Background

FDA’s Bioresearch Monitoring (BIMO) program 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. The program is designed to assure the quality and integrity of data submitted to the agency, as well as helping to protect the rights and welfare of human subjects participating in FDA regulated research.

Prior to FDORA, FDA maintained that the statutory authority for BIMO inspections came from its basic authority for establishment inspections granted under Section 704 of the Food Drug and Cosmetic Act (FDCA), along with other statutory provisions requiring maintenance of clinical trial records for FDA inspection (e.g., Sections 505(k)(2) and 520(g)(2)(B)(ii) of the FDCA). However, some stakeholders questioned whether the authority for BIMO inspections – other than for new products – was sufficient given the lack of explicit authorizing language in the FDCA.

FDA recently published its fiscal year 2021 BIMO inspection metrics, and held a webinar on the BIMO program to inform stakeholders about Clinical Practice (GCP) inspectional processes, compliance evaluations, and enforcement trends. Further, FDA recently updated its BIMO inspection manual for sponsors, reflecting the agency’s increased scrutiny of sponsor processes and procedures related to the selection of investigators, electronic systems, and contract research organization (CRO) oversight, among other updates.

Speaking at the most recent BIMO webinar, CDER GCP Assessment Branch Director Karen Bleich indicated BIMO inspections may be more likely where:

• There is an application for a new molecular entity.
• It is a first marketing application from a firm.
• Specific data concerns have been raised, such as unexpected safety or efficacy results; for example, where site results are highly variable among different locations where the study was conducted.
• Specific trial conduct concerns have been raised; for example, where there are complaints about entities involved in a particular clinical trial.
• Studies are conducted entirely outside of the US.
• The financial disclosure forms submitted with the application raise questions about the potential introduction of bias into the study.

Moreover, as FDA contended with pandemic-related issues over the last three years, the latest agency data reveal that the agency has increasingly relied upon remote assessment tools to evaluate clinical trials and other product development activities. Even though FDA has made significant strides in adopting remote assessment tools, we fully expect that the agency will conduct significantly more on-site inspections in 2023 than it has during the last three years.

FDORA BIMO provisions

Section 3612 of FDORA, “Bioresearch Monitoring Inspections,” both resolves the question around FDA’s authority to conduct BIMO inspections and provides the agency with greater authority in conducting these inspections. Specifically, FDORA makes clear that the purpose of BIMO inspections is to ensure the accuracy and reliability of studies as well as to assess compliance with applicable requirements under the FDCA and Public Health Service Act (PHSA). Below we provide a summary of who can be inspected and the scope of the inspection. Notably, there is no grandfathering rule or restriction on retroactive application of FDA’s BIMO inspection authority. In fact, section 3612 of FDORA explicitly states that FDA previously did not lack the authority to conduct BIMO inspections.

            Who and what can be inspected?

FDORA section 3612 grants FDA broad authority to inspect a number of specific types of entities engaged in a wide range of research and product development activities. To briefly summarize, FDORA lists the following “sites and facilities,” “persons,” and “studies and submissions” covered under the new BIMO inspection authority. FDA’s inspection authority extends to those sites and facilities that are (or were) (i) used for a one of the activities listed below, and (ii) is owned by a “person” as defined in the legislative text.

• Sites and Facilities that are subject to BIMO Inspections (see Section (5)(C)(i)):

• • Those developing an application or other submission related to a marketing authorization for a drug, device, or other product;

  • Those preparing, conducting, or analyzing the results of a study; and 

  • Those holding any records or other information related to a study or submission.

• Persons who are covered by the new BIMO inspection provision (see Section (5)(C)(ii)):

• • Sponsors of applications or submissions to FDA;

  • Parties engaged by a sponsor through a contract or grant to assist in the development of data in support of an application;

    • This could include clinical sites, CROs, study vendors, biostatisticians, labs, IRBs, etc.

  • IRBs or other entities engaged by a non-sponsor through a contract or grant to prepare, collect, or analyze records or other information related to a study or submission to FDA; and

  • Anyone who conducts or has conducted a study.

• Studies and Submissions that are covered by the new BIMO provision (see Section (5)(E)):

• • Clinical and nonclinical studies submitted to FDA in support of applications for marketing authorization;

  • Postmarket safety activities conducted under the FDCA or PHSA (e.g., Phase IV trial, or confirmatory study under Accelerated Approval);

  • Any other investigation of a drug or device under specified sections of the FDCA and PHSA; and

  • Any other submission under the FDCA or PHSA that FDA determines a BIMO inspection is warranted in the interest of public health.

            Scope

FDA BIMO inspections extend to all records and other information related to studies and submissions. This includes records and other information related to the conduct, results, and analysis of studies, as well as the protection of human and animal trial participants.

The law permits FDA to access any electronic information system used by a company to hold, process, analyze, or transfer clinical records. Further, FDA is permitted to record or copy this information.

Recommended actions

As the pandemic ebbs and FDA continues to reinvigorate its on-site inspection program, FDORA section 3612 significantly enhances the agency’s inspectional authority related to clinical trials and associated product development activities. With this in mind, all parties involved in the clinical trial enterprise should carefully assess their inspection readiness and their ability to successfully host BIMO inspections.

Of particular significance, study sponsors should recognize that FDORA may embolden FDA to conduct more frequent and more aggressive sponsor GCP inspections, clinical site pre-approval inspections, and routine CRO inspections. Moreover, FDA may flex its new authority by expanding the scope of the BIMO inspection program to include additional types of study vendors, such as contractors that provide biostatistical support, software tools used in studies, database services, and clinical logistics.

To help avoid negative inspection outcomes that could disrupt or delay product approvals, study sponsors should review their inspection management SOPs, conduct mock inspections of their operations and those of their clinical sites and vendors, and carefully assess their studies’ compliance with GCP standards.

If you have any questions about FDA’s new BIMO inspection authority, please contact one of the authors or the Hogan Lovells attorney with whom you work.

Authored by Robert Church, Blake Wilson, and Heidi Gertner