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Impact of new ISO 14644-1&2:2015 0n GMP Annex 1

Gordon Farquharson, July 2016

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The tabloid headlines

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The real headlines

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ISO 14644-1 revisions

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• Change from:

• Classification by Formula (+ table to illustrate)

TOClassification by Table

+ Formula for Intermediate Sizes

• Keep decimal classes; but now just 0.5 steps (1.5; 2.5;

etc.). More logical related to particle counter size

discrimination capability

• Remove ≥ 5.0 micron limit for ISO 5 (29) & ISO 5.5

Key change - ISO 14644-1:2015The basis for classifcation

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ISO Formula

– retained for intermediate

particle sizes only

ISO Cn = 0.12.08 x 10N(class)

D( )

For example if you needed a class concentration limit for ≥ 0.4 micron

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The formula illustrated

by an Informative

Table

Old - EN/ISO 14644-1:1999Classification by Particles

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Transition to New - ISO 14644-1:2015 Class Table

Remove 29/m3 ISO 5 class limit ~ Counting uncertainty

Very Low values deleted

Low values have sample size warning

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The new classification table

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Now closer to OLD US Fed Std 209EClassification by Table (Particles)

No ≥5.0mlimit in oldClass 100

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The new decimal class table in ISO 14644-1:2015

Concentration of particles (particles/m3) a

ISO classification number (N) 0,1 0,2 0,3 0,5 1,0 5,0

ISO Class 1,5 [32] b d

d d d e

ISO Class 2,5 316 [75] b [32] b

d d e

ISO Class 3,5 3 160 748 322 111

d e

ISO Class 4,5 31 600 7 480 3 220 1 110 263

e

ISO Class 5,5 316 000 74 800 32 200 11 100 2 630

e

ISO Class 6,5 3 160 000 748 000 322 000 111 000 26 300 924

ISO Class 7,5

c c c

1 110 000 263 000 9 240

ISO Class 8,5

c c c

11 100 000 2 630 000 92 400

Examples of intermediate decimal air cleanliness classes

by particle concentration (only 0.5 class steps allowed)

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This proposed change is not a major impact on the principle of classification .

Helps prevent poor selection of size vs class.

Means Annex 1 Grade A and B clearly outside the ISO Class system!

See later how this is dealt with!

Major discussions

• Good science of particle counting removes ≥ 5 micron limit for ISO5

• REMEMBER that the table doesn’t represent typical distribution of particles in a

cleanroom

• How to deal with Annex 1 or the EU/PIC/S GMP. Big influence from EU and

PIC/S GMP nations

ISO 14644-1:2015 changesImpact

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The proposal is to use adapted macro-particle descriptor concept – See Annex C7.

ISO 14644-1:2015 & EU + PIC/S Annex 1 Impact

Class limit of 20 parts ≥ 5.0 micron is also

outside scope of the standard

Class limit of 29 parts ≥ 5.0 micron outside scope of

standard –≥ 5.0 micron cannot be used

for an ISO5 classification

The GMP Grade table from Annex 1.

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Using the macro-particle descriptor for 5 micron particles in ISO 14644-1:2015

GMP should use the macro-particle concept for

Grade A 20 particles/m3 @ ≥ 5.0 micron

Grade B “at rest” 29 particles/m3 @ ≥ 5.0 micron

We use this terminology

ISO M (20;≥ 5.0); LSAPC

M =Macroparticles

20 =Class limit from GMP

5.0 =Considered particle size

LSAPC = Light scattering airborne

particle counter

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This is how we would define Annex 1 Grade A & B using ISO 14644-1:2015An extrapolation of the Macro-particle concept.

Grade A

ISO 5; at rest & operational; ≥ 0.5

ISO M(20≥ 5.0); at rest & operational; LSAPC

Grade B

ISO 5; at rest; ≥ 0.5, and ISO M(29≥ 5.0); at rest, LSAPC.

ISO 7; operational; ≥ 0.5 & 5.0

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Simplification: The 95% UCL Evaluation for 2-9 locations has been removed.

Each sampling location now evaluated independently.

• All locations must comply for room or zone to comply.

There is a ‘Look-up’ table for the number of sampling locations required.

• Based on ensuring 95 % level of confidence that at least 90 % of the cleanroom or

clean zone will comply with the class limit.

• Will increase the number of locations up to 1000m2.

For > 1000m2, very similar to the current Area rule.

Placement of sampling locations: Even distribution, at representative locations

• In N-UDF cleanrooms with non-diffused airflow, avoid placement directly under

HEPA filter supply air terminals.

Key change - ISO 14644-1:2015Improved sampling statistics

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ISO 14644-1:2015Required minimum sampling locations

1. Determine the number of sample locations NL

from table A1.

2. Divide the room/zone into NL equal areas.

3. Select representative sampling locations in each

zone (not under undiffused HEPA filter

terminals).

4. Take a sample at each location (sample size as

old standard).

5. Average raw data at each location if multiple

samples are taken. Convert to per m3.

6. If all measured particle concentrations (or

averages) comply with the class limit, the

classification is met.

7. For larger rooms >1000m2, extrapolate the

location density from the 1000m2 requirement –

equation A.1.

Area of cleanroom (m2) less than

or equal to

Minimum number of sample locations

to be tested (NL)2 14 26 38 410 524 628 732 836 952 1056 1164 1268 1372 1476 15104 16108 17116 18148 19156 20192 21232 22276 23352 24436 25636 261000 27

> 1000 See Equation A.1

Table A.1 — Sample locations related to cleanroom area

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ISO 14644-1:2015Number sampling locations comparison

0

20

40

60

80

100

120

2 4 6 8

10

12

14

16

18

26

28

32

34

36

38

52

54

58

74

78

96

116

138

176

200

300

500

10

00

20

00

50

00

10

00

0

Min

imu

m N

um

be

r o

f s

am

ple

po

ints

Size of Room, m2

Comparison of the number of Sample Points: current and proposed

1999 Square Root rule

2015 look-up

To deal with very large cleanrooms, extrapolate the location density above 1000 m2

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This is an important change to the basic mechanics of classification.

Organisations will have to redefine their classification sampling plans &

data evaluation.

Does not affect real-time monitoring.

Discussions

• How to select the locations – can be randomised or fixed

• You can add locations to deal with Risk-Based requirements

• Allows re-test at same locations after a repair or remediation

• Can now deal with unusually large cleanrooms > 1000 m2

ISO 14644-1:2015 changesImpact

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Thanks for your attention Questions???

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This presentation has been prepared

and delivered by:-

Gordon J Farquharson

Principal

Critical Systems Ltd

Consulting in Safety & Quality Critical Systems

Guildford, Surrey, GU1 2SY, UK

tel +44 (0)1252 703 663

gjf@critical-systems.co.uk

www.critical-systems.co.uk

CRI ICAL

SYSTEMS

CRI ICAL

SYSTEMS

mailto:gj.farquharson@critical-systems.co.ukhttp://www.critical-systems.co.uk/