Chapter 10
Environmental
Monitoring
By the end of this chapter,
you will be able to:
l
l
List the types of
environmental testing
Name three types of checks
that are carried out to ensure
the isolator is working correctly
Introduction
This chapter examines the ways in which we
monitor the cleanroom environments in which
we work and also the operators performing
aseptic manipulations.
Why do we need to monitor
the environment?
Regular monitoring of the environment,
process and finished product must occur
according to a written procedure and in
line with the published written standards
and guidelines. All areas associated with
the aseptic preparation process should be
assessed for compliance with the standards
on commissioning, after routine maintenance
and routinely at a defined frequency. Written
reports should be completed and assessed
so that appropriate action can be taken if
abnormal results are obtained.
Techniques used for monitoring should be
easy to perform, produce meaningful results
and must not contribute to contamination.
Chapter 10: Environmental Monitoring
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Aseptic Processing
What is environmental
monitoring?
Environmental monitoring is testing of the
equipment, cleanrooms and people to:
l
check that the cleanrooms, laminar flow
cabinets and isolators are performing as
expected;
l
ensure that the facilities and equipment
are controlling the environment within the
correct limits; and
l
ensure that the SOPs are being followed to
maintain the cleanroom environment.
Types of environmental testing:
l
Physical Tests
l
Microbiological Tests
l
Chemical Tests
l
Integrity of the filters
l
Particle count
l
Room air change rates
l
LAFC/Isolator velocities
These tests are usually carried out by
quality control (QC)
Microbiological tests include:
Physical tests include:
l
Settle Plates
l
Contact Plates
l
Swabs
l
Gauge checking for pressure and filter
status of rooms
l
Finger Dabs (touch plates)
Pressure and filter status of Laminar Air
Flow Cabinet (LAFC)
l
Active Air samples
l
Chemical tests include:
l
Glove leak test in isolator
l
Isolator leak test
These tests are usually carried out by operators
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Chapter 10: Environmental Monitoring
l
Surface swabs for chemical residues
e.g. cytotoxics
l
Surface wipes for chemical residues
Chapter 10
Environmental Monitoring
Test Yourself
Complete the following sentence:
Environmental monitoring is testing of the ………………...……………......................................
…………………………………………………………………………......................................…..
Write down three reasons why we carry out environmental testing
1.
2.
3.
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What methods and
equipment do we use to
test the environment?
Passive Air Sampling
Microbiological Testing
Active Air Sampling
Biotest RSC Plus Air Samplers
Active air sampling machines are used to test
the air. There are several types available.
Bacterial counts are monitored when a sample
of the air is drawn over a media on which
microbes will grow.
Tests are carried out in the manned
(operational) state and results compared to
standards set for the appropriate grade of
environment.
Settle Plates
Settle plates are used to detect any bacteria
that may be present in the environment that
fall onto the plates whilst they are exposed,
usually for 4 hours.
The plates contain a medium that is ideal for
most bacteria to grow on.
Plates are exposed during each working
session in the work zone.
Plates are usually also exposed at least weekly
in the clean room and hatches.
Plates are incubated at a specific temperature
and then checked for growth after a set period
of incubation.
The number of colonies grown is recorded and
the levels compared against standards in the
Orange Guide.
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Chapter 10: Environmental Monitoring
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Environmental Monitoring
Surface Sampling
Operator Sampling
Surface Swabs
Swabs are taken from areas where dirt
and bacteria are most likely to be present
to check that the cleaning is being carried
out effectively.
Finger Dabs
Finger dabs are carried out by all operators
after a working session.
Contact Plates
Image supplied by BiotestUK
Contact plates have a raised agar surface.
They are placed lightly onto the surface for 15
seconds and then incubated. They also check
that cleaning has been carried out properly.
Sometimes an un-gloved “before” dab is
used to assess hand washing techniques to
ensure all dirt and bacteria are removed when
scrubbing up.
