Contamination Control Strategy - Step-by-step guide to understand and achieve compliance with the new regulatory requirement
Introduction:
Current version of GMP guidelines for different regulatory bodies mention the requirement of having a contamination control strategy for manufacturing of sterile products. A conflict may arise about how to issue, design and develop an effective contamination control strategy. Through the following points we will discuss this issue in details wishing to have a clear understanding of the concept, regulatory bodies requirements, design of effective CCS, implementation steps, then continuous development.
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Firstly, let us see how CCS appeared and developed in current regulations.
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In 2017, the first draft revision of Annex 1 of the EU GMP Guideline was published to mention contamination control strategy as a requirement, this first draft version resulted in more than 6,000 comments in the public consultation. After ?a detailed review, a second draft was published in February 2020. But the final version of Annex 1 was published in 22 August 2022. The deadline for coming into operation of Annex 1 is 25 August 2023, except for point 8.123 which is postponed until 25 August 2024.
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So, in Annex 1 of the EU GMP Guideline; it was the first time to introduce the terminology of Contamination control strategy (CCS) which was mentioned about 51 times.
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On 1st February 2022; Pharmaceutical Inspection Co-operation Scheme (PIC/S) published “Guide to Good Manufacturing Practice for Medicinal products (Annexes) with Document No.: PE 009-16 (Annexes) which also included the importance of having a robust contamination control strategy.
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On 22nd December 2022; WHO Expert Committee on Specifications for Pharmaceutical Preparations published Technical Report Series 1044, annex 2; which is a revision of WHO good manufacturing practices for sterile pharmaceutical products, previously published in the WHO Technical Report Series, No. 961, Annex 6, 2011. The revision was done in collaboration with the European Union and the Pharmaceutical Inspection Co-operation Scheme (PIC/S). in this annex Contamination control strategy was mentioned several times (about 49 times) to highlight the importance of having an effective and robust contamination control strategy.
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What does CCS look like?
Contamination Control Strategy is an holistic, systematic set of control mechanisms which act together to provide a high degree of assurance of elimination of contamination in finished product.
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No clear guidance yet available on content requirements. So, CCS Could be a stand-alone document, like a validation policy or may form part of a high-level document – e.g. Site Master File, Quality Manual.
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Actually, majority of organizations will already have many of the elements of a CCS, but may not be gathered together through a single document, or not linked together in a way that show how this documents integrated with each other to control contamination during manufacturing of sterile pharmaceutical products.
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Some organizations already have documented evidence how they control contamination in their facility either in a form of SOP or QRM study. But it may not contain all aspects which should be included.
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What should be included in Contamination Control Strategy?
Subjects to be considered within a CCS should include (but are not limited to):
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The key purpose of a CCS is allowing assessment of the strategies, controls, processes and systems implemented through ongoing effectiveness evaluation and correction.
Is Contamination Control Strategy (CCS) is a requirement for manufacturing of sterile medicinal products only?
There is no model answer for this question, we can’t easily select “Yes” or “No”.
Although it was mentioned in guidelines related to sterile manufacturing “including but not limited to guidelines mentioned under introduction section”. But same guidelines stated that it may be used to support the manufacture of other products that are not intended to be sterile such as certain:
-????????Liquids.
-????????Creams
-????????Ointments
-????????Low bioburden biological intermediates.
and where the control and reduction of microbial, particulate and endotoxin/pyrogen contamination is considered important.
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In this case, where a manufacturer decides to apply guidance in this document to non-sterile products, the manufacturer should clearly document which principles have been applied and acknowledge that compliance with those principles should be demonstrated with a documented evidence.
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How to develop effective Contamination control strategy?
I recommend to have a CCS in a form of high level document (like SMF), and should include clear definition for the following:
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? Qualification and Validation reports
? Maintenance programs (including calibration programs)
? Monitoring and controls plans (e.g., IPC, QC release instructions)
? SOPs
? Master batch records, product specifications, and release specifications
? Raw or starting material specifications?
? Design of both the plant and processes.
? Premises and equipment.
? Personnel.
? Utilities.
? Raw material controls.
? Product containers and closures.
? Vendor approval.
? For outsourced services, such as sterilization.
? Process risk assessment.
? Process validation.
? Preventative maintenance – maintaining equipment, utilities and premises (planned and unplanned maintenance).
? Cleaning and disinfection.
? Monitoring systems
? Prevention controls; e.g. trending, investigation, corrective and preventive actions (CAPA), root cause determination and the need for more comprehensive investigational tools.
? Continuous improvement based on information derived from the above.
? Pest Control
? Aseptic Process Simulation
? frequency of reviewing ?
? Monitoring results
? Trending results and reports where applicable for each subject.
? Complaint management and complaints related to potential contamination during manufacturing, e.g., foreign particulates.
? Follow-up for any actions required
? Escalation to top management any arising subjects (e.g. to be discussed during management review)
?Conclusion:
In my opinion, Contamination control strategy as a new requirement of GMP for manufacturing of sterile pharmaceutical products is not a new workload or another tons of papers should be filled to comply with regulatory requirements. It should not be a duplication for current documents, systems and processes. Referring to these documents, systems and process in CCS will be enough.
CCS should be a tool that enable organization to identify any gaps in their system and to set the required actions for closing these gaps. So, it can be considered as a continuous improvement process not done once and left forever.
CCS should be a guide for each organization to ensure identity, strength, quality, purity, or potency of their products.
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References:
Lecturer at Swiss German University
2 年Appreciate your kind sharing
Regional QA Manager
2 年Thanks for this brief beneficial summary