Although much has changed in the landscape of clinical trials because of COVID-19, the framework of inspection readiness planning and activities remains the same. It is however crucial to understand how the impacts of COVID-19 play a role in our preparation activities. Our recent Halloran Speaker Series, “Inspection Readiness Framework and Impacts of COVID-19” broke down the elements of the Inspection Readiness Framework and focused on how to incorporate the impacts of COVID-19 into your preparations.
Organizational Readiness Assessments
An Organizational Readiness Assessment is a crucial first step of the inspection readiness framework. This assessment focuses on identifying gaps and risks to critical processes and data collected during the conduct of a clinical study. This allows organizations to have an overall understanding of the risks and mitigations that need to be put into place before a potential inspection. The resultant remediation activities will need to be performed by the organization for any gaps and/or risks that are identified during the assessment.
COVID-19 has caused this element of the Inspection Readiness framework to be more important now than ever. It will be crucial for sponsors to not only have awareness of the impacts of COVID-19 to clinical study elements (e.g. patient safety, impact to primary and secondary endpoints, changes to operational plans, protocol deviations, shifts in monitoring strategy, etc.) but also supporting documentation that will be able to adequately showcase how these impacts or risks were mitigated. It will be essential for sponsors to demonstrate how they re-evaluated the impact on patient safety and critical data and processes during the COVID-19 timeframe. This is an opportunity to leverage risk management tools such as an RACT so that you can document how restrictions related to COVID-19 changed the study conduct, the duration of those changes, which trial participants and/or sites were impacted, and how they were impacted.
Storyboard Activities
Storyboarding is an important activity that can be utilized as a part of an organization’s Inspection Readiness activities. Storyboards serve as useful training tools providing a strong framework for addressing complex or critical aspects of a study. Leveraging your organizational readiness assessment and risk assessment as a guide, you should be able to identify those key topics that may require additional details to adequately convey the story of your study. Storyboarding is the opportunity to create a narrative that can be used in preparation for an inspection so that everyone within your organization can consistently speak to complex topics with inspectors.
When it comes to addressing actions taken during COVID-19, storyboards are a useful way to create the narrative around the ways you evaluated and mitigated risks to patient safety as well as critical processes and data. It will be important for organizations to be able to clearly outline the actions taken during COVID-19 on the study, site, and patient level. Regulatory agencies like the FDA have made it clear that they are going to want to understand the contingency measures implemented to manage study conduct during the disruption of the study as a result of COVID-19 control measures. Understanding the differences in your processes pre and post COVID-19 and being able to convey how and why changes occurred will be a key determinant of the success of your inspection. It will also be important to speak to how you recommenced study activities post COVID-19 as it may look different by study, site, and patient. Creating a storyboard on how you are managing recommencement activities at the site and patient level is a great opportunity to show how you’ve continued to maintain control of your study during this pandemic.
Inspection Readiness Training and 1:1 Behavioral Interviewing Coaching
Conducting Inspection Readiness training and coaching your Subject Matter Experts (SMEs) are important parts of preparing your organization for an inspection. Taking the time to train your organization on the activities that occur before, during, and after an inspection as well as practicing interview skills in “real-life” settings allow your team to become more comfortable and are key to confidence during an inspection.
Depending on the timing of any potential upcoming inspection, training, and coaching. With the must now account for the possibility of a virtual inspection. It will be important to train your SMEs on the use of technology as well as virtual interviewing techniques. This will also provide the organization with an opportunity to become savvier with the logistics of a virtual inspection. Is your organization going to use virtual backgrounds during interviews? How are subject matter experts going to maintain appropriate body language and eye contact during a virtual interview? These are all important elements of an inspection that will need to be practiced ensuring comfortability and strong execution during an actual inspection.
Mock Inspections
Mock Inspections are a critical part of inspection readiness activities. It is an opportunity to gain an independent perspective on how you have interpreted and perceived your risks during the execution of your clinical study. It also allows your team to pressure test the logistical aspects of inspection so that processes can be tweaked accordingly (e.g. ready room logistics, hosting strategy, etc.). A common misconception around mock inspections is that they are an organization’s opportunity to identify gaps. While gaps can certainly be identified during a mock inspection it should not be the primary objective. There should be no huge surprises during a mock inspection if you performed a robust organizational readiness assessment at the front end of your inspection readiness activities. Typically, mock inspections are conducted as close to the actual date of inspection as possible so while there may be minor remediation activities that will occur after there should not be an overwhelming amount of work to be done a month before your inspection.
In thinking about the impacts of COVID-19, we know there is a possibility that inspections will be conducted remotely. This means organizations will need to account for the possibility of a virtual inspection during their mock inspection activities. Organizations will need to ensure that current inspection procedures are adaptable for use during a mock inspection or make updates accordingly. If your upcoming inspection has the potential to be conducted virtually, it will be important to have a plan that outlines how you are going to manage ready room logistics, subject matter expert preparation rooms, and the inspection room. This will be key in ensuring your team can smoothly transition to a virtual inspection. It has been noted that if the FDA performs a virtual inspection that they will be using WebEx for communications and BOX as a secure solution to receive electronic copies of documents requests, so it will be important to work out the logistical aspects of how these systems will be leveraged. As part of your inspection readiness activities, all documents should be digitized so that they can easily be made available to inspectors. The FDA is expecting that any scanned files provided are “certified copies” (this includes clinical site documents). This means they are assuming that a certified copy process exists and was used to when digitizing electronic copies and providing to the inspector.
Conclusion
In the short term, we know that regulatory agencies have limited inspections to those deemed “Mission Critical.” The FDA put out a statement on May 11th reiterating that they will continue to implement additional alternative inspection tools and approaches while postponing domestic and foreign routine surveillance inspections, and this will continue as local, national, and international conditions warrant. Mission-critical inspections will be identified on a case by case basis and conducted with appropriate safety measures. The FDA continues to collaborate with the CDC to develop a process to govern how and where inspections will return but this will likely be a phased approach driven by scientific data. The FDA and other regulatory agencies recognize that inspections are critical, but they are only part of a robust and multi-pronged approach. For inspections taking place onsite, FDA staff are wearing PPE and maintaining social distancing guidelines. This is something to consider for future audits and regulatory inspections, organizations, and sites will need to ensure the availability of adequate space to maintain social distancing.
As we explore the potential future of inspections post-COVID-19 it’s important to evaluate potential changes in inspection procedures that may be adopted by regulators. Regulatory agencies will put more emphasis on risk-based determinations for inspections and perform heavier due diligence before on-site inspections. We have already seen these practices adopted by the EMA. This is going to push organizations to achieve a constant state of inspection readiness. There is a high probability that regulatory authorities will continue to use virtual technology for inspections depending based on risk, so access to key systems (e.g. TMF, EDC) and documentation will need to be available electronically in a controlled and secure way. We also anticipate that information sharing across agencies will replace joint inspections as agencies begin to adopt similar inspection techniques.
In navigating through an inspection post-COVID-19 it is important to note that the Inspection Readiness principles remain the same, but the execution of these activities and focus on impacts (and documentation) during COVID-19 must take a priority. Depending on the timing of a potential inspection, preparation activities must include the possibility of a virtual inspection. As we continue to move forward as an industry it is important to note that changes required to adapt to the impacts of COVID-19 will be the impetus to changing the future state of inspections.