Cleanrooms and associated controlled environments - Biocontamination control

This document establishes the requirements, recommendations and methodology for microbiological contamination control in clean controlled environments. It also sets out the requirements for establishing and demonstrating microbiological control in clean controlled environments.
This document is limited to viable microbiological contamination and excludes any considerations of endotoxin, prion and viral contamination.
There is specific guidance given on common applications, including Pharmaceutical and BioPharmaceutical, Medical Devices, Hospitals and Food.

Reinräume und zugehörige Reinraumbereiche - Biokontaminationskontrolle

Dieses Dokument legt die Anforderungen, Empfehlungen und Methodiken für die mikrobiologische Kontaminationskontrolle in auf Sauberkeit kontrollierten Bereichen fest. Darüber hinaus legt dieses Dokument die Anforderungen an die Erstellung und den Nachweis der mikrobiologischen Kontrolle in auf Sauberkeit kontrollierten Bereichen fest.
Dieses Dokument beschränkt sich auf lebensfähige mikrobiologische Kontamination und schließt alle Betrachtungen endotoxiner, proteinös-infektiöser und viraler Kontamination aus.
Es bestehen spezifische Leitfäden zu gemeinsamen Anwendungen, einschließlich Pharma/Biopharma, Medizinprodukte, Krankenhäuser und Lebensmittel.

Salles propres et environnements maîtrisés apparentés - Maîtrise de la biocontamination

Le présent document établit les exigences, les recommandations et la méthodologie relatives à la maîtrise de la contamination microbiologique en environnement propre maîtrisé. Il définit également les exigences à mettre en œuvre pour établir et démontrer la maîtrise microbiologique en environnement propre maîtrisé.
Le présent document se limite à la contamination microbiologique viable et exclut toute considération quant à la contamination par endotoxine, par prion et par virus.
Il fournit des recommandations spécifiques concernant certains domaines d‘activités courants, comme les secteurs pharmaceutiques et biopharmaceutiques, les dispositifs médicaux, les hôpitaux et l’agro alimentaire.

Čiste sobe in podobna nadzorovana okolja - Kontrola biokontaminacije

General Information

Status
Published
Current Stage
6060 - Definitive text made available (DAV) - Publishing
Due Date
12-Aug-2020
Completion Date
12-Aug-2020

RELATIONS

Buy Standard

Standard
EN 17141:2020
English language
51 pages
sale 10% off
Preview
sale 10% off
Preview

e-Library read for
1 day

Standards Content (sample)

SLOVENSKI STANDARD
SIST EN 17141:2020
01-november-2020
Nadomešča:
SIST EN ISO 14698-1:2004
SIST EN ISO 14698-2:2004
SIST EN ISO 14698-2:2004/AC:2007
Čiste sobe in podobna nadzorovana okolja - Kontrola biokontaminacije
Cleanrooms and associated controlled environments - Biocontamination control
Reinräume und zugehörige Reinraumbereiche - Biokontaminationskontrolle

Salles propres et environnements maîtrisés apparentés - Maîtrise de la biocontamination

Ta slovenski standard je istoveten z: EN 17141:2020
ICS:
13.040.35 Brezprašni prostori in Cleanrooms and associated
povezana nadzorovana controlled environments
okolja
SIST EN 17141:2020 en,fr,de

2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

---------------------- Page: 1 ----------------------
SIST EN 17141:2020
---------------------- Page: 2 ----------------------
SIST EN 17141:2020
EN 17141
EUROPEAN STANDARD
NORME EUROPÉENNE
August 2020
EUROPÄISCHE NORM
ICS 13.040.35
English Version
Cleanrooms and associated controlled environments -
Biocontamination control

Salles propres et environnements maîtrisés apparentés Reinräume und zugehörige Reinraumbereiche -

- Maîtrise de la biocontamination Biokontaminationskontrolle
This European Standard was approved by CEN on 4 November 2019.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this

European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references

concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN

member.

