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CEN ISO cleanroom standards

and expected developments

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Content

Contamination control

Cleanroom

History of cleanroom standards

ISO TC209 Philosophy

Cleanliness standards

Measurement methods

Design to operation standards

Bio-contamination standard

Macro particles

Structure of cleanroom standards

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Contamination control

The aim of contamination control is to keep a product or patient clean by

controlling by the deposition and contact transfer of unwanted contaminants.

The major contamination control solutions are:

1. Create a controlled clean environment (cleanroom).

2. Limit the introduction of contamination sources by controlling the

transfer from outside by shielding (garments) and/or by separation.

3. Limit exposure of the critical surface to the environment.

4. Limit and control the air cleanliness of the environment(s)

where the critical surfaces are exposed.

5. Remove the deposited contaminants by regular cleaning.

6. Monitor the effectiveness of the measures taken.

Cleanroom

A cleanroom is a separated space:

with over pressure to prevent intrusion of uncontrolled dirty air;

where the source strength of contamination sources is limited;

where airborne contamination is diluted (or displaced) with HEPA filtered air

and removed by air flow;

where the air cleanliness is limited according to a target cleanroom class in

at rest and/or in operational state of occupancy;

where all surfaces are cleaned regular and effectively.

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History of cleanrooms

Preventing airborne contamination

Military developments

Watchmakers bell jar (< 1900)

Development of missiles (1945)

• HEPA filters

• Gyroscope production

• Small bearings and gears

Uni-directional airflow (1960)

Space industry (NASA)

• Medical developments • Introduction of aseptic techniques

(< 1900)

• Ventilated operating room (1945)

• Non unidirectional ventilated room

(1960)

• Unidirectional airflow and

occlusive clothing (1980)

• Industrial developments • Semiconductors

• Pharmaceutics

History of cleanrooms

year Events / Publications year Publications

1961 Technical Manual TO 00-25-203 2001 ISO 14644-4

1962 Laminar flow (Willis Whitfield) 2003 ISO 14698-1, 14698-2

1963 Federal Standard 209 2004 ISO 14644-5 and -7, 14698-2/Cor 1

1966 Fed Std 209A 2005 ISO 14644-3

2006 ISO 14644-8

1973 Fed Std 209B 2007 ISO 14644-6

2012 ISO 14644-9

1987 Fed Std 209C 2013 ISO 14644-8, 14644-10

1988 Fed Std 209D 2015 ISO 14644-1 and -2 revision

2016 ISO 14644-14

1992 Fed Std 209E 2017 ISO 14644-13 and -15

1993 ICCCS -> ISO TC209 2018 ISO 14644-12, 16

1999 ISO 14644-1 2019 ISO 14644-3 revision and -17

2000 ISO 14644-2 2020 ISO 14644-4, 8, 9, 10 revision

History of cleanroom standards

Light scattering particle counters ≥0.5 -> 0.1 µm

ISO TC 209 Secretariat ANSI through IEST 23 P-members (nation standards bodies) -> 14 Working groups (8 active) 21 O-members Liaison with ICCCS, CEN/TC 243 and ISO TC 229 Nanoparticles.

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ISO TC209 Philosophy

Cleanrooms are used to apply contamination control

Cleanrooms can be classified with respect to airborne particles

Other cleanliness attributes can be added:

Determine Requirements by Risk Assessment

Establish control plus verification

Demonstrate control by monitoring

Cleanliness standards

Particles in air: ISO 14644-

1. Classification Air Cleanliness (2015)

2. Monitoring Air cleanliness (2015)

3. Supporting Measurement methods (2005/19)

4. Design, construction and start up (2001/20)

-> + other attributes

5. Operations (2004) -> + other attributes

7. Separative devices (2004)

14. Particle emission by equipment (2016)

16. Energy saving (2018)

17. Particle Deposition Rate (2019)

18?. Cleanroom suitability of consumables

Grey: existing, blue: new, italics: expected, red: revision.

