Your Contamination Control Strategy (CCS) is the foundation of your cleanroom. This is where you plan how to avoid contamination, what to do in the event there is a breach, and prove that you have done your homework.
For too many years, a CCS has been an afterthought. The cleanroom was developed, protocols put in place, and segmentation decided on before the CCS was haphazardly put together based on these separate establishments. Now, though, regulatory authorities are putting an emphasis on CCS – and, more importantly, developing your cleanroom around the CCS instead of the other way around.
GMP Annex 1 And Your CCS
For example, the European Union (EU) Good Manufacturing Practice (GMP) for Medicinal Products for Human and Veterinary Use – Annex 1, commonly referred to as GMP Annex 1, published an update in 2022 that shows the shifting emphasis to incorporating CCS into the design and function of your cleanroom.
While Annex 1 is technically only guidelines for pharmaceutical organizations, the standards are applicable to most all cleanrooms and are worth familiarizing yourself with. Its infrastructural approach to Quality Risk Management (QRM) through a detailed and extensive Contamination Control Strategy (CCS) highlights the importance of documentation and personnel knowledge. While it focuses on getting humans out of the cleanroom wherever possible and automation to avoid contamination, it still emphasizes a reliance on and documentation of their knowledge and reasoning behind their choices, as well as more training and more detailed gowning procedures.
Developing Your CCS
Ideally, your CCS would be created or revised when you are making major adjustments to your cleanroom, or developing a new one. This would allow for the ultimate integration of the CCS into the development and infrastructure of the cleanroom. If you are part of the population who only has until August 2023 to come into compliance with the GMP Annex 1 update, this might be a season of transition. For many, though, this is not a feasible reality and you will not be massively changing your cleanroom and, instead, building a CCS around an existing cleanroom and set of protocols.
According to Siegfried Schmitt, vice president, Technical at Parexel, when developing your CCS you should take 3 steps: define, position, and establish.
You can start your CCS by defining its scope. This scope should include sterile products and/or any products or ingredients that require bioburden control. You should also identify potential contaminants that would affect efficacy, sterility, and quality, and, in compliance with GMP Annex 1, their potential source.
This is the definition of what the CCS will aim to achieve: controlling specific contamination.
Next, you will want to position the CCS relative to your process and facility design. According to Schmitt, “The CCS will be related to the site master file and the site’s pharmaceutical quality system (PQS), as well as the life cycles for the products manufactured on site.”
Finally, you’ll want to establish your CCS’s structure. Normally, you will have a Site Master CCS which covers the whole facility, along with a number of more specific CCS documents addressing area and product specific needs.
What Should You Include In Your CCS?
When you’re developing the details of your CCS, you will need to include anything related to contamination. This includes:
- Airflow strategy.
- Filtration strategy.
- HVAC, heating, and ventilation systems.
- Gowning protocols.
- Material storage.
- Personnel flow.
- Material flow.
- Facility design.
- Equipment design.
- Process decision.
- Process controls.
- Preventative maintenance.
- Cleaning and disinfection.
- Outsourced activities.
Essentially, anywhere that contamination can get in and affect the product, you need to create a plan for managing it. GMP Annex 1 dictates that process, equipment, and product knowledge should play a heavy role in developing the CCS.
Beyond the technical control measures that impact process, product, and risks, you should also include organization and control measures based on quality risk management. For example, there should be protocols and plans in place in the event of contamination, including your response, mitigation, and corrective measures.
Documenting Your CCS
You will want to keep written documentation of your CCS, as well as proof of compliance. This is easier to do with more modern equipment that helps you track information in accordance with regulatory requirements. Even with the equipment, you will want to ensure you follow data integrity standards, like ALCOA+.
ALCOA+ is the FDA’s definition of data integrity. It stands for:
- Attributable: The person who recorded the data should be clear, including a signature and date.
- Legible: Data should be easily and clearly understood, including an explanation for any symbols used.
- Contemporaneous: Data should be recorded immediately.
- Original: Only original or a certified copy of the data should be included.
- Accurate: Data should accurately reflect the situation or observation.
- Complete: Records should include everything, such as testing and re-testing.
- Consistent: Data generation should be consistent and time stamps should be sequential.
- Enduring: Data should only be recorded using invalidated electronic systems (or, if unavailable, controlled worksheet in laboratory notebooks).
- Available: Record of the data should be readily available for review and audits for the lifetime of the record.
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