This European Standard exists in three official versions (English, French, German). A version in any other language made by

translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management

Centre has the same status as the official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,

Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,

Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and

United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels

© 2020 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN 17141:2020 E

worldwide for CEN national Members.
---------------------- Page: 3 ----------------------
SIST EN 17141:2020
EN 17141:2020 (E)
Contents Page

European foreword ....................................................................................................................................................... 5

Introduction .................................................................................................................................................................... 6

1 Scope .................................................................................................................................................................... 8

2 Normative references .................................................................................................................................... 8

3 Terms and definitions ................................................................................................................................... 8

4 Establishment of microbiological control ........................................................................................... 11

4.1 General ............................................................................................................................................................. 11

4.2 Establishing a formal system for microbiological control ............................................................ 11

4.3 Microbiological contamination control system quality attributes ............................................ 12

4.4 Identification of all potential sources and routes of microbiological contamination ......... 12

4.4.1 General ............................................................................................................................................................. 12

4.4.2 Sources of microbiological contamination ......................................................................................... 13

4.4.3 Routes of transfer of microbiological contamination ..................................................................... 13

4.5 Risk assessment ............................................................................................................................................ 14

4.6 Establishment of microbiological environmental monitoring plan .......................................... 14

4.6.1 General ............................................................................................................................................................. 14

4.6.2 Monitoring locations ................................................................................................................................... 14

4.6.3 Monitoring frequencies ............................................................................................................................. 14

4.7 Establishment of alert and action limits .............................................................................................. 15

4.8 Establishment of documentation system ............................................................................................ 15

4.9 Personnel education and training ......................................................................................................... 15

5 Demonstration of microbiological control ......................................................................................... 16

5.1 Trending .......................................................................................................................................................... 16

5.2 Verification of the formal microbiological control system ........................................................... 16

5.2.1 General ............................................................................................................................................................. 16

5.2.2 Out of specification (OOS) investigation .............................................................................................. 16

5.2.3 Records ............................................................................................................................................................ 16

5.2.4 Sample tracking ............................................................................................................................................ 17

5.2.5 Integrity of results ....................................................................................................................................... 17

5.2.6 Data recording ............................................................................................................................................... 17

5.2.7 Data evaluation ............................................................................................................................................. 17

5.2.8 Trend analysis ............................................................................................................................................... 18

6 Microbiological measurement methods .............................................................................................. 18

6.1 General ............................................................................................................................................................. 18

6.2 Choice of sampling method....................................................................................................................... 18

6.3 Volumetric air samplers ............................................................................................................................ 19

6.4 Culture media and incubation ................................................................................................................. 19

6.5 Incubators ....................................................................................................................................................... 19

Annex A (informative) Guidance for life science pharmaceutical and biopharmaceutical

applications .................................................................................................................................................... 20

A.1 Introduction ................................................................................................................................................... 20

A.2 Risk/impact assessment ............................................................................................................................ 21

A.3 Demonstrating control ............................................................................................................................... 21

Annex B (informative) Guidance for life science medical device applications ................................... 22

---------------------- Page: 4 ----------------------
SIST EN 17141:2020
EN 17141:2020 (E)

B.1 Introduction ................................................................................................................................................... 22

B.2 Risk assessment ............................................................................................................................................ 22

B.2.1 General ............................................................................................................................................................. 22

B.2.2 Example 1: Sterile - terminal sterilisation is possible from a packaged product ................. 24

B.2.3 Example 2: Sterile – No terminal sterilisation is possible due to product properties ......... 25

B.2.4 Example 3: Non-sterile products ............................................................................................................. 25

B.3 Establishing Microbiological Control .................................................................................................... 26

B.3.1 Microbiological contamination limits ................................................................................................... 26

B.3.2 Additional microbiological control considerations ......................................................................... 27

B.4 Demonstrating microbiological control ............................................................................................... 27

B.4.1 Enumeration as part of measurement methods (Clause 6) .......................................................... 27

B.4.2 Methods for sampling ................................................................................................................................. 27

B.4.3 Microbiological Environmental Monitoring (EM) plan ................................................................... 27