Finger dabs assess operator technique and the
efficiency of item transfer techniques.
If bacteria are present, this could be due to
poor operator technique or poor spraying
and wiping technique when bacteria are still
present on the outer surface of bottles and
containers or components which may have
been passed into the LFC or Isolator.
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Physical Testing
Room Pressure Testing
Particle Testing
Gauges (Manometers)
The differential pressure between the
cleanrooms and the outer environment should
be measured regularly.
A schedule is provided in the Yellow Guide.
Biotest APC handheld Airborne Particle Counter.
At a suitable frequency, the Quality Control
Department will visit to carry out non-viable
airborne particulate counting. This assesses the
number of particles which are present in the air
to check on the level of contamination present
at that time, both in the manned and unmanned
states. Results are compared to standards. If the
results are higher than the limit, investigations
must be carried out to determine the cause of
the problem. This may be due to problems with
the air filtration systems.
All operators should check the room pressure
before using a cleanroom.
Temperature and Humidity
DOP (Dispersed Oil Particulates) Test
This test is carried out to determine the filter
integrity to ensure the filter has not been
damaged. It also checks the filter housing
to ensure there is no air by-pass due to poor
seals. DOP is introduced as a 0.3 micron sized
aerosol into the duct, upstream of the filter
and a sample of the downstream air is passed
across a light source and photometer. A
photometer analyses the penetration and gives
a pass/fail result.
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Chapter 10: Environmental Monitoring
Thermometer
The temperature of cleanrooms should be
20oC ± 2oC
This should be checked regularly together with
the relative humidity.
Chapter 10
Environmental Monitoring
Air Flow and Room Air Change Rate
Anenometer
Image supplied by Envair
Laminar flow cabinets should provide airflow
at 0.45 meters per second on average over the
whole filter face.
Airflow into a cleanroom is also measured so
that the air change rate can be calculated.
Pressure decay (Isolator leak) tests are
also carried out to ensure the integrity of the
internal environment is maintained.
Other Testing
In addition, lighting and noise levels should
also be tested periodically.
Isolator Leak Testing and Glove Leak Testing
Isolators are leak tested on a weekly basis.
Glove leak tests are carried out to check for
holes that may not be visible and that the glove
has been fitted correctly.
Glove leak tests also check the sleeves for
holes.
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Environmental Monitoring
In every manufacturing facility there is a schedule for testing which contributes to validation
of cleaning and disinfection. All results of testing are recorded and results need to be within
acceptable levels.
Below is an example of a schedule of monitoring
Type
Frequency
Where
Manometer readings (gauges)
Dailly
Room
Sessional
LAFC/Isolator
Weekly
Room
Sessional
LAFC/Isolator
Surface Samples
(contact plates, swabs)
Weekly
Room
Finger Dabs
Sessional
Workzone
Settle Plates
Below are the acceptable levels for all the different types of environmental monitoring.
Grade
of room
Finger dabs
/cfu/hand
Settle plates
90mm cfu/4 hrs
Contact plates 55mm
cfu/m3
Active air
sample cfu/m3
A
<1
<1
<1
<1
B
5
5
5
10
C
N/A
50
25
100
D
N/A
100
50
200
Reference: Orange Guide 2007
Any results which are ‘out of limits’ i.e. outside the acceptable levels, must be reported
immediately to the clean room supervisor or person in charge. It must also be documented as
laid down in your SOP. Further actions or remedies must also be recorded.
This is very important to help maintain the quality of the environment.
Validation Tests
Staff are expected to undertake evaluation tests both initially and at a designated frequency to
check their aseptic technique to ensure their working practices do not contaminate the products.
Further Reading: See Chapter 8 Quality Systems for Operators for detailed information on staff
validation tests.
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Chapter 10: Environmental Monitoring
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Environmental Monitoring
Control of Air Flow:
Cleanroom Monitoring
Control of Airflow:
Workstation Monitoring
Positive Air Flow
HEPA Filter Gauges
In order to prevent dirty air entering the facility
when doors or transfer devices are opened,
the facility is maintained at positive pressure.
