EU GMP Annex 1 Volume 5: Taking a Best Practice Approach to Contamination Control 

Contamination control has come to dominate conversations around implementation of the revised European Union’s Good Manufacturing Practice Annex 1 (EU GMP Annex 1). 

Although the updated guidance is collectively designed to enhance the overall production and packaging of sterile medicinal products to protect public health, the practical realities of establishing a contamination control strategy (CCS) have been something pharmaceutical manufacturers have grappled with since the guidelines came into effect in August 2023. 

The previous blog in this series focused on how West has aligned its own operations for EU GMP Annex 1 compliance, embedding a focus on contamination control across our business to ensure our manufacturing operations satisfy the same regulatory demands faced by industry partners. More specifically, we explained how our efforts have been guided by a comprehensive plan that focused on the four key pillars of people, communication, process and continuous improvement. 

These experiences have provided West with an internal framework for effectively addressing contamination control, but they have also provided broader and deeper insights into the challenges associated with the application of EU GMP Annex 1 requirements. We know that, ultimately, the responsibility for compliance sits with pharmaceutical manufacturers, and our ambition is to provide best-practice support in critical areas as a key supply-chain stakeholder with the potential to influence the effectiveness of a partner’s own CCS. 

Described in simple terms, contamination control depends on the management of a web of interconnected manufacturing processes. The CCS incorporates all these elements into a holistic plan, providing a roadmap that sets out a clear direction. The overarching goal is to work towards a state where manufacturing controls in all areas are optimised to limit – or ideally eliminate – contamination risk.

Across the various areas that influence manufacturing output, many individual strands must be managed. Consider, as an example, all the process controls associated with the production of elastomer vial stoppers. Here, raw materials are subject to incoming controls before further controls are applied for mixing, dimensioning, molding, coating, and trimming. Components also undergo a final release testing control prior to shipping, with the potential for this stage to be carried out following steam sterilization for products being deployed directly into a cleanroom manufacturing environment. 

The extensive nature of these product-related process controls highlights the complexity of the challenge involved in implementing best-practice when it comes to contamination management, particularly since this approach must be extended to manufacturing controls covering personnel, equipment, facility, suppliers, and environmental factors. Clearly, adopting an optimised approach across all these areas within a holistic CCS is not something that can be achieved with the flick of a switch. That is why, at West, we have adopted a three-step strategy for evolving the manufacturing base towards a desired future state where knowledge and risk management are integrated together for continuous improvement. 

In the initial foundational phase of this model, emphasis is placed on stabilization and standardization, effectively establishing a robust platform that can continue to be built upon into the future. A key activity here, given the influential role played by personnel, has been the provision of behaviour training to support upskilling in relation to global contamination control. In addition, harmonization measures were adopted in areas such as gowning, pest control, and cleaning and disinfection to provide a consistent quality-driven approach. 

In the second phase of the model, focus is applied to the use of data analytics. Here, the digitization of processes and monitoring systems allows for more efficient data-gathering, which in turn enables knowledge systems to build up a more complex picture of the effectiveness of existing controls. At an immediate level, this close-level tracking can isolate where any gaps or weaknesses exist. Over time, however, deeper insights reveal themselves in the form of historic data trends and predictive indicators, guiding choices over where contamination-control efforts are best focused.

The final phase is achieved when knowledge systems and risk management are closely integrated, and the organization is collectively geared towards the goal of zero defects through continuous improvement. This relies partly on the skills of personnel, who are responsible for unlocking gains, however marginal. At the same time, greater use of automation and process standardization can deliver enhancements in consistency, and Quality by Design principles can inform ever higher standards in materials, processes and facility.

The successful transition to this final stage is more the product of evolution than revolution. It reflects the fact that EU GMP Annex 1 has demanded a complex and fundamental re-engineering of approaches to contamination control, in terms of operations, processes and systems as well as mindset and behaviours.

West’s own deep understanding of that challenge provides pharmaceutical manufacturers with the assurance of working with a trusted supply partner to enable the delivery of sterile medicinal products that are compliant with EU GMP Annex 1. Our clear framework and transparent approach to best-practice provides a strategically effective approach to implementing an effective contamination control strategy – for our own business, for our partners, and for patients reliant on sterile medicinal products for essential disease treatment.