How To Prepare For A GCP Inspection During COVID-19 (And Beyond)

It’s the one thing that everyone dreads, the very worst that could happen according to some, but then that day comes: notification of a good clinical practices (GCP) inspection by the FDA, MHRA, or other global regulatory authority.

Facing an upcoming inspection, in many people’s opinion, is perhaps one of the most stressful experiences when working in clinical trials. Whole swathes of the company switch from their day-to-day tasks, downing tools and priorities to prepare the Trial Master File (TMF) against impending doom (as others desperately try to book annual leave for the inspection duration), while random employees run amok like Corporal Jones from Dad’s Army shouting “Don’t panic!”

But how much of this stress is self-inflicted, and what strategies could be deployed to dissipate and better channel the nervous energy released when the inspector comes a-knocking? This article explores a few of the coping mechanisms for ensuring a smooth run-up to an inspection, as well as how new challenges related to COVID-19 could influence how inspection readiness is performed.

A Culture Of Preparedness

Many of us were Boy Scouts in our childhoods, yet when we grow up we forget that their motto is “Be Prepared.” How many of you reading this article are gnashing your teeth and wishing you’d made time to do certain tasks earlier, which, now that you are in lockdown, may not get done for a long time?

One of the ways to mitigate the impact of unforeseen events is obviously to do the above. It is often easier said than done in practice, as we face daily conflicting priorities, deadlines, and burning tasks that require our immediate attention and squeeze the time and energy available for more mundane activities such as TMF maintenance. Before too long, those mundane tasks can build up, especially if no one is shouting for them to be done.

Yet TMF completeness is an important task, and it is one that regulatory authorities like the MHRA increasingly cite as a recurring inspection observation. Routinely taking a little time from our busy schedules to do some housekeeping, while not sexy, could make a big difference in the long term in the event of an inspection. This is also especially important as inspectorates such as the FDA do not provide advance warning and may simply show up on the day of the inspection itself.

An alternate way of viewing the above is to consider how would we like our work displayed in a court of law, and could we defend our actions when asked to produce evidence? It is tempting to scoff at this notion as unlikely, but I experienced early in my career exactly that, when a TMF had to be sent off for one client who was in litigation. And as anyone who has watched the recorded sessions of the FDA advisory committee panel when they review filed IND submissions will know, circumstances where study activities are analyzed in depth can and do occur.

Leading From The Top

There is sometimes an incorrect perception that organizations need only focus on inspection preparation in periods after product submissions to the regulatory authorities occur, as some inspectorates such as the FDA are more likely to perform an inspection during this time. However, while this is partly true, it is also a red herring for several reasons. First, it sends the wrong message to the average employee that inspection preparedness is a lower priority task when compared against business objectives. And second, such an approach can do an organization more harm than good by overloading project team members with a deluge of housekeeping and preparation tasks in the short term, impacting their effectiveness in the long term and leading to burnout, further mistakes, and increased turnover of valuable personnel essential during an inspection.

The most important challenge for an organization is to ensure senior management engages and recognizes the need to remain inspection ready, especially given that unforeseen events, such as COVID-19, could occur that can rob their ability to act in a just-in-time manner. Adequate time and resources must be allocated to allow readiness activities to occur on an ongoing basis, and not just prior to an inspection itself. It cannot be solely the domain of employees to keep themselves up to date; senior management must actively drive this process as well to set an example.

One of the most effective managers I ever saw literally walked the office floor annually and asked employees what was stored in each cupboard, regularly netting a haul of hoarded documentation for processing. Therefore, the active buy-in of senior management in encouraging inspection readiness within organizations is key to ensuring functions are proactive rather than reactive when tackling inspections.

Practice Makes Perfect

Many large sponsors and contract research organizations have well-established quality management systems to monitor that work is performed to a consistent quality, including assurance functions to sample work output to verify adherence to standards. If such assurance organizations are given the correct remit, resources, and methodology to perform their function, an organization can be kept inspection ready in an incremental manner. This allows for different parts of the organization to be reviewed periodically in inspection-like conditions, while aggregation and comparison of assurance program results at a system level identify potential improvement opportunities.

