FDA issues draft guidances covering BIMO inspections
The US Food and Drug Administration (FDA) has issued two draft guidances on bioresearch monitoring (BIMO) inspections. The first covers information to assist the agency in planning these inspections, while the second covers best practices for communicating to the FDA before, during, or after an inspection. Both cover sponsors that have submitted new drug applications (NDAs), biologics license applications (BLAs), and supplements.The planning guidance should be read in conjunction with the BIMO technical conformance guide issued in August 2022, which covers the specifications for preparing and submitting clinical study information and subject-level data line listings by clinical sites.
The planning guidance states that “reviewers from BMB [CBER’s Bioresearch Monitoring Branch], the Office of Vaccines Research and Review, Office of Therapeutic Products, Office of Blood and Research Review, and the Office of Biostatistics and Pharmacovigilance rely on timely access to accurate data in BLA and NDA submissions to issue inspection assignments as early in the review process as possible.”
The guidance describes where to submit the clinical study-level information, subject-level information by clinical site, and the summary-level clinical site dataset in the electronic Common Technical Document (eCTD).
The second draft guidance addresses the records, information and best practices for communicating with FDA in advance of or during an inspection and its issuance complies with a mandate in the Food and Drug Omnibus Reform Act of 2022 (FDORA).
The BIMO program “is a comprehensive portfolio of programs designed to assess and monitor all aspects of the conduct and reporting of FDA-regulated research as well as certain postmarketing activities through on-site inspections, investigations, and Remote Regulatory Assessments (RRAs),” according to FDA. The program was also created to “assess the quality and integrity” of data submitted to the agency and to protect the rights, safety, and welfare of human trial participants involved in FDA-regulated research.
Companies that are subject to a BIMO inspections “must provide FDA with access to the information to be inspected (including access to all paper and electronic records and access to electronic information systems used to hold, analyze, process, or transfer that information), and permit FDA to inspect relevant facilities and equipment used in generating that information.”
Section 704(a)(5) of the Food Drug and Cosmetic Act also provides safeguards against sponsors’ disclosure of confidential commercial information and trade secrets.
The guidance further states that BIMO inspections are like general inspections and “are to be conducted at reasonable times, within reasonable limits, and in a reasonable manner.”
The agency “intends to make reasonable efforts to contact the establishment, including to discuss inspection plans, and the inspection start date and time.”
FDA does not have to disclose its reasons for conducting an inspection in its pre-announcement.
At the end of an inspection, the FDA investigator will conduct a closeout meeting with the establishment representative to discuss the inspection findings and, if violations are found, issue a written Form FDA 483 report to the firm.
In response to Form 483, companies should address their plans to address the observations, which should include a commitment from senior leadership. Responses should be “well-organized and structured,” address each observation separately, and note whether the establishment agrees or disagrees with the findings.
Firms should also provide both corrective and preventive actions to remedy noted problems and monitor the effectiveness of these action plans. Firms should also submit documentation attesting to corrective action plans.
FDA encourages establishments to provide written responses to the observations within 15 business days after the conclusion of the inspection.
The deadline for commenting on both guidances is 5 August 2024.
FDA draft guidance on format for clinical study reports
FDA draft guidance on BIMO inspection best practices