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Sr. No. Test Parameter ISO-14644 Eu Annex-I WHO TRS-961 2011
Sr. No. Test Parameter ISO-14644 Eu Annex-I WHO TRS-961 2011
Sr.
Test Parameter ISO-14644 EU ANNEX-I WHO TRS-961 2011
No.
Frequency of Test:- Frequency of Test:- 1) Clean rooms should be re-qualified periodically and Frequency of Test:-
1) Air velocity/ Air Changes per 1) Air velocity/ Air Changes per Hour Test:- after changes to equipment, facility or processes 1) Airflow velocity (To verify unidirectional flow
Hour Test:- a) Grade B: 6 months ± 15 working days. based on the principles of QRM. For grade A and B or containment conditions):-
a) Grade B: 6 months ± 15 b) Grade C & Grade D: 12 months ± 30 working zones, the maximum time interval for requalification a) Air velocities for containment systems and
working days. days. is 6 months. For grades C and D, the maximum time unidirectional fl ow protection systems to be
b) Grade C & Grade D: 12 2) Integrity testing of HEPA filters:- interval for requalification is 12 months. measured.
months ± 30 working days. a) Grade B: 6 months ± 15 working days. b) In accordance with ISO 14644-3 Annex B4.
2) Integrity testing of HEPA b) Grade C & Grade D: 12 months ± 30 working 2) Filter leakage tests (To verify filter integrity):-
filters:- days. a) Filter penetration tests to be carried out by a
a) Grade B: 6 months ± 15 3) Measurement of pressure drop across HEPA competent person to demonstrate filter media, fi
working days. filters:- lter seal and fi lter frame integrity. Only required
b) Grade C & Grade D: 12 a) Grade B: 6 months ± 15 working days. on HEPA filters.
months ± 30 working days. b) Grade C & Grade D: 12 months ± 30 working b) In accordance with ISO 14644-3 Annex B6.
3) Measurement of pressure days. 3) Air pressure difference (To verify non cross
drop across HEPA filters:- 4) Non-viable particulate monitoring:- contamination):-
a) Grade B: 6 months ± 15 a) Grade B,C & Grade D: 06 months ± 15 working a) Log of pressure differential readings to be
working days. days. produced or critical plants should be logged
b) Grade C & Grade D: 12 5) Recovery Time Study:- daily, preferably continuously.
1 months ± 30 working days. a) For All Grades: 24 Months± 30 working days. b) A 15 Pa pressure differential between
4) Non-viable particulate 6) Air Flow Direction Test:- different zones is recommended. In accordance
monitoring:- a) For All Grades: 24 Months± 30 working days. with ISO 14644-3 Annex B5.
a) Grade B,C & Grade D: 06 7) Segregation Test:- 4) Particle count test (Verification of
months ± 15 working days. a) For All grades: 12 months ± 30 working days. cleanliness):-
5) Recovery Time Study:- 8) Temperature, Relative humidity and a) Dust particle counts to be carried out and
a) For All Grades: 24 Months± Differential pressure monitoring:- result printouts produced.
30 working days. a) Grade C & Grade D: 12 months ± 30 working b) No. of readings and positions of tests to be in
6) Air Flow Direction Test:- days. accordance with ISO 14644-1 Annex B5
a) For All Grades: 24 Months± 9) Microbial monitoring:- 5) Airflow volume (To verify air change rates):-
30 working days. a) Grade C & Grade D: At the time of a) Airfl ow readings for supply air and return air
7) Segregation Test:- Requalification at rest. grilles to bemeasured and air change rates to be
a) For All grades: 12 months ± calculated.
30 working days. b) In accordance with ISO 14644-3 Annex B13
8) Temperature, Relative 6) Containment leakage (To verify absence of
humidity and Differential cross-contamination):-
pressure monitoring:- a) Demonstrate that contaminant is maintained
a) Grade C & Grade D: 12 within a room by means of:
months ± 30 working days. i) airflow direction smoke tests
PREPARED BY:- MANDEEP PANDEY
Sr.
Test Parameter ISO-14644 EU ANNEX-I WHO TRS-961 2011
No.
9) Microbial monitoring:- ii) room air pressures.
a) Grade C & Grade D: At the b) In accordance with ISO 14644-3 Annex B4.
time of Requalification at rest. 7) Recovery (To verify clean-up time):-
a) Test to establish time that a cleanroom takes
to recover from a contaminated condition to the
specifi ed cleanroom condition. Should not take
more than 15 min.
b) In accordance with ISO 14644-3 Annex B13*.
