NEW VERSION OF EU ANNEX 1

NEW REQUIREMENT: CONTAMINATION CONTROL STRATEGY (CCS) (Part-2)

Annex 1?requires designing an effective?contamination control strategy (CCS)?based on?a scientific assessment?to understand the process and to apply?risk management principles. The latest Annex 1 frequently uses the terms “risk” “justify” and “strategy”, underlying the importance of these concepts.

●??????A documented, facility-wide CCS is now expected.

●??????A CCS is a holistic program that encompasses design, procedural, organizational, technical control measures and the monitoring measures employed to manage risks to product quality and safety. Requires the microbiologist to think more holistically

●??????Intended to provide robust assurance of contamination prevention.

●??????A Contamination Control Strategy (CCS) should be implemented across the entire facility to Define all critical control points

●??????Assess the effectiveness of all the controls and monitoring measures used to manage contamination risks

●??????The CCS should be actively reviewed and updated and drive continuous improvement.

●??????The CCS should consider all aspects of contamination control with ongoing and periodic review.

●??????Updates within the quality system should be made as needed and as appropriate.

●??????Any changes to the systems in place should be assessed for any impact to the CCS both before and after implementation.

●??????The manufacturer should take all steps and precautions required to ensure the sterility of its products.

●??????“Sole reliance for sterility or other quality aspects should not be placed on any terminal process or finished product test.”

●??????Where existing control systems are in place and are appropriately managed, these may not require replacement but should be referenced in the CCS.

●??????THE COLLECTIVE effectiveness of all contamination control steps and measures should be considered together.

●??????The associated interactions between systems should be understood.

James Reason’s “Swiss Cheese” Model

●??????The “Swiss Cheese Model of Accident Causation" was developed by Professor James T. Reason at the University of Manchester about 25 years ago.

●??????Each slice of cheese represents a system component.

●??????The holes in the Swiss cheese represent weaknesses of system components.

●??????In most cases, each component compensates for the weaknesses of another, and covers the holes.

●??????Where the holes align, the system fails.

●??????Elements to be considered within a CCS should include (but are not limited to):

1. ?? Design of both the plant and processes including the associated documentation
2. ????Premises and equipment
3. ????Personnel
4. ????Utilities
5. ????Raw material controls – including in-process controls
6. ????Product containers and closures
7. ????Vendor approval
8. ????Management of outsourced services and availability/transfer of critical information between parties
9. ????Process risk management
10. ????Process validation
11. ????Validation of sterilization processes
12. ????Preventative maintenance (planned and unplanned maintenance)
13. ????Cleaning and disinfection
14. ????Monitoring systems, including assessing feasibility of scientifically sound, alternative methods for optimal environmental contamination detection.
15. ????Prevention mechanisms
16. ????trend analysis
17. ????investigation and root cause analysis,
18. ????including the use of comprehensive investigational tools
19. ????corrective and preventive actions (CAPA)
20. ????The information gathered from the mentioned areas should be used to drive continuous improvement.