Five Steps to Inspection Readiness

Any regulatory inspection, whether it’s the first of the 50th for your organisation, is intensive and can be stressful.

My recommendation: Make sure you focus on inspection readiness even before your study starts. Or start now. Step in wherever you can. The sooner you start the better, but it is never too late.

1. Focus on “First Time Right”

Clinical trials usually need to start yesterday. However, who invests time upfront will definitely save time at the backend. A smart scientific and operational study design avoids unnecessary complexity, limits process or protocol amendments and reduces the extra administrative work resulting from errors and deviations.

Develop your processes and trials with quality objectives in mind:

• Take time to define what you really would like to establish with your clinical trial, and how;
•  Identify (potential) risks and how these risks may be mitigated (see also GCP (ICH E6 (R2) 5.0));
•  Create procedures which build quality into the processes (“Quality by Design”).

Do not only involve representatives from different disciplines in your organisation, but also involve investigators, vendors and suppliers, and, where possible and relevant, patients or patient organisations.

The recently implemented revision 1 of ICH Guideline E8 on general considerations for clinical studies (ICH E8 (R1)) puts emphasis on what has been mentioned above. If you are struggling with the principles of Quality by Design and you are looking for examples of critical to quality factors, have a look at the website of the Clinical Trials Transformation Initiative, Quality By Design – CTTI (ctti-clinicaltrials.org), and also open the principles document which you can find on their website.

2. Focus on Continuous Improvement

hile quality by design may be the best approach to ensure regulatory compliant, efficient and good quality processes, remain focused on opportunities for improvement.

Learn from mistakes or (near) mishaps. Quality control, compliance checks and independent audits will help your organisation to stay on top of things. A good issue management system, including robust root cause analyses and with timely completion of corrective and preventive actions (CAPAs), will help you to work on further improvement of processes and first time right, which will certainly give a regulatory inspector the confidence that your organisation takes care.

3. Create the right organisational culture

A quality culture (and not a culture of quality, in my view -about that in a next blog-) contains those elements that should or will sustain the employee’s intrinsic motivation to show continuous quality and compliance behaviour. Those elements may be explicit (procedures and activities) or implicit (values, behaviour and attitude).

An important aspect is to create an environment of trust and respect, in which individuals are encouraged to speak up and continue to think critically. See also ICH E8 (R1).

In future blogs I will share more about quality culture and the research I have done on elements of a quality culture. It should be clear though that a quality culture contains many different elements and it will take time and efforts from individuals across the entire organisation to build, but hopefully less to sustain, such a culture.

4. Don’t just train: Create awareness

Per GCP (ICH E6 (R2) 2.8), “each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective task(s)”.

Still too often training of procedures, regulations etc. is done through sharing the “what” and the “how”, but seems to be missing the “why”. More than ever, the diversity of clinical trials cannot afford a “one size fits all” approach, so trainees need to understand why things should be done as instructed. In addition, they should be encouraged to share best practices and suggest opportunities for improvement. Critical thinking is key in the current, complex and everchanging clinical research environment, and is part of a mature quality culture.

5. Make sure your organisation is ready

I was hesitating to add step 5, since study files and study teams should always be inspection-ready, right? Although that is true, there is so much to deal with prior to and during an inspection. Even though each inspection is different and lots depends on whether it is remote or on-site, it is good to have procedures or even some kind of script in place so everyone knows how things will be organised.

Consider a mock inspection to see where things in your organisation can be improved. Build in moments to reflect. In my experience mock inspections can be great learning opportunities.

Are you organising mock inspections or inspection readiness visits when an inspection is announced? Avoid extensive audit-like activities, as they can only increase the pressure on individuals. Focus on the organisation and preparation of inspectees. Are all documents readily available (is the TMF complete?), do you have the right individuals in the room, can they explain their role, can they describe what happened in the clinical trial and will they show the right documentation? Work as a team and accept that mistakes can happen, as long as actions are taken promptly to limit the consequences and to prevent recurrence.