CACR

Issue 37
Winter/Spring 2019
ISSN 2042-3268

Air quality indices

and cleanroom
ventilation equations,
Part one: theoretical
Clean Air and Containment Review considerations

Enhance your knowledge of contamination control Things that shouldn’t

happen in a cleanroom
Selection criteria for
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Recent cleanroom
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Events and
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Contents

Contents
Main feature 4
Air quality indices and cleanroom ventilation equations,
and their application in a cleanroom HVAC system,
Part one: theoretical considerations 4
Shuji Chen, Andrew Butterworth, L. Jiang
Things that shouldn’t happen in a cleanroom,
and the consequences 12
Save money and cut carbon Jim Polarine Jr, Beth Kroeger
We can help you achieve
savings of typically 20–50%
Selection criteria for protective garments in cleanrooms
without compromising and controlled environments 18
compliance, quality and comfort.
Steve Marnach

Standards 24
For more information contact:
[email protected]
Recent cleanroom standards and changes to filter standards 24
John Neiger

Life-lines 25

News 26
Absolute Carbon Filters Ltd is your new carbon filters online solution 26
Pharminox Isolation Ltd. offers isolator training
and equipment management 26
From paper to paperless: Tackling the 21CFR11 challenge with PMS 26
Ecolab Life Sciences offers proactive residue
management for cleanrooms 27
Cherwell publishes guide on sterility testing 27
Pharma Clean Tech 2019, SNIEC Shanghai, June 18–20 27
Cleanroom Microbiology Solutions Envair installs new stem cell isolator with integrated
www.cherwell-labs.co.uk
CO2 incubator in Taiwan 28
Email: [email protected] Steris Corporation announces addition of biofilm
Tel: +44 (0)1869 355500 removal claim using ProKlenz® 28
Energy & Carbon Reduction Solutions introduces QASA© Quality
Assured Scientific Approach to cleanroom energy optimisation 28
Clean Room Construction builds SuperFab cleanroom 29
Clean Air and Containment Review
is a quarterly journal aimed at users, Lab Innovations returns to the NEC on 30 and 31 October 2019 29
specifiers, designers, manufacturers, EECO2 launches new training school 29
installers and testers of clean air and
containment equipment. It publishes
Events and Training courses 32
articles of topical, technical and
historical interest, updates on
standards and regulations, news,
views and information on relevant
events, especially training.

Permission to reproduce extracts

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 Editorial

Editorial
Clean Air and
Welcome to
CACR37. This issue
The second paper is a fascinating
account of incidents of cleanroom Containment
Review
features three malpractice actually witnessed by the
longish papers, authors. Reading how not to do things
which might be can often be a very useful part of learning.
thought of as heavy The third paper is a very thorough
reading, but they account of all the criteria that might be Issue 37 | Winter/Spring 2019
cover important relevant in the selection of appropriate ISSN 2042-3268
topics and are well-written, so they are cleanroom garments.
worth the effort and you will learn The standards article shows the scopes
something useful. of four recent additions to the ISO 14644 EDITOR
The first is part one of a two-part series of standards and also explains how John Neiger
study of air quality indices and ventilation ISO standards have replaced most (but T: +44 (0)1494 882094
equations and gives some background not all) of the CEN 1822 high efficiency M: +44 (0)7967 572958
in advance of the publication later this filter standards in Europe. e: [email protected]
year of ISO 14644-16, Part 16: Energy Finally CACR is delighted to
efficiency in cleanrooms and clean air welcome the formation of the EDITORIAL PANEL
devices. The standard is currently Contamination Control Network – Koos Agricola (Holland)
at the FDIS (final draft international see Press Release below. Roberta Burrows (USA)
standard) stage. This first part of Tim Eaton (UK)
the paper sets out the theoretical I hope you enjoy CACR37. Gordon Farquharson (UK)
considerations. The second part, when Didier Meyer (France)
published, will describe experimental John Neiger Berit Reinmuller (Sweden)
work that followed on. Madhu Raju Saghee (India)
Tim Sandle (UK)

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Main feature

Air quality indices and cleanroom ventilation

equations, and their application in a cleanroom
HVAC system, Part one: theoretical considerations
Shuji Chen, Andrew Butterworth, L. Jiang

Abstract standards categorize cleanrooms based shown that velocities as low as 0.3 m/s
This, the first part of a two-part paper on the maximum permitted particle provide low concentrations of airborne
summarizes current understanding concentrations as measured by counting contamination in normal levels
of air quality indices and cleanroom the number of particles in one cubic of occupancy and activity, in
ventilation equations and their use in meter of air. The particle concentration unidirectional rooms.
a cleanroom heating, ventilation and is controlled by the heating, ventilation
2. Non-unidirectional airflow
air conditioning (HVAC) system. The and air-conditioning (HVAC) system
Non-unidirectional airflow is defined
equations for air quality indices, which circulates air in the cleanrooms
in ISO 14644-4 [9] as “air distribution
including the contaminant removal with a relatively high air change rate
where the supply air entering the clean
effectiveness index (CRE) and the air (ACR) [5].
zone mixes with the internal air by means
change effectiveness index (ACE) are Among building energy services,
of induction”. ISO Class 6 through 9
reviewed, based on particles rather HVAC systems consume the most
cleanrooms are recommended to use
than gases, and dispersion rates from energy and account for about 10 -
non-unidirectional airflow designs [9].
personnel and machinery are examined. 20% of final energy use in developed
The concentration of particles is diluted
The cleanroom ventilation equations, countries [6]. Energy consumption due
by mixing with the filtered supply air
together with the air quality index and to the maintenance of environmental
and the mixed air is then removed from
the dispersion rate of particles, are conditions by means of HVAC systems
the critical zone in the exhaust air. This
then used to calculate the minimum accounts for 50% - 70% of the total
process is ACR dependent. For non-
air change rate (ACR) that is required energy consumption for pharmaceutical
unidirectional airflow cleanrooms, the
in non-unidirectional cleanrooms manufacturing [7]. The provision of the
supply air rate, and correspondingly
to achieve less than the maximum supply airflow rate contributes
the ACR, needs only to be sufficient to
specified concentration of airborne significantly to the energy consumption
effectively dilute the particles generated,
particles. The second part of the paper of a cleanroom [8]. The reduction of the
known as the source strength, to an
will describe the experimental work supply airflow rate gives a significant
acceptable concentration.
carried out by EECO2 Ltd. reduction of the overall energy use, with
the associated reductions in cost and 3. Mixed airflow
Introduction carbon footprint. Particles of different Mixed airflow is described in ISO
Cleanrooms are widely employed in sizes behave differently as air moves 14644-4 [9] as combining both
high-technology manufacturing, as in through a room with, as a generalization, unidirectional and non-unidirectional
pharmaceutical, semiconductor and particles >1µm tending to settle out and airflow in the same room. It is well
optoelectronic manufacturing, to meet particles <1µm tending to remain in the understood that higher airflow rates
the stringent requirements of high air airflow. Selection of the airflow patterns in the form of volume for non-
cleanliness levels in the processing is a major step in cleanroom design. unidirectional flow (dilution) and
environment [1]. The high technology There are three different types of velocity for unidirectional flow
manufacturing environment is based airflow in a cleanroom: (displacement) lead to a lower airborne
on a series of cleanrooms whose airborne contamination level [8]. Regulations
1. Unidirectional airflow
particulate levels are controlled. As and expected practice for both
Unidirectional airflow (UDAF) is defined
defined by the international cleanroom cleanroom types have dictated airflow
in ISO 14644-4 [9] as “controlled airflow
standard, ISO 14644-1 [2], a cleanroom rates that in some cases are excessive.
through the entire cross section of a
is a “room within which the number
clean zone with a steady velocity and
concentration of airborne particles is Air quality indices
approximately parallel airstreams.”
controlled and classified, and which is Increased ventilation efficiency could
A note adds “This type of airflow results
designed, constructed and operated in be a significant way to decrease the
in a directed transport of particles from
a manner to control the introduction, amount of energy used to achieve
the clean zone.” It is also specified as
generation and retention of particles effective ventilation of the interior
≤14° from perpendicular when performing
inside the room”. Cleanroom air spaces of buildings [11]. Ventilation
airflow parallelism [10]. Unidirectional
cleanliness classifications are specified efficiency is evaluated by a series of
filtered airflow is used for class ISO 5
according to the use of the cleanroom [3]. indices to characterize the mixing
and cleaner [9]. Particles are swept away
There are two main standards by which behavior of air and the distribution
from the critical zones and the airflow
pharmaceutical cleanrooms are classified: of contaminants within a space [11].
velocity is therefore critical. It has been
EU GMP [4] and ISO 14644 [2]. These Two indices are internationally

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 Main feature

accepted in the research area: effectiveness of the cleanroom’s air Air change effectiveness (ACE) index
contaminant removal effectiveness (CRE) supply in diluting contamination Air change effectiveness (ACE) index
and air change effectiveness (ACE). in the cleanroom and can be used to has long been used to represent the
Tracer gas techniques have been widely calculate the extra air required to ability of an air-distribution system to
used to study the pattern of airflow compensate for rooms with a poorer provide outside air where occupants
and contaminant migration in order clean air supply. breathe. It is a measure of how
to measure ACE and CRE. A series Diffusers are used for mixing the effectively the air present in a room is
of tracer gas tests using CH4 were supply air into the room air. They can replaced by fresh air from the ventilation
performed in in a study [12] to simulate be selected to give near-perfect mixing system [17]. It is defined in ASHRAE 129
contaminant migration and the removal in the room, in which case contaminant [18] as the age of air that would occur
of the contaminant generated by a point removal is by dilution, or to direct clean throughout the space if the air was
source in a residential building. The air to the critical process locations. perfectly mixed, divided by the average
values of relative CRE and removal Different types of diffuser can result age of air where occupants breathe.
effectiveness were calculated from test in different CREs with different values Thus, the ACE index is calculated by
results which can be used to assess air of throw and air patterns directed at means of the following equation:
quality related problems in the building. those critical process locations.
Equation 2
Indoor air quality was evaluated using One of the first indicators that define a
the CRE based on carbon dioxide perceived air quality is the CRE [15]. The
(CO2) concentrations for three schools CRE for tracer gas has been proven to be
where:
equipped with displacement ventilation appropriate for particles. Equation (1) is
is the nominal time constant for the
(DV) systems in Ref. [13]. In Ref. [14], the general formula of the CRE index.
room, which is the reciprocal of the ACR;
CRE and local air change index was
Equation 1 is the mean age of air at a particular
measured in order to characterize
point in the occupied zone.
ventilation effectiveness in the occupied
zone. CO2 was used as the tracer gas Sandberg introduces the concept of the
where:
to determine the CRE. age of air in Ref. [19] which has been
= Contaminant removal
A literature survey shows that the proven to be a useful tool in evaluating
effectiveness index;
common method of measuring the air ventilation efficiency. The age of air is the
= Particle concentration in the exit air
quality indices is by means of a tracer length of time that some quantity of
(either in return or exhaust air);
gas technique. With the tracer gas outside air has been in a building, zone,
= Average particle concentration at
method, the tracer gas, such as CO2 or space. The local mean age of air is
critical points in the cleanroom;
and methane (CH4), is injected into the defined as the average time it takes for
= Particle concentration in the
room whose concentration is measured air to travel from the inlet to any point
supply air.
when the ventilation system is running in the room.
to remove the contaminant. Two indoor air quality (IAQ) The nominal time constant is
The air quality indices theory may indicators, air exchange effectiveness defined as below:
be applied in pharmaceutical cleanrooms, and contaminant removal effectiveness,
Equation 3
but particles are treated as the were studied in Ref. [16]. The results
contaminant instead of tracer gases. show that CRE provides more
However, since there is no correlation informative results for removal of
where:
between gases and particles, the air contaminants with known positions and
is the room volume;
quality indices, designed initially for generation rates. In the original
is the air supply rate.
tracer gas, need to be changed to fit the equation for CRE, the denominator of
concept of particles. Only small particles the equation is the average value of the The mean age of air is calculated using
(≥0.5 µm) should be used as they stay particle concentration in the cleanroom. the following equation:
in the airflow. However, in the method described in
Equation 4
this paper, there are only two particle
Contaminant removal
counters in the cleanroom from which it
effectiveness (CRE) index
is not possible to calculate the average
Calculations for the supply airflow rate where:
particle concentration. They will,
should include a suitable CRE index, to is the initial concentration of the
however, give the average concentration
ensure that the cleanroom will maintain contaminant;
at the points where they are located,
the required conditions during most of is the concentration at a particular
which are, presumably, critical locations
the anticipated variations of the source point in the room at time .
where contaminant removal is required
strength [8]. The mixing of the supply
to be most effective. Therefore, in the For ACE in cleanrooms, it is not easy
air to a cleanroom and the cleanroom
equation for CRE, has been redefined to measure the age of air with particles
air is unlikely to be 100% perfect which
as ‘Average particle concentration since particles cannot be used as the
will lead to the airborne concentration of
at critical points in the cleanroom’. tracer. A gas can be the tracer because it
contamination at some locations within
The ventilation is effective when can mix with a specified amount of the
a cleanroom to be higher or lower than
the concentration of contaminants supplied air perfectly which makes that
average. The CRE is a measure of the
at these critical points is low. part of the air traceable when it flows

www.cleanairandcontainment.com Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 5

