Cleanroom Standards and Updates 14644-1 &- 2 Draft International Standards Fig.1 The basic classification table proposed in ISO DIS 14644-1:2010 ISO Classification Number (N) Maximum

Cleanroom

Standards and

Updates

Cleanroom Standards / Environmental Guides FED-STD 209E: Established Sept, 1992: Cancelled

November 2001

ISO 14644-1: Established May 1999 (replaces Fed-STD 209E, BS 5295)

EU GGMP Annex 1

ISO 14644 DRAFT

Federal Standard 209E CLASS NAME

VOLUME UNITS VOLUME UNIT VOLUME UNIT

S.I. ENGLISH (M3) (FT

3) (M

3) (FT

3) (M

3) (FT

3) (M

3) (FT

3) (M

3) (FT

3)

M1 350 9.91 75.7 2.14 30.9 0.875 10 0.283

M1.5 1 1240 35 265 7.5 16 3 35.3 1

M2 3500 99.1 757 21.4 309 8.75 100 2.83

M2.5 10 12,400 350 2,650 75 1,060 30 353 10

M3 35,000 991 7,570 214 3,090 87.5 1,000 28.3

M3.5 100 26,500 750 10,600 300 3,530 100

M4 75,000 2,140 30,900 875 10,000 283

M4.5 1000 35,300 1,000 247 7

M5 100,000 2,830 618 17.5

M5.5 10,000 353,000 10,000 2,470 70

M6 1,000,000 28,300 6,180 175

M6.5 100,000 3,530,000 100,000 24,700 700

M7 10,000,000 283,300 61,800 17,500

VOLUME UNIT VOLUME UNIT

FED-STD 209

0.1µM 0.2µM 0.3µM 0.5µM 5.0µM

IEST WG 100 has recommended to the GSA (U.S. General Services Group) that they (GSA) “…discontinue the use and maintenance of FED-STD-209”. The next step is for GSA to poll the U.S. Federal Agencies on the proposal that FED-STD-s09 be dropped and that the Federal Agencies use ISO 14644-1 and –2.

Many organizations refuse to change, stating the cost of document changes are too expensive to warrant replacement of the standard.

It is commonly accepted still in some facilities in the United States and in Asia.

ISO 14644-1

ISO Classification

Number0.1µM 0.2µM 0.3µM 0.5µM 1.0µM 5.0µM

VOLUME UNITS VOLUME UNIT VOLUME UNIT VOLUME UNIT VOLUME UNIT VOLUME UNIT

(M3) (M

3) (M

3) (M

3) (M

3) (M

3)

ISO 1 10 2

ISO 2 100 24 10 4

ISO 3 1,000 237 102 35 8

ISO 4 10,000 2,370 1,020 352 83

ISO 5 100,000 23,700 10,200 3,520 832 29

ISO 6 1,000,000 237,000 102,000 35,200 8,320 293

ISO 7 352,000 83,200 2,930

ISO 8 3,520,000 832,000 29,300

ISO 9 35,200,000 8,320,000 283,000

ISO 14644-1 Cleanroom Classification

EU Guide to Good Manufacturing Annex 1 Manufacture of Sterile Medicinal Products

Maximum permitted number of particles / m 3 equal to or above

D

at rest in operation

C 352,000

Not defined

3,520,000

Not defined

29,000

3,520

3,520

20

2,900

3,520

352,000

20

29

2,900

29,000

5µM Grade 0.5µM

A

B

5µM 0.5µM

3,520,000

ISO 14644-1 FED STD

209

EU GMP

(At rest)

EU GMP

(Operation)

1

2

3 1

4 10

5 100 Grade A/B Grade A

6 1000

7 10,000 Grade C Grade B

8 100,000 Grade D Grade C

9

Comparison

ISO 14644-1 Draft International Standard ISO Technical Committee 209 (TC 209) has been working on the revision of the basic airborne cleanliness classification standard for the last 4 years and has voted in favor of revision to update and improve the standard specifically to address the following: ► Simplify the classification process

► Remove the need to evaluate the 95% UCL for 2-9 sample locations

► Review the classification procedure and make it more applicable to rooms in operation.

