ENVIRONMENTAL MONITORING / TESTING

TO CONFORM WITH ISO14644 & TGA GMP

REQUIREMENTS

PRESENTATION TO RACI
20TH APRIL 2016
PAUL MORGAN – DIRECTOR
CRITICAL CERTIFICATION PTY LTD
• CHANGES TO ISO14644 PART 1

• CHANGES TO ISO14644 PART 2

• EXPECTED CHANGES TO ISO14644 PART 3

• HOW WILL THIS LIKELY AFFECT EU / GMP PIC/S

• ISO29643

• PARTICLE COUNTER REQUIREMENTS – ISO21501 PART 4

 CURRENT ISO STANDARDS:

• Part 1: Classification of air cleanliness

• Part 2: Monitoring to provide evidence of cleanroom
performance related to air cleanliness by particle
concentration
• Part 3: Test methods
• Part 4: Design, construction and start-up
• Part 5: Operations
• Part 6: Vocabulary
• Part 7: Separative devices (clean air hoods, gloveboxes,
isolators and mini-environments)
• Part 8: Classification of airborne molecular contamination
• Part 9: Classification of surface cleanliness by particles
(Under preparation)
• Part 10: Classification of air cleanliness by nanoparticles
(Under preparation)
 ISO14644 PART 1: 2015

MAJOR CHANGES:

• EQUIPMENT DESCRIPTION MOVED FROM PART 3

• NUMBER OF LOCATIONS INCREASED SO THAT 95% UPPER

CONFIDENCE LIMIT IS NO LONGER REQUIRED

• SOME REQUIREMENTS TO SAMPLE LARGER MICRON SIZE

PARTICLES REMOVED
 ISO Class Maximum allowable concentrations (particles/m3) for particles equal
number to and greater than the considered sizes, shown belowᵃ
(N) 0.1µm 0.2µm 0.3µm 0.5µm 1.0µm 5.0µm

1 10ᵇ ᵈ ᵈ ᵈ ᵈ ᵉ

2 100 24ᵇ 10ᵇ ᵈ ᵈ ᵉ

3 1 000 237 102 35ᵇ ᵈ ᵉ

4 10 000 2 370 1 020 352 83ᵇ ᵉ

5 100 000 23 700 10 200 3 520 832 ᵈᵉᶠ

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

7 ᶜ ᶜ ᶜ 352 000 83 200 2 930

8 ᶜ ᶜ ᶜ 3 520 000 832 000 29 300

9ᶢ 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
at this particle size inappropriate, due to potential particle losses in the sampling system.
ᶠ In order to specify this particle size in association with ISO Class 5, the macroparticle descriptor M may be adapted
and used in conjunction with at least one other particle size. (See C.7.)
ᶢ This class is only applicable for the in-operation state.
 THE EFFECT OF REMOVING THE
REQUIREMENT FOR HIGHER PARTICLE SIZE:

SECTION A.4.4:
At each sampling location, sample a volume of air sufficient to detect a
minimum of 20 particles if the particle concentration for the largest selected
particle size were at the class limit for the designated ISO Class

In effect, under the previous standard, when the largest particle size of
5.0µm was used for ISO Class 5, then determined that a cubic metre was to
be sampled.

However, this requirement for Class 5 has now been removed, however,
the standard further states:
If measurements are to be made at more than one considered particle size,
each larger particle diameter (e.g. D2) shall be at least 1,5 times the next
smaller particle diameter.
 SAMPLING LOCATIONS:
In the previous standard, the number of locations required to be sampled was determined
as the square root of the floor area. i.e. for 100m² floor area, 10 locations were required.

However, under this standard, that is no longer the case, for instance, in a 100m² room it
is now required that 16 locations are sampled, see table on following slide.

This is required to ensure that it provides at least 95 % confidence that at least 90 % of

the cleanroom or clean zone area does not exceed the class limits.

In order to position the sampling locations

a) use the minimum number of sampling locations NL derived from Table A.1,
b) then divide the whole cleanroom or clean zone into NL sections of equal area,
c) select within each section a sampling location considered to be representative of the
characteristics
of the section, and
d) at each location, position the particle counter probe in the plane of the work activity or
anotherspecified point.
Additional sampling locations may be selected for locations considered critical. Their
number and positions shall also be agreed and specified.
AREA OF ROOM (m²) LESS THAN, OR EQUAL TO MINIMUM NUMBER OF SAMPLE LOCATIONS TO BE TESTED (Nᶫ)
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
636 26
1000 27
Where the size of the room exceeds 100m², the following
formula is to be applied:

NL = 27x ( A )
(1000)

where
NL is the minimum number of sampling locations to be
evaluated, rounded up to the next whole
number;
A is the area of the cleanroom in m².