8) Airfl ow visualization (To verify required airfl
ow
patterns):-
a) Tests to demonstrate air fl ows:
i) from clean to dirty areas
ii) do not cause cross-contamination
iii) uniformly from unidirectional airfl ow units
b) Demonstrated by actual or video-taped smoke
tests.
c) In accordance with ISO 14644-3 Annex B7.
PREPARED BY:- MANDEEP PANDEY
Sr.
Test Parameter ISO-14644 EU ANNEX-I WHO TRS-961 2011
No.
Air velocity:- 1) The velocity can be measured close to the face 1) In Grade Unidirectional air flow systems should
1) Take calibrated anemometer of the terminal supply filters, or within the room. provide a homogeneous air speed in a range of 0.36 –
and put measuring unit at feet 2) The airflow velocity should be measured at 0.54 m/s (guidance value), the point at which the air
per minute (FPM). approximately 150 mm to 300 mm from the filter speed measurement is taken should be clearly
2) Hold the sensor and face. justified in the protocol.
measure the air velocities at 3) The number of measuring points should be 2) During initial qualification and requalification air
downstream of HEPA filter at 6 sufficient to determine the supply airflow rate in speeds may be measured either close to the terminal
inches below the filter grill by cleanrooms and clean zones, and should be the air filter face or at the working height, Where ever
calibrated anemometer square root of 10 times of area in square metres the measurement is taken
3) Take 5 steady readings (4 but no less than 4.
corners and 1 center) as shown 4) Air velocity limit not defined by ISO 14644.
below from each HEPA filter Air velocity for Grade A condition is required,
2 and calculate average air have a guidance airflow velocity of 0.36 to 0.54
velocity from the 5 readings m/s.
(A).
4) The number of air changes
in Grade B, Grade C & Grade D
areas shall not be less than 90,
40 & 20 air changes per hour
respectively
PREPARED BY:- MANDEEP PANDEY
Sr.
Test Parameter ISO-14644 EU ANNEX-I WHO TRS-961 2011
No.
Filter Integrity testing of HEPA Filter Integrity testing of HEPA Filters:-
Filters:- 1) Upstream Concentration:-
1) Ensure compressed air a) The concentration of the aerosol challenge
supply with minimum pressure upstream of the filter should be between 10
of 1.5kg/cm2 is provided to mg/m3 and 100 mg/m3.
aerosol generator container b) Concentrations lower than 20 mg/m3 can
having Poly Alpha Olefin (PAO). reduce the sensitivity for leak detection.
a) For Terminal HEPA Filter: c) Concentrations greater than 80 mg/m3 can
b) Remove the grill of the filter give rise to excessive filter fouling over an
(Terminal HEPA Filters). extended test period.
2) Release PAO aerosol into d) The upstream aerosol concentration
upstream of filter. measurements taken immediately upstream of
3) Measure the upstream the filters should not vary more than ± 15 % in
concentration at upstream time about the average measured value. (This all
port. The concentration should mention in old ISO 14644 3 2015).
be between 20-80 mg/m3 or A) According to ISO 14644 3 2019:-
µg/liter. i) The concentration of the aerosol challenge 1) HEPA filter - High efficiency particulate air filter Filter penetration tests to be carried out by a
4) Adjust the photometer to upstream of the filter should be between with minimum 0.3 μm particle retaining efficiency of competent person to demonstrate filter media,
3 read upstream as 100%. 1 mg/m3 and 100 mg/m3. 99.97 percent. filter seal and filter frame integrity. Only required
5) Scan entire area of the filter ii) Not all photometers are capable of using 1 2) HEPA filter integrity test like Upstream and on HEPA filters. In accordance with ISO 14644-3
by passing the Photometer mg/m3 as the upstream challenge. Downstream not explain in EU ANNEX-I clearly. Annex B6
scanning probe with a scan iii) This aerosol concentration should be used as
rate of not more than 5 the upstream 100 % reference for the
cm/sec. in overlapping strokes photometer.
across the face and perimeter iv) the probe should then be traversed at a scan
of the filter. Take the print rate not exceeding 5 cm/s using overlapping
from Photometer and note strokes (1 cm recommended). The probe should
down the percentage of be held in a distance of 3 cm or less from the
downstream leakage through downstream filter face or the frame structure;
the filter v) scanning should be performed over the entire
6) Down-stream concentration downstream face of each filter, the perimeter of
of PAO should be less than each filter, the seal between the filter frame and
0.01% of the upstream the grid structure, including its joints;
concentration of the challenge 2) Downstream Concentration:-
concentration. If the leakage is a) Evaluation of the supply airflow rate without a
greater than 0.01 % at the filter flow hood may be done with an anemometer
surface the filter must be downstream of each final filter. The supply
PREPARED BY:- MANDEEP PANDEY
Sr.
