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U.S. Department of Health and Human Services

Medical Devices

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Sponsor's Responsibilities For Significant Risk Device Investigations (Nov. 1995)

This document is intended to assist sponsors in identifying and complying with their responsibilities in connection with the conduct of clinical investigations of medical devices that are deemed "significant risk" by the reviewing IRB or by FDA. For a complete description of their responsibilities, sponsors should refer to the actual text of the regulations cited below. In addition, sponsors should be aware that a clinical investigation must be conducted in accordance with any requirements imposed by the reviewing IRB, by institutional policies, or by state law.

General Duties (21 CFR 812.40)

  • Submitting the IDE application to FDA
  • Obtaining both FDA and IRB approvals for the investigation and submitting certification of IRB approval to FDA before shipping the device to any investigator
  • Obtaining FDA approval and IRB approval for a supplemental application before beginning that portion of the investigation
  • Selecting qualified investigators
  • Ensuring proper monitoring
  • Ensuring patient informed consent is obtained

Selection of Investigators (21 CFR 812.43)

  • Assuring selection of investigators qualified by training and experience
  • Shipping the investigational device only to participating investigators
  • Obtaining a signed investigator's agreement containing:
    • investigator's curriculum vitae
    • statement of investigator's relevant experience, including dates
    • location, extent, and type of experience
    • if an investigator was involved in an investigation or other research that was terminated, an explanation of the circumstances that led to the termination
    • statement of the investigator's commitment to:
      • conduct the investigation in accordance with the agreement, the investigational plan, Parts 50, 56, and 812, and any conditions of approval imposed by the IRB or FDA
      • supervise all testing of the device involving human subjects
      • ensure that the requirements for informed consent are met (21 CFR Part 50)
    • Providing investigators with the necessary information to conduct the investigation including, but not necessarily limited to:
    • the investigational plan
    • the report of prior investigations

Monitoring (21 CFR 812.46)

  • Selecting monitor(s) qualified by training and experience to monitor the progress of the investigation
  • Securing compliance of all investigators in accordance with the signed investigator's agreement, the investigational plan, the requirements of this part or other applicable FDA regulations, or any condition of approval imposed by the reviewing IRB or FDA. If compliance cannot be secured, shipment of the device to the investigator and the investigator's participation in the investigation must be discontinued
  • Ensuring that significant new information about the investigation is provided to all reviewing IRBs, FDA, and investigators
  • Evaluating all unanticipated adverse device effects and terminating the investigation, or portions of it, if that effect presents an unreasonable risk to subjects (reporting requirements are listed below.)
  • Resuming terminated investigations only after both FDA and IRB approvals are obtained.

Controlling Distribution and Disposition of Devices

Although investigators are responsible for ensuring that investigational devices are made available only to persons who are legally authorized to receive them (see 21 CFR 812.110(c)), sponsors also bear responsibility for taking proper measures to ensure that devices are not diverted outside of legally authorized channels. Sponsors may ship investigational devices only to qualified investigators participating in the clinical investigation (§ 812.43(b)). Sponsors must also maintain complete, current, and accurate records pertaining to the shipment and disposition of the investigational device (§ 812.140(b)). Records of shipment shall include the name and address of the consignee, type and quantity of device, date of shipment, and batch number or code mark. Records of disposition shall describe the batch number or code marks of any devices returned to the sponsor, repaired, or disposed of in other ways by the investigator or another person, and the reasons for and method of disposal.

To further ensure compliance with these requirements, sponsors should take appropriate measures to instruct investigators regarding their responsibilities with respect to recordkeeping and device disposition. The specific recordkeeping requirements for investigators are set forth at § 812.140(a). Upon completion or termination of a clinical investigation (or the investigator's part of an investigation), or at the sponsor's request, an investigator is required to return to the sponsor any remaining supply of the device or otherwise to dispose of the device as the sponsor directs (§ 812.110(c)).

Prohibition of Promotion and Other Practices (21 CFR 812.7)

The IDE regulations prohibit the promotion and commercialization of a device that has not been first cleared or approved for marketing by FDA. This prohibition is applicable to sponsors and investigators (or any person acting on behalf of a sponsor or investigator), and encompasses the following activities:

  • Promotion or test marketing of the investigational device
  • Charging subjects or investigators for the device a price larger than is necessary to recover the costs of manufacture, research, development, and handling
  • Prolonging an investigation beyond the point needed to collect data required to determine whether the device is safe and effective
  • Representing that the device is safe or effective for the purposes for which it is being investigated.