Main feature

through the cleanroom. A particle is to measure the recovery rate at different that the recovery rate at that location is
solid so it cannot be mixed with the air points in the room in order to obtain less than the average recovery rate. At
perfectly. Thus, the ACE concept had to the average recovery rate. some locations, the ACE value could be
be modified to fit the use of particles. Thus, the ACE can be redefined greater than 1, which demonstrate that
W. Whyte et al redefined the ACE in as below: the air distribution at those locations
Ref. [20] as below: provides a faster recovery rate than the
Equation 7
air change rate.
Equation 5 The ACR is defined by the following
expression:
Dispersion rate of particles
The sources of airborne particle
The new formula of the ACE was contamination in cleanrooms are
derived in Ref. [20] from the original Equation 8 machinery and personnel, and the total
ACE formula for tracer gas [18] and the dispersion rate is calculated as follows:
theory of recovery rate for particles
Equation 9
[21]. W. Whyte et al indicated that the where:
“air change rate at a location” could is the supply airflow rate;
be measured by the “decay rate at a is the room volume.
location”. And the decay rate can be
To calculate the ACE at a particular
calculated using the method described
location in a cleanroom using Equation
in Ref. [21].
(7), the denominator is the ACR in the There will also be some re-dispersion
The cleanliness recovery rate between
room calculated by Equation (8) and the from the floor during walking, but in a
two successive measurements is calculated
numerator is calculated by Equation (6). typical cleanroom, it is less than 1% [23].
from the following equation [21]:
An ACE value of less than 1 indicates Typical dispersion rates are shown in
Equation 6

where:
is the cleanliness recovery rate;
is the time elapsed between the
first and second measurement;
is the initial concentration;
is the concentration after time
.

Air change rate (ACR) is defined in

Ref. [21] as the “rate of air exchange
expressed as number of air changes per
unit of time and calculated by dividing
the volume of air delivered in the unit
of time by the volume of the cleanroom
or clean zone”. With this definition of
ACR, the calculation of ACR requires
a known volume. However, with the
“air change rate at a location”, there
is no known volume. For this reason,
“air change rate at a location” should
be replaced with “recovery rate at a
location” in Equation (5) as that is
what is measured in Ref. [14]. However,
if “recovery rate at a location” is the
numerator in the ACE equation, the
denominator should be the average
recovery rate so that the numerator
and the denominator are in the same
units. In fact, with perfect air mixing,
the recovery rate for the room can be
demonstrated to be the same as the air
change rate in the room [22]. Therefore
the “air change rate in the room” can
be used as the denominator in the ACE
equation and there is no need to attempt Figure 1: Number of particles generated per second per person.

6 Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 www.cleanairandcontainment.com

 Main feature

[24], [25] and [26]. The contamination the dispersion of contamination from in building services textbooks such as
index for various personnel activities personnel varies according to activity Ref. [32] and Ref. [33]. These equations
ranges from 100,000 particles per minute and clothing. are normally used to determine the
to 30,000,000 particles per minutes of concentration of undesirable or toxic gases
Dispersion rate of particles generated
0.3m in size and larger according to during the build-up, steady state, and
by machinery and equipment
different levels of actions [27]. Ref. [28] decay, in ventilated rooms or buildings.
Dispersion rates of particles from
gives an indication of particulates Equations used to calculate the airborne
machinery and other equipment vary
generated by personnel within a concentration of particles and microbe-
according to type, and it is best to
cleanroom as shown in Figure 1. carrying particles (MCPs) in the build-up,
obtain information about the dispersion
The particle shedding experiments steady-state and decay conditions in
rate from the manufacturer of the
shown in Ref. [29] present the number non-unidirectional cleanrooms have been
machinery or equipment. Alternatively,
of particles shed per minute by test discussed by W. Whyte et al [34] [30].
the total dispersion rate can be obtained
subjects in personal clothing as shown The equation for an estimate of the
experimentally using the method
in Table 1. The tests were carried out in concentration of airborne particles is
outlined in ISO 14644-14 [31]. This
a body box. proposed in Ref. [8]. By rearranging this
method can also be used to include
equation in Ref. [30], the air supply rate
Dispersion rate of particles from personnel operating the machinery,
for a given concentration of small particles
personnel in a cleanroom so that the total dispersion rate of all
can be calculate.
The dispersion of particles from personnel sources in the cleanroom is obtained.
is usually the most important source in Equation 10
the cleanroom. To determine the exact Ventilation equations for
value of the dispersion rate is difficult, ACR calculation
as the rate of particle dispersion is The greatest effect on the particle where:
dependent on each person, the design concentration in non-unidirectional = Supply airflow rate (m3/s);
of the cleanroom garments, the occlusive airflow cleanrooms is from the supply = Total particle dispersion rate from
nature of the fabrics used to manufacture airflow rate and dispersion rates personnel and machinery (counts/s);
garments, and the activity of personnel from personnel and machinery. = Required airborne particle
[8]. It is clear from dispersion chamber The derivation and application of the concentration (counts/m3) in the
experiments presented in Ref. [30] that ‘ventilation equations’ can be obtained considered location.

Table 1: Number of particles shed per minute by test subjects in personal clothing [29].

Test-person Sex Average number Average number Average number Average number
of particles/ of particles/ of particles/ of particles/
minute1 minute1 minute1 minute1
standing walking standing walking
M/F ≥0.5µm ≥0.5µm ≥5µm ≥5µm
1 M 268 4,650 3 61
2 F 65 1,460 2 49
3 M 184 4,398 5 100
4 F 113 2,179 8 52
5 F 182 2,287 18 67
6 F 346 5,547 7 112
7 M 404 13,367 10 316
8 F 189 3,895 1 35
9 M 154 2,626 5 76
10 F 58 798 6 33
11 F 53 657 6 30
12 F 13 1,998 0 92
13 M 337 4,784 32 209
Average on all 182 3,742 8 95
measurements
Actual numbers of 86,007 1,768,346 3,781 44,785
particles (projected)2

Notes:
1 As measured by the particle counters in the body box in which the tests were conducted
2 Adjusted to take into account the ratio of the airflow through the particle counters to the total airflow through the body box

www.cleanairandcontainment.com Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 7

Main feature

Equation (10) is based on the Equation (11) can then be used to estimate Conclusion
condition of particle “perfect mixing” the minimum supply airflow rate This first part of the paper has
with room air which rarely occurs in required. The calculations should only introduced the air quality indices, CRE
actual cleanrooms. Therefore, the air be used as a guide and should include and ACE, and demonstrated how they
quality index is used to include the any required compensating factors. The have been developed for use with
factors of “actual mixing” condition and designer should determine the current particles rather than tracer gases. The
the effectiveness of various airflow contamination source strengths for theory of the dispersion rate of particles
patterns. Thus, the ventilation equation existing cleanrooms and estimate has been discussed and the measured
can be derived as: all potential contamination source values from other papers have been
strengths for new cleanroom builds. shown. The ventilation equations for
Equation 11
Sufficient flexibility should be built ACR calculation have been developed
into the design to allow progressive with the introduction of the air quality
airflow tuning to take place as shown indices based on particles. The second
where:
in Figure 2. part of the paper, to be published later,
= the air quality index (CRE or ACE).
Ref. [7] provides discussion, will describe the experiments carried
Both and should refer to the same
guidance, and examples on the use of out to research these equations and
occupancy state, and to the specified
ICH Q9 “Quality Risk Management present the results.
particle size under consideration. If an
(QRM)” when reducing HVAC ACRs
air change rate is required, it can be
within manufacturing and supporting References
calculated from the cleanroom’s physical
operations. As defined in Ref. [35], [1] C. Y. Khoo, C. C. Lee and S. C. Hu,
volume as follows:
QRM is “a systematic process for the “An experimental study on the
Equation 12 assessment, control, communication, influences of air change rate and
and review of risks to the quality of the free area ratio of raised-floor on
drug (medicinal) product across the cleanroom particle concentrations,”
where: product lifecycle”. Ref. [7] demonstrates Building and Environment, vol. 48,
= Air change rate per hour; that a reduction in airflows or ACR can pp. 84-88, 2012.
= Cleanroom volume (m3). only be considered if an appropriate
[2] ISO 14644-1, “Cleanrooms and
QRM is conducted and approved. Use of
The emission data given in [24], [25] associated controlled environments
the QRM approach provides an effective
and [34] should be used to estimate the – Part 1: Classification of air
method to ensure that the requirements
contamination source strength depending cleanliness,” 2015.
from all stakeholders in the process are
on the number of personnel, the clothing
identified and assessed. [3] T. Sandle, Cleanrooms and
to be used and the process equipment.
environmental monitoring, In

Stage 1
To define:
1. Particle generation
• Personnel
Design • Equipment
To determine Q1
2. Alert limit Clim for particle concentration
3. Compensation factor

Stage 2
To provide testing for
Testing To define different Q values. To find Q2<Q1 for
(considered sequence of Q To determine particle which cleanliness
occupancy state) for testing concentration for level is provided
different experiments N.

Stage 3
Monitoring and
Operation confirmation that
At Q2 or Q3
Clim≤Cclass for Q2
Figure 2: Design-testing-operation [8], Q1 is the design, airflow rate, Q2 is the airflow rate
determined by testing and Q3 is the operational airflow rate if this is different from Q2.

8 Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 www.cleanairandcontainment.com

 Main feature

Pharmaceutical Microbiology, Oxford: “Contaminant Removal [23] W. Whyte, W. M. Whyte, W. M.

