• Maintaining IRB approval throughout investigation

The investigational device or its immediate package must have a label that states:

• Name and place of business of the manufacturer, packer or distributor
• Quantity of contents, if appropriate 
• The statement: “CAUTION – Investigational device. Limited by Federal (or United States) law to investigational use.” (21 CFR 812.5(a))
• The label or other labeling must describe all relevant contraindications, adverse effects, hazards, interfering substances or devices, warnings and precautions
• Labeling should not include any statements that may be false or misleading and should not represent the device as safe or effective for the purposes for which it is being investigated. 

Securing compliance or discontinuing shipment or terminating participation

• If sponsor discovers an investigator is not complying with the signed agreement, the investigational plan, applicable FDA regulations or any FDA/IRB conditions of approval, s/he must:
  • Secure compliance or 
  • Discontinue shipments of the device to the investigator and terminate the investigator's participation in the investigation
  • Require the investigator to dispose of or return the device, unless this action would jeopardize the rights, safety, or welfare of a subject.

Immediately evaluating unanticipated adverse device effects

• As sponsor, if you determine an unanticipated adverse device effect poses unreasonable risk to subjects, you must terminate all investigations or parts of investigations presenting that risk as soon as possible.  Termination must occur:
  • No later than 5 working days after this determination AND
  • No later than 15 working days after first receiving notice of the effect
• Obtaining approval for resumption of terminated studies
  • IRB approval is required to resume a terminated investigation
  • FDA approval is required if the investigation was terminated because the unanticipated adverse device effect posed an unreasonable risk.

Ensure that investigator’s maintain required records and submit required reports

• Described below under “Sponsors must ensure that investigators” section.

Maintain the following records in one location; make available for FDA inspection & copying:

• 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 that has reviewed the investigation
• A statement of the extent to which the good manufacturing practice regulation in part 21 CFR 820 will be followed in manufacturing the device
• Any other information required by FDA
• Records of adverse device effects (whether anticipated or unanticipated) and complaints

For investigational devices, sponsors must report the following: 

To FDA, all reviewing IRB's and participating investigators 

• Unanticipated adverse device effects. 
  • Report evaluation results 
  • Within 10 working days after the sponsor first receives notice of the effect. 
  • Submit additional reports concerning the effect per FDA requests.
• Withdrawal of IRB approval. 
  • Notify any withdrawal of approval or a part of an investigation by a reviewing IRB 
  • Report within 5 working days after receipt of the withdrawal of approval.

To FDA and all reviewing IRB's

• Recall and device disposition. 
  • Any request that an investigator return, repair, or otherwise dispose of any units of a device. 
  • State why the request was made.
  • Report within 30 working days after the request is made 
• Other
  • Upon request by a reviewing IRB or the FDA, provide accurate, complete, and current information about any aspect of the investigation.

To all reviewing IRB's and participating investigators

• Withdrawal of FDA approval 
  • Any withdrawal of FDA approval of the investigation
  • Report within 5 working days after receipt of notice of the withdrawal of approval.

To all reviewing IRBs

• Progress reports 
  • Submit at regular intervals 
  • Submit at least yearly in an annual report
• Final report 
  • Submit within 6 months after termination or completion.

To FDA

• A current investigator list
  • Include names and addresses of all participating investigators 
  • Submit at 6-month intervals
  • Send the first list 6 months after FDA approval
• Device use without consent
  • A copy of any report by an investigator of such use 
  • Submit within 5 working days of receipt of notice of such use. 
  • (See the “Sponsors must ensure that investigators” section below) 

21 CFR 812.2(b) 

&

21 CFR 812.150 (b) (1-3) & (5-10)

• For each subject at each participating site 21 CFR 50
• Unless the IRB waives documentation 21 CFR 56.109(c)

21 CFR 812.2(b)(1)(iii)

• Case histories include case report forms and supporting data:
  • Signed and dated consent forms
  • Documentation that informed consent was obtained prior to participation in the study
  • Medical record information - Doctors progress notes and the nurses notes 
• Study documents evidencing informed consent for 
  • Any use of a device by 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.

21 CFR 812.140

(a)(3)(i)

Prepare & submit the following complete, accurate and timely reports to:

The sponsor and reviewing IRB

• Unanticipated adverse device effect: 
  • A report of any unanticipated adverse device effect occurring during an investigation 
  • Report as soon as possible  
  • Report no later than 10 working days after the investigator first learns of the effect
• Informed consent: 
  • Uses of a device without obtaining informed consent
  • Report within 5 working days after the use occurs

The Sponsor

• Withdrawal of IRB approval: 
  • Any withdrawal of approval by the reviewing IRB of the investigator's part of an investigation 
  • Report within 5 working days of notification

     The reviewing IRB or FDA

• Other: upon request, an investigator must provide accurate, complete, & current information about any aspect of the investigation.

If the data from an investigational device study is submitted in a marketing application, financial disclosure applies.

• The investigator must disclose to the sponsor sufficient and accurate financial information that 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 
  • Throughout the investigation 
  • For one year following completion of the study. 

21 CFR 54

21 CFR 812.110(d)