► Generally update the standard as required to current thinking and industry requirements

► Avoid any radical change to the principles of the current ISO cleanliness classes 1-9

ISO 14644-1 Draft International Standard The DIS (draft International Standard).

The revised standard has some important new and revised requirements:

► The classification would be based on a table (see fig.1.),

► With the well known formula used for the intermediate decimal classes

► In the current standard, the table is provided in an informative annex (see

fig.3.). By using a look-up table as the basis for classification, it is easier to constrain the reader to appropriate particle sizes for specific classes

ISO 14644-1 &- 2 Draft International Standards

Fig.1 The basic classification table proposed in ISO DIS 14644-1:2010 ISO Classification

Number (N)

Maximum allowable concentrations (particles / m³) for particles equal to and greater than the considered sizes shown below

0.1µm 0.2µm 0.3µm 0.5µm 1.0µm 5.0µm

ISO Class 1 10

ISO Class 2 100 24 10 4

ISO Class 3 1,000 237 102 35 b 8

ISO Class 4 10,000 2,370 1,020 352 83

ISO Class 5 100,000 23,700 10,200 3,520 832 29

ISO Class 6 1,000,000 237,000 102,000 35,200 8,320 293

ISO Class 7 352,000 83,200 2,930

ISO Class 8 3,520,000 832,000 29,300

ISO Class 9 35,200,000 8,320,000 293,000

ISO 14644-1:1999 Cells in Yellow Reflect the omitted values in :DIS 2010

ISO 14644-1 &- 2 Draft International Standards

Fig.1 The basic classification table proposed in ISO DIS 14644-1:2010 ISO Classification

Number (N)

Maximum allowable concentrations (particles / m³) for particles equal to and greater than the considered sizes shown below a)

0.1µm 0.2µm 0.3µm 0.5µm 1.0µm 5.0µm

ISO Class 1 10 b d d d d e

ISO Class 2 100 24 10 b d d e

ISO Class 3 1,000 237 102 35 b d e

ISO Class 4 10,000 2,370 1,020 352 83 b e

ISO Class 5 100,000 23,700 10,200 3,520 832 e

ISO Class 6 1,000,000 237,000 102,000 35,200 8,320 293

ISO Class 7 c c c 352,000 83,200 2,930

ISO Class 8 c c c 3,520,000 832,000 29,300

ISO Class 9 c c c 35,200,000 8,320,000 293,000

a All concentrations in the table are cumulative, e.g. for ISO Class 5, the 10 200 particles shown at 0,3 µm include all particles equal to and greater than this size.

b These concentrations will lead to large air sample volumes for classification. Sequential sampling procedure may be applied; see Annex D.

c Concentration limits are not applicable in this region of the table due to very high particle concentration.

d Sampling and statistical limitations for particles in low concentrations make classification inappropriate.

e Sample collection limitations for both particles in low concentrations and sizes greater than 1 μm make classification inappropriate, due to potential particle losses in the sampling system.

ISO 14644-1 Draft International Standard The current standard had a simple calculation for the minimum number of sample points: In DIS: The selection of number of sample locations has been based on a more rational basis intended to confirm with 95% confidence that 90% of the cleanroom will meet the intended classification.

ISO 14644-1 &- 2 Draft International Standards

The selection of number of sample locations has been based on a more rational basis intended to confirm with 95% confidence that 90% of the cleanroom will meet the intended classification.

Area of cleanroom (m²)) less than or equal to Minimum number of sample Locations to be tested (N L )

1 1

2 1

4 2

6 3

8 4

10 5

24 6

28 7

32 8

36 9

52 10

56 11

64 12

68 13

72 14

76 15

104 16

108 17

116 18

148 19

156 20

192 21

232 22

276 23

352 24

436 25

500 26

NOTE 1 The number of sample locations are based on area units of 1, 2, and 4 m², to achieve 95 % confidence that at least 90 % of the total area does not exceed the class limit.

ISO 14644-1 &- 2 Draft International Standards

The selection of number of sample locations has been based on a more rational basis intended to confirm with 95% confidence that 90% of the cleanroom will meet the intended classification.