Supplemental Applications [21 CFR 812.35(a) and (b)]

Supplemental applications are required to be submitted to, and approved by, FDA in the following situations:

  • Changes in the investigational plan: FDA approval is required for any change that may affect the scientific soundness of the investigation or the rights, safety or welfare of the subjects. IRB approval is also required for changes that may affect the rights, safety or welfare of the subjects. The change in the investigational plan may not be implemented until FDA approval (and IRB approval, if required) is obtained.
  • Addition of new institutions: IRB approval is also required for new institutions. The investigation at the new institution(s) may not begin until both FDA and IRB approval(s) are obtained, and certification of IRB approval is submitted to FDA.

Maintaining Records [21 CFR 812.140(b)]

A sponsor shall maintain the following accurate, complete, and current records relating to an investigation (also See Table I, next page):

  • Correspondence (including reports) with another sponsor, monitor, investigators, an IRB or FDA
  • Records of shipment, including:
    • name and address of consignee
    • type and quantity of device
    • date of shipment
    • batch numbers or code marks
  • Records of disposition, describing:
    • Batch number or code mark of devices returned, repaired, or disposed of by the investigator or other persons
    • Reasons for and method of disposal
  • Signed investigator agreements
  • Adverse device effects (whether anticipated or unanticipated) and complaints
  • Any other records that FDA requires by regulation or by specific requirement for a category of investigation or a particular investigation

    Table I

    Responsibilities for Maintaining Records for a Significant Risk Device Study

    Records Maintained by Investigator Maintained by Sponsor
    All Correspondence Pertaining to the Investigation X X
    Shipment, Receipt, Disposition X X
    Device Administration and Use X -
    Subject Case Histories X -
    Informed Consent X -
    Protocols and Reasons for Deviations from Protocol X -
    Adverse Device Effects and Complaints X X
    Signed Investigator Agreements - X
    Membership/Employment/Conflicts of Interest - X
    Minutes of Meetings - -

Submitting Reports [21 CFR 812.150(b)]

A sponsor shall prepare and submit the following complete, accurate, and timely reports (also see Table II).

  • Unanticipated adverse device effects (with evaluation) to FDA, all IRBs, and investigators within 10 working days after notification by the investigator. Subsequent reports on the effect may be required by FDA.
  • Withdrawal of IRB approval
  • Withdrawal of FDA approval
  • Current 6­month investigator list
  • Annual progress report ­ see format for IDE progress report
  • Recall and device disposition (within 30 working days after the request was made)
  • Final report ­ see format for progress reports
  • Use of device without obtaining patient informed consent
  • Significant risk determinations by the IRB when proposed to be nonsignificant risk
  • Other reports requested by the IRB or FDA

Table II

Responsibilities for Preparing and Submitting Reports for Significant Risk Device Studies

Type of Report Prepared by Investigators for Prepared by Sponsors for
Unanticipated Adverse Effect Evaluation Sponsors and IRBs FDA, IRBs and Investigators
Withdrawal of IDE Approval Sponsors FDA, IRBs, and Investigators
Progress Report Sponsors, Monitors and IRBs FDA and IRBs
Final Report Sponsors and IRBs FDA, IRBs, and Investigators
Emergencies (Protocol Deviations) Sponsors and IRBs FDA
Inability to Obtain Informed Consent Sponsors and IRBs FDA
Withdrawal of FDA Approval N/A IRBs and Investigators
Current Investigator List N/A FDA
Recall and Device Disposition < N/A FDA and IRBs
Records Maintenance Transfer FDA FDA
Significant Risk Determinations N/A FDA

Inspections [21 CFR 812.145]

Sponsors are required to permit FDA to enter and inspect (at reasonable times and in a reasonable manner) any establishment where devices are held (including any establishment where devices are manufactured, processed, packed, installed, used, or implanted or where records or results from use of devices are kept). FDA may also inspect and copy all records relating to an investigation including, in certain situations, records which identify subjects.