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A friend of mine tells a story: A week before guests are scheduled to visit for Thanksgiving, both she and her husband come down with the flu. The day before the holiday, they've finally recovered enough to get out of bed, but the house is a mess and nothing has been done: shopping, cooking, cleaning, laundry. She's running around frantically cleaning up, making beds, writing lists, etc. and sees her husband walk through the room with a can of paint and a paintbrush. "What are you doing?" she asks.
"Painting the doorknobs before the guests arrive," he answers.
The human mind, when faced with a deadline, works in mysterious ways. In an effort to exert control, we can't help seizing on some minor yet achievable task that we know we can execute perfectly. So it goes with GCP inspection readiness. What we really need to do is vast and hard to get our heads around. What we CAN do is experiment with the fonts on the slide presentations. Serif or sans? What about some kind of cursive? Maybe with shadows?
As a rough guide, here's where you should be expending your energy on inspection readiness activities:
- Trial Master File: About half of your team's energy should be devoted to reviewing, QCing, and remediating the Trial Master File. The people who will be put in front of the inspector should be directing this effort and participating in it. This post discusses how tracking efforts help the team ensure completeness.
- Data Review: Set aside a small, knowledgeable team to look for irregularities and inconsistencies in the data and audit trails that might be of concern to a regulatory inspector. Is one site's or region's data substantially different than the others? Do audit trails for regulated systems raise any red flags, like changes without reason for change, or changes executed by the system? Were any back-end changes NOT captured in the audit trail? How easy is it to trace a data point from the Clinical Study Report back to the Electronic Data Capture System, and back further to the source?
- Interviewee Prep for Expected Questions: Inspection teams are fond of "deep dives" into study history but sometimes neglect to ensure that interviewees can answer the simple questions. What profiteth a man to be able to quote each amendment chapter and verse if he be tripped up by something simple like, "What was your role on the study?" (In a future post we'll look at standard BIMO questions that are deceptively difficult to answer.)
- Interviewee Prep for Substantive Gaps: An authoritative explanation can paper over the rough spots where documentation is missing or inadequate. It's definitely worth the time to compile thoughtful answers about tricky situations, emphasizing the quality cycle, and then train a small number of people to answer.
- Logistics: Speedy delivery of documents that effectively respond to the inspector's questions will instill the inspector with a sense of confidence that the competence displayed in the inspection room must also spill over into the clinical study.
- SOPs: If significant gaps or inconsistencies regarding regulated topics are identified in SOPs, take some time to revise them before the inspection. Even if they weren't in effect for the activities in question, you will "get credit" for addressing the gap before the inspector found it.
Which doorknobs should you refrain from painting?
- Gathering documents outside the TMF: As discussed in the previous post, leave them in the Trial Master File and figure out how to get what you need when you need it.
- Audits: Formal audits require a lot of effort from auditors and auditees alike. This is a good time for QA to drop the "independent" role and work collaboratively with the study team. Take a risk-based approach, issue findings quickly and informally, and don't require formal responses. The team can use that time for other activities.
- Extensive training beyond the inspection team and key SMEs: The inspection team needs to be trained in inspection logistics, and personnel who will be put forward as subject-matter experts need extensive training and coaching in responding to inspection questions. This training is most effective if delivered at short intervals in the month leading up to the inspection; any earlier, and trainees will forget it. Other personnel need only about an hour of training in how to avoid the inspection room, how to summarize their role at the company, and how to answer general process questions, performed the week before the inspections.
- Notes to file: When a gap or issue is identified, some teams have a strong instinct to document it in a note to file, as a way of signposting that they found the issue before the inspector did. While notes to file can be helpful tools, used sparingly, to explain a situation that would not be readily apparent from the available documentation, they serve no point if they highlight an issue without any solution. It's a better use of time to generate a deviation and develop a CAPA plan to address the issue according to the prevailing SOP. If your SOPs don't cover GCP deviations and CAPAs, see the last bullet point in the previous section
Most teams start preparing a year before their first inspection. It's a long road with lots of other things going on: don't waste effort on activities that will add little value.
Denise DeRenzo Lacey, RQAP-GCP, has over twenty years’ experience in clinical Quality Assurance and clinical development operations. Her practice focuses on application of quality risk management techniques for clinical studies, including risk-based approaches to auditing, data quality and integrity, and SOP development. She has provided consulting services to a wide range of pharmaceutical, medical device, biotech and CRO clients in the US and Europe and has held senior positions at Vertex Pharmaceuticals and Radius Health.