Does the thought of a BIMO inspection make you break into a cold sweat?
It’s worth remembering that although BIMO FDA inspections might feel like a pop quiz, this is one test the FDA wants you to pass. That’s why the FDA provides detailed guidance on what its investigators will review, similar to a study guide.
To prepare your site to pass, take time to review our BIMO FDA inspection cheat sheet.
What’s Covered In A BIMO FDA Inspection?
(As detailed in the FDA Guidance)
Organization & Personnel
The inspector must determine the overall organization of clinical research activities and monitoring of the selected studies. To do so, they will:
- Obtain relevant organizational charts and responsibilities
- Obtain a list of all outside vendors and contractors, including CROs, monitors, labs and IRBs and their locations
- Obtain copies of any written agreement transferring responsibilities from a sponsor to a CRO (not applicable for medical device studies)
- Obtain a list of all monitors, along with their job descriptions and qualifications
Clinical Study Registration
Applicable clinical trials must be registered on clinicaltrials.gov within 21 calendar days of enrolling the first subject. To verify registration, the inspector will:
- Determine whether the study is an applicable clinical trial
- Determine whether the study was registered within the required time frame
- Determine whether the sponsor has completed Form FDA 3674, Certification of Compliance
Selection & Monitoring Of Clinical Investigators
The inspector will obtain a list of all investigators and determine if each has a signed investigator agreement in place. They will also:
- Determine the sponsor’s criteria for selecting clinical investigators
- Determine if the sponsor/CRO provided investigators with all necessary information prior to the start of the trial, including clinical protocols and investigational plans
- Determine how the sponsor/CRO handles serious deviations from the approved investigational plan
Monitoring Procedures & Activities
Regulations do not prescribe a specific monitoring technique, simply stating that sponsors are required to select monitors qualified by training and experience to monitor the investigational study (21 CFR 312.53(d) and 812.43(d)). To evaluate monitoring, the inspector will:
- Review the procedures, frequency, scope and process used in monitoring
- Obtain a copy of the sponsor/CRO’s written procedures for monitoring and determine if they were followed during the study
- Review pre-trial and periodic site visit monitoring reports
- Determine if the monitor documented the study in accordance with the investigational plan
- Review site records to determine if monitoring visits included a comparison of individual subject records and other source documents with case report forms (CRFs) and determine if all CRFs are verified during monitoring visits
- Determine if a form is used for data verification and obtain a copy
- Determine how the sponsor assures IRB approval is obtained prior to enrolling subjects in the study
- Determine how the sponsor/CRO assured informed consent is obtained
Clinical trial quality assurance units (QAUs) are not required by regulation, but many sponsors obtain independent audits and data verifications to determine their compliance with clinical trial SOPs and FDA regulations. If a sponsor has a QAU, the inspector will:
- Obtain a copy of any written procedures and guidelines for QA audits
- Determine the separation of functions between QA auditing and monitoring
Safety & Adverse Event Reporting
To evaluate safety and adverse event reporting, the inspector will:
- Determine if adverse device effects were reported to FDA, to participating investigators and to reviewing IRBs (for device studies) as required by regulations
- Review the procedures (e.g., frequency, scope) the sponsor/CRO uses for the receipt, evaluation, and monitoring of safety information/unanticipated adverse device effects, as well as the process for updating the investigator brochure
- Review the composition and function of the safety team/committee (if applicable)
- Obtain copies of any notification to investigators relating to safety information or adverse device effects
Data Collection & Handling
Sponsors are required to submit analyses of all clinical studies pertaining to a proposed drug or device used in any marketing application. They must also submit data tabulations on each subject in each trial. To evaluate data collection, the inspector will:
- Review the sponsor’s written procedures (SOPs and guidelines) to assure the integrity of safety and efficacy data collected from clinical investigators
- Verify that the procedures were followed and document any deviations
The inspector will verify that the sponsor maintained required records for the prescribed period of time, in accordance with 21 CFR 312.57(c) and 812.140(d).
The inspector will determine if the sponsor obtained financial disclosure information from each investigator before his/her participation in the clinical trial.
Electronic Records & Signatures
The inspector will ensure the sponsor has complied with 21 CFR Part 11 pertaining to electronic records and signatures by:
- Validating the computer system used for electronic records
- Reviewing procedures used to create, modify and maintain electronic records
- Determining how the sponsor documents there are sufficient personnel with the necessary education, background, training and experience to manage electronic records
How To Prepare Your Sites To Pass
Many sponsors take responsibility for ensuring sites are prepared when the FDA inspector announces a visit. Having a strong working knowledge of FDA regulations and using them to guide decisions during clinical trials is a good place to start. Regularly reviewing FDA warning letters to be aware of the most common violations will also help to ensure the sites included in their studies are not making the same mistakes.
For more proactive steps sponsors can take to prepare their sites, download our latest whitepaper.