Area of cleanroom (m²)) less than or equal to

DIS CURRENT

1 1

2 1 2

4 2 2

6 3 3

8 4 3

10 5 4

24 6 5

28 7 6

32 8 6

36 9 6

52 10 8

56 11 8

64 12 8

68 13 9

72 14 9

76 15 9

104 16 11

108 17 11

116 18 11

148 19 13

156 20 13

192 21 14

232 22 16

276 23 17

352 24 19

436 25 21

500 26 24

Comparison DIS verse CURRENT.

ISO 14644-1 Draft International Standard

► A semi-random sampling technique is proposed based on a "hypergeometric" distribution, which is the statistical model for sampling without replacement.

► This is a significant change from current practice, and means that each time a zone is classified, the sample locations may be different.

► If a firm has determined through a risk assessment, that certain locations need to be examined specifically, then these should be designated in addition to the randomly selected locations

ISO 14644-1 Draft International Standard

► Recognizing that the <=5.0 micron class limit for ISO 5 has been removed in the revised standard, parties wishing to use the standard for classifying the environments EU GMP Grade A, and B "at rest" will have to use the macro-particle descriptor retained in the standard.

What about 5.0µm in

Grade A and B?

ISO 14644-1 International Standard Particle Counter Calibration Normative reference The following normative document contains provisions, which, through reference in this text, constitute provisions of this part of ISO 14644. Subsequent amendments to or revisions of this publication do not apply.

However, parties to agreements based on this part of ISO 14644 are encouraged to investigate the possibility of applying the most recent editions of the normative document indicated below. ISO 21501-4:2007, Determination of particle size distribution — Single particle light interaction methods — Part 4: Light scattering airborne particle counter for clean spaces

ISO 14644-2 Draft International Standard Title Change: Old: 2000 Cleanrooms and associated controlled environments Part 2: Testing and monitoring to prove continued compliance with ISO 14644-1 New: 2010 Cleanrooms and associated controlled environments Part 2: Specifications for monitoring and periodic testing to prove continued compliance with ISO 14644-1

ISO 14644-2 Draft International Standard Frequency intervals removed 4.2 Monitoring and periodic testing plan Requires a documented “monitoring and periodic testing” plan Plan to be based upon an assessment of risks

ISO 14644-1 &- 2 Draft International Standards Recertification: ► Table One Removed

Every Year Now for ALL Classes

Classification Maximum time interval Test method

≤ ISO Class 5 6 months Annex B ISO 14644-1:1999

> ISO Class 5 12 months Annex B ISO 14644-1:1999

NOTE: Particle Count tests will normally be performed in the operational state, but may also be

performed in the at-rest state in accordance with the designated ISO classification

Table 1 --Schedule of testing to demonstrate compliance

with particle concentration limits.

It’s a Draft, Baby, only a Draft ► If you really care and want to comment:

http://drafts.bsigroup.com/Home/Details/657 http://www.iso.org/iso/iso_technical_committee.html?commid=54874

TC 209 - Cleanrooms and associated controlled environments Participating countries: 22 Observing countries: 19

Participating Countries: 22 Secretariat: USA (ANSI)

Australia (SA) Kenya (KEBS)

Belgium (NBN) South Korea (KAT)

Brazil (ABNT) Netherlands (NEN)

China (SAC) Norway (SN)

Denmark (DS) Philippines (BPS)

Finland (SFS) Portugal (IPQ)

France (AFNOR) Russian Federation (GOST R)

Germany (DIN) Sweden (SIS)

Ireland (NSAI) Switzerland (SNV)

Italy (UNI) United Kingdom (BSI)

Japan (JISC)

Observing Countries: 19

Argentina (IRAM) Poland (PKN)

Bosnia and Herzegovina (BAS) Romania (ASRO)

Bulgaria (BDS) Saudi Arabia (SASO)

Cuba (NC) Serbia (ISS)

Czech Republic (UNMZ) South Africa (SABS)

Egypt (EOS) Thailand (TISI)

Hungary (MSZT) Turkey (TSE)

India (BIS) Ukraine (DSSU)

Iran (ISIRI)

Jamaica (BSJ)

Malaysia (DSM)