Newsletter_12-2022_EN

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NEWSLETTER
www.cleanroom-online.com Edition EN 12-2022 | Page 4/42
On the subject of wet loads, this is the most worrying factor. When
steam enters the autoclave chamber and contacts with the product, it
is important that the steam collapses (condenses) on the product. This
is in order for the heat to be released to the load. However, the formation
of water must be discharged through condensate management
or re-vaporized in order to prevent contamination of the product. Removal
of the excess water is important to prevent insulation of the
load from the steam.
We also need to be mindful of pressure and its relationship to
temperature. Given that autoclaves destroy microorganisms by direct
steam contact at the required temperature and pressure for a specified
time, pressure control is important. Poor pressure control can
cause variations in steam velocities.
Critical issues in autoclave sterilization
What are the main critical issues in autoclave sterilization processes?
Some of the key issues are based on the failure modes. Understanding
these modes is important for controlling the critical issues. One that
stands out is load design. Many companies will use a matrix approach,
whereby worst case load configurations are validated with a view to
allowing other load combinations to be used without undergoing
validation. Here care must be taken with the design of the matrix so
that anything relating to the load that can affect the distribution of
the incoming steam or which can affect uniformity of temperature is
identified and accounted for. The assessment should also take into account
anything that can take heat away from the chamber can affect
temperature uniformity.
Often mass is used for the matrix. However, there are other factors
that can affect sterilization. These include the shape of the equipment,
where narrow pipework or hoses presents a particular challenge in
terms of steam penetration (here center of the length of hose is the
most difficult to sterilize); whereas with worst-case location within a
bottle, flask or cylinder the worst case is the center near the bottom
of the container.
The orientation of the equipment is also important, and this affects
whether the item is capable of free-draining. Where there is uncertainty
about what constitutes worst case some initial work can be
undertaken thermometrically (heat penetration evaluation tests); this
allows data to be collected about heat distribution, and this ‘hard to
heat’ study is generally recommended. Account should be taken, with
liquid loads, oft the viscosity of the liquid since this can affect heat
penetration.
A further factor is the type of material, such as elastomeric materials
and stainless steel. If these types of materials are used in combination,
then a balance of both may be needed for the worst case. However, if
in practice the materials are sterilized separately, this may prompt two
types of worst case loads.
Materials: risks of medical paper and Tyvek® advantages
Let’s talk about materials: despite the strong presence of cellulose,
many continue to use medical paper. What are the risks and how,
with the new Annex 1 is it necessary to deal with them?
Packaging materials, used to wrap the items to be sterilized, are
probably one of the most important parts of the sterilization process.
Packaging provides a protective barrier for the sterile item and prevents
it from becoming re-contaminated. When used in aseptic processing,
the packaging should be of low particle generation.
Cellulosic paper is not suitable for higher grade cleanrooms, especially
due to the potential for fibers to be released. Annex 1 emphasizes
that products need to be free of visible particulates. Non-autoclaved
cellulosic paper is also probe to microbial contamination, given
the range of microbes that are capable of cellulose hydrolysis.
An alternative is Tyvek® and Tyvek®/PET-PP. Tyvek® material is
made of continuous strong fibers of pure high-density polyethylene,
is low linting and free of inherent contaminants that could represent
a risk in critical environments. Tyvek® retains its dimensional stability
and integrity and maintains its tensile strength, microbial barrier and
the required air permeability to enable effective sterilization.
In making the correct choice, packaging needs to be well designed
and of sufficient porosity so that steam can pass through packaging.
In addition, packaging should be water repellent to provide a
sterile “field.” Furthermore, the packaging material must not change
significantly during sterilization or release any substances that might
interfere with the action of the steam.
Autoclave load validation processes
New Annex 1 requirements will force pharmaceutical manufacturers
to revise their autoclave load validation processes.
Validation needs to be designed carefully to avoid failures (or failures
with re-validation). The Annex expects a greater level of detail
and investigation. Failure to inactivate biological indicators is normally
due to inadequate air removal rather than inadequate conditions of