B.5 Other informative annexes for Medical Device applications ........................................................ 29

Annex C (informative) Guidance for healthcare/hospital applications ................................................. 30

C.1 Introduction ................................................................................................................................................... 30

C.2 Establishing control in a healthcare/hospital application ............................................................ 30

C.3 Risk assessment for operating room hospital applications .......................................................... 30

Annex D (informative) Guidance for food applications ............................................................................... 31

D.1 Introduction ................................................................................................................................................... 31

D.2 Establishment of microbiological control ........................................................................................... 31

D.3 Microbiological cleanliness levels for monitoring ........................................................................... 32

D.4 Demonstration of microbiological control .......................................................................................... 33

D.5 Example for food manufacture ................................................................................................................ 33

Annex E (informative) Guidance on culture based microbiological measurement methods

and sampler verification ............................................................................................................................ 35

E.1 General ............................................................................................................................................................. 35

E.2 Air sampling ................................................................................................................................................... 35

E.2.1 Volumetric air samplers............................................................................................................................. 35

E.2.2 Settle plates..................................................................................................................................................... 37

E.3 Surface sampling ........................................................................................................................................... 37

E.3.1 General ............................................................................................................................................................. 37

E.3.2 Contact plates and strips ............................................................................................................................ 37

E.3.3 Swabs and sponges ....................................................................................................................................... 38

E.4 Microbiological growth media ................................................................................................................. 38

E.4.1 General ............................................................................................................................................................. 38

E.4.2 Media suitability (media sterility and ability to support growth) .............................................. 38

E.4.3 Media dehydration ....................................................................................................................................... 39

E.4.4 Media disinfectant inhibition ................................................................................................................... 39

E.4.5 Plate incubation ............................................................................................................................................ 39

E.5 Validation of air samplers ......................................................................................................................... 39

E.5.1 General ............................................................................................................................................................. 39

E.5.2 Physical collection efficiency.................................................................................................................... 39

E.5.3 Biological collection efficiency ................................................................................................................ 40

E.6 Experimental method ................................................................................................................................. 40

E.6.1 Aerosol chamber method .......................................................................................................................... 40

E.6.2 Simplified laboratory method .................................................................................................................. 42

E.6.3 Incubation ....................................................................................................................................................... 43

E.6.4 Collection efficiency calculations from testing results ................................................................... 43

E.6.5 Air sampler revalidation ............................................................................................................................ 44

---------------------- Page: 5 ----------------------
SIST EN 17141:2020
EN 17141:2020 (E)

Annex F (informative) Rapid microbiological methods (RMM) and alternative real time

microbiological detection methods (AMMs) ...................................................................................... 45

F.1 General ............................................................................................................................................................. 45

F.2 Implementation of RMMs and AMMs .................................................................................................... 45

F.3 Validation of RMMs and AMMs ................................................................................................................ 46

F.3.1 General ............................................................................................................................................................. 46

F.3.2 Acceptance criteria considerations ....................................................................................................... 47

F.3.3 Verification test execution considerations ......................................................................................... 47

F.4 Action and alert levels ................................................................................................................................ 47

F.4.1 Setting action and alert levels ................................................................................................................. 47

F.4.2 Result outside of action and alert levels .............................................................................................. 47

Bibliography ................................................................................................................................................................. 48

---------------------- Page: 6 ----------------------
SIST EN 17141:2020
EN 17141:2020 (E)
European foreword

This document (EN 17141:2020) has been prepared by Technical Committee CEN/TC 243 “Cleanroom

technology”, the secretariat of which is held by BSI.

This European Standard shall be given the status of a national standard, either by publication of an

identical text or by endorsement, at the latest by February 2021, and conflicting national standards

shall be withdrawn at the latest by February 2021.

Attention is drawn to the possibility that some of the elements of this document may be the subject of

patent rights. CEN shall not be held responsible for identifying any or all such patent rights.

This document supersedes EN ISO 14698-1:2003, EN ISO 14698-2:2003 and
EN ISO 14698-2:2003/AC:2006.

