Office of Human Research
SOP No.: 303 INVESTIGATOR'S BROCHURE
Author: Office of Human Research
Effective Date: October 1, 2007
Supercedes document dated: N/A
Last Reviewed on: N/A
Results of Review: N/A
This SOP pertains to: Any investigation product (drug, biologic, medical device).
Responsibility for executing this SOP: Investigator and Designated Research Personnel
J. Bruce Smith, MD
Associate Vice President for Research
(signature on file at OHR)
Steven E. McKenzie, MD, Ph.D.
Vice President for Research
(signature on file at OHR)
This procedure provides a process for developing, reviewing, approving and distributing Investigator Brochures or similar documents that are intended to inform participating Investigators about the investigational product(s) they will be using in an FDA-regulated human subject research study.
2. GENERAL INSTRUCTIONS AND RESPONSIBILITIES
- The Investigator or qualified designee is responsible for preparing the initial draft of the document, then forwarding the draft to all designated individuals for review and approval, and distributing the final approved Investigator Brochure or comparable document(s) to all participating Investigators at all sites.
- The Investigator is responsible for forwarding final, internally approved Investigator Brochures or comparable documents to the FDA (as part of the applicable regulatory submission) and other applicable external regulatory authorities, for their review and approval as required.
- Investigators are responsible for submitting the Investigator Brochure or comparable document(s) to the IRB, and other internal regulatory authorities as applicable (e.g., Radiation Safety Committee, Institutional Biosafety Committee or IBC, etc.)
3. SPECIFIC PROCEDURES
3.1 Investigator Brochure (Drug/Biologic Studies)
- The Investigator or designee should develop the Investigator Brochure before the clinical protocol is written, as the information in the Investigator Brochure will contribute substantially to the development of the protocol.
- Follow SOP 102 for developing, reviewing and approving the Investigator Brochure, which is a controlled document.
- The Investigator Brochure must address the following:
- Brief description of the drug/biologic substance and the formulation, including the structural formula, if known
- Summary of the pharmacological, toxicological and/or biological effects of the drug/biologic in animals and, to the extent known, in humans
- Summary of the pharmacokinetics and biological disposition of the drug/biologic in animals and, if known, in humans
- Summary of information relating to safety and effectiveness in humans obtained from prior clinical studies; reprints of published articles on such studies appended when useful and available
- Description of possible risks and side effects (all known or expected adverse events) to be anticipated on the basis of prior experience with the drug/biologic under investigation or with related drugs/biologics, and of precautions or special monitoring to be done as part of the investigational use of the drug/biologic
- Each Investigator should receive a copy of the Investigator Brochure prior to beginning the clinical study (i.e., during the qualification and/or initiation site visit(s), for distribution to key study personnel.
- The Investigator also must ensure that each participating Investigator submits the Investigator Brochure to his/her IRB of record and any other applicable institutional regulatory authority.
- The Investigator will include the original Investigator Brochure (if applicable) as part of the IND submission, as well as submissions to any other applicable institutional and external regulatory authorities.
- If any studies are conducted outside the United States using an investigational drug or biologic, the Investigator Brochure serves as that's country's source document on the investigational product.
- The Investigator will update the Investigator Brochure regularly and as frequently as necessary to keep it current, as the study proceeds through the clinical phases of testing (phases 1, 2, 3 and 4) or as new information becomes available.
- The Investigator will submit the updated Investigator Brochure as an amendment to the IND (at the time of updating) and in the IND Annual Report to include all changes that occurred during the prior year (Reference SOP 201).
- If any adverse event occurs that is not listed in the Investigator Brochure, it must be treated as an unexpected adverse event and reported accordingly (Reference SOPs 202, Required Reports for FDA, 203, NIH Requirements for OBA-Reviewed Research and 605 Adverse Event Recognition and Reporting).
- The Investigator will update all participating Investigators, and ensure they notify their IRB(s) of record to changes in the Investigator Brochure, and provide them with revised copies of the document.
- In addition to the Investigator Brochure, the Investigator should use all other available information tools for keeping Investigators informed about the investigational drug, e.g., published reprints of articles and letters to editors, adverse event reports, etc.
