21 CFR Part 812

If an investigation outside the US is submitted in support of a premarket approval application, how long must the sponsor retain those records?

For 2 years after an agency decision on that submission or application is made

True or False: If the device is NOT a significant risk device, the sponsor can resume a terminated investigation without IRB and FDA approval

False - Sponsor cannot resume a terminated investigation without IRB and FDA approval

What is treatment use of an investigational device?

Use of a device that is not approved for marketing in patients with a serious or immediately life-threatening disease for which no comparable or satisfactory alternative device or other therapy is available

The Sponsor will select monitors qualified by _________________________ and __________________________ to monitor the investigational study

training experience

A sponsor shall select investigators qualified by _______________________ and __________________________ to investigate the device

training and experience

When can an investigation begin?

1. 30 days after the FDA receives the application for the investigation of a device 2. FDA approves an IDE for the investigation

What are the 3 decisions the FDA may make about an application?

1. Approve the investigation as proposed 2. Approve the investigation with modifications 3. Disapprove the investigation

The report of prior investigations must include what 4 pieces of information?

1. Bibliography of all publications relevant to the evaluation of the safety or effectiveness of the device 2. Summary of unpublished information related to the safety or effectiveness of the device 3. Statement specifying that all nonclinical lab studies were conducted in accordance with GLP or explanation as to why that was not the case 4. Statement saying that data from clinical investigations conducted in the US were conducted per 21 CFR Part 50 and 56 regulations

What supplemental applications could be required?

1. Changes in investigational plan 2. Changes effected for emergency use 3. Changes effected with notice to FDA within 5 days

What 4 kinds of records must the investigator maintain?

1. Correspondence (other investigators, sponsor, monitors, FDA, IRB) 2. Records of receipt of the device 3. Each subject's CRFs 4. Protocol and deviations

What 7 kinds of records must the sponsor maintain?

1. Correspondence (other sponsors, investigator, monitor, FDA, IRB) 2. Records of device shipment 3. Signed investigator agreements and FDFs 4. Information about the device (name and use, objectives, whether it's a significant risk device) 5. Name and address of each investigator 6. Name and address of each IRB that reviewed the investigation 7. GMP will be followed when making the device

What are the 4 criteria for treatment use of an investigational device?

1. Device is intended to treat/diagnose a serious or immediately life-threatening disease 2. There is no comparable or satisfactory alternative device or therapy 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 4. The sponsor of the investigation is actively pursuing marketing approval/clearance of the investigational device with due diligence

What are the 4 general responsibilities of investigators?

1. Ensuring that an investigation is conducted according to the signed agreement, investigational plan, and FDA regulations 2. Protecting the rights, safety, and welfare of subjects 3. Protecting the control of the device(s) 4. Ensuring that informed consent is obtained in accordance with 21 CFR Part 50 regulations

What 3 pieces of information regarding an investigational device is confidential per the FDA?

1. Existence of an IDE 2. Availability of summaries or data 3. Reports of adverse effects

What 3 pieces of information must be included in a waiver request?

1. Explanation of why the sponsor's compliance with 21 CFR Part 812 is unnecessary or cannot be achieved 2. Description of an alternative submission or course of action that satisfies the purpose of the requirement 3. Other information justifying a waiver

In what 5 circumstances can the FDA disapprove or withdraw approval of an application?

1. Failure to comply with requirements of 21 CFR Part 812 or other conditions set by the FDA and IRB 2. Application contains untrue statement or omits material that is required 3. Sponsor fails to respond to a request for additional information within the timeframe set forth by the FDA 4. Reason to believe that the risks to the subjects are not outweighed by the anticipated benefits, knowledge gained is inadequate, consent is inadequate, the investigation is scientifically unsound, or the device is ineffective 5. Inadequacy of the report of prior investigations, inadequacy of the methods used to process, pack, store, and install the device, and inadequacy related to monitoring of the investigation

How long must the investigator or sponsor maintain the records?

1. For a period of 2 years after the latter of the following 2 dates: - date on which the investigation is terminated or completed - date that the records are no longer required for purposes of supporting a premarket approval application

What 2 documents must the sponsor supply the investigator with?

