One of the biggest challenges in any cleanroom is setting up a suitable monitoring program. Which instruments are used, how frequent samples should be, how much sampling is
required, what guidelines need to be followed? All of
these questions need a firm understanding of the different technologies capturing cleanroom air samples
in portable particle counters and air samplers, as well
as a firm grasp on cGMP and regulatory guidelines.
Let’s start by reviewing the current guidelines;
then let’s look at the technologies used to capture air
samples and the evaluation of these samples to verify
your cleanroom is compliant to the classification it
was designed to operate in.
In terms of cleanroom classification, ISO 14644-
1:2015 classification of air cleanliness by particle
concentration is the current guideline that has been
widely used internationally. The update in 2015 was
significant in terms of particle counter sampling
volumes in ISO 5 environments, as well as a new
lookup table based on cleanroom area and the number of sampling locations. There are nine ISO classes
based on the level of air cleanliness—ISO 1 being the
highest.
In pharmaceutical aseptic
manufacture, ISO 14644-1
is the main standard used to
classify or certify cleanrooms
worldwide as a unified international standard. In 1989
the European Union adopted
its own GMP guide to Good
Manufacturing Practice, which
was equivalent to PICs GMP
guide, which was updated on
Jan. 1, 2017. The original PICs
Basic Standards came out in
1972, derived from the WHO
GMP Guide. The aim of these
standards and the continuous
improvements to the documentation ensure high-quality
medicines are produced.
Therefore, following the
latest guidelines and under-
standing how to implement
them is an important factor when developing an
environmental monitoring program and classifying
or routinely testing the classification status of your
cleanroom in at rest or operational conditions.
ISO 14644-1 and cGMP comparisons
• ISO 14644-1:2015 table has 9 ISO Classes
• ISO 14644-1:2015 table focuses on ≥0.1μm,
≥0.2μm, ≥0.3μm, ≥0.5μm, ≥1.0μm and
≥ 5.0μm particle sizes
• In ISO 14644-1:2015 ≥ 5.0μm size is makes
classification inappropriate based on low concentrations and potential particle losses in the
sampling system
• PICs PE 009-13 GMP Guide has 4 Classes,
Grade A-D
• PICs focuses on 0.5 and 5.0μm particle sizes
• Each table is based on a sample of 1 cubic meter
• PICs PE 009-13 GMP Guide has an “At Rest”
and “In Operation” Cleanroom state
• For Grade A the particle concentrations are
identical
• For Classification in Grade A zones a minimum of 1m³ sample volume is required
• Grade A is considered IS0 4. 8 when ≥ 5.0μm
are considered
• Grade B (at rest) is considered to be equivalent
to ISO 5 for ≥0.5μm and ≥ 5.0μm
• Grade C (at rest and in operation) is equivalent
to ISO 7 and ISO 8 respectively
• Grade D (at rest) equivalent to ISO 8.
• PICs PE 009-13 GMP Guide states that the
ISO 14644-1 methodology to define the number of sampling locations and the sample size
based on the class limit of the largest considered particle size is to be followed.
How are cleanrooms classified?
Using an Airborne Particle Counter
For classification based on non-viable particles an
airborne particle counter is used to classify a cleanroom and either ISO or PICs tables are used. An
airborne particle counter cannot distinguish between
a viable and non-viable particle, so all particle types
are counted. Non-viable particles are known to
act as vehicles for viable particle transportation in
Understanding how to implement the latest regulatory guidelines is just
one important factor when developing a monitoring program.
Jason Kelly, Director
of Systems
Lighthouse Worldwide Solutions
Selecting the Right Monitoring Instruments
Testing a ceiling filter
using an airborne particle
counter and scanning
probe.
All images: Lighthouse
Worldwide Solutions