approved by the New Drug Application process is now governed by the PMA regulations. The original NDA approval number is maintained.

Question 4

What types of changes would require a pre-approval of supplemental application? (IDE)

Answer 4

a) Changes in Investigational Plan – most of the time, changes that are made in the Investigational Plan, need to be pre-approved by FDA. Examples of these changes are:
1. Changes in the Investigational Plan or Protocol
-Affecting the validity of data/information,
-Patient risk to benefit relationship,
-Scientific soundness of investigational plan,
-Right, safety or welfare of subjects.
2. Developmental Changes that present a significant change in design or basic principle of operation
3. IRB approval of new facility-a Sponsor

Question 5

Exceptions to the pre-approval requirements are:

Answer 5

1. Changes Effected for Emergency Use-are considered to be changes in the investigational plan to protect the life or well-being of the subject in the case of
   emergency. However, these changes must be reported to the FDA within 5- working days.
2. Non-significant changes in design or manufacturing - those changes should also be reported to the FDA within 5-working days.
3. Other minor changes that could be reported as a part of Progress Report

Question 6

Can a sponsor make certain changes without prior approval of a supplemental application? If so what is the timeline?

Answer 6

Yes – 1. Changes Effected for Emergency Use-are considered to be changes in the investigational plan to protect the life or well-being of the subject in the case of emergency.
2. Non-significant changes in design or manufacturing

Imp: Sponsor must notify FDA within 5 working days

Question 7

For a significant risk device, the sponsor must notify FDA and all reviewing IRBs within …..days of the completion or termination of the investigation.

Answer 7

30 working days

Question 8

For a significant risk device, the sponsor must submit a final report to FDA and all reviewing IRBs and participating investigators within….. after the completion or termination of the investigation.

Answer 8

6 months

Question 9

For a nonsignificant risk device, the sponsor must submit a final report to all reviewing IRBs within…… after completion or termination.

Answer 9

6 months

Question 10

Define “Treatment use of an investigational device”

Answer 10

A device that is not approved for marketing may be under clinical investigation for a serious or immediately life-threatening disease or condition in patients for whom no comparable or satisfactory alternative device or other therapy is available.

Question 11

Treatment use of an investigational device

Answer 11

During the clinical trial or prior to final action on the marketing application, it may be appropriate to use the device in the treatment of patients not in the trial under the provisions of a treatment investigational device exemption (IDE).

Question 12

FDA shall consider the use of an investigational device under a treatment IDE if:

Answer 12

(1) The device is intended to treat or diagnose a serious or immediately life-threatening disease or condition;
(2) There is no comparable or satisfactory alternative device or other therapy available to treat or diagnose that stage of the disease or condition in the intended patient population;
(3) The device is under investigation in a controlled clinical trial for the same use under an approved IDE, or such clinical trials have been completed; and
(4) The sponsor of the investigation is actively pursuing marketing approval/clearance of the investigational device with due diligence.

Question 13

What is IDE

Answer 13

An approved investigational device exemption (IDE) permits a device that otherwise would be required to comply with a performance standard or to have premarket approval to be shipped lawfully for the purpose of conducting investigations of that device

Question 14

An IDE approved under §812.30 or considered approved under §812.2(b) exempts a device from the requirements of the sections of

Answer 14

Federal Food, Drug, and Cosmetic Act (the act) and regulations

Question 15

The investigator shall submit to …..and … a report of any unanticipated adverse device effect occurring during an investigation as soon as possible, but in no event later than …working days after the investigator first learns of the effect.

Answer 15

a) the sponsor b) the reviewing IRB c) 10

Question 16

An investigator shall report to the …… within …… working days, a withdrawal of approval by the reviewing IRB of the investigator’s part of an investigation

Answer 16

a) Sponsor, b) 5

Question 17

True/False. An investigator shall notify the sponsor and the reviewing IRB of any deviation from the investigational plan to protect the life or physical well-being of a subject in an emergency.

Answer 17

True; Such notice shall be given as soon as possible, but in no event later than 5 working days after the emergency occurred

Question 18

If an investigator uses a device without obtaining informed consent, the investigator shall report such use to the sponsor and the reviewing IRB within …working days after the use occurs.

Answer 18

5

Question 19

The sponsor who conducts an evaluation of an unanticipated adverse device effect ) shall report the results of such evaluation to…..within … working days after the sponsor first receives notice of the effect.

Answer 19

1) FDA and to all reviewing IRB’s and participating investigators

2) 10

Question 20

The sponsor shall notify…. of any
withdrawal of approval of an investigation or a part of an investigation by a reviewing IRB within… working days after receipt of the withdrawal of approval.

Answer 20

1) FDA and all reviewing IRB’s and participating investigators
2) 5

Question 21

A sponsor shall notify all reviewing IRB’s and participating investigators of any withdrawal of FDA approval of the investigation, and shall do so within….. working days after receipt of notice of the withdrawal of approval.

Answer 21

5

Question 22

A sponsor shall submit to FDA current list of the names and addresses of all investigators participating in the investigation.