1. Investigational Plan (i.e., the protocol) 2. Report of Prior Investigations (i.e., the IB)

If an IRB determines that an investigation involves a significant risk device, is should notify what 2 parties?

1. Investigator 2. Sponsor

What 12 contents must an IDE application include?

1. Name and address of the sponsor 2. Report of prior investigations and summary of the investigational plan 3. Description of the methods, facilities, and controls used for processing, packing, storage, and installation of the device 4. Names and addresses of the investigators 5. Certification that all investigators participating in the investigation have signed the agreement 6. Name, address, and chairperson of each IRB that will review the clinical investigation 7. Name and address of any institution where the investigation will be conducted if not previously identified 8. Sale price of the device and explanation of why sale does not constitute commercialization 9. Cali for categorical exclusion or an environmental assessment 10. Copies of all labelling 11. Copies of all forms and informational materials given to subjects to obtain consent 12. Other info FDA requests

What 5 elements must be included on a label for an investigational device?

1. Name of the device 2. Place of business of the manufacturer, packer, or distributer 3. Quantity 4. The following statement: "Caution - Investigational Device. Limited by Federal (or US) law to investigational use." 5. Hazards/warning/precautions

What 12 pieces of information must the Sponsor provide to the FDA for clinical investigations conducted outside the US?

1. Names of the investigators, names and addresses of the research facilities where records of the investigation are maintained 2. Investigator's qualifications 3. Description of the research facilities 4. Detailed summary of the protocol and results of the investigations 5. Statement specifying that the device used in the investigation outside the US is identical to the device that is the subject of the submission/application 6. Discussion demonstrating that the data and information constitute valid scientific evidence 7. Name and address of the IRB that reviews the investigation 8. Summary of the IRB's decision to modify or approve the investigation 9. Description of how informed consent was obtained 10. Description of what incentives were provided to subjects 11. Description of how the sponsor monitored the investigation 12. Description of how investigators were trained to comply with GCP

Prohibition of Promotion and Other Practices - A Sponsor cannot do what in regards to promoting an investigational device?

1. Promote or test market the device prior to FDA approval 2. Commercialize a device by oversharing the PI and subjects 3. Unduly prolong an investigation 4. Represent that the device is safe and effective for the purposes of which it is being investigated

If a sponsor finds that an investigator is not complying with the signed agreement, the investigational plan, or other FDA regulations, what action must the sponsor take?

1. Promptly secure compliance OR 2. Discontinue shipments of the device to the investigator and terminate the investigator's participation in the investigation

The investigational plan of an IDE must include what 10 elements?

1. Purpose - name of device, intended use, duration, and objectives of the investigation 2. Protocol 3. Risk analysis 4. Description of the device 5. Monitoring procedures 6. Labeling 7. Consent materials 8. IRB information 9. Other institutions 10. Additional records and reports

What information will the Notice of Disapproval/Withdrawal contain?

1. Reasons for the disapproval 2. Statement that the sponsor has an opportunity to request a hearing

What are the 6 general responsibilities of sponsors for clinical investigations involving investigational devices?

1. Selecting qualified investigators 2. Providing investigators with the information they need to conduct the investigation 3. Ensuring proper monitoring of the investigation 4. Ensuring that IRB review and approval are obtained 5. Submitting an IDE application to the FDA 6. Ensuring that any reviewing IRB and the FDA are informed of significant new information about an investigation

In what circumstances must the sponsor submit an application to the FDA in the case of investigational devices?

1. Sponsor wants to use a significant risk device 2. Sponsor intends to conduct an investigation that involves an exception from informed consent 3. FDA notifies the sponsor that an application is required

An investigator will prepare and submit the following 7 types of reports:

1. Unanticipated adverse device effects 2. Withdrawal of IRB approval 3. Progress 4. Deviations from the investigational plan (i.e., protocol deviations) 5. Informed consent 6. Final report 7. Anything else requested by the FDA

The sponsor must submit the following 10 types of reports:

1. Unanticipated adverse device effects 2. Withdrawal of IRB approval 3. Withdrawal of FDA approval 4. Current investigator list 5. Progress reports 6. Recall and device disposition 7. Informed consent 9. Significant risk device determinations 10. Other reports requested by the IRB and FDA

When must the investigator update his or her financial disclosure information?

