A New Guideline is published from ECA called Contamination Control Strategy (CCS). It is the aim of this Guideline to support industry with the implementation of this important requirement.
Moreover, ECA would like to invite representatives from regulatory authorities and inspectorates to discuss the proposals made in this Guideline document in order to support harmonisation.
The latest draft of the revision of EU GMP Annex1 contains the following statement:
"Contamination Control Strategy (CCS) - A planned set of controls for microorganisms, pyrogens and particulates, derived from current product and process understanding that assures process performance and product quality. The controls can include parameters and attributes related to active substance, excipient and drug product materials and components, facility and equipment operating conditions, in- process controls, finished product specifications, and the associated methods and frequency of monitoring and control."
This is the first time that an overview strategy is required for the area of contamination control that links the various aspects of contamination control and associated measures, records the interactions and facilitates a corresponding analysis for gaps in the system.
This can be used in existing companies to meaningfully record, coordinate and supplement existing measures or, in newly emerging facilities, to coordinate the implementation of the necessary contamination control measures across departments.
The ECA Guide contains a 3-stage-approach to achieve CCS readiness -
Stage 1: Development (or review and refinement/improvement) of the CCS
State 2: Compilation of the CCS documents
Stage 3: Evaluation of the CCS
This document is intended to provide guidance for two possible cases:
1. For a new plant, new equipment, e.g., for:
- Mapping of the manufacturing processes to identify possible sources of contamination.
- Carrying out a risk assessment to evaluate the risk of contamination.
- Establishing preventive measures and their controls in a holistic system (including the definition of responsibilities).
- Assessing and managing the residua lrisk of contamination.
2. For an existing facility that has already carried out a risk assessment, e.g., for:
- Evaluation of existing contamination control measures
- Analysis and overview of possible gaps
- Risk assessment and, if necessary, the addition of further measures and integration into the overall system (including determination of responsibilities)
- Managing the residual risk of contamination
The ECA offers this Guideline document at no costs for all colleagues in pharmaceutical industry and authorities.
Table of Content (of a suggested template)
0. Introduction
0.1. Objective
0.2. Definitions and Abbreviations
1. Design of both, the plant and processes
1.1. The Processes
1.1.1. Terminally Sterilized Products
1.1.2. Aseptic Manufacturing
1.1.3. Low Bioburden Processes / Bioburden-Controlled Processes
1.2. The Plant
1.2.1. General
1.2.2. Terminally Sterilized Products
1.2.3. Aseptically Manufactured Products
1.2.4. Low Bioburden Processes / Bioburden-Controlled Processes
2. Premises and Equipment
2.1. Premises
2.2. Equipment
For major equipment, consider making reference to the SMF – or copy from SMF
3. No. 3 is empty – left out - in Annex 1 Draft
4. Personnel
4.1. General
4.2. Gowning Requirements
4.3. Clean Room Clothing
4.4. Personnel Monitoring
5. Utilities
5.1. Water
5.1.1. Purified Water
5.1.2. WFI
5.2. Steam
5.3. Gases
5.3.1. Product-contact-compressed air (direct or indirect product contact)
5.3.2. N2
5.3.3. CO2
5.3.4. O2
5.3.5. Further Gases
6. Raw Material Controls – including in-process controls
6.1. Raw Material (Starting Material) Controls
6.2. In-Process Controls
7. Product Containers and Closures
8. Vendor approval – such as key component suppliers, sterilization of components and single use systems (SUS), and services
8.1. General processes
8.2. Detailed information regarding vendors
9. For outsourced services, such as sterilization, sufficient evidence should be provided to the contract giver to ensure the process is operating correctly
9.1. General processes
9.2. Detailed information regarding suppliers
10. Process Risk Assessment
11. Process Validation
12. Preventative maintenance – maintaining equipment, utilities, and premises (planned and unplanned maintenance) to a standard that will not add the significant risk of contamination
13. Cleaning and Disinfection (Decontamination and Sterilization)
13.1. Equipment
13.2. Clean Rooms / Clean Areas
13.3. Clean Room Clothing
14. Monitoring Systems - including an assessment of the feasibility of the introduction of scientifically sound, modern methods that optimize the detection of environmental contamination
14.1. General Procedures
14.2. Monitoring of Systems
14.2.1. Water and Steam
14.2.2. Clean Rooms
14.2.3. Gases
14.3. Personnel
15. Prevention – trending, investigation, corrective and preventive actions (CAPA), root cause determination, and the need for more comprehensive investigational tools
16. Continuous improvement based on information derived from the above
17. Further relevant aspects – e.g. about viral safety
Developing a CCS must be based on an in-depth understanding of the specific processes and products, fundamental and scientific know-how in sterile manufacturing, QRM, and contamination control.
Fundamental requirements are laid down in numerous guidelines, regulations, codes and standards, and technical reports, which outline state-of-the-art approaches.