Newsletter_12-2022_EN

www.reinraum.de
NEWSLETTER
www.cleanroom-online.com Edition EN 12-2022 | Page 3/42
Overall impact of new Annex 1
in pharmaceutical industry
Annex 1 and sterilization process: an interview with Tim Sandle
The revision of Annex 1 is requiring a major effort from the life sciences industry; from ‘setting up new processes, to training staff, to managing
noncompliance, the industry needs to adapt particularly to new requirements regarding contamination control strategy and the
essential elements needed to develop a robust sterility assurance system.
One of the most discussed processes involves autoclaving and the risks associated with it.
We talked about it with Tim Sandle, a microbiologist, author and science journalist, known as one of the leading experts in the field.
Our interview opens with an assessment of the overall impact of the
new Annex 1 on contamination control strategies in the pharmaceutical
industry. Dr. Tim Sandle, the new Annex 1 revision is distinguished
by a “holistic” view of contamination control. What are the most
immediate consequences of this new approach?
Many facilities have developed approaches to contamination control,
but the call within the Annex is for pulling everything together to
provide a holistic overview of the facility, the rationale, the gaps, the
level of risk for each gap, and the remediation steps. A contamination
control strategy is a system that considers all the integral elements of
pharmaceutical product manufacturing. This is best achieved using
quality risk management principles and supporting risk assessments
for contamination control and monitoring (the detectability of contamination
event).
As a governing ethos, processes, equipment, facilities and manufacturing
activities should be managed in accordance with risk management
principles that provide a proactive means of identifying,
scientifically evaluating and controlling potential risks to quality.
The strategy at each facility will vary, but common themes will
include: microbial contamination, cleaning and disinfection, sterility
assurance, facility design, chemical and particle contamination.
Outside of the microbial, other forms of contamination that can
arise from mix-ups, damaging primary or secondary packaging, distribution
problems, and environmental fluctuations. Overall, a focus will
need to be with reducing contamination likelihood and cross-contamination
potentials. This needs science and technical procedures and
controls.
The format would be as one document or series of connected documents
developed to reflect the site-wide strategy for minimizing
contamination control.
Importantly, the strategy should be a living document and be updated
in relation to change controls, process development, recurrent
deviations and in relation to other quality records.
Challenges in sterilization processes
What are the challenges facing the pharmaceutical industry
in sterilization processes with respect to the requirements of
the new Annex1?
Perhaps the most significant change is in relation to equipment sterilization
when used for aseptic processing. The 2017 draft stated that critical
surfaces with direct impact need to be sterilized (such as a filling
manifold or stopper bowl); however, with the 2020 revision this now
requires direct and indirect contact parts to be sterilized. This could
present challenges to facilities with both isolators and RABS devices.
There is a specific update for freeze-dried products in terms of
freeze-dryers (or lyophilizers). This is for lyophilizers which are manually
loaded or manually unloaded. Here the freeze-dryers should be
sterilized before each load.
Other important Annex 1 points include the requirement that the
feed water to a pure steam (clean steam) generator should be appropriately
purified, to achieve the required chemical and endotoxin
levels, as assessed by the Water-for-Injections pharmacopeial monitoring
and testing requirements. With the chemical requirement, this
is because steam used as a direct sterilizing agent must not contain
additives at a level which could cause contamination of product or
equipment. This part of the process needs to be validated. The steam
must also consistently meet the parameters for non-condensable gases,
dryness value (dryness fraction) and superheat.
The Annex also specifies that each item sterilized needs be inspected
for damage, packaging material integrity and moisture on removal
from the autoclave. Any item found not to be fit for purpose, either damaged
or where there is evidence of a ‘wet load’, should be removed
from the manufacturing area and an investigation performed.