The Annex 1 is being enforced. Do your CCS program in place?

Read our blog regarding implementing a robust Contamination Control Strategy (CCS)

In 2015, the European Medicines Agency (EMA) and the Pharmaceutical Inspection Co-operation Scheme (PIC/S) announced their plan to revise Annex 1, which pertains to the manufacturing of sterile drug products. The main objective of this revision was to enhance contamination control practices for sterile products and emphasize the use of modern quality risk management (QRM) systems, as mandated by Good Manufacturing Practices (GMPs). After a lengthy period of seven years and twelve drafts, the much-anticipated revision was finally released in August 2022.

Contamination control plays a crucial role in biomanufacturing as it minimizes the risk of process contamination and improves operational efficiency. Annex 1 focuses on establishing and implementing effective practices to mitigate contamination risks through a structured risk strategy. The recommended approach for this process is the adoption of a Contamination Control Strategy (CCS), which involves managing processes, equipment, facilities, and manufacturing activities in line with QRM principles. The CCS serves as a proactive method to identify, scientifically assess, and control potential risks to product quality. Implementing the CCS throughout the facility enables the identification of critical control points and evaluation of the effectiveness of all controls (including design, procedural, technical, and organizational) and monitoring measures employed to manage contamination risks.

A well-designed CCS should prioritize the following areas:

  1. Environmental Monitoring: Conducting regular testing of the facility and equipment to ensure that contamination levels remain within acceptable limits. This includes monitoring the air, surfaces, and water for potential contaminants.
  2. Equipment Design and Maintenance: Designing biomanufacturing equipment with contamination control in mind. This involves employing closed systems and implementing appropriate maintenance and cleaning protocols to prevent contamination.
  3. Raw Material Control: Exercising strict control over raw materials used in biomanufacturing to minimize the risk of contamination. This includes sourcing from validated and qualified suppliers and testing raw materials for microbial and other types of contamination.
  4. Process Control: Monitoring the biomanufacturing process to ensure it operates within established parameters. This entails monitoring factors such as temperature, pH, and other relevant parameters to ensure the process functions as intended.

The question remains, are you prepared to implement this CCS approach?

This contamination prevention strategy should encompass all potential sources of risk and variability, including human factors (personnel), technological aspects (equipment), material components (supplies), procedural methods (processes), and the manufacturing facility environment (cleanroom). All these factors must be managed with a deep understanding of their purpose and the interdependencies and overall impact of all the preventive measures taken collectively.

At Genesis, we recognize the significance of process and facility attributes in implementing a CCS. Our approach begins with a comprehensive risk assessment using established hazard control analysis principles. By analyzing facility design, equipment layouts, process and personnel flows, and day-to-day operational strategies, manufacturing enterprises can identify potential sources of contamination, assess associated risks, and develop appropriate control measures.

Through our experience with numerous CCS development projects, we have learned that the strategy must drive continuous improvement and yield tangible results. It should not be a static document but should be periodically reevaluated and adjusted as needed. By analyzing process, utility, and environmental monitoring data trends, as well as considering revisions to the overall facility design, valuable insights can be gained regarding the effectiveness of the CCS. Through proper analysis of risk assessment data, an effective CCS empowers our customers to focus on product-specific elements without the risk of sharing confidential information during the process.

Implementing a CCS is not a one-size-fits-all endeavor. It requires a cross-functional team of experts with proven proficiency in manufacturing, QRM, and regulatory practices. This is where the Genesis team can collaborate with your in-house experts to develop a robust strategy, whether it’s in the early stages of conceptual development or an ongoing evaluation aimed at enhancing contamination control efforts.

Are you in compliance? If not, read on. Showing the right path forward is key. Demonstrate that you have fully evaluated the requirements, performed a gap analysis, and that measures to address any gaps are now underway. EMA expects that these gaps have been tackled, especially for those considered critical. If not, an inspector will issue an observation and the renewal of your GMP certificate will depend on the impact (risk) of these observations on quality and sterility of your product. However, as long as you show that proactive work is ongoing regarding your contamination control strategy and appropriate risk-based measures, inspectors are likely to be satisfied and simply make a note to closely monitor progress and final delivery of compliance.

Let Genesis’ CCS experts help you pave the way.

Read our Contamination Control Strategy (CCS) White Paper  and contact us for a consultation.

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About Genesis AEC

Genesis AEC – an award-winning consulting, architecture, engineering, and construction management firm – has partnered with life sciences companies for more than 25 years to complement the scientific expertise of our clients as they usher in the next generation of life-saving therapies, treatments, and technologies. Whether it’s providing AE support for existing sites; commissioning, validation, and qualification (CQV) for specific processes or equipment; or turnkey design-build solutions, our team blends sound science and technical expertise with quality assurance and safety measures to deliver unparalleled results.