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associated controlled environments generation from humans - a
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— Part 16: Code of practice for method for experimental studies in
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Research, 1985.
Air Quality and Climate, 2005.
[9] ISO 14644-4, “Cleanrooms and
[18] ANSI/ASHRAE Standard 129-
associated controlled environments [27] P. R. Austin, Design and Operation
1997, “Measuring air-change
– Part 4: Design, construction and of Clean Rooms, Detroit: Business
effectiveness,” American Society of
start-up,” 2001. News Publishing Company, 1970.
Heating, Refrigerating and
[10] E. Bordelon, “The 4 Elements of Air-Conditioning Engineers, [28] “ISPE Good Practice Guide
Cleanroom Design, Certification Atlanta, USA, 2002. HVAC,” 2009.
and Maintenance Part 2,” 2014.
[19] M. Sandberg, “What is ventilation [29] “Study into human particle
[Online]. Available: https://
efficiency,” Building and shedding,” 2011. [Online].
amcleanroombuild.com/news/
Environment, vol. 16, pp. 123-135, Available: https://www.
the-4-elements-of-cleanroom-
1981. cleanroomtechnology.com/
design-certification-and-
technical/article_page/Study_into_
maintenance-part-2. [20] W. Whyte, S. Ward, W. M. Whyte
human_particle_shedding/62768.
and T. Eaton, “Decay of airborne
[11] J. F. Monteiro and O. S. Castro,
contamination and ventilation [30] W. Whyte, W. M. Whyte, T. Eaton
“Comparison of contaminant
effectiveness of cleanrooms,” and N. Lenegan, Calculation of air
removal effectiveness and air
International Journal of Ventilation, supply rates for non unidirectional
change efficiency as indicator of air
vol. 13, no. 3, pp. 1-10, 2014. airflow cleanrooms, EJPPS, vol 19,
diffusion quality,” in 13th
no 4, pp. 121-129, 2014.
International Conference on Indoor Air [21] ISO 14644-3, “Cleanrooms and
Quality and Climate (ISIAQ), 2014. associated controlled environments [31] ISO 14644-14, “Cleanrooms and
– Part 3: Test methods,” 2005. associated controlled environments
[12] F. Haghighat, P. Fazio and J. Rao,
— Part 14: Assessment of suitability
“A procedure for measurement [22] W. Whyte, W. M. Whyte and T.
for use of equipment by airborne
of ventilation effectiveness in Eaton, “The application of the
particle concentration”.
residential buildings,” Building and ventilation equations to cleanrooms;
Environment, vol. 25, no. 2, pp. Part 2: Decay of contamination,”
163-172, 1990. Clean Air and Containment Review,
no. 20, pp. 4-9, 2014.
[13] B. Ouazia, I. Macdonald, M. Tardif,
A. Thompson and D. Booth,

www.cleanairandcontainment.com Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 9

Main feature

[32] W. P. Jones, Ventilation and a decay

equation. In: Air Conditioning Shuji Chen is the control systems specialist engineer at
Engineering (fifth edition), London: EECO2 Ltd, energy efficiency consultancy, in Macclesfield, UK.
Butterworth-Heinemann, 2002, He came to the UK from China in the year 2010 to study at the
pp. 475-482. University of Liverpool where he received his BEng degree in
electrical engineering in 2012 and his PhD in 2017. His PhD
[33] T. D. Eastop and W. E. Watson,
research areas included system analysis, modelling, control
Mechanical Services for Buildings,
system design, simulation validation, and hardware
UK: Longman Scientific and
implementation for applications of power systems, heating, ventilation and air
Technical, 1992.
conditioning (HVAC) systems and cleanrooms.
[34] W. Whyte, W. M. Whyte and T.
Eaton, “The application of the Andrew Butterworth is products division manager at
ventilation equations to EECO2. His background is as a HVAC controls engineer.
cleanrooms; Part 1: The He has worked for BMS controls companies as a
equations,” Clean Air and commissioning and service engineer and more recently
Containment Review, no. 12, as a hospital estates manager.
pp. 4-8, 2012.

[35] “International Conference on

Harmonisation of Technical
L. Jiang received his BSc and MSc degrees in electrical
Requirements for Registration of
engineering from Huazhong University of Science and
Pharmaceuticals for Human Use,
Technology (HUST), China, in 1992 and 1996 respectively and
Quality Risk Management: Q9,”
his PhD degree from the University of Liverpool, UK, in 2001.
2005. [Online]. Available: http://
He is a Senior Lecturer in the University of Liverpool. His current
www.ich.org/fileadmin/Public_
research interests are control and analysis of power systems,
Web_Site/ICH_Products/
smart grid, renewable energy and demand-side response.
Guidelines/Quality/Q9/Step4/
Q9_Guideline.pdf.

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www.cleanairandcontainment.com Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 11

Main feature

Things that shouldn’t happen in a cleanroom,

and the consequences
Jim Polarine Jr, Beth Kroeger

Abstract in the cleanroom which is typically the

This paper is an account of bad practices dirtiest area of the room. These types
in cleanrooms, as observed by the authors. of activities can and will lead to
These bad practices are examined under enhanced risk of contamination in
the headings of personnel practices, the cleanroom operation.
operator behavior, aging facilities, items
Where are all the pens?
brought into cleanrooms and cleaning
Operators not having the necessary
and disinfection failures. Examples
items to perform their daily tasks
include evidence of food being eaten
efficiently leads to shortcuts which may
in cleanrooms, SOPs stored on the
consist of removing a pen, calculator, or
cleanroom floor, post-it notes on
phone from their scrubs/blues/uniform
cleanroom walls, gowning rooms
pocket by having to unzip their protective
crowded with supplies, horse-play,
cleanroom coverall to try to manipulate
no differentiation of “clean” and “dirty”
the forgotten item up and out of their
areas, a mouse seen in a cleanroom (!)
coveralls or bunny suit. Needless to
and many more. A couple of FDA
say, items removed from the inside of
Warning Letters are quoted.
a cleanroom coverall are not adequately
cleaned into the area. Having an
Introduction Figure 1: Double-stick tape on the surface of
appropriate number of these items
Contamination control in cleanroom an ISO 7 Cleanroom
stocked to a par level will eliminate
operations can be a complicated
such behavior. In one case management
balancing act. There have been many Items tacked onto the walls should
questioned the need for a reoccurring
instances in the past few years where be removed to allow for access when
order of 10 snips, 12 calculators, and
personnel practices, operator behavior, cleaning and disinfecting or affixed to
10 boxes of indelible ink pens per month.
aging facilities, items brought into walls with a bead of silicone around
The mystery of the missing pens and
cleanrooms, and cleaning and disinfection the edges so that no liquid can dwell
calculators was never solved, though it
failures have led to contamination in behind them. Additionally, we see
was noted that the Quality Assurance
cleanrooms. The goal should be to find dry erase boards and post-it notes
group inexplicably had the same items
the sources of contamination and to used throughout some facilities. It is
on their desks. As more sites transition
proactively prevent contamination from considered best practice not to have
to electronic batch records, this will
reoccurring in the cleanroom. these in cleanrooms, though we
become less of an issue, but the lesson
occasionally see these used without
is the same; provide operators the items
Personnel practices regulatory issue. The sticky material
they need to effectively perform their
There have been many examples we on the post-it notes can harbor
tasks without unnecessary interruptions
have seen over the years of personnel microorganisms and the dry erase
looking for miscellaneous items or
practices in cleanrooms leading to boards shed particulates and are not
having to reach inside of their gowning
elevated levels of bioburden and routinely cleaned. Per FDA guidance, 1
for items. Keeping the area 5S’d i will
contamination. There was an instance “Floors, walls, and ceilings should be
assist with this.
where a cleanroom manager was smoking constructed of smooth, hard surfaces that
a cigarette in the cleanroom which is We all need reminders every can be easily cleaned…Cleanrooms also
something that should never happen. now and then: should not contain unnecessary equipment,
Another incident of concern involved an Dry erase boards and post-it notes are fixtures, or materials.” A variation of
operator using a straw to drink a can of common ways in business by which we this is found in Health Canada’s
Coke in the cleanroom while working in remind ourselves of our daily or weekly guidance document 2 which gives their
a bunny suit. There have also been times tasks. Often, when assessing critical interpretation of the GMP regulations,
where we have seen food wrappers and environments such as ISO 7 and ISO 8 stating that “Floors, walls, and ceilings
candy wrappers on the floors in cleanroom cleanrooms, we see items affixed to walls permit cleaning. Brick, cement blocks, and
operations. There was one facility where such as job aides or reminders with other porous materials are sealed. Surface
the operator kept the SOPs on the floor double stick tape. (Figure 1). materials that shed particles are avoided.”

i. 5S is a system for organizing spaces so work can be performed efficiently, effectively, and safely. This system focuses on putting everything where it
belongs and keeping the workplace clean, which makes it easier for people to do their jobs without wasting time or risking injury. The term 5S
comes from five Japanese words which are often translated to: Sort – Set in order – Shine – Standardize – Sustain.

12 Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 www.cleanairandcontainment.com

 Main feature

Lastly, all this goes without saying that removed. (Figure 2). The gowning room at a lesser grade, it is best practice to
information should never be written should only contain cleanroom garments certify the room equal to the space being
on a gloved hand. Not only does this and items required for gowning. The entered. EU Annex 1 3 and WHO Annex
involve data integrity issues, it also gowning material should be housed 6, 11.7 both state, “Changing rooms should
adulterates the glove which could lead in plastic, stainless, or similar type be designed as airlocks and used to provide
to contamination. of substrate which can withstand physical separation of the different stages
frequent cleaning. of changing and so minimize microbial and
Where’s the line?
Frequently we encounter no separation particulate contamination of protective
The following is a personal pet peeve
of clean or dirty space in the gowning clothing. They should be flushed effectively
and usually happens due to growth
room. While gowning, it is preferable to with filtered air. The final stage of the
of a site without necessarily providing
separate the areas so that captive shoes changing room should, in the at-rest state,
additional manufacturing space.
or covers do not come into contact with be the same grade as the area into which
What results is usually convoluted
the environment where “street” shoes it leads.”. Cleanroom access should
entry practices and no differentiation
are worn. The entry of the gowning be controlled by Standard Operating
of “clean” and “dirty” entry space or
room should be considered the same Procedures (SOPs), physical or
delineation of the gowning room/area/
environment on the “clean” side of the mechanical barriers and operator
personnel air lock. We have seen
line of demarcation as the environment vigilance. It’s best practice to have an SOP
gowning rooms that are uncontrolled/
to which it leads and cleaned per the governing cleanroom access reference
unclassified and gowning rooms crowded
same frequency, even though the entire any other SOP required for entry, so the
with supplies that should be organized,
area may be operated at a lesser grade or trainee has a complete understanding
preferably into plastic, cleanable bins
classification. Although it may be operated of what is necessary for entry.
and corrugated cardboard materials
The floor is lava:
Just like the children’s game “The floor
is lava” which is a game where players
pretend the floor is made of lava and thus
avoid touching the ground, gowning
material should not be in contact with
the floor. In one instance, I was at a site
gowning in for a tour and noticed an
operator dropped his sterile coveralls
to the floor (onto a tacky mat) and then
used the same coveralls to gown. Since
the floor in the cleanroom is generally
considered the “dirtiest”, a gown that
touches the floor should never be donned,
especially when it touches a tacky mat
meant to capture debris. Gowning
practices should be governed by a detailed
gowning SOP, outlining the process for
gowning including how to gown and
not just what protective equipment or
apparel is required.
Gowning rooms should be divided
with a boundary or a line of demarcation
which is typically identified by a line
on the floor or a bench that divides the
area into two separate areas requiring
different gowning requirements.
Personnel would enter on the “dirty
side” and first, sanitize their hands
and then put on gloves. Gloves should
then be sanitized using 70% Isopropyl
Alcohol or Ethanol. Gowning should
then be performed from top down
starting with safety glasses, hair cover,
mustache/beard cover if required,
followed by garment and lastly, putting
on new boot covers and stepping over
the line of demarcation onto the “clean”
side after each boot cover is donned.
Figure 2: Crowded gowning room

www.cleanairandcontainment.com Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 13