Test Parameter ISO-14644 EU ANNEX-I WHO TRS-961 2011
No.
rejected airflow rate is determined from the airflow
velocity multiplied by the area of exit.
b) A curtain may be used to exclude disturbances
to the unidirectional airflow.
c) The test is performed by introducing the
specific challenge aerosol upstream of the
filter(s) and searching for leaks by scanning the
downstream side of the filter(s) and the grid or
mounting frame system with the photometers
probe
d) the probe should then be traversed at a scan
rate not exceeding the value for Sr stated in
section B.6.2.5, using slightly overlapping strokes.
The probe should be held in a distance of
approximately 3 cm from the downstream filter
face or the frame structure;
e) scanning should be performed over the entire
downstream face of each filter, the perimeter of
each filter, the seal between the filter frame and
the grid structure, including its joints;
f) Designated leaks are deemed to have occurred
where a reading greater than 10−4 (0,01 %) of
the upstream challenge aerosol concentration.
Alternative acceptance criteria may be agreed
between the customer and the supplier.
e) For correlation with the acceptance criterion
of the photometer method (see B.6.2), the
maximum allowable penetration could be
adapted to 0,01 % for filters with an integral
penetration of 0,05 % and 0,005 %. In this case,
the mean particle size of aerosol should be
approximately 0,8 (± 0,2) μm.
PREPARED BY:- MANDEEP PANDEY
Sr.
Test Parameter ISO-14644 EU ANNEX-I WHO TRS-961 2011
No.
Containment leakage :-
1) This test is performed to determine if there is
intrusion of contaminated air into the clean zones
from surrounding non-controlled areas and to
check pressurized ceiling systems for leaks.
2) Light-scattering airborne-particle counter
(LSAPC) method
A) Measure the particle concentration outside
the cleanroom enclosure immediately adjacent to
the surface or doorway to be evaluated. This
concentration should be greater than the
cleanroom concentration by a factor of 103, and
equal to at least (3,5 ⨯ 106) particles/m3 at the
particle size to be measured. If the concentration
is less, generate an aerosol to increase the
concentration.
B) To check for leakage through construction
joints, cracks or service conduits, scan inside the Containment leakage:-
enclosure at a distance of not more than 5 cm 1) Demonstrate that contaminant is maintained
from the joint, seal or mating surfaces to be within a room by means of:-
tested at a scan rate of approximately 5 cm/s. A) airflow direction
C) Acceptance Critera:-All readings greater than B) smoke tests room air pressures.
10−2 times the measured external aerosol 2) In accordance with ISO 14644-3 Annex B4
4 Containment leakage This test not defined clearly in EU Annex-I guideline
particle 3) Containment can normally be achieved by
concentration at the appropriate particle size. application of the displacement concept (low
3) Aerosol photometer method:- pressure differential, high airflow), or the
A) Produce an aerosol outside the cleanroom or pressure differential concept (high pressure
device in accordance with B.7.2.2 in differential, low airflow), or the
concentration high enough to cause the aerosol physical barrier concept.
photometer to exceed 0,1 %.
B) A reading in excess of 0,01 % indicates a leak.
To check for leakage through the construction
joints, cracks or seams scan inside the enclosure
at distance of not more than 5 cm from the joint,
or seal surface to be tested, at a scan rate of
approximately 5 cm/s.
C) To check for intrusion at open doorways,
measure the concentration inside the enclosure
at a distance of 0,3 m to 1 m from the open door.
D) Acceptance criteria:- All readings in excess of
0,01 % of the photometer scale.
PREPARED BY:- MANDEEP PANDEY
Sr.
Test Parameter ISO-14644 EU ANNEX-I WHO TRS-961 2011
No.
Calculation of Sampling point for 1) Derive the minimum number of sampling location NL from table A1 provide the number
NVPC Count:- of sampling locations related to the area of the area of each cleanroom or clean
1) If calculated area falls zone to be classified and provides at least 95% confidence that at least 90% of
between two figure of the area the cleanroom or clean zone area does not exceed the class limits.
than sample points shall be
considered as per the sample
points of higher area. (Example
if calculated area are found 6.1
then sampling location shall be
consider 4). 2) If the area falls
˃1000, then sample points shall
be calculated as per details
mentioned at the end of table as
per equation A.
For initial classification the minimum number of Sampling location calculation not clearly defined
7
sampling locations can be found in ISO 14644 Part 1. in WHO TRS 961.
PREPARED BY:- MANDEEP PANDEY
Sr.