3.2 Investigational Plan (Device Studies)
- While the clinical protocol is being developed, the Investigator or designee also should be developing the Investigational Plan.
- The general procedure for developing, reviewing and approving controlled documents, Document Development and Change Control, should be followed for developing, reviewing and approving the documents that constitute the Investigational Plan.
- The Investigational Plan must include, in this order
- Purpose: the name and intended use of the device and the objectives and duration of the investigation
- Protocol: a written protocol describing the methodology to be used and an analysis of the protocol demonstrating that the investigation is scientifically sound
- Risk analysis: a description and analysis of all increased risks to which participants will be exposed by the investigation; the manner in which these risks will be minimized; a justification for the investigation; and a description of the study population, including the number, age, sex, and condition
- Description of device: 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
- Monitoring procedures: the Investigator's written procedures for monitoring the investigation and the name and address of any Monitor
- Labeling: copies of all labeling for the device
- Consent materials: copies of all forms and informational materials to be provided to participants to obtain informed consent
- IRB information: a list of the names, locations, and chairpersons of all IRB's that have been or will be asked to review the investigation, and a certification of any action taken by any of those IRB's with respect to the investigation
- Other institutions: the name and address of each institution at which a part of the investigation may be conducted that has not been identified in item 3.2.viii above
- Additional records and reports: a description of records and reports that will be maintained on the investigation in addition to those prescribed in 32 CFR 812 Subpart G (Records and Reports)
- The Investigator or other designated Author should reference the IDE Submission Checklist, for additional guidance on format for the Investigational Plan.
- In some cases, a detailed clinical protocol may include additional applicable elements of the Investigational Plan, or even all its elements. Any remaining elements not covered in the protocol must be provided as a separate document.
- The Investigator will include the Investigational Plan as part of the IRB and FDA IDE submissions, as well as submissions to other applicable regulatory authorities.
- The Investigator will ensure that each participating Investigator receives a copy of the Investigational Plan prior to beginning the clinical study (i.e., during the qualification and/or initiation site visit(s).
- The Investigator will update the Investigational Plan as the study proceeds through the clinical phases of testing or as new information becomes available.
- The Investigator will update FDA and the IRB on changes in the Investigational Plan through appropriate submissions (IDE supplement, other written notification).
3.3 Report of Prior Investigations (Device Studies)
- While the Investigational Plan (including the clinical protocol) is being developed, the Investigator also should be developing the Report of Prior Investigations.
- The general procedure for developing, reviewing and approving controlled documents in SOP 102, Document Development and Change Control, should be followed for developing, reviewing and approving the documents that constitute the Report of Prior Investigations.
- The Report of Prior Investigations includes reports of all prior clinical, animal, and laboratory testing of the investigational device and must be comprehensive and adequate to justify the proposed investigation.
- The Report of Prior Investigations also includes:
- A bibliography of all publications, whether adverse or supportive, that are relevant to an evaluation of the safety or effectiveness of the device, copies of all published and unpublished adverse information, and, if requested by an IRB or FDA, copies of other significant publications
- A summary of all other unpublished information (whether adverse or supportive) in the possession of, or reasonably obtainable by, the Investigator that is relevant to an evaluation of the safety or effectiveness of the investigational device
- If information on non-clinical laboratory studies is provided, a statement that all such studies have been conducted in compliance with applicable requirements in the Good Laboratory Practice regulations in 21 CFR 58, or if any such study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance (failure or inability to comply with this requirement does not justify failure to provide information on a relevant non-clinical test study)
- The Investigator or other designated Author should reference IDE Submission Checklist for additional guidance on organizing the Report of Prior Investigations (See SOP 201 Attachment G)
- The Investigator will include the Report of Prior Investigations as part of the IRB and FDA IDE submissions, as well as submissions to other applicable regulatory authorities.
- The Investigator will ensure that each participating Investigator receives a copy of the Report of Prior Investigations prior to beginning the clinical study (i.e., during the qualification and/or initiation site visit(s)