If the considered area falls between two values in the table,

the greater of the two should be selected.
I.e. If the floor area = 42m², then 10 positions are required
ISO 14644 PART 2: 2015 - Monitoring to provide evidence of
cleanroom performance related to air cleanliness by particle
concentration

The previous version of this standard was titled

“Specifications for testing and monitoring to prove continued
compliance with ISO 14644-1“

This standard is now directed more towards Continuous

Monitoring.

However, this leaves a problem as the schedule for retesting

has now been removed from this standard
ISO14644 Parts 1 & 2 have now been published.

Part 3 was to have been published at the same

time, however this did not occur.

Major changes:
Table for scheduled testing has been moved form
Part 2 and will be included in Part 3.

Determination of Room Recovery Rates has been

amended.
 ISO14644 PART 3

3.7 Occupancy states

3.7.1 as-built
condition where the installation is complete with all services connected and
functioning but with no production equipment, materials, or personnel present

3.7.2 at-rest
condition where the installation is complete with equipment installed and
operating in a manner agreed upon by the customer and supplier, but with no
personnel present

3.7.3 operational
condition where the installation is functioning in the specified manner, with the
specified number of personnel present and working in the manner agreed upon
 ISO14644 PART 3

A3 Pre-test conditions:

Special care should be taken when determining the

sequence for performing tests for cleanroom
performance.
The results of each cleanroom test may be
dependent upon other pre-conditioning requirements
being met.
For example, some pre-conditions for the Pressure
Difference Test are stated in B1.2.
 ISO14644 PART 3
Table A2 – Typical Test Frequency

Type of selected test Typical period to retest

Pressure differentials 12 months
Air supply volume in non-unidirectional airflow 12 months
Air velocity in unidirectional airflow 12 months
Installed filter system leakage - non-unidirectional airflow cleanroom 24 months
Installed filter system leakage - unidirectional airflow cleanroom 12 months
Air direction & visualisation
Recovery rate
Containment test
Particle desposition rates
Segregation tests
Temperature & humidity 12 months
Electrostatic & ion generator
 Revision to Room Recovery Rates

Section B.4:
• For non-unidirectional cleanroom only

• This test now incorporates 100:1 and 10:1 tests.

• Test should be performed when the clean room is in the ‘As

Built’ or ‘At Rest’ states, or after major modification to the
cleanroom, or its operation.

• No requirement to retest every 2 years.

• It is not recommended that the 100:1 test be used for ISO 8 & 9
B4.3.4 Evaluation of Recovery rate:

Recovery performance can be determined from the slope of particle concentration decreasing
curve, as follows:

a) Commence measurements and record time and concentration continuously. Sampling time
should be as short as possible but sampling should be such that the count has statistical
relevance. Time intervals between the samplings should be as short as possible.

b) Plot the data of decreasing particle concentration on a semi-log chart (concentrations on

the ordinate by the logarithmic scale, and the time values on the abscissa by the linear scale)

c) Decide upper and lower concentration limits as to the decreasing curve measured is
accepted as almost straight line.

d) Cleanliness recovery rate is obtained from the slope of the line between the upper and
lower concentrations.

The cleanliness recovery rate between two measurements is calculated from the following
equation:

r = -2.3 x 1 log ( C1)

t ( C0)
Where

r is the cleanliness recovery rate;

t1 is the time elapsed between measured concentration crosses C0 and C1
C0 is the upper concentration;
C1 Is the lower concentration at t1
If it is possible to measure concentration at plural timing until the cleanliness is
recovered, recovery rate can be evaluated using the least squares method.

Average five to ten of recovery rate values obtained in a measurement.

The recovery rate and 100:1 recovery time can be related as follows:

