Responsibilities

Responsibilities of Sponsors for Significant Risk Device Studies

General responsibilities (§812.40)

Sponsors are responsible for selecting qualified investigators and providing them with the information that they need to conduct the investigation properly. They must also ensure proper monitoring of the investigation and IRB review and approval, submit an IDE application to FDA for significant risk device studies, and inform the IRB and FDA promptly of any significant new information about the investigation.

FDA and IRB approval (§812.42)

A sponsor cannot begin an investigation or any part of an investigation until an IRB and FDA have both approved the application or supplemental application.

Selecting Investigators (§812.43)

A sponsor is responsible for selecting investigators qualified by training and experience to investigate the device.

Selecting Monitors (§812.43)

A sponsor must select monitors qualified by training and experience to monitor the investigational study in accordance with the IDE and other applicable FDA regulations.

Device Control (§812.43)

A sponsor can ship investigational devices only to qualified investigators participating in the investigation.

Investigator Agreements (§812.43)

A sponsor must obtain a signed agreement from each participating investigator that includes;

the investigator's curriculum vitae,
a statement of the investigator's relevant experience, including the dates, location, extent, and type of experience, where applicable,
an explanation of the circumstances that led to termination of a study if the investigator was involved in an investigation or other research that was terminated,
a statement of the investigator's commitment to:
- conduct the investigation in accordance with the agreement, the investigational plan, the IDE and other applicable FDA regulations, and conditions of approval imposed by the reviewing IRB or FDA,
- supervise all testing of the device involving human subjects. and
- ensure that the requirements for obtaining informed consent are met.
sufficient accurate financial disclosure information to allow the sponsor to submit a complete and accurate certification or disclosure statement as required under 21 CFR 54, Financial Disclosure by Clinical Investigators. The sponsor shall also obtain a commitment from the clinical investigator to promptly update this information if any relevant changes occur during the course of the investigation and for one year following completion of the study. (The financial certification or disclosure is submitted in the PMA or Premarket Notification 510(k) application. It should not be submitted in the IDE application.)

Informing investigators (§ 812.45)

A sponsor must supply all investigators participating in the investigation with copies of the investigational plan and a report of prior investigations of the device.

Monitoring (§ 812.46)

Securing Compliance

A sponsor who discovers that an investigator is not complying with the signed agreement, the investigational plan, the IDE requirements, any other applicable FDA regulations, or any conditions of approval imposed by the reviewing IRB or FDA must promptly either secure compliance, or discontinue shipments of the device to the investigator and terminate the investigator's participation in the investigation. A sponsor must also require that the investigator dispose of or return the device, unless this action would jeopardize the rights, safety, or welfare of a subject.

Unanticipated Adverse Device Effects

The sponsor must immediately conduct an evaluation of any unanticipated adverse device effect. A sponsor who determines that an unanticipated adverse device effect presents an unreasonable risk to subjects must terminate all investigations or parts of the investigations presenting that risk as soon as possible. Termination must occur no later than 5 working days after the sponsor makes this determination and no later than 15 working days after the sponsor first received notice of the effect.

Resumption of Terminated Studies

For significant risk device investigations, a sponsor may not resume a terminated investigation without IRB and FDA approval. For a nonsignificant risk device investigation, a sponsor may not resume a terminated investigation without IRB approval. If the nonsignificant risk study was terminated for unanticipated adverse device effects, the sponsor must also obtain FDA approval.

Sponsor records (§ 812.140)

The sponsor must maintain accurate and complete records relating to the investigation. These records include;

all correspondence including required reports,

records of shipment of the device,

records of disposition of the device

signed investigator agreements including financial disclosure information,

records concerning complaints and adverse device effects whether anticipated or not,

any other records that FDA requires to be maintained by regulation or by specific requirement for a category of investigation or a particular investigation.

See Records for additional information on recordkeeping requirements.

Sponsor Reports (§812.150)

The sponsor must provide the following reports in a timely manner to FDA, the IRB's, and/or the investigators.

Unanticipated Adverse Device Effects

Withdrawal of IRB Approval

Withdrawal of FDA Approval

Current List of Investigators

Progress Reports

Recalls and Device Disposition

Final Report

Informed consent

Significant Risk Device Determination

Other Reports

See Reports for more information regarding required reports.

