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FDA BIMO Inspections: Insights for Researchers

The FDA’s Bioresearch Monitoring Program (BIMO) plays a critical role in ensuring the integrity and compliance of clinical trials involving human subjects. For clinical researchers, particularly those working with complex drug or biologic trials, a thorough understanding of BIMO inspections is essential. These inspections play a vital role in ensuring the integrity and compliance of clinical trials, protecting both participants and data quality. This blog will delve into BIMO inspections, how to prepare for them, what to expect during the process, and common findings.

What is the FDA BIMO Inspection?

FDA BIMO monitors all aspects of the conduct and reporting of FDA-regulated research through a comprehensive program of on-site inspections, data audits, and remote regulatory assessments. Designed to ensure the quality and integrity of data submitted to the FDA, BIMOs support new product approvals and marketing applications while protecting the rights and welfare of human and animal subjects involved in FDA-regulated research. During the COVID-19 pandemic, FDA introduced Remote Regulatory Assessments (RRA), which are remote evaluations of data and processes conducted via video teleconference.

Scope of BIMO Inspections

BIMO is a cornerstone of the FDA premarket approval process for new drugs, medical devices, food and color additives, veterinary products, and tobacco products introduced to U.S. consumers. It also plays a role in postmarketing pharmacovigilance activities for drugs. Implemented both domestically and internationally, BIMO results in over 1,000 inspections annually. These programs address:

  • Non-clinical testing laboratories in accordance with Good Laboratory Practice (GLP)
  • Clinical investigators in compliance with Good Clinical Practice (GCP)
  • Sponsors, contract research organizations (CROs) and clinical trial monitors
  • In vivo bioequivalence facilities
  • Institutional Review Boards (IRBs, independent committees that review and approve research protocols to ensure they meet ethical and safety standards for human subjects)
  • Radioactive Drug Research Committees
  • Postmarketing Adverse Drug Experience (PADE) reporting
  • Risk Evaluation and Mitigation Strategy (REMS) reporting

Unique in its scope, the BIMO program regulations are shared by all six FDA centers: Center for Biologics Evaluation and Research (CBER), Center for Devices and Radiological Health (CDRH), Center for Drug Evaluation and Research (CDER), Center for Food Safety and Applied Nutrition (CFSAN), Center for Tobacco Products (CTP) and Center for Veterinary Medicine (CVM).

FDA inspectors conduct a BIMO inspection to ensure bioresearch compliance and accuracy.
FDA inspectors conduct a BIMO inspection to ensure bioresearch compliance and accuracy.

Preparing for a BIMO Inspection

The FDA’s Bioresearch Monitoring Technical Conformance Guide provides specifications, recommendations, and considerations for submitting clinical data electronically, aiding in the planning of BIMO inspections for new drug applications (NDAs), biologics license applications (BLAs), and related submissions. Understanding the applicable regulations, including International Council for Harmonisation Good Clinical Practice (ICH GCP) guidelines and 21 CFR Part 54 for GCP, is crucial for researchers to prepare effectively.

Pre-Inspection Checklist

Preparation is crucial for a successful BIMO inspection. Here’s a comprehensive checklist to help you get ready:

  1. Review Study Protocols: Ensure that all study protocols are up-to-date and that any amendments have been properly documented and approved by the IRB.
  2. Organize Documentation: Gather all necessary documents, including Trial Master File, Investigator Site Files, informed consent forms, case report forms, and protocol deviation logs. Make sure they are complete, accurate, and easily accessible.
  3. Train Staff: Conduct refresher training sessions for all study personnel on the study protocols, informed consent process, and good clinical practice (GCP) guidelines.
  4. Audit Records: Perform an internal audit of all study records to identify and rectify any discrepancies or incomplete data.
  5. Prepare Facilities: Ensure that the physical facilities where the study is conducted are in compliance with regulatory standards such as 21 CFR parts 50, 54, 56, and 312 or 812 and ready for inspection.
  6. Communication Plan: Develop a communication plan for the inspection, designating point-of-contact personnel who are knowledgeable about the study and prepared to interact with inspectors.

Document Management

Effective document management is a cornerstone of compliance. Here are some best practices to follow:

Adopt a systematic approach to organizing documents. Use clearly labeled folders and a consistent naming convention for files.