1. When changes occur during the course of the investigation 2. 1 year after the study has completed

If an investigation outside the US is submitted in support of an IDE, the sponsor must maintain those records for how long?

2 years after the termination or completion of the IDE

IRBs for clinical investigations involving medical devices will follow what regulations?

21 CFR Part 56 regulations

How many copies of the Application for an Investigational Device Exemption must the sponsor submit?

3

Within _____ months after termination or completion of the investigation, the investigator must submit a final report to the sponsor and reviewing IRB

3 months

How long must the IRB maintain records?

3 years

The FDA will provide a written determination _________ days after receiving an IDE for a clinical investigation involving an exception from informed consent?

30 days

How soon after the submission of the treatment IDE application can treatment begin?

30 days after the FDA receives the treatment IDE submission (unless the FDA notifies the sponsor in writing of an earlier start date)

In the case of a significant risk device, the sponsor will notify the FDA within ________ working days of the completion or termination of the investigation and the sponsor will submit a final report to the FDA, IRB, and investigators within ________ months after the investigation has completed or terminated

30 working days 6 months

If an investigator used a device on/in a subject without obtaining consent, the sponsor will notify the FDA within what timeframe upon notice of the use?

5 working days

If the investigator uses a device without obtaining subject consent, the investigator must report this to the sponsor and IRB within _______ working days after the use occurs

5 working days

If there are changes to the clinical protocol or developmental changes that meet the definition of credible information, those changes can be made without prior FDA approval if the sponsor submits a notice of the change to the IDE no later than _______ days after making the change?

5 working days

The sponsor will notify the FDA, IRB, and investigator of any withdrawal of approval by an IRB within _____ working days after receipt of the withdrawal of approval

5 working days

If a sponsor determines that an unanticipated adverse device effect presents unreasonable risk to subjects, the sponsor will terminate all investigations presenting that risk ASAP. Termination shall occur not later than ______ working days after the sponsor makes the determination and not later than ______ working days after the sponsor first received notice of the effect

5 working days 15 working days

The sponsor will notify the IRB and investigators of the withdrawal of FDA approval of the investigation within what timeframe?

5 working days after receipt of notice of the withdrawal

Define Noninvasive

A device that does not... 1. Penetrate or pierce the skin/membranes of the body, ocular cavity, or urethra 2. Enter the ear beyond the external auditory canal, nose beyond the nares, mouth beyond the pharynx, anal cavity beyond the rectum, or vagina beyond the cervical os

Define Implant

A device that is placed into a surgically or naturally formed cavity of the human body if it will remain there for 30 days or more

Define Transitional Device

A device that the FDA considers to be a new drug or an antibiotic drug before 28 May 1976

Define Custom Device

A device within the meaning of section 520(b) of the Federal Food, Drug, and Cosmetic Act

What is an Investigational Device?

A device, including a transitional device, that is the object of an investigation

Define Institution

A person/agency who engages in the conduct of research on subjects, delivery of medical services to individuals, or as an adjunct to providing residential or custodial care to humans

The sponsor must obtain what 5 items from each participating investigator?

A signed agreement that includes: 1. PI's CV 2. Statement of the PI's experience 3. If a PI was involved in a trial that was terminated, an explanation as to why the trial was terminated 4. Statement of the investigator's commitment to: - conduct investigation in accordance with the FDA, IRB, and investigational plan - supervise all testing of the device involving human subjects - ensure that the requirements for obtaining informed consent are met 5. Financial disclosure information

Define Significant Risk Device

An investigational device that: 1. Is an implant and presents a potential for serious risk to the health, safety, and welfare of a subject 2. Is used for supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject 3. Has importance in diagnosing, curing, mitigating, or treating disease and presents a potential for serious risk to the health, safety, and welfare of the subject 4. Otherwise presents a potential for serious risk to the health, safety, and welfare of the subject

Define Unanticipated Adverse Device Effect

Any serious adverse effect on health or safety Any life-threatening problem or death caused by, or associated with, a device

The sponsor must submit progress reports to the IRB how often?