Labeling (§812.5)

Under §812.5 an investigational device or its immediate package must bear a label with the following information:

the name and place of business of the manufacturer, packer, or distributor;
the quantity of contents, if appropriate; and
the statement, "CAUTION Investigational device. Limited by Federal (or United States) law to investigational use."

The label must also describe all relevant contraindications, hazards, adverse effects, interfering substances or devices, warnings, and precautions.

The labeling of an investigational device must not contain any false or misleading statements nor imply that the device is safe or effective for the purposes being investigated.

The sponsor should provide detailed information on device labeling in the investigational protocol. This information may vary depending on the device and the nature of the study. Product labeling should be sufficient to ensure stability of the test article for the duration of the study (storage requirements, calibration procedures), bear sufficient directions for proper administration, and detail procedures to follow in the event of patient injury.

Promotion of Investigational Devices (§812.7)

Under §812.7, a sponsor, investigator, or any person acting for or on behalf of a sponsor or investigator cannot:

Promote or test market an investigational device, until after FDA has approved the device for commercial distribution.

Commercialize an investigational device by charging the subjects or investigators a higher price than that necessary to recover costs of manufacture, research, development, and handling.

Unduly prolong an investigation. If data developed by the investigation indicate that premarket approval (PMA) cannot be justified, the sponsor must promptly terminate the investigation.

Represent that an investigational device is safe or effective.

However, the sponsor may advertise for research subjects to solicit their participation in a study. Appropriate advertising methods include but is not necessarily limited to: newspaper, radio, TV, bulletin boards, posters, and flyers that are intended for prospective subjects.

Advertisements should be reviewed and approved by the IRB to assure that it is not unduly coercive and does not promise a certainty of cure beyond what is outlined in the consent and the protocol. No claims should be made, either explicitly or implicitly, that the device is safe or effective for the purposes under investigation, or that the test article is known to be equivalent or superior to any other device.

FDA considers direct advertising for study subjects to be the start of the informed consent and subject selection process.

Additional guidance is available in the following guidance documents:

"Information Sheets: Guidance for Institutional Review Boards and Clinical Investigators, 1998 - Recruiting for Study Subjects"
http://www.fda.gov/oc/ohrt/irbs/toc4.html

Preparing Notices of Availability of Investigational Medical Devices and for Recruiting Study Subjects
http://www.fda.gov/cdrh/comp/2229.html
http://www.fda.gov/cdrh/comp/2229.pdf

Responsibilities of Sponsors of Nonsignificant Risk Device Studies

Sponsors of nonsignificant risk studies must comply with the abbreviated IDE requirements set forth in (§812.2(b). The sponsor must:

Label the device in accordance with §812.5.

Under §812.5 an investigational device or its immediate package must bear a label with the following information:

the name and place of business of the manufacturer, packer, or distributor;
the quantity of contents, if appropriate; and
the statement, "CAUTION Investigational device. Limited by Federal (or United States) law to investigational use."

The label must also describe all relevant contraindications, hazards, adverse effects, interfering substances or devices, warnings, and precautions.

The labeling of an investigational device must not contain any false or misleading statements nor imply that the device is safe or effective for the purposes being investigated.

The sponsor should provide detailed information on device labeling in the investigational protocol. This information may vary depending on the device and the nature of the study. Product labeling should be sufficient to ensure stability of the test article for the duration of the study (storage requirements, calibration procedures), bear sufficient directions for proper administration, and detail procedures to follow in the event of patient injury.

Obtain IRB approval of the investigation as a nonsignificant risk device study after presenting the reviewing IRB with a brief explanation of why the device is not a significant risk device and maintain such approval.

Ensure that each investigator participating in an investigation of the device obtains informed consent under 21 CFR 50 for each subject under the investigator’s care and documents the consent, unless documentation is waived by an IRB under §56.109(c).

Comply with the requirements of §812.46 with respect to monitoring investigations.

Securing Compliance

Unanticipated Adverse Device Effects

Resumption of Terminated Studies

Maintain certain records and submit required reports.

The following records must be maintained in one location and available for FDA inspection [§812.140(b)(4)]:

the name and intended use of the device;

the objectives of the investigation;

a brief explanation of why the device is not a significant risk device;

the name and address of each investigator;

the name and address of each IRB;

a statement of the extent to which the good manufacturing practices (21 CFR 820) will be followed in manufacturing the device.

any other information required by FDA

The sponsor must maintain records concerning complaints and adverse device effects whether anticipated or not [§812.140(b)(5)].

