Standards Development

Scope

This document establishes the requirements, recommendations and methodology for microbiological contamination control in clean controlled environments. It sets out the requirements for establishing and demonstrating a state of microbiological control in clean controlled environments, using both engineering controls and operational controls in a holistic manner.

This document is limited to viable microbiological contamination and excludes any considerations of endotoxin or prion contamination.

This document provides guidance for the determination of impact and need for microbiological control in common applications in cleanrooms and associated environments, including pharma/biopharma, medical devices, hospitals and food.

 Recognizing that cleanrooms and associated environments can be used for many purposes, this document provides guidance regarding the following:

• performing an impact assessment regarding the potential detrimental effects of micro organisms or types of microorganisms on a product, process or service performed in a cleanroom and associated environment;

• considering sources of microorganisms in cleanrooms and associated controlled environments including personnel, water, air, surfaces, raw materials, components, consumables, equipment, manufacturing processes and utilities;

• understanding the processes and routes of transfer as microorganisms can originate from a number of sources and have different routes of transfer to locations where adverse impact can occur;

• identifying preventative actions to establish a state of control using facility design and engineering controls as well as operational controls such as personnel gowning, behaviour and cleaning and disinfection, to reduce the release of microorganisms into the cleanroom and associate controlled environment and prevent their proliferation;

• development of a monitoring program as can be needed, and commensurate with the specific use and results of the impact assessment. The monitoring program can be applicable to engineering and process control features or biological assessments. • documentation.

This document does not provide the following: 

• requirements for prescriptive limits or levels of viable and culturable microorganisms in a cleanroom and associated controlled environment;

• prescriptive requirements for an environmental monitoring program.

• requirements for alignment of microbial limits or levels associated with airborne particle classifications as described in EN ISO 146441;

• requirements on the possible presence of prions or microbiological the byproducts of bacterial growth such as endotoxins/exotoxins.

Purpose

This NWIP is designed to provide further clarity and guidance and harmonise with other parts of ISO 14644 family of Cleanroom standards. In particular the revision addresses concerns microbiologists expressed on the subject of cleanrooms and microorganisms around uncertainty, variability, multiplicity of types and species, logarithmic scale issues around indirect sampling vs measurement methods, etc.

1. Concern with the term “Biocontamination Control” There is a need to carefully differentiate between control as in the physical world and the “control” of microorganisms, which are quite different. While physical parameters like airborne particles, temperature, relative humidity and room differential pressures, can be measured and controlled in realtime for example, this is very different from the ability to “control” micro organisms. Therefore “Biocontamination” will be replaced with “Microbiological Contamination” Control

2. The importance and microbiological contamination contribution of People is not emphasised The importance of the contribution of people in terms of microbiological contamination, ca 80% is not reflected fully and the importance and significance of People interactions, manipulations and interventions should be emphasised in the revision, along with the role of ISO 146445 (Operations) and 7 (Separative Devices).

3. Perceived emphasis on monitoring vs the management of microbiological contamination There are significant uncertainties and limitations in recovery as part of traditional EM with sampling, incubation and then enumeration by CFUs, with results days if not up to 2 weeks later. The control of the physical environment is important and monitoring is required to demonstrate this.

4. Perceived Link between Particles and Microorganisms from Life Science Regulators There should be NO expected or intended direct linkage particle concentrations and microorganisms, type or quantity. EN 17141 should not impose any direct linkage between a cleanroom classification in accordance with ISO 146441 and a “state of control” for microbiological contamination.

5. Decouple link to ISO 146441 if the term Cleanroom or Cleanzone is NOT used If “Cleanroom” and Cleanzone” are not used then the document should allow the option of declaring a clean controlled environment and does not have to have a fixed link to the classes as defined in ISO 146441.

The revised EN 17141 should be very clear on what needs to be and can be controlled in the physical world, and separately the challenges in managing and mitigating hazards from microbiological contamination inside a cleanroom, for different applications, as they can be diverse.

The revision of EN 17141 will deal with the following:

1. The title and a clear emphasis in addressing the above 4 areas of concern, in the Introduction, Scope, definitions and then Normative sections and Informative sections and annexes;

2. Engineering controls – leveraging the new ISO 1546444:2022, Normative and/or Informative;

3. People and Materials, including Gowning and Behaviour, leveraging the revisions to ISO 1546445 Operations, Normative and/or Informative;

4. Ongoing Cleaning and Disinfection, leveraging the revisions to ISO 1546445 Operations, Normative and/or Informative;

5. Separative Devices, leveraging the revisions to ISO 1546447 Separative Devices, Normative and/or Informative;

6. Gaps vs ISO 14698, i.e. Cleanroom Garment Laundry;

7. Role of ARMM and in particular BFPC (BioFluorescent Particle Counting);

8. General updates and clarifications based on feedback and application of EN 17141;

9. Sequence of Informative Annexes to align with the Normative sections.