Implement a robust version control system to ensure that only the most current and approved versions of documents are used. Keep a log of all document changes, including the reason for each change and the date it was made.

Regularly back up all study-related documents in multiple secure locations. This includes both electronic and paper records.

Limit access to sensitive documents to authorized personnel only. Implement strong access control measures to ensure the integrity and confidentiality of study data.

Follow regulatory requirements for document retention. Ensure that all study-related documents are retained for the required period, and have a clear policy for archiving and disposing of documents when appropriate.

Conduct regular internal audits of document management practices to identify and correct any issues promptly. This helps ensure that your documentation remains in compliance with regulatory standards.

By meticulously preparing and managing your documentation, you’ll be better equipped to handle a BIMO inspection, demonstrating your commitment to maintaining high standards of research integrity and regulatory compliance.

The FDA has recently issued two draft guidances (guidance for clinical study report format and Processes and Practices Applicable to Bioresearch Monitoring Inspections) to assist in planning BIMO inspections and to outline best practices for communication before, during, and after an inspection. These guidances apply to sponsors submitting NDAs, BLAs, and supplements, ensuring a streamlined inspection process. FDA welcomes comments for these guidances by 5 Aug 2024.

Need help with Inspections?

During the BIMO Inspection

Conducting the Inspection

  • Initial Meeting: Inspectors introduce themselves and outline the inspection scope. Provide requested documents, including study protocols and informed consent forms.
  • Facility Tour: Show inspectors around key areas like laboratories and storage. Ensure cleanliness and compliance.
  • Review of Documents and Data: Have well-organized documents ready. Inspectors will verify data accuracy and consistency.
  • Staff Interviews: Ensure staff are prepared to answer questions about their roles and study protocols.
  • Observation of Procedures: Inspectors may observe clinical procedures. Demonstrate strict adherence to protocols and SOPs.
  • Responding to Findings: Address minor issues immediately and document all findings.
  • Exit Interview: Listen to inspectors’ feedback and clarify next steps, including the timeline for the formal report and responses.

Interactions with Inspectors

Maintain clear and professional communication with FDA inspectors. Be honest and transparent in your responses. If you don’t know the answer to a question, it’s better to admit it and offer to find the information rather than guessing.

Common Findings and How to Address Them

Common findings during BIMO inspections include inadequate informed consent processes, protocol deviations, and insufficient documentation. Identifying and understanding these issues can help in addressing them proactively. The following were the most predominant findings since 2017:

  • Failure to comply with the requirements of the Statement of Investigator, Form FDA 1572 (an agreement signed by the investigator to provide certain information to the sponsor and to assure that he/she will comply with FDA regulations related to the conduct of a clinical investigation).
  • Inadequate protection of subjects, issue with informed consent.
  • Failure to adhere to the investigational plan.
  • Insufficient or inaccurate medical history and/or study records.
  • Insufficient accountability and control of investigational product.
  • Poor reporting and recording of adverse events.
  • Lack of IRB meeting minutes in sufficient detail to show attendance at the meeting, voting, quorum issues.
  • Not having a majority of IRB members present for the review of research proposals other than expedited reviews.
  • Failing to keep the IRB members informed of proposed research that has been approved for expedited review.
  • Failure to comply with FDA regulations regarding expedited review procedures.
  • Inadequate documentation of IRB activity, insufficient copies of research proposals and related documentation.

Corrective Actions

When issues are identified, it’s important to develop and implement corrective action plans. These should include a root cause analysis and specific steps to prevent recurrence.

Inspection Report

After the inspection, you will receive an inspection report outlining any findings. It’s crucial to respond promptly and comprehensively, addressing each observation with a detailed corrective action plan.

Key Takeaways

Understanding and navigating FDA BIMO inspections is essential for clinical researchers. By preparing thoroughly, maintaining robust documentation practices, and addressing findings proactively, researchers can ensure compliance and uphold the integrity of their trials. Maintaining compliance is an ongoing effort. Regular internal audits, continuous staff training, and staying updated with regulatory changes are essential for long-term success.

References

Nirekshana Krishnasagar

Nirekshana Krishnasagar

Computer Systems Validation Specialist