Other attributes in air: ISO 14644-

8. Air cleanliness chemical (ACC) (2013)

12. Air cleanliness nanoparticles (2018)

15. Emission of chemical by materials (2017)

Contaminants on surfaces: ISO 14644-

9. Surface cleanliness by particles (SCP) (2012)

10. Surface cleanliness by chemicals (SCC) (2013)

13. Cleaning for SCP and SCC (2017)

17. Particle Deposition Rate (2019)

Micro organisms (viables): ISO 14698-

1,2. Air/surface cleanliness by viables (2003, 2004)

EN17141 Air/surface cleanliness by viables (2019)

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Structure TC209 standards

Contaminants Risk assessment Requirements

Establish Control design, construction, verification

Demonstrate Control Monitoring

Particles/ macroparticles

Cleanliness: Air: ISO 14644-1,2,17 Surface: ISO 14644-9,17

Sources: ISO 14644-14 (particles) ISO 14644-15 (chemicals) ISO 14644-18 (p and ch) Cleanroom: ISO 14644-4/16 Separation: ISO 14644-7 Operations: ISO 14644-5 + cleaning: ISO 14644-13 Verification: ISO 14644-1,3 + cleanliness attributes: ISO 14644-2,8,9,10,12 and ISO 14698-1,2

Cleanliness: Air: ISO 14644-2,17 Surface: ISO 14644-9,17 Cleanroom: ISO 14644-1,3

Chemicals Cleanliness: Air: ISO 14644-8 Surface: ISO 14644-10

Cleanliness: Air: ISO 14644-8 Surface: ISO 14644-10 Cleanroom: ISO 14644-1,3

Nanoparticles Cleanliness: Air: ISO 14644-12 Surface: NA

Cleanliness: Air: ISO 14644-12 Surface: NA Cleanroom: ISO 14644-1,3

Micro-organisms/ viables

Cleanliness: Air: ISO 14698-1,2 Surface: ISO 14698-1,2

Cleanliness: Air: ISO 14698-1,2 Surface: ISO 14698-1,2 Cleanroom: ISO 14644-1,3

Measurement methods

In principle the measurement methods to use a particular standard are in the standard:

Particles in air (part 1) Particles on surfaces (part 9)

Chemicals in air (part 8) Chemical on surfaces (part 10)

Nanoparticles in air (part 12)

Viables in air (14698) Viables on surfaces (14698)

Supporting measurement methods are in ISO 14644-3: measurement methods:

Air pressure difference Airflow

Airflow direction &visualisation Recovery

Temperature Humidity

Installed filter system leakage Containment leak

Electrostatic and ion generator Particle deposition

Segregation

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Design to operation standards

ISO 14644-4: Design, Construction and Start up:

Requirements (particle and other cleanliness attributes)

Use ISO 14644-14 and 15 to get source data

Design (conceptual, basic and detailed), supporting calculations

Construction (project plan, work plan, health and safety plan, clean build protocol,

change management)

Start up (verification, setting to work, training, documentation, hand over).

ISO 14644-16: Improving energy efficiency:

Ventilation calculations

Component selection: filters and fans

Adaptive control

Turn down

Heating and cooling.

ISO 14644-4Design, Construction and Start-up Guidance

Flowchart

Basic

Detailed

Design

IDEA

ISO

146

44-4

SC

OPE

Conceptual

CleanroomUser Requirements

Requirements

General

Construction

Start-up

Operations&

Maintenance

Set to work

Verification

Handover

Bio-contamination standard

In Europe ISO 14698-1,2 will be replaced by EN17141 Biocontamination

This standard can be used for a wide range of applications:

Life Sciences (pharma/biopharma and medical devices),

healthcare/hospitals and food.

Start with impact (risk) assessment to determine measurement method

(classical or rapid microbiological methods (RMM)), critical locations and

critical contamination levels.