Main feature

As a further precaution, gloved hands environments. While I have never seen contamination and spread of bioburden
should be sanitized once more upon entry. the operators put any process or product in the cleanroom facility. The duct work
at risk it is important that management and stainless steel also require routine
Operator behavior is cognizant of behavior in the cleanroom maintenance over time as they are a
There have been numerous times where and try to minimize activities that may common concern for contamination
operator behavior has played a role in impact the environment. An example of in the cleanroom. One site audited
contamination. One facility site visit had a minor infraction is where one operator many years ago had an actual hole in
over twenty operators going into and was working under the Biological Safety the flooring from damage years ago
out of the gowning room continuously Cabinet (BSC) and carried his personal and the way contamination was treated
which is an easy way to spread phone into the cleanroom under his in the hole was to pour concentrated
contamination into the cleanrooms. coveralls. Every time the operator’s quaternary ammonium disinfectant
It is best to keep the numbers to phone rang, as “punishment”, another into the hole.
essential personnel only, however, operator would spray the operator Drains in cleanrooms can also
the room must be qualified, in operation, working under the BSC with a stream of corrode over time and be an ongoing
with the maximum number of personnel Isopropyl Alcohol in the back. While source of mold spores and biofilms.
Sporicides should routinely be used in
drains to alleviate spore and biofilm
“Penicillium spores have also caused the shutdown of a concerns in drains. If it is not possible
to use a sporicide on a drain due to
cleanroom at a facility where the source ended up being corrosion concerns, then using a
plywood that was used in construction of the sliding doors disinfectant would be the next best
option for a decontamination step.
for the two ISO 7 cleanrooms.” As facilities age, issues with the
air-handling units (AHUs) may become
more prevalent. Dampers stick, belts
which will be allowed in the area. This technically no harm was done and it
burn up, and humidity may increase in
may also be governed by occupancy was all in good fun, the gowning
the area. We were working at one facility
permits. After auditing a few different material should be considered adulterated
where there was visible condensation
cleanroom facilities, I have seen instances since liquid provides a conduit for
in the area on the surfaces of the walls
of operators keeping interlocking doors microbial contamination. It could have
and floors after an incident to the
opened to go in and out of the room and also been a safety issue if the operator
AHU. When this occurs, the risk of
in another instance an operator was sitting turned around and was sprayed in the
contamination increases due to the
on a trash receptacle. The cleanroom face, not to mention possible impact to
excess moisture in the area. It is best
gowning practices are always an the culture should the operator working
practice to bring the area back into
opportunity to be a vector for bringing in the BSC became distracted.
a state of control and follow with a
bioburden into the facility through poor
remedial clean.
practices. Cleanroom SOP’s should Aging facilities
clearly state the gowning procedures Cleanroom facilities that are around
Items brought into cleanrooms
and the procedures for breaks or holes 20 years old frequently have signs
Pass thru decontamination and bringing
in gloves or gowning materials. The of wear and tear that can lead to
items into cleanrooms is the second most
facility should also have policies in place contamination concerns. Hopefully,
common source of contamination in
for makeup, jewelry, tattoos, piercings, improvements have occurred over the
the cleanroom. Yeast, fungal spore and
infections, transdermal patches, sunburns, years to update the area, however, due
bacterial spore contamination can be
and sickness of operators and visitors. to cost and expansion, sometimes sites
easily spread into cleanrooms when
There have been recent cases where have to make-do with what they have
items, carts, markers, materials, and
operators with piercings and tattoos unless the item comes up in a regulatory
intervention equipment are brought into
developed staphylococcus infections audit. When we started in industry,
cleanrooms. There was an instance where
which spread into filled vaccine products. we had a drinking fountain in an ISO 7
the tip of a black sharpie marker that was
The most common types of bioburden environment. A DRINKING FOUNTAIN!
brought into the cleanroom was the
spread into the cleanroom operation by Needless to say, this became a regulatory
source for Aspergillus brasiliensis spores
poor gowning practices are Staphylococcus issue and was addressed. However,
which shut down a cleanroom facility.
and Micrococcus. Training on gowning sometimes we miss the good old days
A site had a contamination issue from
and personnel practices can be very when you could saunter into the hallway
Acremonium which is not a common
beneficial in reducing contamination between the suites after a big cell-culture
fungal spore seen in cleanroom
rates in cleanrooms. split and pull down your facemask for
operations. The facility had contamination
a cool refreshing drink.
Horseplay: in a product and had also seen a hit
Several times cleanroom epoxy or
It happens. The high stress, close quarters, from Acremonium on a process skid.
vinyl flooring that has aged and the
and long hours may lead to the operators The key is finding a plausible source
sealant layer has broken down has been
having some good natured fun in the for this mold contamination and
a cause for concern. The more porous the
cleanroom, even in the strictest eliminating the source.
flooring becomes the higher the risk for

14 Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 www.cleanairandcontainment.com

 Main feature

Penicillium spores have also caused In one facility we visited, there were often, while assessing a site’s cleaning
the shutdown of a cleanroom at a at least three procedures for cleaning program, we discover there is no
facility where the source ended up and disinfection of the facility grouped indication of how long a use-dilution may
being plywood that was used in by whether the area was considered be used or when to discard due to the
construction of the sliding doors for a non-controlled area, moderately solution being dirty. Spent solutions may
the two ISO 7 cleanrooms. controlled area, or a high controlled contribute to residue and contamination
Bacillus cereus and Bacillus sphaericus area. It was extremely difficult to discern issues. Expiration dates should be
have also been recent sources of the requirements for any area which led established for use-dilutions as well as
contamination at cleanrooms sites. to issues with SOP compliance. There open-container expiry for disinfectant
The Bacillus cereus has been a source were multiple disinfectants used in each concentrates. Manufacturers of
of contamination in raw materials area with various dilutions and a choice disinfectants should be able to provide
in a fermenter and as a source of for use of a disinfectant or sporicidal this information. The use-dilution should
contamination in alcohol pads. agent. Use of cleaning and disinfection be changed out for a two or three bucket
Bacillus sphaericus was a source of products should preferably be routine cleaning routine every 600ft2 (60 m2) for
contamination at a pharmaceutical site and preventative and not reactionary or an ISO 5 or ISO 6 cleanroom and every
where it was used as a pesticide against used based on management discretion. 1,000ft2 (100 m2) for an ISO 7 or ISO 8
mosquitos to reduce West Nile virus In doing so, there is no way to know if cleanroom operation.5 During audits I
concerns. Yeast has been a source of the cleaning program is in a state of have observed sites using black water and
bioburden at a site where one of the control. To further exacerbate the issue, I have seen things floating in the mop
operators worked over at a brewery there were no dedicated personnel to water which are definite reasons to have
at another job and ended up transferring perform facility cleaning and the a routine bucket change out frequency.
this organism into the cleanroom site. janitorial staff was responsible for There have also been facilities that
And no Karl, this wasn’t you. disinfecting the controlled area use expired disinfectant or sporicide in
rather than a trained staff. the cleanroom. There should be control
It’s a zoo out there:
Contact time is another common error systems in place so that expired products
If you work in a cleanroom long enough,
in cleanroom applications. The biocide are not used in cleanrooms. 6 There have
or visit as many sites as we do, you will
should be on the surfaces in the cleanroom also been sites that used 70% isopropanol
see a lot of strange things. One would
for the validated contact time. FDA or a low concentration of bleach as their
think that with all of the controlled
regulators have used stop watches in only decontamination product and the
access and cleaning there will never
cleanrooms to monitor the wet contact time facility lacks a sporicide. Recent FDA
be any incidents of pests entering the
on cleanroom surfaces. If there are issues Warning Letters have highlighted
cleanroom. I’m still amazed to this
with high number of air changes in ISO 5 the lack of a sporicide being used in
day that we had a field mouse get into
cleanrooms or RABS then the product can cleanroom operations. 7
our restricted area. An area which was
either be reapplied or additional coupon There was recently a case highlighted
accessed through a bathroom door,
studies can be completed at reduced in an FDA Warning Letter where the
a locker room door, badge access
contact time reflecting the bioburden cleanroom facility was using damaged
gowning area, followed by a double
in the area of concern. and corroded equipment to apply
door automatic badge access set of
interlocking doors to the controlled
hallway. I don’t know how the mouse
was able to get in, all I know is I had a
“I’m still amazed to this day that we had a field mouse get
mouse in a container on the desk when into our restricted area. An area which was accessed through
I arrived for work at 0700 the next
morning. At another site, a snake was
a bathroom door, a locker room door, badge access gowning
in the interstitial and dropped through area, followed by a double door automatic badge access set
the ceiling of the gowning room.
In both instances, the corrective action
of interlocking doors to the controlled hallway.”
was to revise site wide pest control
procedures, inspect for access areas,
Ineffective cleaning methods are disinfectants and sporicides to cleanroom
and perform a remedial clean.
also a common cause for failures. When surfaces. This kind of practice could
water is used in the rinse bucket instead present a high risk for contamination
Cleaning and disinfection failures
of use-dilution of disinfectant there have and increasing particles in cleanrooms.
One of the most common causes of
been instances where only the water In addition to not using damaged and
cleaning and disinfection failure is not
is being applied to surfaces and not the corroded equipment, equipment should
diluting the disinfectant or sporicide
disinfectant use-dilution. The condition be properly stored when not in use.
correctly. Typically using a graduated
of the equipment can also be an issue Mops should be hung so they dry
cylinder or a unit dose packet reduces
as equipment with rusting, pitting, or completely or discard the mop heads.
large errors in making the correct
paint chips has been highlighted by Handles and mop buckets should be
dilution. Another common cause for
the FDA in recently warning letters. 4 cleaned after use or consider using
cleaning and disinfection failure is
Another common issue is changing disposable liners in mop buckets. Often,
overly complicated cleaning procedures.
out the use-dilution of disinfectant. Quite we see used mops left in buckets with

www.cleanairandcontainment.com Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 15