Test Parameter ISO-14644 EU ANNEX-I WHO TRS-961 2011
No.
1) The recovery test can be performed using an
LSAPC or an aerosol photometer.
2) Recovery performance is evaluated by using
the 100:1 or 10:1 recovery time and/or the
cleanliness recovery rate. The 100:1 or 10:1
recovery time is defined as the time required for
decreasing the initial concentration by a factor of
100 times (or 10 times).
3) The 100:1 test is not recommended for ISO
Classes 8 and 9.
Recovery Failure:-
4) Commence measurements at not more than 1
1) The recovery test is
min intervals and record time and concentration.
performed to determine
5) set up the particle counter in accordance with
whether the AHU is capable of
the manufacturer's instructions and the
returning to a specified
apparatus calibration certificate;
cleanliness level within a
6) The particle size used in this test should be less
defined time, after being
than 1 μm. It is recommended that the size
exposed briefly to a source of
channel used by the LSAPC corresponds to that of
non-viable particle challenge. Test to establish time that a cleanroom takes to
the maximum number concentration of the
This test is recommended for recover from a contaminated condition to the
aerosol; Recovery failure test not mention/defined in EU
8 non-unidirectional airflow specified cleanroom condition. Should not take
7) The cleanroom area to be examined should be ANNEX-1
systems because the recovery more than 15 min. In accordance with ISO 14644-
contaminated with an aerosol while the air-
performance is a function of air 3 Annex B13*
handling units are in operation;
re-circulation ratio, inlet-outlet
8) raise the initial particle concentration to more
airflow geometry and air
than 10 or 100 times depending on the target
distribution characteristics
cleanliness level.
within controlled zone. This
9) Commence measurements at not more than 1
test is applicable for grade B
min intervals and record time and concentration.
and grade C.
Evaluation procedure:
2) Acceptance criteria:-NMT 15
a) note the time when the particle concentration
Min
reaches the 10⨯ or 100⨯ target concentration
threshold (t10n or t100n);
b) note the time when the particle concentration
reaches the target cleanliness level, tn;
c) the 10:1 recovery time is represented by t0,1 =
(tn − t10n);
d) the 100:1 recovery time is represented by
t0,01 = (tn − t100n).
e) Acceptance criteria not given in IS0 14644 3
2019 guideline.
PREPARED BY:- MANDEEP PANDEY
Sr.
Test Parameter ISO-14644 EU ANNEX-I WHO TRS-961 2011
No.
11 Viable count limit not defined in ISO 14644 Viable count not defined in WHO TRS 961
PREPARED BY:- MANDEEP PANDEY
Sr.
Test Parameter ISO-14644 EU ANNEX-I WHO TRS-961 2011
No.
A) Temperature:-
1) The purpose of this test is to verify the
capability of the installation to maintain the air
temperature level within the control limits and
over the time period agreed between the
customer and supplier for the particular area
being tested. Refer to ISO 7726[28] and other
related documents for details of suitable test
methods.
2) The temperature test should be performed
using a sensor that has accuracy as defined in ISO
7726,[28]for example: 1) Where appropriate, temperature and relative
a) thermometers; humidity should be controlled, monitored and
b) resistance temperature devices; recorded, where relevant, to ensure compliance
Temperature and RH test:-
c) thermistors. with requirements pertinent to the materials and
1) The purpose of this test is to
The apparatus should have a valid calibration products and provide a comfortable environment
demonstrate the capabilities of
certificate. for the operator where necessary.
the clean room air handling 1) Other characteristics, such as temperature and
B) Relative Humidity:- 2) Maximum and minimum room temperatures
systems to maintain air relative humidity, depend on the product and nature
1) The purpose of this test is to verify the and relative humidity should be appropriate.
12 temperature and relative of the operations carried out. These parameters
capability of the installation to maintain the air Alert and action limits on temperatures and
humidity levels within the should not interfere with the defined cleanliness
humidity level (expressed as relative humidity or humilities should be set, as appropriate.
control limits over the time standard.
dew point) within the control limits and over the 3) The operating band, or tolerance, between the
periods specified by the
time period agreed acceptable minimum and maximum
customer for the area being
between the customer and the supplier for the temperatures should not be made too close.
tested.
area being tested. Refer to ISO 7726[28] and Tight control tolerances may be diffi cult to
other related documents for details of suitable achieve and can also add unnecessary installation
test methods. and running costs.
2) Humidity tests should be performed using a
sensor that has accuracy appropriate to the
measurement as stated in ISO 7726[28].
Typical sensors are:
a) dielectric thin film capacitor humidity sensor;
b) dew point sensor;
c) psychrometer.