According to the CEN-CENELEC Internal Regulations, the national standards organisations of the

following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,

Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland,

Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of

North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the

United Kingdom.
---------------------- Page: 7 ----------------------
SIST EN 17141:2020
EN 17141:2020 (E)
Introduction

Clean controlled environments are used to control and limit microbiological contamination where there

is a risk to product quality, patient or consumer.

In this document the term “clean controlled environments” is used to cover cleanrooms, clean zones,

controlled zones, clean areas and clean spaces.

This document gives guidance on best practice for establishing and demonstrating control of airborne

and surface microbiological contamination in clean controlled environments. This document describes

the requirements for microbiological contamination control and provides guidance on the qualification

and verification of clean controlled environments.

In order to establish microbiological control, it is important to understand the risks of microbiological

contamination. This is achieved by considering the sources of microbiological contamination, the

associated microbiological concentrations and the likelihood of transfer and the impact on product

quality, the patient or the consumer.

A formal system of microbiological control identifies, controls and monitors microbiological

contamination on an ongoing basis. This is a process of continuous improvement and the principles of

Plan – Do – Check – Act (PDCA) apply, as shown in Figure 1.
Figure 1 — Application of PDCA as the system for microbiological control

This document provides general guidance and considerations for a number of different applications. It

is expected to have particular use in the Pharmaceutical, Biopharmaceutical, Medical Devices and other

Life Science industries, as well as in Healthcare and Hospitals, Food, and related applications which use

clean controlled environments.

In the regulated Pharmaceutical and Biopharmaceutical manufacturing sector there are already many

applicable standards and regulatory guidelines. These include the EU Annex 1 GMP [31] guidance on the

manufacture of Sterile Medicinal products and the FDA Aseptic Processing guidance [32]. The European

and United States Pharmacopoeias also provide some guidance on certain related topics. There are

numerous other documents and technical papers available from industry associations including the

Parenteral Drugs Association (PDA), International Society of Pharmaceutical Engineering (ISPE) and

Pharmaceutical Healthcare Sciences Society (PHSS). While there are regulations and standards on risk

management of medical devices, for example EN ISO 14971 [2], there is less guidance on the

microbiological control of clean controlled environments.

In the Healthcare and Hospital sector there are EU Directives, including the Tissue and Blood Directives

for specialist and similar clean controlled environments. There are national standards and guidelines

for specialised Operating Theatres, Isolation units, Immuno-compromised wards as part of infection

---------------------- Page: 8 ----------------------
SIST EN 17141:2020
EN 17141:2020 (E)

control. In addition, Hospital Pharmacy aseptic compounding units, Radiopharmacies and specialist

laboratories such as Stem Cell typically refer to Life Science industry guidance documents.

In the Food and consumer related industries, while there are regulations and standards on food,

beverages and cosmetics for example there is insufficient guidance regarding microbiological control in

clean controlled environments.

This document includes a number of informative annexes that provide further guidance on

biocontamination control in specific applications, and includes, for example:

— tables of microbiological cleanliness levels for monitoring of microbiological contamination in

certain types of clean controlled environments;

— guidance in specific areas of microbiological control relating to the choice of environmental

monitoring (EM) sampling methods, the management and trending of collected data and the role of

alternative and real time microbiological detection systems;

— appropriate methods for establishing control, selecting appropriate alert and action levels and

target levels as necessary;

— establishing a microbiological environmental monitoring plan as part of demonstrating control of

the clean controlled environment.
---------------------- Page: 9 ----------------------
SIST EN 17141:2020
EN 17141:2020 (E)
1 Scope

This document establishes the requirements, recommendations and methodology for microbiological

contamination control in clean controlled environments. It also sets out the requirements for

establishing and demonstrating microbiological control in clean controlled environments.

This document is limited to viable microbiological contamination and excludes any considerations of

endotoxin, prion and viral contamination.