This means that air will always flow out of
the facility and dirty air cannot enter and
contaminate the environment.
Pressure gauges (manometers) between
rooms should be checked in accordance with
the SOP to ensure that the pressure is correct
and that air is flowing in the right direction.
Gauges are present that display the pressure
differences between the areas in the facility.
The gauges record values, which are between
limits marked on the gauges or laid down in
standard operating procedures (SOPs).
Limits are 10Pa difference between cleanto-clean areas and 15Pa difference between
clean-to-dirty areas.
If the limits are not achieved, then no work
is to take place until the correct pressure is
established. This decision will be made by the
Unit Manager.
If the agreed values are not met/exceeded,
then there may be a problem with the filters
and so work should be suspended until this
can be investigated.
Calibration checks are carried out on
manometers by Quality Control to assess the
accuracy of the gauges.
The HEPA gauge on workstation cabinets
should be checked to monitor the blocking of
the HEPA filter.
The Laminar Air Flow Cabinet (LAFC) gauge
should be checked to ensure:
l
The cabinet is switched on and functioning
within acceptable limits
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The HEPA filter is functioning within limits
Isolator gauges should be checked to ensure:
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The isolator is switched on and operating to
protect the operator and product
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The HEPA filter is functioning within limits
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The total air change rate is operating within
acceptable limits.
The Laminar Air Flow Cabinets and isolators
are specially designed workstations with super
clean air in which the products should be
prepared. Laminar Air Flow Cabinets should
be left running at all times. Clean up times
after interruptions, i.e. power failures, should
be validated.
Pa = Pascals: This is the international unit
of pressure.
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Aseptic Processing
Environmental
Monitoring Systems
In this example we will look at a computer
system which monitors the particles and
pressures using monitors placed throughout
an aseptic unit.
Overview screen
This screen shows a graph of the differential
pressures of the unit for one day. Peaks and
troughs show when the unit is occupied and
operators move from one area to another.
A Particle Monitoring System
This screen display shows the full plan of an
aseptic unit. Green symbols indicate that these
zones are within limits. In an alarm state the
symbols change to red, indicating increased
levels of particles or pressures.
Differential Pressure displays
The software allows a number of ways of
viewing the displays.
This screen shows the pressure differentials
between rooms. Positive pressure must be
maintained throughout. The green squares
will change to red if the pressure falls
below 10 Pascals (minimum standard
between cleanrooms).
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Chapter 10: Environmental Monitoring
Here is a close up of one of the particle
monitors in the unit. This one is situated on
a wall in the assembly room. They are also
fitted into the ceilings. This unit has 24 ports
situated throughout the entire unit.
Chapter 10
Environmental Monitoring
This image shows a particle monitor within a
LAFC. It is connected via tubing to an outlet
in the wall. The pump in the plant room draws
the air sample into the machine which then
counts the particles in the area.
A screen displays the values received by the
particle monitors around the unit. The system
can count particles ranging is size from 0.3
micron to 25 micron.
(The other device is a CCTV camera used
for checking – see Chapter 8: Aseptic
Services CCTV Checking Systems for
further information).
The air samples are pulled into the main
controls which are situated in the pharmacy
plant room by a system of ultra clean
Bevaline® tubing.
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Aseptic Processing
Questions
Q1
Complete the table to show examples of each type of environmental test.
Physical
Microbiological
Chemical
1.
2.
3.
Q2
What methods do we use to test the quality of the following?
Air:
Surfaces:
People:
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Chapter 10: Environmental Monitoring
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Environmental Monitoring
Q3
Give 2 examples of tests that we use to monitor HEPA filters.
1.
2.
Q4
How often are isolators leak tested?
Name the types of leak tests for Isolators?
(4)
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Chapter 10: Environmental Monitoring