Main feature

residual liquid at the bottom which is 4. FDA Warning Letter Public Health 6. FDA Warning Letter Public Health
then placed into a small, dark area until Service Food and Drug Service Food and Drug
the next use. Any liquid remaining Administration, November 27, 2013. Administration, May 23, 2016.
increases the chance for microbial Available at: https://www.fda.gov/ Available at: https://www.fda.gov/
contamination. Equipment should be ICECI/EnforcementActions/ ICECI/EnforcementActions/
stored like any other equipment in a WarningLetters/2013/ucm377891.htm WarningLetters/2016/ucm505566.htm
critical environment; clean, dry, and
5. Anne Marie Dixon, Ch. 11, Cleaning 7. FDA Warning Letter Division of
covered/protected from the environment.
of Non-Product Contact Surfaces, Pharmaceutical Quality Operations
It is best practice to use some type of
p 226, in Cleaning and Cleaning IV., July 30, 2018. Available at: https://
labeling/tracking system for traceability
Validation for the Pharmaceutical and www.fda.gov/ICECI/Enforcement
and define a period of use. Typically,
Medical Device Industries, Vol. 1 Actions/WarningLetters/2018/
disposable equipment such as brushes
Basics, Expectations, and Principles. ucm618434.htm
or mop heads are used for a period up
Paul L. Pluta, Ed., PDA, Bethesda,
to one month, but this may be defined
MD, and DHI Publishing, LLC, River
on a visual basis or periodic inspection
Grove, IL. 2009.
frequency.
Lastly, maintain control of items
used for cleaning purposes in the
environment. In one instance, a facility
was using cellulose sponges, containing Jim Polarine Jr is a senior technical service manager at STERIS
“Stay fresh antimicrobial technology”. Corporation. He has been with STERIS Corporation for
While there is nothing inherently wrong eighteen years. His current technical focus is microbial control
with this technology, the sponges are in cleanrooms and other critical environments. Mr. Polarine is
household commodities and should not a 2019 PDA Michael S. Korczynski Award recipient. He has
be used in Pharma operations since they lectured in North America, Europe, Middle East, Asia, and
are raw materials that lack control and Latin America on issues related to cleaning and disinfection in
may come into contact with product cleanrooms. Mr. Polarine is a frequent industry speaker and published several
contact parts. Residues from the sponges PDA book chapters and articles related to cleaning and disinfection and
may be deposited on the surfaces in the contamination control. He is active as co-chair on the PDA’s microbial
cleanroom which could interfere with investigations task force. He was a co-author on PDA’s Technical Report #70 on
the efficacy of disinfectants, analytical Cleaning and Disinfection. Mr. Polarine teaches the cleaning and disinfection
detection methods and possibly with course module at the PDA Aseptic Processing Course and at the University of
the efficacy and quality of the drug Tennessee’s Parenteral Medications Course. Mr. Polarine is currently President
product itself. Elect for the PDA Missouri Valley and Technical Coordinator for the IEST. Mr.
As can be seen from the above Polarine graduated from the University of Illinois with a Master of Arts in
examples, there are a lot of things that Biology. He previously worked as a clinical research coordinator with the
shouldn’t happen in a cleanroom but do. Department of Veterans Affairs in St. Louis, MO and as a biology and
If you work in a clean room long enough, microbiology instructor at the University of Illinois. His main hobby is storm
contamination or strange events are chasing and is very active in tornado research and tornado safety.
inevitable. The goal is to be able to
address the issues effectively and not Beth Kroeger is a Technical Services Manager for the Life
create procedures that are overly Sciences Division of STERIS Corporation. She currently
cumbersome or complicated. provides global technical support related to process research
cleaners, cleaning validation and critical environments and
References frequently speaks on these topics for the Institute of Validation
1. FDA Guidance for Industry, Sterile Technology (IVT), United States Pharmacopeia (USP),
Drug Products Produced by Aseptic Parenteral Drug Association (PDA), International Society
Manufacturing –Current Good for Pharmaceutical Engineering (ISPE) and the National Institute for
Manufacturing Practice. Sep. 2004. Bioprocessing Research (NiBRT). Beth has over 20 year’s industry experience
in Biopharmaceutical and Oral Solid Dose manufacturing operations. Her areas
2. Health Canada Good Manufacturing
of expertise include large-scale Bioprocess systems and downstream operations
Practices (GMP) Guidelines – 2009
including large-scale purification processing, viral removal, UF and final fill.
(GUI-0001) Archived content.
Beth has held positions in R&D, Compliance, Cleaning Validation, Operations
3. EU Guidelines to Good Management and as the manufacturing lead on a cross-functional team
Manufacturing Practice, Medicinal responsible for the scale-up and technical transfer of four biopharmaceuticals.
Products for Human and Veterinary She earned a Bachelor of Science in Biochemistry from the University of
Use, Annex 1, Manufacture of Sterile Missouri, St. Louis.
Medicinal Products, 2008.

16 Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 www.cleanairandcontainment.com

 Advertisement

www.cleanairandcontainment.com Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 17

Main feature

Selection criteria for protective garments in

cleanrooms and controlled environments
Steve Marnach

Abstract operators represent at the source rather assess the contamination risks of the
This document provides guidance on the than to rely on air filtration or cleaning cleanroom, but to assess as well the
selection criteria for protective cleanroom procedures to eliminate the contamination risks the operators may be facing.
garments and accessories, and covers of the cleanroom. It is therefore
key selection principles valid for end users appropriate to define and apply
operating in cleanrooms and controlled garment selection criteria to manage Human contamination
environments within the Life Sciences, the contamination risks stemming Since every cm2 of our skin hosts millions
Pharmacy and Healthcare industries. from both the garment and the of microorganisms and since our body
Aspects, such as the required level of operator wearing these garments. is constantly shedding skin flakes having
cleanliness, product and operator a size between 0.5µm and 10µm, it is
protection, fabric performance, garment Understanding the important that the cleanroom garments
lifecycle, regulatory requirements and contamination risks being worn retain as many of these
documentation, traceability of garments The contamination risks coming from particles as possible. Several studies
and supply chain, provide valuable data, operators wearing cleanroom garments (such as Moschner C. 2011 or Ljungqvist
in order to assist end users in both the can be divided into three categories. B. and Reinmüller B. 2006) have shown
evaluation of the benefits and limitations 1. Human contamination: that the type of cleanroom garment
of different cleanroom garment systems Even when the operators are not worn inside the cleanroom has a direct
available on the market and in the moving and they are respecting high impact on the contamination risk.
selection of solutions suitable for standards of personal hygiene, they Whereas some garments systems have
different types of cleanroom applications. are shedding hundreds of thousands good particle retention properties,
of non-viable and microbe carrying others do not. The fabric out of which
Introduction particles every minute, hence the the garments are made as well as the
The draft revision of GMP Annex 1 GMP requirements that no skin garment design (i.e. type of seam,
from December 2017 defines special may be exposed in the cleanroom sewing thread, zipper, facial closure,
requirements to minimize risks of manufacture of sterile products. etc.) and the manufacturing quality
microbiological, particulate and pyrogen The cleanroom garment system all have an impact on the filtration
contamination during the manufacture plays a crucial role in ensuring that efficiency of the garments.
of sterile products. Risk assessments this human contamination inside In order to assess the fabrics used
should be carried out to detect, evaluate the cleanroom is as low as possible. for making cleanroom garments, it
and eliminate or reduce as much as Therefore, it is important to is essential to evaluate the filtration
possible any risk of contamination. understand and assess the particle efficiency of the materials used. The
Several studies (such as Akers, J. et al., retention properties of the garments particle filtration efficiency (PFE) as per
2004; Ramstorp M, 2000 or Whyte and during the validation process. EN 14683, ASTM F2100 and F2299 and
Hejab, 2007) have demonstrated that ISO 11155-1 and EN 143 evaluates the
2. The cleanroom garments themselves:
operators represent the highest source non-viable particle retention or filtration
The fabric that is used, the garment
of contamination inside the cleanroom, efficiency of filter media and other
manufacturing, the washing process,
both for dry particles and microbe filtration devices at sub-micron levels.
the handling and the packaging of the
carrying particles. Since, to date, it has The higher the PFE, the better the
cleanroom garments can introduce
not been either technically or economically barrier to dry particulates and the better
contamination into the cleanroom.
feasible to automate processes inside the protection of the process.
It is therefore critical to understand
cleanrooms manufacturing sterile ASTM F2299 works with
and assess the entire value chain 1 of
products to such an extent that human monodispersed polystyrene 0.1μm latex
garment manufacturing and handling
operators are no longer needed inside spheres that are nebulized, dried, and
as well as their performance over time.
cleanrooms, it is necessary to assess passed through the test material. The
these risks of contamination and to 3. In high hazardous processes, particles that pass through the test
reduce them to a strict minimum by the risk of cleanroom operators material are counted using a laser
implementing the necessary measures. themselves getting exposed particle counter. This test is mostly
From a risk management process, and/or being contaminated with used for masks. ISO 11155-1 uses
it makes more sense to eliminate or dangerous substances: potassium chloride (KCl) with particle
reduce the contamination risk that the It is therefore important not only to sizes of 0.3-0.4μm, 0.4-0.5μm,

1. Editor’s note: Value chain is defined as the process or activities by which a company adds value to an article, including production,
marketing, and the provision of after-sales service.

18 Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 www.cleanairandcontainment.com

 Main feature

0.5-0.6μm, 0.6-1.0μm, 1.0-2.0μm, new fabrics, there are significant garments also influences the particle
2.0-3.0μm and 3.0- 5.0μm and a fixed differences between the various contamination, it is possible through
face velocity. EN 143 works with sodium materials used for making cleanroom repeated series of tests to evaluate
chloride (NaCl) with a particle size garments (see Figure 1). There seems to the overall particle retention
of 0.3μm with a fixed flow rate. All of be a direct correlation between average performance of different garment
these tests provide interesting data fabric pore size (typically between 1µ for systems (Moschner C. 2011).
on the particle filtration efficiency of single-use fabrics and 5-6µ for uncoated As it is necessary to assess the
the fabrics used for making cleanroom polyester fabrics) and PFE and BFE. The contamination risk each time a cleanroom
garments and should be part of the smaller the pore size, the higher the garment is worn inside the cleanroom,
risk assessment. filtration efficiency. it is recommended to assess the particle
Since the PFE cannot measure viable Both PFE and BFE are measured retention properties of the garments
particles, it is equally important to assess using swatch samples of fabric only. during their entire lifetime. The studies
the bacterial filtration efficiency (BFE) However, the material is not the only from Ljungqvist B. and Reinmüller B.
as per EN 14683, ASTM F2100 and F2101 element that influences the particle (2003, 2004 and 2006), from Whyte, W.
because it allows the measuring of the retention properties of garments. The and Hejab, M. (2007) and the study
percentage of bacteria going through seams, sewing thread, garment design from DuPont (2017) all show that the
the fabrics. and manufacturing quality play an filtration efficiencies of reusable
The BFE test is performed to equally important role. The body box cleanroom garments deteriorate over
determine the filtration efficiency test method (as per IEST-RP-CC003.3) time due to wear and tear as well as
by comparing the upstream bacterial can help in assessing the filtration washing and sterilization. All of these
control counts to downstream test efficiency of complete garment systems. studies have shown increased cleanroom
material counts. A suspension of The body box test method has been contamination after 25 wash and
Staphylococcus aureus is aerosolized accepted by cleanroom users to qualify sterilization cycles: 0.5µm particles
using a nebulizer and delivered to the the relative cleanliness of a garment increased by 675%, 5µm particles
test material at a constant flow rate. system. By testing the particle shed increased by 777% and cfu/second by
The challenge delivery of colony and particle containment of the entire 128% (Ljungqvist B. and Reinmüller
forming units (CFU) is maintained with garment system, the body box provides B.2004). Moreover, the study published
a mean particle size at 3.0 μm ± 0.3μm. data about overall performance. by DuPont in 2017 has demonstrated that
These bacteria are part of the normal During the body box test, a fully washing and sterilization also reduces
flora of the human body. They are gowned subject is placed in a HEPA- the mechanical properties of polyester
frequently found in the nose, respiratory filtered air “box” and performs a series cleanroom fabrics. These performances
tract and on the skin. The higher the of activities during a 10 minutes test not only determine how many times a
BFE, the better the filtration efficiency period. The activities include a double cleanroom garment can be worn, but
of the fabric to bacteria. For example, arm reach activity for 5 minutes, march they also determine the number of the
a garment demonstrating a BFE of 90% and slap chest activity for 5 minutes operators that can work inside the
will provide a better barrier to bacteria and doing five deep knee bends in one cleanroom, based on the air filtration
and will protect the process from human minute. These activities are separated capacity of the HEPA filters used
contamination better than a garment by one minute intervals of standing still. (Ljungqvist B. and Reinmüller B.2004).
showing a BFE of 50%. This makes the The air is sampled and sent to a particle Special care should also be given
BFE an important element in the risk counter. The data is reported as the to the repair procedures of reusable
assessment of cleanroom garment average number of particles of sizes cleanroom garments as repairs can also
performance in reducing the risk of 0.3 μm and 0.5 μm and larger per minute negatively impact the particle retention
human cleanroom contamination. during the 10 minutes test period. performances.
Our studies have shown that in both Even though repeated studies have For the risk assessment, it is therefore
tests (BFE and PFE), even for brand- shown that the operator wearing the important to assess the filtration capacity
of the garments being worn each time
operators work inside the cleanroom. As
it is impossible to guarantee that all the
reusable cleanroom garments have the
same filtration properties, it is
recommended to take the worst-case
performances into account for the
risk assessment in order to avoid
limit excursions.