The sponsor must provide the following reports in a timely manner to FDA, the IRB's, and/or the investigators [§812.150(b) (1) through (3) and (5) through (10)].

Unanticipated Adverse Device Effects

Withdrawal of IRB Approval

Withdrawal of FDA Approval

Progress Reports

Recalls and Device Disposition

Final Report

Informed consent

Significant Risk Device Determination

Other Reports

See Reports for more information regarding the required reports.

Ensure that participating investigators maintain the records of each subject’s case history and exposure to the device under §812.140(a)(3)(i) and ensure that participating investigators make the following required reports:

Unanticipated Adverse Device Effects [§812.150(a)(1)]

Withdrawal of IRB Approval [§812.150(a)(2)]

Informed consent [§812.150(a)(5)]

Other reports requested by a reviewing IRB or FDA [§812.150(a)(7)]

See Reports for more information about required reports.

Comply with the prohibitions in §812.7 against promotion and other practices

Under § 812.7, a sponsor, investigator, or any person acting for or on behalf of a sponsor or investigator cannot:

Promote or test market an investigational device, until after FDA has approved the device for commercial distribution.

Commercialize an investigational device by charging the subjects or investigators a higher price than that necessary to recover costs of manufacture, research, development, and handling.

Unduly prolong an investigation. If data developed by the investigation indicate that premarket approval (PMA) cannot be justified, the sponsor must promptly terminate the investigation.

Represent that an investigational device is safe or effective.

However, the sponsor may advertise for research subjects to solicit their participation in a study. Appropriate advertising methods include but is not necessarily limited to: newspaper, radio, TV, bulletin boards, posters, and flyers that are intended for prospective subjects.

Advertisements should be reviewed and approved by the IRB to assure that it is not unduly coercive and does not promise a certainty of cure beyond what is outlined in the consent and the protocol. No claims should be made, either explicitly or implicitly, that the device is safe or effective for the purposes under investigation, or that the test article is known to be equivalent or superior to any other device.

FDA considers direct advertising for study subjects to be the start of the informed consent and subject selection process.

Additional guidance is available in the following guidance documents:

"Information Sheets: Guidance for Institutional Review Boards and Clinical Investigators, 1998 - Recruiting for Study Subjects"
http://www.fda.gov/oc/ohrt/irbs/toc4.html

Preparing Notices of Availability of Investigational Medical Devices and for Recruiting Study Subjects
http://www.fda.gov/cdrh/comp/2229.html
http://www.fda.gov/cdrh/comp/2229.pdf

Responsibilities of Investigators for Significant Risk Device Studies

The investigator is responsible for protecting the rights, safety, and welfare of subjects. An investigator must conduct the investigation in accordance with the signed agreement with the sponsor, the investigational plan, the IDE regulation and other applicable FDA regulations, and any conditions of approval imposed by an IRB and FDA. (§812.100)

While waiting approval of an IDE application, an investigator may determine whether or not potential subjects would be interested in participating in an investigation, but cannot request written informed consent or allow any subjects to participate before obtaining IRB and FDA approval. (§812.110)

Informed Consent

An investigator is responsible for obtaining informed consent under 21 CFR Part 50.

Supervision of device use (§812.110)

An investigator can permit use of the investigational device only with subjects under his/her supervision and cannot not supply an investigational device to any person not authorized under the IDE regulation to receive it.

Financial Disclosure (§812.110)

The clinical investigator must disclose to the sponsor sufficient accurate financial information to allow the IDE applicant (or sponsor) to submit certification or disclosure of financial interests under 21 CFR 54. The investigator must update the information if any relevant changes occur during the course of the investigation and for one year following completion of the study.

Device Disposal (§812.110)

Upon completion or termination of a clinical investigation or the investigator's part of the investigation or at the sponsor's request, an investigator must return to the sponsor any remaining supply of the device or dispose of the device as the sponsor directs.

Records (812.140)

The investigator must maintain accurate and complete records relating to the investigation. These records include;

all correspondence including required reports,

records of receipt, use, or disposition of the investigational device,

records of each subject's case history and exposure to the device,

the protocol and documentation (date and reason) for each deviation from the protocol,

any other records that FDA requires to be maintained by regulation or by specific requirement for a category of investigation or a particular investigation.