Answer 22

True; at 6 months intervals

Question 23

Recall and device disposition: A sponsor shall notify ….of any request that an investigator return, repair, or otherwise dispose of any units of a device within ….. working days after the request is made and shall state why the request was made.

Answer 23

1) FDA and all reviewing IRB’s
2) 30

Question 24

A sponsor shall submit to FDA a copy of any report by an investigator of use of a device without obtaining informed consent, within …working days of receipt of notice of such use.

Answer 24

5

Question 25

If an IRB determines that a device is a significant risk device, and the sponsor had proposed that the IRB consider the device not to be a significant risk device, the sponsor shall submit to FDA a report of the IRB’s determination within ….working days after the sponsor first learns of the IRB’s determination.

Answer 25

5

Question 26

Records Retention period: An investigator or sponsor shall maintain the records required by this subpart during the investigation and for a period of …. after the latter of the following two dates: The date on which the investigation is terminated or completed, or the date that the records are no longer required for purposes of supporting a premarket approval application, a
notice of completion of a product development protocol, a humanitarian device exemption application, a premarket notification submission, or a request for De Novo classification.

Answer 26

2 years

Question 27

Yes/No. An investigator or sponsor may withdraw from the responsibility to maintain records and transfer custody of the records to any other person who will accept responsibility for them

Answer 27

Yes. Notice of a transfer shall be given to FDA not later than 10 working days after transfer occurs.

Question 28

Investigational Plan should include:

Answer 28

a) purpose
b) protocol
c) risk analysis
d) description of device
e) monitoring procedures.
f) labeling
g) consent materials
h) IRB information
i) Other institutions
j) Additional records and reports

Question 29

Purpose

Answer 29

name of the device
intended use of the device
objectives of the investigation.
duration of the investigation.

Question 30

Protocol

Answer 30

A written protocol describing:
-the methodology to be used
-analysis of the protocol
demonstrating that the investigation is scientifically sound.

Question 31

Risk analysis

Answer 31

A) A description and analysis of all increased risks to which subjects will be exposed by the investigation;
B) the manner in which these risks will be minimized;
C) a justification for the investigation; and
D) a description of the patient population, including the number, age, sex, and condition.

Question 32

Description of device

Answer 32

A description of
each important component, ingredient,
property, and
principle of operation of the device and
of each anticipated change in the device during the course of the investigation.

Question 33

Responsibilities of a sponsor

Answer 33

a) selecting qualified investigators and providing them with the information they need to conduct the investigation properly,
b) ensuring proper monitoring of the investigation,
c) ensuring that IRB review and approval are obtained,
d) submitting an IDE application to FDA, and
e) ensuring that any reviewing IRB and FDA are promptly informed of significant new information about an investigation.

Question 34

A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both approved the application or supplemental application relating to the investigation or part of an investigation.

Answer 34

True

Question 35

A sponsor shall supply all investigators participating in the investigation with copies of

Answer 35

investigational plan and prior investigations of the device.

Question 36

A sponsor who determines that an unanticipated adverse device effect presents an unreasonable risk to subjects…

Answer 36

a) shall terminate all investigations or parts of investigations presenting that risk as soon as possible.
b) Termination shall occur not later than 5 working days after the sponsor makes this determination and not later than 15 working days after the sponsor first received notice of the effect.

Question 37

If the device is a significant risk device, a sponsor may not resume a terminated investigation without

Answer 37

IRB and FDA approval.

Question 38

If the device is not a significant risk device, a sponsor may not resume a terminated investigation

Answer 38

without IRB approval

Question 39

Specific responsibilities of investigators.

Answer 39

a) Awaiting IRB and FDA Approval to start study
b) Compliance
c) Financial Disclosures
d) Supervising use of device
e) Disposing device

Question 40

For a significant risk or non-significant risk IDE, how often does a sponsor need to submit an annual report and to who?

Answer 40

For all IDE’s: At least yearly progress reports to IRB.

For SR IDE’s: At least yearly to IRB AND to FDA.

Question 41

What types of devices are considered IDE exempt?

Answer 41

-In commercial distribution before May 28, 1976
-Diagnostic device that is noninvasive, does not require invasive sampling, does no introduce energy into the subject and requires the confirmation of another medically established diagnostic product.
-Device undergoing consumer preference testing, testing a modification or testing a combination of 2 marketed devices with no risk to the patient
-Device for veterinary use.
- Device only shipped for research on or with laboratory animals
-Custom Device

Question 42

Custom Device

Answer 42

-devices created or modified in order to comply with the order of an individual physician or dentist;
*-the potential for multiple units of a device type (not to exceed 5 units per year) qualifying for the custom device exemption; and
*-annual reporting requirements by the manufacturer to FDA about devices manufactured and distributed under section 520(b) of the FD&C Act.

Question 43

For IDE, when and to who does the investigator have to submit a final report after finishing a clinical trial?

Answer 43

Investigator submits a final report to the Sponsor AND to the IRB within 3 months of finishing the trial