Food and Drug Administration (FDA) Guidance
The Food and Drug Administration (FDA) publishes many helpful guidance documents, which represents the Agency's current interpretation on a particular subject. Links to the guidance documents from the following centers are listed below:
- FDA Guidance Documents
- CDRH (Center for Device and Radiological Health)
- CDER (Center for Drug Evaluation and Research)
- CBER (Center for Biologics Evaluation and Research)
Office for Human Research Protections (OHRP) Guidance
The OHRP's website provides multiple guidance documents which represents their current thinking on a topic. These documents should be viewed as recommendations.
The OHRP website also has a 'Frequently Asked Questions' section that serves as a good reference for IRBs, sponsors and investigators.
FDA and OHRP Compliance Findings
OHRP: Significant findings and concerns noted in compliance oversight determination letters over the last several years are outlined on the OHRP website:
FDA: Each year the FDA posts the prior year's most common observations from bioresearch monitoring. FY 2015 findings can be found here.
Examples of common non-compliance issues noted during routine FDA audits of clinical investigators, institutional review boards, and sponsors are highlighted in these selected determination letters. Of note, the letters also address whether proposed corrective actions are found acceptable by the FDA.
Clinical Investigator Examples
- Failure to conduct the investigation according to the signed agreement, the investigational plan, applicable FDA regulations, and any conditions of approval imposed by an Institutional Review Board (IRB) or FDA.
- Failure to maintain accurate, complete, and current records of disposition of a device.
- Example 1
- Failure to obtain Institutional Review Board (IRB) approval for changes in the research prior to implementing the changes
- Example 2
- Failure to ensure that the investigation was conducted according to the investigational plan
- Example 3
- Failure to ensure that the investigation was conducted according to the signed investigator statement, the investigational plan, and the applicable regulations, and to protect the rights, safety, and welfare of subjects under your care
- Failure to administer the drug only to subjects under the investigator’s personal supervision or under the supervision of a subinvestigator responsible to the investigator
- Failure to prepare and maintain adequate and accurate case histories that recorded all observations and other data pertinent to the investigation on each individual administered the investigational drug. Case histories include case report forms and supporting data
- Failure to obtain the informed consent of each human subject to whom the drug was administered in accordance with the provisions of 21 CFR Part 50.
- Example 4
- Failure to personally conduct or supervise the clinical investigations
- Failure to assure that an IRB that complies with the requirements set forth in part 56 was responsible for the initial and continuing review and approval of the proposed clinical study
- Example 5
- Failure to maintain adequate records of the disposition of the drug, including dates, quantity, and use by subjects
- Failure to promptly report to the IRB all unanticipated problems involving risk to human subjects or others
- Example 6
- Failure to include all appropriate elements of informed consent.
- Failure to provide the investigators with information needed to conduct the investigation properly and failure to ensure proper monitoring of the investigation
- Failure to obtain signed investigator agreements and sufficient accurate financial disclosure information.
- Failure to maintain accurate, complete, and current device shipment and disposition records.
- Example 7
- Failure to obtain Institutional Review Board approval of the investigation
- Failure to maintain required records under § 812.140(b)(4) and make the reports required under § 812.150(b)(1) through (3) and (5) through (10) [21 CFR 812.2(b)(1)(v]
- Example 8
- Failure to ensure proper monitoring of the investigations and failure to ensure that the investigations are conducted in accordance with the general investigational plan and protocols contained in the IND
- Failure to obtain from an investigator sufficient financial information to allow the sponsor to submit complete and accurate certification or disclosure statements required under 21 CFR part 54
- Failure to properly document informed consent, to maintain accurate, complete and current records evidencing informed consent, and to conduct an investigation according to applicable FDA regulations for protecting the rights, safety, and welfare of subjects under the investigator’s care.
- Failure to maintain accurate, complete, and current records of each subject’s case history and exposure to the device.
- Example 9
- Failure to fulfill membership requirements
- Failure to review proposed research at convened meetings at which a majority of the members of the IRB are present, including at least one member whose primary concerns are in nonscientific areas
- Failure to prepare and maintain adequate documentation of IRB activities
- Example 10
- Failure to prepare, maintain, and follow required written procedures governing the functions and operations of the IRB
- Failure to notify investigators and the institution in writing of its decision to approve or disapprove proposed research activities or of modifications required to secure IRB approval of the research activity
- Failure to ensure that basic elements of informed consent are included in the IRB-approved consent form
- Example 11
- Failure to prepare, maintain, and follow written procedures for conducting initial and continuing review of research
- Failure to review proposed research at convened meetings at which a majority of the members of the IRB are present
- Failure to report promptly to the FDA any suspension or termination of approval and failure to prepare written procedures
- Failure to prepare and maintain a list of IRB members identified by name, earned degree, representative capacity, and the relationship between each member and the institution
- Example 12
- Failure to retain IRB records for at least 3 years after completion of the research.
- Failure to prepare and maintain adequate documentation of IRB activities including minutes of IRB meetings that are of sufficient detail to show the actions taken at the meeting and the vote on these actions
- Example 13
- Failure to determine at the time of initial review that studies involving children are in compliance with 21 CFR Part 50, Subpart D, Additional Safeguards for Children in Clinical Investigations
- Failure to ensure that no member participated in the initial or continuing review of a project in which the member had a conflicting interest, except to provide information requested by the IRB
- Failure to conduct continuing review of research at intervals of not less than once per year
- Example 14