See Records for additional information on recordkeeping requirements.

Investigator Reports (812.150)

The investigator must provide the following reports in a timely manner to the sponsor and/or the IRB.

Unanticipated Adverse Device Effects
Withdrawal of IRB Approval
Progress Reports
Deviations from the Investigational Plan
Informed Consent
Final Report
Other Reports

See Reports for more information regarding required reports.

Responsibilities of Investigators for Nonsignificant Risk Device Studies

Informed Consent

An investigator is responsible for obtaining informed consent under 21 CFR Part 50.

Records

Clinical investigators must maintain the records of each subject’s case history and exposure to the device under §812.140(a)(3)(i). Case histories include case report forms and supporting data, including signed and dated consent forms and medical records, including progress notes of the physician, the individual’s hospital chart(s), and the nurses’ notes. Records must include documents demonstrating informed consent and, for any use of a device the investigator without informed consent, any written concurrence of a licensed physician and a brief description of the circumstances justifying the failure to obtain informed consent. The case history of each individual must document that informed consent was obtained prior to participation in the study.

Reports

Clinical investigators must make the following required reports:

Unanticipated Adverse Device Effects [§812.150(a)(1)]
Withdrawal of IRB Approval [§812.150(a)(2)]
Informed consent [§812.150(a)(5)]
Other reports requested by a reviewing IRB or FDA [§812.150(a)(7)]

See Reports for additional information regarding specific reports.

Financial Disclosure

If the data in a nonsignificant risk device study is submitted in a marketing application, then 21 CFR 54, Financial Disclosure, applies. The clinical investigator must disclose to the sponsor sufficient accurate financial information to allow the IDE applicant (or sponsor) to submit certification or disclosure of financial interests. The investigator must update the information if any relevant changes occur during the course of the investigation and for one year following completion of the study. (§ 812.110)

Responsibilities of Monitors

The sponsor is responsible for selecting monitors qualified by training and experience to monitor the investigational study. Monitors may be employees of the sponsor or an organization contracted by the sponsor to perform the duties of the study monitor.

The monitor is responsible for securing compliance with the requirements of the IDE regulation (§ 812.46). The monitor must assure that the investigators are complying with the signed agreement, the investigational plan, the IDE requirements, any other applicable FDA regulations, or any conditions of approval imposed by the reviewing IRB or FDA.

The IDE regulation requires that the sponsor identify the name and address of the monitor and provide written monitoring procedures [§812.25(e)]. While the IDE regulation does not specify the content of the written monitoring procedures, FDA has published a guideline, "Guideline for The Monitoring of Clinical Investigations, January 1988" on acceptable approaches to monitoring clinical investigations involving FDA-regulated products.

References:

21 CFR 812 Subpart C
21 CFR 812 Subpart E
21 CFR 812.140
21 CFR 812.150

Sponsor's Responsibilities For Significant Risk Device Investigations (Nov. 1995)
http://www.fda.gov/cdrh/manual/sponsor.html

Investigators' Responsibilities For Significant Risk Device Investigations (Nov. 1995)
http://www.fda.gov/cdrh/manual/invest.html

Guideline for The Monitoring of Clinical Investigations
http://www.fda.gov/ora/compliance_ref/bimo/clinguid.html

Guidance for Clinical Trial Sponsors on the Establishmentand Operation of Clinical Trial Data Monitoring Committees (Draft)
http://www.fda.gov/cber/gdlns/clindatmon.htm
http://www.fda.gov/cber/gdlns/clindatmon.pdf

Guidance on IDE Policies and Procedures
http://www.fda.gov/cdrh/ode/idepolcy.pdf
http://www.fda.gov/cdrh/ode/idepolcy.html

"Information Sheets: Guidance for Institutional Review Boards and Clinical Investigators, 1998 - Recruiting for Study Subjects"
http://www.fda.gov/oc/ohrt/irbs/toc4.html

Preparing Notices of Availability of Investigational Medical Devices and for Recruiting Study Subjects
http://www.fda.gov/cdrh/comp/2229.html
http://www.fda.gov/cdrh/comp/2229.pdf

Last modified date July 21, 2003