There is specific guidance given on common applications, including Pharmaceutical and

BioPharmaceutical, Medical Devices, Hospitals and Food.
2 Normative references

The following document is referred to in the text in such a way that some or all of their content

constitutes requirements of this document. For dated references, only the edition cited applies. For

undated references, the latest edition of the referenced document (including any amendments) applies.

EN ISO 14644-1:2015, Cleanrooms and associated controlled environments — Part 1: Classification of air

cleanliness by particle concentration (ISO 14644-1:2015)
3 Terms and definitions

For the purposes of this document, biocontamination control and microbiological control are

synonymous, and the following terms and definitions apply.

ISO and IEC maintain terminological databases for use in standardization at the following addresses:

— IEC Electropedia. available at http://www.electropedia.org/
— ISO Online browsing platform: available at http://www.iso.org/obp
3.1
action level

level set by the user in the context of controlled environments, which, when exceeded, requires

immediate intervention, including investigation of cause, and corrective action
3.2
alert level

level set by the user in the context of controlled environments, giving early warning of a drift from

normal conditions, which, when exceeded, should result in increased attention to the process

3.3
clean controlled environment

defined zone in which microbiological contamination is controlled by specified means

---------------------- Page: 10 ----------------------
SIST EN 17141:2020
EN 17141:2020 (E)
3.4
cleanroom

room within which the number concentration of airborne particles is controlled and classified, and

which is designed, constructed and operated in a manner to control the introduction, generation, and

retention of particles inside the room
Note 1 to entry: The class of airborne particle concentration is specified.

Note 2 to entry: Levels of other cleanliness attributes such as chemical, viable or nanoscale concentrations in

the air, and also surface cleanliness in terms of particle, nanoscale, chemical and viable concentrations may also be

specified and controlled.

Note 3 to entry: Other relevant physical parameters may also be controlled as required, e.g. temperature,

humidity, pressure, vibration and electrostatic.
[SOURCE: EN ISO 14644-1:2015, 3.1.1, [1]]
3.5
clean zone

defined space within which the number concentration of airborne particles is controlled and classified,

and which is constructed and operated in a manner to control the introduction, generation, and

retention of contaminants inside the space
Note 1 to entry: The class of airborne particle concentration is specified.

Note 2 to entry: Levels of other cleanliness attributes such as chemical, viable or nanoscale concentrations in

the air, and also surface cleanliness in terms of particle, nanoscale, chemical and viable concentrations may also be

specified and controlled.

Note 3 to entry: A clean zone(s) may be a defined space within a cleanroom or may be achieved by a separative

device. Such a device may be located inside or outside a cleanroom.

Note 4 to entry: Other relevant physical parameters may also be controlled as required, e.g. temperature,

humidity, pressure, vibration and electrostatic.
[SOURCE: EN ISO 14644-1:2015, 3.1.2, [1]]
3.6
colony forming unit

formation of a single macroscopic colony after the introduction of one or more microorganisms to

microbiological growth media
Note 1 to entry: One colony forming unit is expressed as 1 cfu.
3.7
critical control point

specific point, procedure, or step in the process at which control can be exercised to reduce, eliminate,

or prevent the possibility of microbiological contamination
3.8
critical zone

designated space within the clean controlled environment used to control microbiological

contamination
---------------------- Page: 11 ----------------------
SIST EN 17141:2020
EN 17141:2020 (E)
3.9
culturable

having the ability to grow and form colony forming units (cfu), using microbiological culturing

techniques
3.10
environmental monitoring

measurement of specified parameters at periodic intervals within a clean controlled environment

3.11
microorganism
entity of microscopic size encompassing bacteria fungi protozoa and viruses
Note 1 to entry: Microbe is synonymous with microorganism.

Note 2 to entry: The use of the term microorganism in this standard includes bacteria, yeast and moulds only.

[SOURCE: ISO 17665-1:2006, 3.25, [50]]
3.12
microorganism of interest
microbiological contamination
...

Questions, Comments and Discussion

Ask us and Technical Secretary will try to provide an answer. You can facilitate discussion about the standard in here.