When a clinical study will be used to support an FDA market authorization application, it’s likely the agency will require a Bioresearch Monitoring (BIMO) inspection. Similar to our advice on clinical study design, it’s critical to “begin with the end in mind,” meaning you should think about your BIMO process well before the first subject is enrolled. In today’s blog post, our CEO and Founder Andrea Fenton Abbs shares five tips to help you prepare for a successful BIMO inspection.
Overview of a BIMO Inspection
As described by FDA, BIMO is “a comprehensive program of on-site inspections and data audits designed to monitor all aspects of the conduct and reporting of FDA regulated research” that has become a “cornerstone of the FDA preapproval process” for new medical devices, drugs, and other biotechnology.
BIMO inspections of clinical investigators, institutional review boards, and sponsors are intended to ensure the following:
- Quality data are provided to FDA as support for new market authorization applications
- The rights, safety, and welfare of study subjects are protected
- Clinical studies are conducted in compliance with good clinical practices (GCP) and applicable regulations
The five tips below will guide you to ensure careful management of key study areas that receive rigorous scrutiny during BIMO inspections.
1. Clearly Document Qualifications & Training
“Training, training, training” is the clinical study equivalent of the real estate mantra “location, location, location.” Despite not being emphasized in BIMO compliance policy guidance, in our experience, training records are one of the first things requested by FDA inspectors and they are reviewed thoroughly. Therefore, it is imperative to document how the sites were selected and qualified and to demonstrate that study personnel were adequately trained to participate in your study. This includes sponsor personnel, clinical research organization (CRO) clinical study lead, monitors, core laboratory, principal investigators (PIs), research coordinators, and other site staff. Records supporting their experience and knowledge of GCP and the study protocol may include curriculum vitae, GCP certifications, and study-specific training records that identify names of the trainer and trainees, training content, and the date the training occurred. Site personnel with an active study role should be listed on a delegation of authority log and should not be allowed to do study-related work until they’re authorized to do so (i.e., essential regulatory documents are collected; GCP and other required training completed).
In addition to sponsor and site personnel training, make sure to clearly document the qualifications and contracts describing the scope of work for key study vendors, such as a CRO, safety committee members, database builder, and/or core laboratory.
2. Maintain Adequate Records
FDA often cites “failure to maintain adequate records” as an observation during BIMO inspections. In addition to the training records discussed above, key records include financial disclosures, investigator agreements, informed consent process, investigational product accountability, and, most importantly, accurate and complete subject data that supports the study endpoints. Ensure your data and essential document repositories, like your study database and trial master file, are appropriately and consistently managed by authorized personnel. This means personnel who leave the study team no longer have access to the database and unauthorized personnel cannot make changes to site data. When substantive changes are necessary for your protocol, related study plans, or database, conduct a thorough change impact assessment and document the results.
3. Ensure Robust Study Monitoring
Think of your trained and qualified monitors as dedicated inspectors for your study. They play an essential role in ensuring that each site is following the protocol, appropriately trained, and authorized personnel are fulfilling their delegated study responsibilities, and the data generated aligns with source documentation. When non-compliances are identified, monitors can help identify solutions, communicate possible protocol clarifications to study leadership, or retrain staff to avoid future issues that could derail your study. Make sure your monitors are following an established monitoring plan; action items are documented, shared with the appropriate audience and resolved in a timely manner; and any corrective or preventative measures taken to address issues are documented. These records will demonstrate awareness of study activities and a good faith effort toward compliance.
4. Properly Record & Report Adverse Events
A common observation made by BIMO inspectors is the failure to report and/or record adverse events (AEs). This should be a key aspect of your monitoring plan. AEs are recorded on case report forms, and oftentimes their causes and outcomes are reviewed and adjudicated by independent safety committees. Ensure your monitor is reviewing and documenting their review of the source for unreported adverse events. Further, ensure that your safety committee members are trained and qualified and that their charters, reviews, and outcomes are clearly documented. In addition, when AEs meet certain criteria defined in the regulations and your study protocol, ensure that they are properly reported to the sponsor, the institutional review boards (IRBs), and FDA. Clear and timely documentation of this critical safety information is of utmost importance to protect subjects and inform the safety profile of your product.
5. Communicate Regularly with the Study Team
To play off another sales strategy mantra, your clinical study team should follow ABC: Always Be Communicating. Frequent communication between the sponsor, CRO, sites, safety committees, and core laboratory demonstrates an engaged study team with their finger of the pulse of study execution and any safety concerns. Study management meeting minutes and other essential correspondence regarding key study decisions should be thorough, timely, and well-organized within your trial master file.
Conclusion
While there are many details and complexities to oversee in clinical research, some are more critical than others, as evidenced by FDA inspection metrics and our first-hand experience hosting BIMO inspections. We recommend special diligence when planning and managing personnel qualifications and training, study records, monitoring, adverse events, and communication. Focusing on these critical topics will go a long way toward helping you clear that final hurdle on the way to the finish line, ensuring high-quality clinical data that meets the expectations of GCP and your BIMO inspector.