Cleanroom garments as source

of contamination
The garments themselves can lead to
cleanroom contamination: the fabric
Figure 1: Average bacterial filtration efficiency (BFE), can shed particles, the sewing thread
Source: Tests performed for DuPont by an external laboratory may lint, elastics may shed particles

www.cleanairandcontainment.com Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 19

Main feature

when they are stretched, the garment an irradiated or sterilized garment is not substances that are of moderate to very
may not be sterile, etc. All these elements necessarily a clean garment. The garment high toxicity levels for the operators,
need to be taken into consideration for manufacturers and/or laundries should where the acceptable human exposure
the risk assessment. also measure the cleanliness of their levels range between 1µg and 10µg/day.
The most frequent test method used garments using Helmke drum or body Through technical measures and proper
for evaluating the cleanliness of cleanroom box tests. training the contamination risk to the
garments is the Helmke drum (IEST- One element that is often neglected in operators can be significantly reduced,
RP-CC003.4.). The garments to be the validation process is the packaging but if the risk cannot be reduced to 0 for
tested are placed into a rotating drum that the garments come in. It is strongly 100% of the time, the cleanroom
and tumbled to release particulate recommended to make sure that the employers are obliged to equip their
matter from the garment. An automatic packaging used is a validated cleanroom operators with the personnel protective
particle counter is used to sample the packaging because it can introduce equipment (PPE) offering protection
air within the drum to determine the contamination into the cleanroom when from the chemical and/or biological
average particle count during the 10 the bags are opened. hazards that may be encountered
minutes test period. Results are reported In order to reduce the contamination (Council Directive, 89/656/EEC on the
minimum health and safety requirements
for the use by workers of personal protective
equipment at the workplace). In such
The cleanliness of the garments must be assessed for the cleanrooms, it is therefore mandatory
entire lifetime of the garments. Several studies have shown to use garments that are both certified
as category III PPE and suitable for use
that wear and tear as well as the washing and sterilization inside cleanrooms.
all increase the particle shedding of cleanroom garments. For sterile manufacturing, it is
important to ensure that the cleanroom
garments used have been CE certified
by category. Category I, which is the risk due to the garment, it is recommended as category III chemical and/or biological
best possible result according to this test to evaluate, assess, validate and audit protective garments after sterilization
method, requires less than 1200 the entire value chain of the cleanroom because sterilization impacts negatively
particles of >0.5μm/minute and less garments: the fabrics used, the garment on the fabric properties. Also, post-
than 2000 particles of >0.3μm/min. conversion workshops, the cleanroom sterilisation of CE certified garments
Additional test methods performed laundry, the aseptic folding and the done by a third-party (such as a
on the outside and the inside of the packaging. The garment maker and/or distributor or a laundry) or by the
garment can provide information on laundry should supply all requested garment manufacturers themselves
particle shedding while the garment documentation and guarantee the after the manufacturing of the garments
is being worn. This typically occurs traceability of their garments through de facto annulls the CE certification and
under the armpits, in the crotch area the entire value chain. During multi- the garments should be recertified (see
and at the elbows. The above- mentioned year contracts, it is recommended to European Union PPE regulation
body box test can also provide other assess these elements not only for the 2016/425). For reusable garments, it is
valuable information. initial garment introduction, but also important to ensure that the category
The cleanliness of the garments must for the repairs done and the replacement III specification is maintained and
be assessed for the entire lifetime of the garments supplied during the full guaranteed after each wash and
garments. Several studies have shown duration of the contract. All the elements sterilisation cycle during the entire
that wear and tear as well as the washing listed above must meet the validated lifetime of the garments. Also, it is
and sterilization all increase the particle specifications during the entire duration important to clearly define the handling
shedding of cleanroom garments. It is of the contract. procedures for contaminated garments
important to take this factor also into in order to avoid contaminating the
consideration for the risk assessment. Contamination risks during high operators responsible for collecting,
Another important aspect for sterile hazard manufacturing processes sorting, inspecting and washing or
manufacturing is to guarantee the sterility Cleanrooms producing or compounding disposing of worn garments.
of each cleanroom garment used during hazardous drugs, such as cytotoxic or In cleanrooms producing hazardous
production. It is therefore recommended other HPAPI drugs, face a dual risk of drugs a proper chemical and/or
that the selected garment manufacturer contamination: not only to the cleanroom biological risk assessment shall define
and/or cleanroom laundry has a validated due to the risks listed above, but also the protection properties required from
and documented sterilization process to the operators in case of accidental the cleanroom garments meeting the
according to ANSI/AAMI/ISO 11137-1 or unavoidable exposure to the HPAPI. cleanliness requirements defined by
and that they can ensure a sterility Both need to be taken into account the cleanroom class they operate in.
assurance level (SAL) 10-6. A simple during the risk assessment. The garment manufacturers and/or
irradiation or autoclaving process as The recent report published in 2018 laundries should supply all information
well as an SAL 10-4 may not be enough by Carrero B. and Paris S. show that needed for both aspects of these risk
to guarantee the sterility of the garments 38% of all pharmaceutical products that assessments.
and thus lead to limit excursions. Also, are manufactured in Europe contain

20 Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 www.cleanairandcontainment.com

 Main feature

Conclusion IEST – Institute of Environmental https://www.nelsonlabs.com/Test/

Cleanroom garments play a crucial role Sciences and Technology, IEST-RP- Bacterial-Filtration-Efficiency
in reducing the risk of cleanroom CC004: Evaluating Wiping Materials
contamination and therefore it is of the Used in Cleanrooms and Other Controlled Nelson Laboratories LLC, Particle
utmost importance to evaluate the Environments, http://www.iest.org/ Filtration Efficiency, ASTM F2100,
benefits and to understand the limitations Standards-RPs/Recommended- EN 14683 & ASTM F2299,
of the different cleanroom garment Practices/IEST-RP-CC004 https://www.nelsonlabs.com/Test/
systems available on the market in order Particle-Filtration-Efficiency-(PFE)
to specify the right solution for the International Organization for
different types of cleanroom applications Standardization, ISO 11137-1:2006 Official Journal of the European Union,
(non-hazardous and hazardous). It is Sterilization of health care products – Regulation (EU) of the European
equally important to understand, assess, Radiation – Part 1: Requirements for Parliament and of the Council of 9 March
validate and audit the entire value development, validation and routine control 2016 on Personal Protective Equipment and
chain of the garments: from the fabric of a sterilization process for medical Repealing Council Directive 89/686/EEC,
manufacturing, garment conversion, devices, https://www.iso.org/ https://eur-lex.europa.eu/legal-content/
to packaging and sterilization and, if standard/33952.html EN/TXT/?uri=CELEX%3A32016R0425
applicable, to the laundry process as
well. Companies, such as DuPont, can International Organization for Ramstorp, Matts, Introduction to
provide tools and help for these types Standardization, ISO/TS 11155-1: Air Contamination Control and Cleanroom
of risk assessments. filters for passenger compartments – Part 1: Technology, Wiley-VCH; 1 edition,
Test for particulate filtration devices, December, 2000, pp. 2–7
References https://www.iso.org/standard/34308.html
Akers, J. et al., Development of a Highly Romano F., Ljungqvist B., Reinmüller B.,
Automated PAT- Compatible Aseptic Ljungqvist B. and Reinmüller B., Gustén J. and Joppolo C.M., Performance
Processing System, paper presented at Cleanroom Clothing Systems: People as a test of technical cleanroom clothing systems,
the A3P congress, Biarritz, France, Contamination Source, River Grove, IL, Performance test of technical cleanroom
Oct. 19–21, 2004. USA: PDA/DHI Publishing, LLC; 2004 clothing systems, Proceedings of Indoor
ISBN 1-930114-60-5, 2006 Air 2016, 14th International Conference
Carrero B. and Paris S., Implications on Indoor Air Quality and Climate, p990,
of PDE calculation as exposure limit Ljungqvist B. and Reinmüller B., Ghent, Belgium, 2016. [Nr. 245692],
for risk analysis in shared facilities, Aseptic Production, Gowning Systems, http://www.isiaq.org/docs/Papers/
GMP Publishing, Germany, 2018 and Airborne Contaminants, 2004 Paper990.pdf

Council Directive, 89/656/EEC on the Ljungqvist B. and Reinmüller B., People Verein Deutscher Ingenieure, Cleanroom
minimum health and safety requirements as a Contamination Source: Cleanroom Technology: Consumables in the Cleanroom,
for the use by workers of personal protective Clothing after 1, 25, and 50 Washing / VDI 2083, January 2017, ICS 13.040.30,
equipment at the workplace, Sterilizing Cycles, European Journal of pp. 23-29
(http://eur-lex.europa.eu/legalcontent/ Parenteral & Pharmaceutical Sciences
EN/TXT/? uri=CELEX:01989L0656- 8 (3), 2003, pp. 75–80 Whyte, W. and Hejab, M., Particle and
20070627 1989) microbial airborne dispersion from people,
Moschner C., Study into Human Particle European Journal of Parenteral and
DuPont de Nemours, A Life Cycle Shedding, Cleanroom Technology, Pharmaceutical Sciences, 12 (2).
Assessment of Reusable Garment August 2011, pp. 25-28 pp. 39-46. ISSN 0964-4679, 2007
Properties, in Cleanroom technology,
pp. 15-18, June 2017 Nelson Laboratories LLC, Bacterial This paper was presented at ISCC’18
Filtration Efficiency, ASTM F2100, in The Hague in September 2018
European Commission, revision draft of EN 14683 & ASTM F2101, and is reproduced here with the kind
Annex 1 “Manufacture of Sterile Medicinal permission of the committee.
Products”, 2017, https://ec.europa.eu/
health/sites/health/files/files/
gmp/2017_12_pc_annex1_consultation_ Steve Marnach graduated with a Masters’ degree in Business
document.pdf Administration and joined DuPont in 1995. After holding various
positions in the company, he is currently EMEA Training Manager
IEST – Institute of Environmental and Critical Environments Sales and Marketing Specialist for
Sciences and Technology, IEST-RP- DuPont Personal Protection, the chemical protective garments
CC003: Garment System Considerations business that he has been working for since 2003. In this role, Steve
for Cleanrooms and Other Controlled provides training on the selection and safe handling of chemical
Environments, http://www.iest.org/ protective garments used in, amongst others, pharmaceutical production and GMP
Standards-RPs/Recommended- Grades B, C and D cleanroom operations as well as giving technical support to health
Practices/IEST-RP-CC003 and safety specialists. [email protected] www.ipp.dupont.com

www.cleanairandcontainment.com Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 21

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www.cleanairandcontainment.com Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 23

