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
FED-STD 209
CLASS NAME 0.1µM 0.2µM 0.3µM 0.5µM 5.0µM
VOLUME UNITS VOLUME UNIT VOLUME UNIT VOLUME UNIT VOLUME UNIT
S.I. ENGLISH (M3) (FT3) (M3) (FT3) (M3) (FT3) (M3) (FT3) (M3) (FT3)
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

 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 14644-1 Cleanroom Classification
ISO Classification
0.1µM 0.2µM 0.3µM 0.5µM 1.0µM 5.0µM
Number
VOLUME UNITS VOLUME UNIT VOLUME UNIT VOLUME UNIT VOLUME UNIT VOLUME UNIT
3 3 3 3 3 3
(M ) (M ) (M ) (M ) (M ) (M )
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
EU Guide to Good Manufacturing Annex 1
Manufacture of Sterile Medicinal Products
Maximum permitted number of particles / m 3
equal to or above
at rest in operation
Grade 0.5µM 5µM 0.5µM 5µM
A 3,520 20 3,520 20

B 3,520 29 352,000 2,900

C 352,000 2,900 3,520,000 29,000

D 3,520,000 29,000 Not defined Not defined

Comparison
ISO 14644-1 FED STD EU GMP EU GMP
209 (At rest) (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
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
 Fig.1 The basic classification table proposed
Maximum allowable in ISO
concentrations DIS 14644-1:2010
(particles / m³) for particles equal
ISO Classification to and greater than the considered sizes shown below
Number (N)
ISO 14644-1 &- 2 Draft
ISO Class 1
0.1µm

10
0.2µm 0.3µm 0.5µm 1.0µm 5.0µm

International Standards
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
 Fig.1 The basic classification table proposed
Maximum allowable in ISO
concentrations DIS 14644-1:2010
(particles / m³) for particles equal to
ISO Classification and greater than the considered sizes shown below a)
Number (N)
ISO 14644-1 &- 2 Draft
ISO Class 1
0.1µm

10 b
0.2µm

d
0.3µm

d
0.5µm

d
1.0µm

d
5.0µm

International Standards
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.
 Area of cleanroom (m²)) less than or equal to Minimum number of sample Locations to be
tested (N L )
1 1

ISO 14644-1 &- 2 Draft 2

4
1
2
6 3

International Standards 8
10
4
5
24 6
28 7
The selection of number
32
of sample locations has been based 8on a more
rational basis intended
36 to confirm with 95% confidence that 990% of the
cleanroom will meet 52 the intended classification. 10
56 11
64
NOTE 1 The number of 12
68 sample locations are based 13
72 on area units of 1, 2, and 4 14
76
m², to achieve 95 % 15
104 16
108
confidence that at least 90 % 17
116 of the total area does not 18
148 exceed the class limit. 19
156 20
192 21
232 22
276 23
352 24
436 25
500 26
Area of cleanroom (m²)) less than or DIS CURRENT
equal to
1 1

ISO 14644-1 &- 2 Draft

2
4
1
2
2
2
6 3 3

International Standards
8
10
4
5
3
4
24 6 5
28 7 6
The selection
32
of number of sample locations
8
has been based on a more
6
rational basis
36 intended to confirm with 95%
9 confidence that 90% of6 the
cleanroom will
52 meet the intended classification.
10 Comparison 8
56 11 8
64 12
DIS verse 8
68 13 CURRENT. 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
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
What about
5.0µm in
Grade A and B?

► 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.
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
Table 1 --Schedule of testing to demonstrate compliance
with particle concentration limits.
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

Every Year Now for ALL Classes

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) Observing Countries: 19

Argentina (IRAM) Poland (PKN)
Australia (SA) Kenya (KEBS)
Bosnia and Herzegovina (BAS) Romania (ASRO)
Belgium (NBN) South Korea (KAT)
Bulgaria (BDS) Saudi Arabia (SASO)
Brazil (ABNT) Netherlands (NEN)
China (SAC) Norway (SN) Cuba (NC) Serbia (ISS)
Denmark (DS) Philippines (BPS)
Czech Republic (UNMZ) South Africa (SABS)
Finland (SFS) Portugal (IPQ)
Egypt (EOS) Thailand (TISI)
France (AFNOR) Russian Federation (GOST R)
Hungary (MSZT) Turkey (TSE)
Germany (DIN) Sweden (SIS) India (BIS) Ukraine (DSSU)
Ireland (NSAI) Switzerland (SNV) Iran (ISIRI)
Italy (UNI) United Kingdom (BSI) Jamaica (BSJ)
Japan (JISC) Malaysia (DSM)