In a previous blog post, “What is 21 CFR and why is it important?, we discussed 21 CFR Part 11. Here, we’ll focus on 21 CFR Part 56, which covers working with IRBs and being prepared for an associated audit.
Remember that 21 CFR is the section in the Code of Federal Regulations (CFR) that sets the FDA guidelines for pharmaceuticals and medical devices. There are more than 1,500 parts underneath nine volumes of data within 21 CFR. Part 56 serves up guidelines for Institutional Review Boards (IRBs), groups charged with reviewing and monitoring biomedical research that involves human subjects.
The primary purpose of IRBs is to protect the rights and welfare of human subjects involved in research activities. The IRBs have the authority to approve, require modifications to, or disapprove any research. So, understanding and fully complying with 21 CFR Part 56 will help you to ensure that your protocol and study materials pass IRB review.
IRB Responsibilities - The Basics
The IRB reviewing a research study has the responsibility to conduct initial and ongoing reviews of research and reporting decisions and findings. IRBs pay particular attention to information given to subjects as part of documented informed consent. The IRB is required to perform at least annual reviews and may even observe the consent process and research conduct.
IRBs are looking for 7 general criteria in order to approve research:
- Risks to subjects are minimized
- Risks to subjects are reasonable in relation to the anticipated benefit and the importance of the expected results
- Subject selection is equitable – protecting vulnerable patient populations
- Informed consent is sought
- Informed consent is documented
- There is adequate provision of monitoring to ensure patient safety
- There is adequate protection of the confidentiality of patient data
IRB ongoing review of research ensures that the investigator promptly submits progress reports to all members and that one member is assigned responsibility to review them. These are evaluated to establish if the study should be allowed to continue, be amended, or be terminated. IRBs ensure that the protocol and consent materials used are those that have been previously approved, and unanticipated risks to patients and adverse events are reviewed.
FDA Inspections - The Basics
The FDA performs clinical site and IRB inspections through its Bioresearch Monitoring (BIMO) Program. Both clinical trial sites and IRBs should be prepared for an FDA audit at any time. It also helps to be aware of the FDA violations that are most common, and most likely to result in a Form 483 or Warning Letter.
How does the FDA select sites for audit? The agency employs its Clinical Investigator Site Selection Tool (CISST) for that purpose. The CISST provides a science-based approach for site selection to ensure that sites that pose the highest risk to public health are selected.
Typically, the FDA will announce pre-approval and routine inspections five calendar days in advance, but auditors may show up unannounced at sites with a poor track record. Also, the FDA will not always alert sites before performing compliance follow-up and ‘for cause’ inspections.
Top 5 Tips for Sites Preparing for an FDA Inspection
Good preparation can help move the inspection process along. Below are five key tips for being well prepared:
- Educate your sites on FDA inspection procedures and ensure audit standard operating procedures are in place and people know where to find them.
- Ensure all basic study information is available at all times in a central location – for example, in a single electronic document repository.
- Compile any product complaints and corrective and preventative actions (CAPAs) that occurred since your last inspection and have them readily available.
- Provide adequate workspace for the FDA inspector. Be sure that the space offers some privacy.
- Run mock FDA inspections with your sites.
Make preparation for IRB submissions and regulatory agency visits part of your regular clinical study process. Set up checklists and information pathways to ensure that your staff is ready at all times. It will make life a lot easier should an inspection or audit occur.
Software technology and services can help. Investing in systems that automate various aspects of inspection and audit readiness is an investment in future success.