At least yearly

How often must the sponsor submit to the FDA a current list of the names and addresses of the investigators participating in the clinical investigation?

Every 6 months

True or False: A sponsor does NOT need to submit a separate IDE for a clinical investigation involving an exception from informed consent

False - the sponsor must submit a separate IDE for a clinical investigation involving an exception from informed consent

True or False: An investigator can obtain the informed consent of a subject prior to the investigation receiving IRB and FDA approval

False - Investigator must wait until IRB and FDA approval are granted

True or False: A sponsor can begin an investigation for which FDA approval of an application is needed before the FDA has approved the application?

False - Sponsor cannot begin until the FDA approves the application

What does 21 CFR Part 812 cover?

Investigational Device Exemptions The procedures for the conduct of clinical investigations of devices

Under what circumstance will the FDA grant the waiver?

If doing so is in the interest of the public health

The Investigator/Sponsor must permit an investigational device to be used only with subjects under the investigator's supervision and not supply an investigational device to any person not authorized to receive it

Investigator

The Investigator/Sponsor must disclose to the Investigator/Sponsor financial information to allow the applicant to submit complete and accurate certification of disclosure statements

Investigator Sponsor

Labeling of investigational devices cannot be what?

Misleading and claim that the device is safe and effective for the purposes for which it is being investigated

In the event of a deviation from the investigational plan that was intended to protect the life or physical well-being of a subject, the investigator must report this event to the sponsor and IRB within what timeframe?

No later than 5 working days after the emergency occurred

How often must the investigator submit progress reports to the sponsor, IRB, and monitor?

No less than annually

If an investigator or sponsor decides to transfer record retention responsibility to another person, when must the FDA be notified?

Not later than 10 working days after the transfer occurs

What is needed before a person can export an investigational device?

Prior FDA approval

How often must the sponsor of a treatment IDE submit progress reports to the FDA and reviewing IRB until the filing of a marketing application? When a marketing application if filed, how often must the sponsor submit progress reports?

Semi-annually (2 times a year) Once a year

Define Termination

The end of an investigation either by... - discontinuance by the sponsor before the investigation's completion - withdrawal of the FDA or IRB before the investigation's completion

True or False: A person who imports an investigational device will be the agent of the foreign exporter and will act as the sponsor of the clinical investigation or ensure that another person acts as the agent of the foreign exporter and the sponsor of the investigation?

True

True or False: A sponsor can request a waiver from the FDA for investigational device requirements

True

True or False: An investigator or sponsor can withdraw from the responsibility of record retention and transfer custody of this responsibility to another person

True

True or False: If the device is a significant risk device, the sponsor may not resume a terminated investigation without IRB and FDA approval

True

True or False: The sponsor must immediately conduct an evaluation of any unanticipated adverse device effects

True

True or False: The sponsor who submits data from a clinical investigation conducted outside the US to support an IDE or device marketing application must provide a description of the actions the sponsor took to ensure that the research conformed to GCP

True

When must the Investigator submit unanticipated adverse device effects to the sponsor and IRB?

Within 10 working days after the investigator becomes aware of the event

The sponsor must submit unanticipated adverse device effects to the FDA, IRB, and investigators within what timeframe?

Within 10 working days after the sponsor first receives notice of the effect

If the investigator is required to return, repair, or dispose of the investigational device, the sponsor must notify the FDA and IRB within what timeframe?

Within 30 days after the request is made

If the IRB withdraws approval of a clinical investigation, when must the investigator inform the sponsor?

Within 5 working days

If the IRB determines that a device is a significant risk device, but the sponsor originally proposed that the device was not a significant risk device, the sponsor must submit the IRB's determination to the FDA within what timeframe?

Within 5 working days after the sponsor learns of the IRB's determination

Will the FDA accept information on a clinical investigation conducted outside the US to support an IDE or a device marking application?

Yes - if the investigation is well-designed and well-conducted and the following conditions are met: 1. Statement specifying that the investigation was conducted in accordance with GCP 2. FDA is able to validate the data from the investigation through an onsite inspection or other means

A sponsor will ship investigational devices only to ___________________________________________________

qualified investigators participating in the investigation