“Processes and Practices Applicable to Bioresearch Monitoring Inspections: Guidance for Industry” is a draft guidance document issued by the FDA in June of this year. The intent is to provide clarity on the procedures and practices related to Bioresearch Monitoring (BIMO) inspections. This document is designed to help industry stakeholders understand what to expect during FDA inspections of sites and facilities involved in FDA-regulated research, ensuring compliance with statutory requirements and safeguarding the integrity of data and the welfare of clinical trial participants.
It provides critical insights for industry stakeholders involved in FDA-regulated research. This document, mandated by the Food and Drug Omnibus Reform Act of 2022, outlines the FDA’s expectations and procedures during inspections of clinical research sites and facilities. The guidance covers everything from the types of inspections to expect, both domestic and international, to best practices for communication before, during, and after inspections.
The document highlights the importance of preparedness, clear communication, and timely responses to any inspection findings, particularly those documented on Form FDA 483. It also provides valuable resources for further understanding the FDA’s inspection processes, ensuring that research establishments can maintain Good Clinical Practice (GCP) compliance and uphold the integrity of their research data. This guidance provides answers to many questions that come up with supporting a client through preparing for a regulatory inspection. The following is a summary of key points from the guidance.
How will an organization receive notification of an FDA inspection?
An organization will typically receive notification of a regulatory BIMO inspection through a pre-announcement from the FDA. This pre-announcement is intended to ensure that the appropriate records and establishment personnel will be available during the inspection.
The pre-announcement process generally involves the FDA making reasonable efforts to contact the organization, often by phone or email, to discuss the inspection plans, including the start date and time of the inspection. In general, pre-announcements for domestic inspections are done via phone and for international inspections it may be phone or email. The FDA may also provide a general idea of the records that may be requested during the inspection.
However, it’s important to note that not all inspections are pre-announced. The FDA may choose not to pre-announce an inspection if prior notification might impact the effectiveness of the inspection. This is particularly relevant for inspections where unannounced visits are deemed necessary to ensure the integrity of the inspection process.
For foreign inspections, pre-announcement is generally given further in advance due to country clearance requirements. In all cases, the FDA aims to ensure that the organization is prepared for the BIMO inspection by making the necessary arrangements ahead of time.
What type of communication can be expected during the inspection?
During an FDA inspection, the organization can expect several types of communication with the FDA personnel:
- Requests for Records and Information: FDA personnel will request records or other information as part of the inspection. The organization will have the opportunity to discuss the nature, process, and timeline for these requests. Establishment staff can ask clarifying questions and should be prepared to provide the requested records promptly.
- Discussion of Observations: FDA personnel may discuss any observations with the organization’s staff either as they are observed or on a daily basis during the inspection. These discussions may cover findings that might not be formally documented on the FDA Form 483, allowing the organization to provide clarification or additional information as needed.
- Technical Discussions: If the organization uses electronic information systems to hold, analyze, process, or transfer pertinent information, FDA personnel will discuss the technical details of accessing these systems. The FDA may require read-only access to these electronic records or other methods of viewing the data, and the organization should be prepared to provide copies of these records as needed.
- General Communication: Throughout the inspection, there will be ongoing communication between FDA personnel and the organization’s representatives to ensure the inspection process is understood, and any concerns are addressed in real-time.
This communication is designed to facilitate a transparent and effective BIMO inspection process, ensuring that the organization can respond appropriately to any issues identified by the FDA during the inspection.
What is the recommended response to a Form FDA 483?
When an organization receives a Form FDA 483, which documents observations of objectionable conditions found during an FDA inspection, the FDA recommends the following approach for responding:
- Acknowledge and Understand the Observations: The response should demonstrate that the organization acknowledges and understands the observations noted on the Form FDA 483.
- Commitment from Senior Leadership: The response should include a clear commitment from senior leadership to address the observations and implement corrective and preventive actions.
- Address Each Observation Separately: The response should address each observation on the Form FDA 483 individually. For each observation, the organization should:
- Indicate whether they agree or disagree with the observation and provide a rationale.
- Outline both corrective and preventive actions to address the observation.
- Include a timeline for completing these actions.
- Detail Corrective and Preventive Actions: The response should include specific details about the corrective actions already taken or planned and preventive measures to avoid future occurrences of the issues identified.
- Verification and Monitoring: The response should describe how the organization will verify or monitor the effectiveness of the corrective and preventive actions.
- Provide Documentation: The response should include relevant documentation to support the actions taken, such as updated Standard Operating Procedures (SOPs), training records, corrective action plans, or other relevant records.
- Timely Submission: The FDA encourages organizations to submit their written response within fifteen (15) U.S. business days after the end date of the inspection. A timely response is important as it may influence the FDA’s decision regarding further action.
- Include FDA Establishment Identification: For domestic inspections, the response should be sent to the OBIMO division contact listed on the Form FDA 483 and should include the FDA Establishment Identification (FEI) of the inspected location. For foreign inspections, the response should be directed to the FDA center point of contact provided by the investigator.
By following these recommendations, the organization can effectively address the issues raised by the FDA and potentially mitigate further regulatory action.
Conclusion
For research establishments, understanding and adhering to this guidance is crucial to avoid potential compliance issues and ensure the smooth operation of FDA inspections. The FDA encourages establishments to familiarize themselves with these processes and engage proactively with FDA inspectors to address any concerns or observations promptly.
Authored by Donna Dorozinsky, Founder & CEO, Just in Time GCP
Leveraging 30+ years of experience and having been a part of over 100 inspections, Donna frequently reports on the latest regulations and industry trends related to TMF optimization and GCP inspection readiness.
If your organization is anticipating an upcoming FDA inspection or recently received an FDA Form 483, the Just in Time GCP team of consultants is available to support you in your next steps. Whether it is understanding the story of your study, remediating your TMF, or responding to a regulatory finding, Just in Time GCP is here to support you.
