Preparing for GCP Inspections: The Truth, the Whole Truth, and Nothing But the Truth

By Triona Coll – Quality Assurance. i3 Research

Every sponsor or CRO can expect their country’s regulatory agency to arrive on their premises periodically to conduct routine inspections. In the UK, for instance, the Medicines and Healthcare products Regulatory Agency (MHRA) conducts routine periodic inspections approximately every three years. Apart from these, the MHRA also conducts “for cause” and “follow up” inspections, and they also take part in the third-country inspection program. Because all inspections may be either announced or unannounced, a perpetual state of preparedness is critical.

The purpose of inspections

The purpose of inspections is to verify compliance with ICH GCP, EU Directive 2001/20/EC and Statutory Instrument 1031 (UK legislation), and confirm that sponsors or CROs are:

• Submitting reliable and verifiable data
• Protecting the rights and safety of patients

Inspectors will be looking at the entire system for clinical trials and:

• Testing all component parts
• Testing the way component parts interact
• Verifying compliance with regulations

Inspection format and agenda

The inspection will assume the following format or sequence:

1.       Pre-inspection information gathering

2.       In-house systems inspection (the number of days dependent on the size of your organization)

3.       Investigator site inspection(s) (a number of sites for UK studies will be chosen to be inspected on different dates)

4.       Inspection report (responses required)

5.       MHRA issues GCP statement

Inspections adhere to a standard agenda that begins with an introductory meeting and is followed by the inspection itself, which consists of reviews and interviews. A review of facilities is then conducted prior to an exit meeting, at which time discrepancies are reviewed, disputed findings are clarified, and findings are classified overall to provide context.

Preparing for an inspection

When preparing for an inspection, it is important to decide on an Inspection Process. For instance, you will probably want to:

• Write a standard operating procedure (SOP) to cover the whole process of handling inspections
• Gain commitment from senior management
• Appoint an inspection coordinator
• Appoint the inspection team
• Communicate with all staff
• Gather information on pre-inspection requirements
• Arrange the logistics of inspection
• Have meetings with the core inspection team
• Prepare staff for interviews
• Review previous audits and inspections for learnings
• Confirm roles and responsibilities
• Confirm inspection details

You will also want to prepare documents that may be required in-house, such as:

• SOPs
• Training records for interviewees
• Example contracts and agreements
• TMF for selected studies (MHRA will pre-select studies for review during the inspection)
• CSR templates and QC documentation
• QA Audit Plans
• Data management files for selected studies
• Biostatistics files for selected studies
• Computer systems validation documentation for clinical systems
• Disaster Recovery Procedure

And don’t forget at-site documentation, including:

• Investigator file
• Source records
• CRFs
• Informed consent documents
• Pharmacy records (drug accountability)

Conduct during inspections

So what conduct is appropriate for an inspection? It depends on which of the two involved parties you have in mind. For the sponsor or CRO, you’ll want to assign appropriate accommodation for the inspection; provide a host, a runner, and other personnel who can focus on taking notes; and you’ll want to make sure your staff is ready to respond to requests for documentation in a timely and efficient manner. As for inspectors, you can expect them to be polite, courteous, reasonable and professional.

The expectations of inspectors

Inspectors’ expectations may vary by individual, but in general, they are verifying that sponsors or CROs have appropriately qualified personnel who possess:

• A good working knowledge of SOP requirements
• Knowledge of interaction with other departments
• Knowledge of selected studies
• The ability to answer specific queries on selected studies
• A characteristic openness and honesty

Questions asked by inspectors

Inspectors will ask many questions, most of which will centre around:

• An individual’s training and background
• Study start-up
• Investigator selection
• Collection of essential documents
• Site initiation, routine monitoring, and close-out
• SDV
• Involvement in SAE/SUSAR reporting
• Handling persistent non-compliance
• Verifying PI involvement

At site, inspectors will also ask about:

• Study site staff responsibilities
• Regulatory and ethics submissions/approvals
• Subject recruitment, informed consent, medical care
• Serious Adverse Event reporting
• Study drug management

Inspection learning points

These include:

• Know your internal experts
• Train staff in inspection procedure
• Providing training in interview technique
• Provide sample interview questions
• Have an inspection coordination team
• Support staff
• Everyone should know their role
• Stay calm!

"Rules” for successful inspections

• Be friendly, non-defensive, and establish a trusting, cooperative relationship
• Repeat questions for clarification
• Answer the question asked
• Ask for help when needed
• Communicate effectively
• Above all, be honest and know the rules (e.g., company rules on photocopying documents for inspectors, etc.)

Remember, a good inspection will lead to peace of mind, give your company credibility with the regulatory agency and potentially mean fewer “for cause” inspections in the future.

Summary

In closing, a few points to keep front-of-mind:

• Let QA host the inspection
• You know your company, so have information readily available
• Prepare your staff for their role in the inspection

And good luck with your inspection!