A Brief Overview of the FDA Bioresearch Monitoring (BIMO) Program

The U.S. Food and Drug Administration (FDA) held a webinar on the Bioresearch Monitoring program (BIMO) last month (2/16/2022).

The FDA BIMO program is a comprehensive on-site inspections and data audit program for the clinical research industry. It is meant to monitor all types of conduct and report to FDA about the research that is going on, which may include all the data submitted to the FDA in the process of product approval, marketing applications, and related to the rights and welfare of all the subjects, human and animal, involved in the trials, has high quality and is an accurate representation of what is going on. BIMO is a cornerstone of the preapproval process carried out by FDA new medicines, devices, food and color additives, veterinary products, and new tobacco products. (1)

The BIMO program is also unique in its scope and has been implemented within the United States and beyond its borders, doing over 1000 inspections every year. BIMO is connected with national and international partners, which ensures it is carried out as comprehensively as possible.(1)

There are several compliance programs that are part of BIMO. These include: In Vivo Bioavailability-Bioequivalence Studies, the Inspection of Nonclinical Laboratories Conducting Animal Rule-Specific Studies, Good Laboratory Practice (GLP) Program for Nonclinical Laboratories, and another for Nonclinical Laboratories in regards to Data Audit Inspections. There are also the IRB, Radioactive Drug Research Committee, Sponsors and CRO, Clinical Investigators and Sponsor-Investigators, Postmarketing Adverse Drug Experience (PADE) Reporting Inspections, and Risk Evaluation and Mitigation Strategies (REMS) compliance programs in order to prevent critical compliance issues. (2)

More specifically, the webinar was intended to offer value mostly to clinical investigators, clinical research personnel (e.g., sub-investigators, study coordinators, regulatory specialists), sponsors, contract research organizations (CROs), sponsor-investigators and institutional review board (IRBs), and other involved audiences. (3)

The BIMO works not only with legal bases, but also compliance with Good Clinical Practice (GCP) which  ensures that the data that is sent is accurate and reliable and also that the ethics are respected in each situation. In particular, the well-being and confidentiality of the subjects are a big priority for the program. The practices are updated consistently to remain current.

Regarding clinical trials, GCP is very important, because it ensures that the study is being carried out properly and that the data resulting from it is reliable. It also ensures that the participants of the study are treated adequately, keeps  a strict record of everything going on in the study, follows the protocols, and guarantees safety and confidentiality throughout. But beyond this, it involves being able to prove these measures to FDA if there is an inspection (3).     

Furthermore, the FDA inspections are carried out retrospectively, in real- time, and can be conducted remotely and on-site. The focus of BIMO is mostly on the research and the compliance and safety of each specific study and organization, and the organization uses a risk management approach to select the sites for the inspection, which considers a variety of factors, such as complaints and discontinuation rates. The core three elements of the inspection are the study participants, especially that their rights and safety are respected, protocol adherence, and data verification. (3)

After an inspection, FDA will determine if the inspected sites are in compliance with applicable laws and regulations. FDA may issue Untitled Letters to the areas evaluated, the results can be one of three classifications, no action indicated (NAI), voluntary action indicated (VAI), or potential official action indicated (OAI). Any  Serious noncompliance can involve repeated failure to follow guidelines, putting subjects at risk or compromising their data, and delivering falsified or compromised data. Upon delivering the results, the inspected organization can submit a response and documentation to challenge the claim, clarify the results, or take steps to mitigate it. (3)

At present, FDA is developing and implementing new protocols for BIMO. One interesting aspect is the use of remote inspections, which were a response to COVID-19, and the ongoing need to continue inspections despite the pandemic restrictions. The remote protocols for inspection are likely to remain in the future thanks to the benefits they offer. (3)

Understanding BIMO is essential for sponsors and investigators, and the webinar offers a comprehensive introduction to the program, as well as an understanding of what inspectors are looking for with specific examples of noncompliance and the studies that have been shut down because of it. FDA releases continuous updates to its documents and manuals. There are opportunities for training and education concerning the program. If you want to get more information about BIMO or bio pharma products, Pharmasources would be a great choice.

BIMO can offer significant challenges for investigators and sponsors. It is important to keep in mind the possibility of the inspection, its focus, and its requirements. Mock BIMO audits and inspections could support a successful outcome. Documentation and extensive preparation, as well as preventive and immediate actions to address non-compliance, are also factors to consider. (3)

Therefore, this is of special interest to sponsors and study organizers who will ultimately take responsibility for compliance and have the position and the power to ensure compliance, as well as to take action to prepare everything for a possible inspection. Clinical investigators should also be appraised of the work and documentation they need to be doing to prepare and the important elements that might be taken as noncompliance. (3)

In short, the BIMO program is an essential FDA program that has a wide reach and authority for different types of research. It is concerned with adequate research, protocol adherence, compliance with safety and confidentiality guidelines, and the sharing of reliable data. It is a program that must be understood on all levels of clinical and non-clinical research to ensure compliance. The BIMO program will involve inspections that can lead to studies being shut down or having to undergo extensive revisions for compliance, so it’s always better to prepare beforehand and understand the requirements and demands of an inspector representing the Bioresearch Monitoring program.

References

1. FDA (2020) Bioresearch Monitoring Program Information. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/fda-bioresearch-monitoring-information/bioresearch-monitoring-program-information

2. FDA (2021) Bioresearch Monitoring Program (BIMO) Compliance Programs.  https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/compliance-program-manual/bioresearch-monitoring-program-bimo-compliance-programs

 FDA (2022) CDER BIMO GCP Compliance and Enforcement. https://www.fda.gov/drugs/news-events-human-drugs/cder-bimo-gcp-compliance-and-enforcement-02162022

About the Author:

Lin Zhang, M.D., senior director of a health care industry company in the United States. With the experience in clinical medicine, biotechnology, health industry and other fields, he is responsible for the research and development of plant medicine, functional food and health products. He was a clinician and worked for the National Cancer Institute, FDA and the National Cancer Center of Japan for many years.