Standards

Recent cleanroom standards

and changes to filter standards
John Neiger

Cleanroom standards cleanroom surfaces, surfaces of equipment • health and safety considerations;
Work on the ISO cleanroom standards in a cleanroom and surfaces of materials • environmental aspects such as waste
is continuing apace. The first thing that in a cleanroom. Under consideration are disposal, emissions, etc.;
I look at when I see a new standard is all surfaces (external or internal) that • selection and use of statistical
the scope which can be previewed on are of interest. It provides guidance on methods.
the ISO website prior to purchase. Four the assessment of cleaning methods for
completely new Parts in the ISO 14644 achieving the required surface
series of standards have been published cleanliness by particle concentration Part 14: Assessment of suitability for
since 2016 and their scopes are (SCP) and surface cleanliness by chemical use of equipment by
reproduced here:. concentration (SCC) classes and which airborne particle concentration
techniques should be considered to (ISO 14644-14:2016)
achieve these specified levels.
Part 12: Specifications for monitoring Scope
The appropriateness of cleaning
air cleanliness by nanoscale particle This part of ISO 14644 specifies a
techniques will make reference to the
concentration (ISO 14644-12:2018) methodology to assess the suitability of
cleanliness classes and associated test
equipment (e.g. machinery, measuring
Scope methods found in ISO 14644-9 and
equipment, process equipment,
This document covers the monitoring ISO 14644-10.
components and tools) for use in
of air cleanliness by particles in The following matters of general
cleanrooms and associated controlled
terms of concentration of airborne guidance will be provided:
environments, with respect to airborne
nanoscale particles. • expected surface cleanliness levels;
particle cleanliness as specified in
For monitoring purposes, only • suitability of cleaning methods;
ISO 14644-1. Particle sizes range from
populations of particles with a lower • compatibility of surfaces with
0,1 µm to equal to or larger than 5 µm
size limit of 0.1 microns (100 nm) or the cleaning technique;
(given in ISO 14644-1).
less – “nanoscale” – are considered. • assessment of cleaning
NOTE Where regulatory agencies
The monitoring given in this document appropriateness.
impose supplementary guidelines
is for use mainly in “operational” states.
The following will be excluded from or restrictions, appropriate adaptation
NOTE 1 For the purposes of this
this document: of the assessment methodology can
document, reference is made to
• classification of cleaning methods; be required.
“nanoscale particles”, which means
• product produced within a cleanroom; The following items are not covered
all nano-objects having one (nanoplate),
• specific surface-related by this part of ISO 14644:
two (nanofibre) or three (nanoparticle)
cleaning methods; • assessment of suitability with respect
dimensions in the nanoscale.
• detailed description of cleaning to biocontamination;
NOTE 2 As a consequence,
mechanisms, methods and procedures • testing for suitability of
the specifications for monitoring air
of various cleaning methods; decontamination agents
cleanliness by nanoscale particle
• detailed material characteristics; and techniques;
concentration of the cleanroom in
• description of damage mechanisms • cleanability of equipment
operational state also considers
by cleaning processes and time- and materials;
process specifics, e.g., used equipment,
dependent effects; • requirements on design of equipment
personnel behaviour, etc.
• references to interactive bonding and selection of materials;
NOTE 3 Health and safety
forces between contaminants and • physical properties of materials
considerations are excluded from
surfaces or generation processes (e.g. electrostatic, thermal properties);
this document.
that are usually time-dependent • optimizing performance of equipment
and process-dependent; for specific process applications;
Part 13: Cleaning of surfaces • other characteristics of particles • selection and use of statistical
to achieve defined levels of such as electrostatic charge, ionic methods for testing;
cleanliness in terms of particle and charges, etc.; • protocols and requirements for
chemical classifications • chemical reactions between molecular local safety regulations.
(ISO 14644-13:2017) contaminants and surfaces;
• microbiological aspects of surface
Scope
cleanliness;
This document gives guidelines for
• radioactive aspects of contamination;
cleaning to a specified degree on

24 Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 www.cleanairandcontainment.com

 Standards/Life-lines

Part 15: Assessment of suitability for Three parts are to be reviewed, been withdrawn and superseded by the
use of equipment and materials by primarily to have their terminology equivalent ISO 29463 standards. EN
airborne chemical concentration (ISO revised to reflect the fact that they 1822 Part 1 has remained in place. The
14644-15:2017) are monitoring standards not filter standards in Europe are now:
classification standards:
Scope EN1822-1:2009
• Part 8: Classification of air
This document provides requirements High efficiency air filters (EPA, HEPA
cleanliness by chemical
and guidelines for assessing the chemical and ULPA). Classification, performance
concentration (ACC)
airborne cleanliness of equipment and testing, marking
materials which are foreseen to be used • Part 9: Classification of surface This is being revised to include
in cleanrooms and associated controlled cleanliness by particle reference to EN ISO 29463 Parts 2 – 5.
environments which are linked to the concentration
EN ISO 29463-2:2018*
ISO standard for cleanliness classes by
• Part 10: Classification of surface High-efficiency filters and filter media
chemical concentration (see ISO 14644-8).
cleanliness by chemical for removing particles in air. Aerosol
The following are outside the scope
concentration production, measuring equipment and
of this document:
particle-counting statistics
• health and safety requirements; Two new Parts are currently
• compatibility with cleaning agents in preparation EN ISO 29463-3:2018*
and techniques; • Part 16: Code of practice for High-efficiency filters and filter
• cleanability; improving energy efficiency in media for removing particles in air.
• biocontamination; cleanrooms and clean air devices Testing flat sheet filter media
• specific requirements of equipment
• Part 17: Particle deposition EN ISO 29463-4:2018*
and materials for processes
rate applications High-efficiency filters and filter media
and products;
for removing particles in air. Test
• design details of equipment. CEN is developing a new standard,
method for determining leakage of
prEN 17141: Cleanrooms and
filter elements. Scan method
associated controlled environments
Other work on
-- Biocontamination control. If this EN ISO 29463-5:2018*
cleanroom standards
draft is adopted as a standard it will High-efficiency filters and filter
Two Parts are currently under
apply in Europe and ISO 14698 Parts 1 media for removing particles in air.
periodic review:
and 2 will be withdrawn. Test method for filter elements
• Part 3: Test methods

• Part 4: Design, construction Filter standards *These are the same as ISO 29463:2011
and start-up Readers in Europe may not yet have Parts 2 – 5 but dated 2018 as that is the
spotted that EN 1822 parts 2 – 4 have year in which they were adopted by CEN.

Life-lines
Quotations of Ogden Nash Quotations of Benjamin Franklin

Among other things I think humor is a The door of a bigoted mind opens It takes many good deeds to build a
shield, a weapon, a survival kit. So here outwards so that the only result of the good reputation, and only one bad one
we are several billion of us, crowded pressure of facts upon it is to close to lose it.
into our global concentration camp for it more snugly.
Any fool can criticize, condemn and
the duration. How are we to survive?
Progress might have been all right complain - and most fools do.
Solemnity is not the answer, any more
once, but it’s gone on too long.
than witless and irresponsible frivolity Tell me and I forget. Teach me and I
is. I think our best chance lies in There has been a lot of progress during remember. Involve me and I learn.
humor, which in this case means a wry my lifetime, but I’m afraid it’s heading
Diligence is the mother of good luck.
acceptance of our predicament. We in the wrong direction.
don’t have to like it but we can at least
Wind is caused by the trees waving
recognize its ridiculous aspects, one of
their branches. Quotation of Otto von Bismarck
which is ourselves.
Too much Chablis can make
Whenever you’re wrong, admit it; Politics is the art of the possible, the
you whablis.
whenever you’re right, shut up. attainable — the art of the next best.

www.cleanairandcontainment.com Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 25

News

Absolute Carbon Pharminox Isolation Ltd. offers isolator

Filters Ltd is training and equipment management
Pharminox Isolation Ltd. covers all aspects of isolators, but there has been a recent
your new trend towards isolator training and equipment management.
Training has been carried out for both manufacturers and users of isolators. The
carbon filters theory and operation of vapour phase hydrogen peroxide bio-decontamination is a
popular topic, extending into hands-on demonstration of cycle development
online solution techniques. This training is based on extensive experience with a variety of different
VPHP devices, aiming to dispel the myths surrounding the technology.
Absolute Carbon Filters Ltd is your
In addition, Pharminox has begun to extend capacity for the management of
new independent manufacturer and
clean air equipment in research laboratories, which have a number of varied devices
supplier of carbon filters for many
such as isolators, microbiological safety cabinets and fume hoods. Keeping track of
brands offering options for both
the maintenance of these devices is a serious safety issue, often beyond the remit of
standard sized units or more
the laboratory staff. Pharminox works in co-operation with other specialist
customised applications. Having
companies to keep the equipment up-to-date and safe.
launched its new eStore in February
For further information please contact Dr Helen Hale on +44 (0) 1954 267359 or
2019, the company is proud to
e-mail [email protected]
provide products you can depend
on at competitive prices, and to
tight deadlines.
Whether you require a
simple replacement carbon filter,
From paper to paperless: Tackling the
customisation, full-fitting or
re-testing, Absolute Carbon Filters
21CFR11 challenge with PMS
can provide the service you need. Today, both the MHRA and FDA are highly focused on data integrity and discourage
In addition, the UK manufacturing methods which manually record data. Modern data management systems provide
facility and access to in-house filter secure data transfer, automated reporting without data integrity fears, and electronics
experts to discuss requirements, batch release approval processes.
allows fast delivery and on-the- Bringing manufacturing processes and controls to a new level can appear simple
ground support. in theory but provides many challenges in application. Attend a free webinar
Their carbon filters have been supported by Particle Measuring Systems on June 6th to learn more about
independently tested by the complying with the new requirement.
University of Portsmouth to validate Using the example of a standard Data Management implementation, this
effectiveness and reliability. The webinar provides a variety of insights including:
UoP found the cartridges were • Mitigating the risks of unplanned for steps.
“manufactured to a very high
• Fulfilling Data Integrity requirements.
standard and perform to the highest
standards expected” and that “These • Leveraging the project to enhance process efficiency and Quality System
impressive chemical penetration Management compliance to recent regulations.
figures would equal or better any
If you can’t make the 6 June event, register at https://www.pmeasuring.com/en/
carbon filter previously tested here.”
special-content/webinars/from-paper-to-paperless-tackling-the-21cfr11-chall and
Buy your filters online or set up an
you will be notified shortly following the live presentation and provided a link to the
account at www.absolutecarbonfilters.
recorded version.
co.uk . If you need specialist advice,
call 01252 788096 or contact
[email protected] .

Presenters: Industry experts Daniele Pandolfi (left) and Maurizio Della Pietra

26 Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 www.cleanairandcontainment.com

 News

Ecolab Life Sciences offers proactive Pharma Clean

residue management for cleanrooms Tech 2019,
Disinfectant residues impact many areas of the cleanroom. Additionally, increasing
regulatory demands around residues mean life sciences cleanroom managers need SNIEC Shanghai,
to have a residue management strategy in place for their facilities.
Both Annex 1 and Eudralex Annex 15 require that a cleaning process should be June 18–20
validated to ensure the removal of residues and any subsequent consequences from
Concurrently with P-MEC China
them, e.g. the effect on environmental monitoring results or on disinfectant, as applied.
and CPhI China, Pharma Clean
By minimising the initial residue, as well as the build-up of residues over time,
Tech 2019 will launch its 14th
Ecolab Life Sciences can offer a less disruptive, scientifically sound approach to
edition during June 18-20, 2019
controlling residues as part of the cleaning and disinfection process.
in SNIEC Shanghai, China.
James Tucker, Ecolab’s Senior Marketing Manager for Global Innovation, concludes:
Pharma Clean Tech 2019 is
“We have developed a range of low residue products which are proven to reduce
an international and high-quality
residues on both initial and repeated applications*. Klercide Low Residue Quat, for
annual exhibition, attracting over
example, can be applied
70,000 professionals in the pharma
up to 10 times with less
and clean tech industry from China
residue accumulation
and abroad. Over 100 Chinese
than even one
and overseas pharma clean tech
application of other
exhibitors such as Dynaco, Gusu,
standard disinfectants.”
MAX, Sinoarch, Linsen, and Sujing,
For more
etc. will showcase the upgraded
information, visit
purification products and equipment,
www.
latest cleanroom technology and
ecolablifesciences.com,
policy, pharma cleanroom project
or call your Ecolab
cases and solutions.
Account Manager.
Concurrently with P-MEC
* Data on file.
China and CPhI China, the total
www.ecolab.com
exhibition will occupy 17 halls with
a total area of 200,000 m2 and over
3,200 exhibitors.

