5 Top Tips on Qualification & Validation – Avoiding Common Pitfalls

Article By Michelle Yeomans, EPiC Operations Manager

Here at EPiC, our consortium of pharma compliance consultants includes engineering expertise, with experience of successfully completing a wealth of EU GMP Annex 15 compliant engineering projects. 

At EPiC’s GMDP symposium November 2024, Mark Thompson, Pharmaceutical & Engineering Consultant highlighted common pitfalls encountered during the qualification and validation of GMDP premises and equipment and offered practical advice of how these can be avoided.

Mark explained that companies focus on the main qualification stages described in EU GMP Annex 15, but often do not consider additional guidance such as ISPE and GAMP to apply appropriate stage gates to manage the project chronology, and often waste time qualifying things that have no impact on product Critical Quality Attributes (CQA).: 

Drawing from the knowledge shared by Mark Thompson during his insightful presentation, here are our top tips for performing qualification and validation activities that can help you add value rather than just generating paperwork:  

1. Implement a ‘Before Order’ Stage Gate – Ensure time is built into the project plan for the upfront work necessary to understand what it is you are going to order, to enable you to perform a system impact assessment using ICH Q8, GAMP and Data Integrity guidance. This will help you to understand the risks associated with the equipment or system and the impact on the critical process parameters (CPPs) and critical quality attributes (CQAs) of the product. This work is essential to inform the development of the User Requirement Specification (URS) and should be completed upfront before an order is placed to avoid the time and cost of trouble shooting quality and reliability issues later down the line.

2. Focus on the critical – When the equipment or system design is poorly understood, time and effort can be wasted by attempting to qualify every aspect of the equipment and or process, however it is only direct impact systems that require qualification. You can use the output from the system impact assessment completed during the ‘Before Order’ stage gate and Design Qualification (DQ) to understand and differentiate which aspects are critical. Without the differentiation everything is critical, and you will be wasting time, effort and cost qualifying equipment and system component parts that have no direct impact on product quality and patient safety.  

3. Evidence of Compliance –There is a common misunderstanding that qualification testing needs to be witnessed or verified by a second person to provide evidence that compliance has been met. EU GMP Annex 15 requires there to be systems in place to ensure confidence in the data, but there are better ways of enabling this than witnessing e.g. printouts from qualified systems, independent measurements from calibrated equipment, by auditing the equipment or system supplier to give confidence in supplier data, or documented competency assessment/training records of qualification personnel.    

4. Knowing the value of Commissioning – Commissioning provides the opportunity to acquire knowledge of the CQAs, CPPs and how limits of CPP are going to be established and challenged, and yet most project plans do not include time for commissioning. Once there is an understanding of how the equipment or system works, commissioning helps to understand the impact of varying parameters using trial runs to see if good results are still achievable and to identify “worst case” conditions where results are compromised. This enables the upper and lower operating limits to be determined. Whilst qualification provides evidence that something is going to do what it’s going to do, commissioning gives confidence that it is going to do it reliably and that the settings have been optimised to maintain quality based on an understanding of “worst case” conditions so that limits are set away from the edge of failure.      

5. Maintaining the Qualified State – This relies on much more than performing a regular requalification which is just a snapshot of performance at the time. It is much better to draw on information from an integrated approach to qualification, which provides confidence based on having established a well-designed system operating within its limits, and with those limits being monitored and alarmed. Maintenance also plays a big part in maintaining the qualified state and a documented maintenance plan should be established that follows the equipment manufacturer’s recommendations, with any exceptions justified. The output from the risk assessments you have conducted during the qualification process and expertise from subject matter experts should also be built into the maintenance plan to ensure continued optimal performance as equipment gets older, e.g. availability of spare parts may result in the need to repair rather than replace.     

Although qualification and validation activities are an essential GMDP requirement, the focus should be on identifying and qualifying those aspects critical to product quality to ensure activities are value-adding and not just a box-ticking exercise .

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