Establish control and verify this using selected measurement methods.

Demonstrate control with selected measurement methods.

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Macroparticles

Airborne particles can be removed by air flow.

Larger particles will deposit on all surfaces.

Deposited particles are removed by cleaning.

In non unidirectional ventilation:

The percentage depends on the particles size and the air change rate

(example ACR=7,5-15 – 30 -60);

The air cleanliness depends on the total sources strength and the air supply volume and

removal efficiency.

The fraction of microbe carrying particles m increases with particle size, m =

cfu/N.

In unidirectional air flow the removal efficiency depends on the air supply volume

and the unidirectionality.

0,0

0,2

0,4

0,6

0,8

1,0

0 20 40 60 80 100 120 140 160 180 200

m

Particle size in µm

Estimated of value m,

ratio microbial and particle deposition

ISO 8

ISO 7

ISO 6

ISO 5

Product surface cleanliness and air cleanliness

The major product surface contamination

mechanism is particle deposition (ISO 14644-17

Particle deposition rate applications).

In a cleanroom at rest there is no deposition of

particles ≥ 5 µm.

For small macro particles < 30 µm there is a

relation between the airborne contamination of

macroparticles and the particle deposition rate of

macro particles.

For particles ≥ 30 µm the operational procedures

are most important.

Especially the cleaning program.

Particle removal

Particle deposition

50 %

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Monitoring to demonstrate control

Consider requirements and recommendations in ISO 14644-2 :2015.

test and measurement frequency;

description of test and measurement methods,

(reference to standards and guidelines);

action plan in the event of non-compliance;

frequency required for analysis of

performance data to enable trends to be

analysed.

Monitoring air and surface cleanliness

Impact air handling

Real time monitoring with particle counter:

Particles ≥ 0,5 µm at rest to check cleanroom installation;

Particles ≥ 0,5 µm and ≥ 5 µm to check cleanroom performance.

Impact operation

Realtime particle deposition monitoring

Particles ≥ 10, 20, 30, 50, 100, 200, 500 and 1000 µm to check

operational procedures.

Surface cleanliness

Particles ≥ 10, 25, 50, 100, 250, 500 and 1000 µm to check cleaning program.

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Real time particle deposition monitoring Particle deposition rate determines risk of particle contamination.

Particle deposition rate data gives guidance to the operational quality.

Time information indicates specific activities, such as:

Transfer

Preparation

Behaviour

Particle size information shows type of required improvements:

Cleaning

Garment selection

Entry and exit procedures

Working methods

Awareness of personnel

APMON

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Number of Particles > 15 µm & Cumulative PAC

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Overview of TC 209 standards on Cleanroom and Associated Controlled Environments For full titles and year of publication see www.iso.org or www.icccs.net

ISO 14644-1 Classification of cleanroom air

cleanliness

ISO 14644-2 Air Cleanliness wrt Particles

ISO 14644-8 Air Cleanliness wrt Chemicals

ISO 14644-9 Surface Cleanliness wrt Particles

ISO 14644-10 Surface Cleanliness wrt

Chemicals

ISO 14644-12 Air Cleanliness wrt Nanoscale

particles

ISO 14644-17 Particle Deposition Rate

applications

ISO 14698-1,2 Biocontamination

EN17141 Biocontamination

ISO 14644-3 Measurement Methods

ISO 14644-4 Design, Construction and Start-up

ISO 14644-5 Operations

ISO 14644-7 Separative Devices

ISO 14644-13 Cleaning

ISO 14644-14 Determining the emission of

particles by equipment

ISO 14644-15 Determining the emission of

chemicals by materials and equipment

ISO 146-44-16 Energy saving

ISO 14644-18 Cleanroom suitability of

consumables

Thank you for

your attention

a g r i c o l a @ b r o o k h u i s . c o m

https://www.brookhuis.com/cleanroom