Within the last few years, there has been an industry push to increase the amount of inspection readiness being performed. While such a desire is well intentioned, its execution is often deeply flawed in practice, potentially duplicating work or undermining the profile and work of established quality assurance functions, while also heaping housekeeping tasks on project teams busy winding up studies or even moving to new assignments.

In addition, as such work is often performed in the shadow of a looming submission, it may be too late in the day to effect any real change if issues are identified. The result may be to apply a metaphorical Band Aid to an imperfect job, which will only highlight possible issues for any visiting inspectorate. And lastly, as stated in the previous section, events might also overtake the ability of an organization to mount a coordinated inspection readiness drive for a specific purpose.

Organizational Stress-Testing

Specific inspection readiness activities can pay dividends in situations where an organization may lack inspection experience or where it may be advantageous to prepare an organization through exposure to an unfamiliar inspection type. These usually take the form of mock inspection activities, which can be tailored to include practice interviews through to full-blown mock inspections.

Mock inspection activities can have many benefits by stress-testing an organization in new and unforeseen ways to expose potential risks and weaknesses that require addressing. It is often desirable to bring in external contractors to lead mock inspection activities due to their wider experience and operational independence; however, it is important this is done with developmental purposes in mind, including engaging the internal quality assurance function, both to reinforce their remit as well as provide an opportunity to upskill and refresh their own quality assurance methodologies for use in future mock inspection activities.

Inspection Challenges In The COVID-19 Period

One newcomer to the inspection readiness discussion that we have already touched on briefly is how to remain ready in the face of the evolving challenge posed by the COVID-19 pandemic, as travel increasingly becomes unfeasible and organizations become more decentralized due to quarantine measures.

Global regulatory authorities are scrambling to adapt their inspection programs and ensure they do not grind to a halt in the medium to long term. In the short term, many inspectorates such as the MHRA are taking a risk-based approach by limiting their on-site inspection programs to focus on inspecting key actors involved in developing COVID-19 treatments and vaccines. In the medium to long term, many routine inspections may be executed in a more remote manner, which will put pressure on organizations to assess and ensure adequate technology and infrastructure exists to host inspections remotely and provide inspectors with virtual access to study documentation.

The current situation may also speed collaboration by travel-restricted inspectorates and could mean the performance of more hybrid inspections, making it more important to ensure an organization is prepared for multiple inspection scenarios and styles.

All this puts added emphasis on organizations to ensure their daily processes, procedures, and operations have inspection readiness baked into them from the start and that personnel are given space to place constant inspection readiness on a level equal to other operational priorities.

Conclusion — Forewarned Is Forearmed

It is clear there is great value in organizations striking a balance between operational priorities and performing ongoing housekeeping to foster a strong culture of day-to-day inspection readiness. This is particularly the case as the COVID-19 pandemic continues to strain organizations and restricts opportunities to assign precious additional resources purely for inspection preparation purposes.

However, the greater challenge within the wider industry as a whole is to encourage a sustained mind-set change within corporate management to move away from reactive compliance to proactive assurance to enable a constant state of readiness to be maintained. Rather than seeing the current COVID-19 pandemic as a hindrance to operations, industry leaders should seize the opportunity to break with past dogma and fundamentally refocus how their organizations approach inspection readiness in the future.

About the Author:

Iain Pulley, director of Closed Loop Quality, is a freelance GCP auditor with over 12 years of experience auditing both global pharmaceutical organizations and clinical trials. With a BSc (Hons) in product design, he is passionately process-oriented and places strong emphasis on ensuring quality management systems add value to achieve right-first-time results. Pulley has also successfully assisted and coached various organizations in preparation for receiving regulatory authority inspections. His interests in his spare time include skiing, woodwork, and wine-making. You can email him at  iain.pulley@closedloopquality.com and connect with him on LinkedIn.