r = -2.3 x 1 log¹º ( 1 ) = -2.3 x 1 (-2) = 4.6 x 1

t0.01 (100) t0.01 t0.01
where
r is the cleanliness recovery rate;
t0.01 is the time elapsed between measured concentration crosses initial and 0.01 of
initial concentration.;
Annex ‘C’ lists the Test apparatus required for each test.
This annex describes the measuring apparatus that should be used for the
recommended tests given in this part of ISO 14644.
In this annex, data given in Tables C.1 to C.22 indicate the minimum necessary
requirements for each item of apparatus. Items are listed and numbered to
correspond with Annex B, e.g. the apparatus numbered C.1 is used in the test
procedure given in B.1. Those responsible for planning tests may refer to Annex
C for the selection of test apparatus and to Annex A for a checklist of
recommended tests of an installation and the sequence in which to carry them
out. Measuring apparatus should be chosen subject to agreement between the
customer and supplier.
This annex is informative, and should not prevent the use of improved apparatus
as it becomes available. Alternative test apparatus may be appropriate and may
be used subject to agreement between customer and supplier.
Test apparatus should be selected with measurement limits and range that are
appropriate for its application.
The apparatus should also be calibrated with calibration points covering the
range of its intended use. All test apparatus sensitivity should be 1.
 Major differences when comparing ISO14644 Part 3 to
testing performed by most Australian Testing Companies:

• Many different piece of test equipment can

be utilised.

• Other test methods included in Part 3, not

normally performed in Australia i.e.
 Sample testing of installed duct HEPA
Filter installations.
 Testing of HEPA filters using DPC (Discrete
Particle Counter).
 Air volume testing using Airflow Hoods /
pitot tubes
 ISO29643
ISO29643 ‘High efficiency filters and filter media for
removing particle in air’ is the new ISO Standard for
HEPA Filters.
It was published in October, 2011.
It is broken into 5 parts, as follows:

• Part 1: Classification, performance testing & marking

• Part 2: Aerosol production, measuring equipment &

particle counting statistics

• Part 3: Testing flat sheet filter media

• Part 4: Test method for determining leakage of filter

elements – Scan method

• Part 5: Test method for filter element

 COMPARISON OF ISO29643 & EN1822

Efficiency (%) Penetration (%)

E 10 > 85 ≤ 15
ISO 15 E E 11 > 95 ≤5
ISO 20 E > 99 ≤1
ISO 25 E E 12 > 99,5 ≤ 0,5
ISO 30 E > 99,9 ≤ 0,1
ISO 35 H H 13 > 99,95 ≤ 0,05
ISO 40 H > 99,99 ≤ 0,01
ISO 45 H H 14 > 99,995 ≤ 0,005
ISO 50 U > 99,999 ≤ 0,001
ISO 55 U U 15 > 99,999 5 ≤ 0,000 5
ISO 60 U > 99,999 9 ≤ 0,000 1
ISO 65 U U 16 > 99,999 95 ≤ 0,000 05
ISO 70 U > 99,999 99 ≤ 0,000 01
ISO 75 U U 17 > 99,999 995 ≤ 0,000 005
 PARTICLE COUNTERS – ISO21501 PART 4

The new released version ISO14644 Part 1 states:

Not all instruments will be able to meet the

requirements of this standard, in this case, the use
of non compliant instruments will require an
additional explanations
 PARTICLE COUNTERS – ISO21501 PART 4
ISO 21501 has the title Determination of particle size distribution—Single
particle light interaction methods.
Included with ISO 21501 are four parts:
• Part 1: Light scattering aerosol spectrometer
• Part 2: Light scattering liquid-borne particle counter
• Part 3: Light extinction liquid-borne particle counter
• Part 4: Light scattering airborne particle counter for clean spaces

The documentation and approval of ISO 21501-2, -3, and -4 subsequently

replaces and cancels ISO 13323-1:2000. The ISO 21501 standard widens
the scope of analysis to include methodology for airborne particle counting
and liquid particle counting (both light scattering and extinction methods).
Specifically, ISO21501-4 provides a calibration procedure and verification
method for airborne particle counters to minimize inaccurate
measurements and reduce variations between different instruments.
These new guidelines require pulse height analysis (PHA) for particle
counter calibrations, which reduces inconsistencies.
Pulse Height Analyzer (PHA)
Particle counters employ solid-state photodetectors that
convert detected light energy into electrical signals. The
particle signals, known as pulses, leave the detector with
proportional amplitudes of energy that represent the particles
or photons witnessed by the detectors. If these pulses are
sorted according to their height or magnitude, we could equate
the pulses to energy received from the particle or photon.
Electronic systems that analyze particle pulses and categorize
their respective intensities are called Pulse Height Analyzers
(PHAs).
Single channel PHAs count only
pulses of certain amplitudes,
which are equivalent to a particle’s
or photon’s “perceived” energy.
Each pulse is placed into a
counting bin, called a channel,
and totaled with other pulses that
are of the same amplitude.

In effect, many smaller 0.1cfm

DPC’s, and those manufactured
prior to say 2009 are no longer
compliant with this standard.
THE END!!!

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