Cherwell publishes guide In addition, Pharma Cleanroom

Technology Forum 2019 and Pharma

on sterility testing Clean Tech Matchmaking Event

will be organized at the same time
Cherwell Laboratories has published an eBook titled, “Failure is not an option: and are expected to gather over
Why sterility testing is so important” which is available to download from 100 audience and VIP buyers from
Cherwell’s website. The guide offers a full overview of sterility testing, as well as pharmaceutical enterprises and
the challenges and current solutions available. biotechnology industry. Pharma
The guide covers why the sterility test is considered such an important requirement Clean Tech 2019, concurrently with
for the manufacture of sterile products. It addresses the role of environmental monitoring P-MEC China and CPhI China,
programs and how these are critical to successful sterility testing, product quality and are your gateway to successfully
business reputation. grow your business at the 2nd
Topics covered within the eBook include: the sterility test principle; what the largest pharma market in the world.
expectations are within the pharmacopoeia and GMP; key considerations in the Whether you are looking for
sterility testing process; how to tackle a sterility test failure and practical steps to sourcing new business or getting
minimise risk of contamination. the latest market insight, this is
your one-stop shop pharmaceutical
The new sterility testing guide
platform in Asia.
can be downloaded at:
For more information visit
https://www.cherwell-labs.co.uk/
http://en.pmecchina.com or e-mail
why-sterility-testing-is-so-
[email protected]
important-lp

The Sterility Testing Guide from Cherwell Laboratories

www.cleanairandcontainment.com Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 27

News

Envair installs Steris Corporation announces addition of

new stem cell biofilm removal claim using ProKlenz®
STERIS Corporation announces the addition of a biofilm removal label claim in the
isolator with United States for STERIS ProKlenz® ONE alkaline cleaner following an update of the
past registration with the Environmental Protection Agency (EPA). This performance
integrated claim, in addition to the product’s claims as a disinfectant and virucide, demonstrates
the efficacy of ProKlenz ONE as both a cleaner and disinfectant. This new label
CO2 incubator claim is the result of extensive testing and development in the removal of biofilms
from hard, non-porous surfaces.
in Taiwan ProKlenz ONE alkaline cleaner is a detergent specially formulated to meet the
unique cleaning demands found in the pharmaceutical, biotechnology, cosmetic,
A bespoke all stainless steel
nutraceutical, and other industries requiring an effective validatable cleaner. It is a
ENVAIR CDC Isolator has recently
high-performance alkaline cleaner that is also a disinfectant and virucide
been installed in a new stem cell
formulated to remove difficult process residues.
research facility in Taiwan. The
A proprietary blend of a concentrated alkalinity source, advanced surfactant
isolator, complete with integrated
system and other performance enhancing ingredients provides multiple cleaning
CO2 incubator, was a difficult and
mechanisms and microbial efficacy. This low-foaming product removes a wide
challenging installation due to site
range of process residues from fermentation by-products to silicone-based
logistical constraints which
emulsions and lubricants and is ideal for use in CIP and COP applications.
required a modular approach to its
An extensive support package is available to meet your validation objectives.
manufacture and assembly. The
Customers can contact their local STERIS Life Sciences Account Manager
isolator is equipped with Envair’s
for more information or to order.
standard operator interface, a
For more information about this and other STERIS Laboratory technologies,
SIEMENS Simatic HMI panel
please visit www.sterislifesciences.com and select the “Biofilm” market application.
which benefits from a recent and
comprehensive software refresh. All
alarms are time and date stamped
and retained in the PLC for
reference. The PLC system controls
Energy & Carbon Reduction Solutions
the interlocking and timing of
transfer chamber doors. Each door
introduces QASA© Quality Assured
has its own independent timer,
which can be set to any time
Scientific Approach to cleanroom
between 10 seconds and two
minutes. The pressure decay leak
energy optimisation
test is a fully automatic procedure Cleanroom energy reduction is a hot topic in the pharmaceutical sector, and we
that only requires the operator to have been at the forefront of these discussions for over a decade. But as this
initiate the test on the touchscreen opportunity to save energy and reduce CO2 moves from niche to norm, the risk of
control panel. failure grows exponentially. Sometimes people forget we are changing the validated
For further information please state of highly regulated and controlled GMP systems.
contact [email protected] or visit Customers have spoken to us about energy optimisation projects which had to be
http://www.envair.co.uk abandoned due to poor change control, rushed and blind execution and failed
re-qualification. The root cause being an ill-informed decision made at the outset
without a stage gated approach and professional expert advice and impact assessment.
To mitigate this risk, we have developed the QASA© approach to energy
optimisation where nothing is left to chance. We have used this to deliver many
successful energy optimisation projects
high efficiency
air filter for our pharmaceutical customers. The
most recent being last year for a
company whose energy use and CO2
emissions in their EU GMP Grade C
and D manufacturing environments
was reduced by >30%, paying back
their investment in less than 18
months.
production
equipment For further information,
please contact nigel.lenegan@
air extract energyandcarbon.co.uk or visit
Picture from Cleanroom Technology www.energyandcarbon.co.uk
by W. Whyte, courtesy of W. Whyte

28 Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 www.cleanairandcontainment.com

 News

Clean Room Construction builds EECO2 launches

SuperFab cleanroom new training
A new world-class nanofabrication facility, housed in an ISO Class 5 cleanroom
designed and built by Clean Room Construction (CRC), will be officially launched school
in April.
Focussing on HVAC and Cleanroom
The official opening of the SuperFab nanofabrication facility ([email protected].
training, leading experts from EECO2
uk) at Royal Holloway, University of London in Surrey will take place on 2nd April.
share best practice and learned
Richard Rowe, CRC’s Project Director, said:
methods of energy efficiency,
“Clean Room Construction is extremely proud to have been chosen to work
regulations and standards and Good
directly with the university to design and build this state-of-the-art cleanroom
Engineering Practice (GEP).
facility which is now home to the UK Centre for Superconducting and Hybrid
Training syllabus for the 2-day
Quantum Systems.
HVAC & Cleanroom Training
The 315m² cleanroom has been engineered to incorporate a photolithography
Course includes:
area, close control e-beam area to +/- 0.1 degrees Celsius control band and an
• Concepts and principals of Good
anti-vibration foundation pad
Engineering Practice (GEP) in
for process equipment. The
GMP cleanroom
leading-edge facility is set to
play a pivotal role in the • GMP & non-GMP HVAC
development and small-scale Fundamentals: Technology,
industrial production of the System Design & Application
next generation of
• HVAC energy saving in the
superconducting quantum
context of GMP & non-GMP
devices.”
systems
CRC is at the forefront of
cleanroom design and build • Quality Risk Management
for science and (QRM) in a GMP context
technology sectors
• Workshops to discuss case
www.crc-ltd.co.uk
studies, to practice action plan
creation for improving efficiency
on a real-life site issue

Lab Innovations returns to the NEC Next courses:

• 2nd July 2019
on 30 and 31 October 2019 • 15th October 2019
More than 150 leading
Location: EECO2 Head Office -
scientific suppliers and 3,000
Macclesfield, Cheshire
attendees will descend on
This location includes a
Lab Innovations on 30 & 31
cleanroom test facility, where
October 2019 at the NEC,
theories of HVAC and cleanroom
Birmingham, to discover,
control can be tested and trialled
debate and discuss the latest
using the grade B/C cleanroom
scientific developments and
as a controlled test environment.
equipment. Now in its 8th
Interested? Contact EECO2
year, the UK’s only trade
at [email protected] or call
show dedicated to the
+44 (0) 1625 660718
laboratory industry continues
www.eeco2.com
to enjoy support from some of the UK’s leading scientific institutions and will this
year boast its largest ever exhibitor and visitor base, providing more exciting product
launches, innovation and discussion than ever before.
For cleanroom specialists, the Cleanroom Hub, in collaboration with Cleanroom
Technology, will provide a dedicated zone for suppliers of cleanroom-specific
equipment. It incorporates a seminar pod with 2 days of educational content for
cleanroom professionals, a networking lounge and dedicated exhibitor pavilion.
With a clear demand for this type of content at Lab Innovations following a 68%
increase in cleanroom attendees in 2018, this zone is set to create another buzz
at this year’s edition.
For more information please visit
https://www.easyfairs.com/lab-innovations-2019/lab-innovations-2019/

www.cleanairandcontainment.com Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 29

Advertisements

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30 Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 www.cleanairandcontainment.com

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www.cleanairandcontainment.com Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 31

Events and Training courses

Events
Dates Event Organiser
April 3 Challenges in Sterile Product Manufacture 2019, Knutsford, UK PHSS
April 29 – May 2 ESTECH 2019, Las Vegas,Nevada IEST
April 30 – May 1 Making Pharmaceuticals, Coventry, UK Stepex Ltd
May 6-7 R3 Nordic Symposium & Exhibition, Stockholm, Sweden R3Nordic
May 21-22 Cleanroom Technology Conference 2019, Birmingham, UK HPCi Media
June 18-20 EP & Clean Tech at P-MEC China 2019, Shanghai, China UBM
August 16-18 Cleanroom Guangzhou 2019, Guangzhou (Canton), China Guangzhou Grandeur
International Exhibition
Group
September 18-19 Making Pharmaceuticals, Milan, Italy Step Exhibitions
October 9-10 Pharmaceutical Cleanroom Technology Europe, London, UK SMi
October 15-17 International Congress A3P, Biarritz, France A3P
October 30-31 Lab Innovations, Birmingham, UK Easyfairs
November 12-15 Fall Conference, Rosemont, Illinois IEST
November 28-19 Pharmig 26th Annual Microbiology Conference, Nottingham, UK Pharmig

Training courses
IEST (Institute of Environmental Sciences and Technology) www.iest.org

2019 Event Location

April 29 IEST ISO 14644 Fundamentals Certificate: Estech, Las Vegas, Nevada
Understanding the Cornerstone Cleanroom Standards:
ISO 14644-1 and 14644-2
April 30 IEST ISO 14644 Fundamentals Certificate: Estech, Las Vegas, Nevada
Application of ISO 14644-3
May 1 IEST ISO 14644 Fundamentals Certificate: Estech, Las Vegas, Nevada
Universal Cleanroom Operations Guidelines with ISO 14644-5
June 18 IEST Cleanroom Fundamentals Certificate: Schaumburg, Illinois
Cleanroom Basics: What is a Cleanroom and How Does it Work?
June 19 IEST Cleanroom Fundamentals Certificate: Schaumburg, Illinois
Beyond Cleanroom Basics: Fundamental Information
for Cleanroom Operations
June 20 IEST Cleanroom Fundamentals Certificate: Schaumburg, Illinois
Cleanroom Classification Testing and Monitoring

CCN (Contamination Control Network) www.theccnetwork.org

2019 Event Location

May TBA CTCB-I Technology training course Birmingham, England
July 9-11 CTCB-I Testing and certification course Liphook, England
November 12-14 CTCB-I Testing and certification course Liphook, England

32 Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 www.cleanairandcontainment.com

 Training courses

ICS (Irish Cleanroom Society) www.cleanrooms-ireland.ie

2019 Event Location

September TBA CTCB-I Cleanroom Technology Dublin
November 26 CTCB-I Cleanroom Testing & Certification Dublin
For other courses run by ICS see https://www.cleanrooms-ireland.ie/2017_training_programme/

R3Nordic (Scottish Society for Contamination Control) www.r3nordic.org

2019 Event Location

For courses run by R3Nordic see https://r3nordic.org/

VCCN (Association of Contamination Control Netherlands)

2019 Event Location

For a complete list of courses including CTCB-I courses, please see www.vccn.nl/agenda

Note:
CTCB-I Certification: Cleanroom Testing and Certification Board International Certification,
see CTCB-1 website: www.ctcb-i.net/index.php

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www.cleanairandcontainment.com Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 33

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34 Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 www.cleanairandcontainment.com

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www.cleanairandcontainment.com Clean Air and Containment Review | Issue 37 | Winter/Spring 2019 35

 HERE

G TO SEE H

NOT E
IN

HE
ER

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RE
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E…
OR

RE
HE

HE
E
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HERE

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© 2019 Ecolab USA Inc. All rights reserved. 25FEB19/EU