From HVAC and Facility design to Contamination Control Strategy Management

The update of the Eudralex Annex 1 (EUGMP) is coming soon and many companies of the health sector are already trying to prepare for it. In this update, Contamination Control Strategy appears to be a key concept to improve sterility insurance. But is it really a new approach? Do pharmaceutical companies need to start from scratch to be compliant with it? What are the roles of facility and HVAC on this subject?

In this article you will discover first level advisement to accompany your customer or your company on their journey to Annex 1 compliance.

Control Contamination Strategy Meaning

Let’s start with baseline requirements for room classification. The specifications about number of particles per size won’t change and remain as:

First good news for pharma industries, as long as their environmental monitoring system is under control, they can make a reference to it into their CCS. In any case, it is a good opportunity to challenge the risks and the way rooms are monitored.

Nevertheless, contamination is not only a matter of particles even if they are the main vector for shipping virus, bacteria or fungi. Shortly linked to it, presence of human or any other living beings represents another high risk of contamination, so it is important to highlight in the CCS how to handle them and find solution to move them away as much as possible. Creating barrier as using isolator or RABS (Restricted Access Barrier System)  is clearly highlighted in the annexe 1 (which is quite rare to get a solution described in the GMPs). On the other hand, using such equipment is not mandatory and getting a clear and factual rationales showing (with data) that contamination risks are under control is fully possible, probably more and more challenging but possible.

Second good news for pharma industries, they don’t necessarily need to change their main equipment, but they need to think objectively how new technology could help monitor and control the contamination risks. The recommendation would then be to perform and formalise technology watch and to include conclusion as part of the CCS. This is clearly a key aspect of a global continuous improvement strategy.

Moving the process in a fully closed system sounds quite impossible, so the way the building is designed and the way the HVAC system is functioning are also key on this battle and must be included in the CCS. 

How to build a CCS

The PDA (Parenteral Drug Association) developed an approach to describe a CCS roadmap by following a step-by-step tool: Contamination Control Strategy: Implementation Road Map | PDA Journal of Pharmaceutical Science and Technology (paid article).

According to the PDA approach, inputs above and to move forward in a global approach, here is a flow to determine the CCS. 

As mentioned above, to design the facility, process specification and constraints must be taken into account. Indeed, it is not always required that the pressure cascade comes from grade A to lower grade. It is sometimes more important to secure outside environment like in industries that handle radioactivity. In that kind of industry, cascade is reversed to preserve people and environment.

In addition, don’t minimize the importance of pest control in the strategy, nor the cleaning procedure.

Third good news for pharma industries, this flow is most likely already applied in each process, the task will then be to combine all the risk analysis, thinking globally and put them into the CCS.

For a new facility, it requires starting from scratch about the definition of the strategy to control contamination, meaning that it puts the concept of Quality By Design on top of pre-requisites because it will clearly help to combine process needs and constraints to technical solutions and building design.

Application of annex 1 on building and HVAC (non-exhaustive):

• Segregate material flow in, material flow out and human flow
• Pressure differential between rooms
• Air recirculation with filters
• Angles removal on floors and roof
• Floor material & design
• Shape of lamps/electrical sockets
• Installation of HVAC equipment
• Design of technical area: access for maintenance and cleaning
• Pest control strategy
• Building maintenance & cleaning
• …

Conclusion

Pharmaceutical industry has already all the tools to implement a robust Contamination Control Strategy. It needs to break down all potential silos between departments for developing a global view on the whole production steps and way to monitor processes in terms of contamination.

By starting the CCS from process and factory design, facility has obviously a key role to play. Design of the building, handling of flow, choice of materials to be applied are all essentials for being included in the CCS.

CCS is not only a question of barriers, but also a matter of monitoring and continuous improvement, matter of trending, matter of maintaining, matter of process robustness, matter of process knowledge…