In the context of the EU GMP guidelines, the concept of pollution control (Contamination Control) is not novel, and the basic principles are already included in Chapter 5 on cross-contamination and Annex 2 on the specific risks of biological products.

 However, the development of this concept is further highlighted in the revised Annex 1, namely the Pollution Control Strategy (Contamination Control Strategy, CCS) and, in fact, it is one of the few new requirements in the revised Annex 1.

 In the Pollution Control Strategy CCS, an additional quality assurance tool was introduced in the latest Annex 1, designed to control potential sources of microorganisms, bacterial endotoxin / pyrogen and particles through the use of overall plant-wide measures and multi-module control.

 To this end, the risk of contamination of the entire plant, including potential interactions, can be identified through the use of QRM principles and a full understanding of the process technology. Determine critical control points, take appropriate preventive, monitoring and control measures, and fully consider all relevant outcomes.

Through the overall assessment of the collective effectiveness of all measures and continuous CCS, the ultimate goal: maximizing sterility assurance.

 Of the pollution control strategy CCS, established by No

The implementation of appropriate pollution control strategies (CCS) poses some challenges for many companies. Since the new Annex 1 does not provide any specific requirements in this regard, and the decision on the concept and form of CCS is in the hands of the pharmaceutical companies, if all the necessary elements are included, and thus the purpose of CCS in the new Annex 1 is achieved.

Based on the current findings, the implementation described below (structurally similar to the broadest sense site primary document SMF or the design of the validation primary document VMP) seems both appropriate and feasible:

The concept of viewing the CCS as the primary document:

· Definition of the CCS purpose and its underlying principles

· Methods for identifying relevant elements and key control points

· List / list of relevant elements identified

· Identified key control points and relevant monitoring measures

· Evaluate whether existing elements and systems (such as existing risk analysis, change, deviation management, etc.) are suitable for inclusion in CCS, such as through gap analysis

· Description of the methods to assess the collective effectiveness of all CCS measures

· Procedures for keeping CCS up to date and continuously improving CCS through ongoing and regular reviews (including determining the frequency of review)

· List appropriate, when reference, or subordinate, documents, such as existing elements, systems, documents, such as:

o risk analysis

o SOPs (e. g. personnel qualification, supplier management)

O. Environment, personnel, and public media monitoring system

Integrate the above CCS document into the Pharmaceutical Quality System (PQS) as a quality assurance tool with an emphasis on sterility assurance:

· A reasonably structured, concise and easy to understand document;

· Link with other related PQS elements (such as Quality risk management QRM, Product Quality Review PQR, CAPA, etc.), system and subordinate documents (risk analysis, SOP, etc.);

· Content and format conform to EU GMP, Chapter 4 of the Guide, similar to other normative documents developed by the Company.

Who is responsible for the CCS preparation, review, and approval?

 As CCS is a new requirement, there is no best practice experience in determining preparation, review and approval responsibilities. It is likely that the perception of this role allocation will vary, especially during the initial phase of monitoring. For now, the following role assignments may seem obvious:

· The creation and development of CCS was conducted by a multidisciplinary team under the leadership of the Quality Assurance Department (QA) consisting of experts (SME) with specific expertise from all relevant departments.

· Key personnel, including production leaders, quality control leaders, and other qualified personnel, shall participate in the process as the authors or reviewers of the document.

· Final approval is approved by the Management Committee (the Mamagement Board), so the Management Committee fulfills both its task of overall supervision and the responsibility of providing the necessary resources for the CCS.

 Expectations for the first examination

The concept of the pollution control strategy CCS has been proposed in the first draft of the new Annex 1 in 2017. The draft 2020 revision clearly shows that this is a very important new content that may be included in the final version of the document. Thus, the affected companies and institutions have ample opportunity to familiarize themselves with the concept and make the necessary preparations. It is expected that during the first examination, the CCS has been implemented or is imminent. Given that CCS is a comprehensive, far-reaching and demanding new requirement in aseptic production, it will take some time to form the recognized procedure or so-called gold standard for the implementation of CCS before sufficient practical experience is gained.