Contamination is almost always related to human error and there is a clear drive to reduce human implications in aseptic operations.
This can be achieved in multiple ways. Some solutions include:
- Isolation of the operator: the use of barriers such as isolators and restricted access barrier systems (RABS) are more and
more frequently used to separate the filling area from the operator. This trend has been reinforced by the tendency of regulatory
authorities to increase their scrutiny on aseptic filling facilities that use old designs, such as clean rooms.
- Use of disposables: disposables can reduce the cost of operations, including labour work in cleaning, cleaning validation
and QA/QC. The cost of disposables is, of course, higher, but the total cost is reduced.
- Reduction of exposure: exposure is recognised as a contamination risk. Few people claim that the filling environment is guaranteed
contamination free. Therefore, several technologies have been developed to help reduce exposure, such as by using specialised
containers; for example, many people have reported projects being launched using Blow-Fill-Seal (BFS) containers in recent
years. BFS is well known to strongly minimise exposure thanks to the very short cycle times before the container is fully
closed.
Benoît Verjans
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When it comes to equipment, the main contamination risks are the contact parts, exposure risk and operator intervention, but
specialised equipment, particularly barrier systems, can help to minimise all of these. Barrier systems have multiple advantages.
Firstly, the operator, is kept away from the filling area by physical separation. The quality of such design has been recognised
by authorities and led to significant changes in facility design. For example, isolators are usually located in ISO8 clean
room instead of ISO7 clean room with all the savings attached to the simplification of the facility design and the ease of
operations.
Operations such as clean-in-place (CIP) and steam-in-place (SIP)—though designed to optimise the sterility assurance level
of product contact parts—remain complex and, consequently, are a source of contamination because of potential errors. Compared
with these operations, the use of connectors to cross barriers and disposable sterile product paths are simple solutions to
set up product path in robust aseptic conditions. In addition, containers may help to minimise contact parts. For example,
the insides of ampoules, BFS and Crystal vials are never in contact with equipment contrary to vials and prefilled syringes
with their respective stoppers and plungers in contact with vibrating bowls and ramps.
Length of exposure to the environment is also an issue because the probability of contaminants entering the container is higher
if the exposure time is longer. On that basis, containers that require very short operating time are preferable to ones requiring
longer steps. Three container bodies help minimise exposure to the environment: prefilled syringes, which are supplied sterile
in tubs and immediately processed through filling and plunger placement; BFS, which is immediately filled after moulding at
high temperature; and the closed vial which is kept permanently closed and immediately processed to filling and laser re-sealing.
On the contrary, open classical glass vials and ampoules wait a long time fully open from the hot air tunnel to the filling
and closing stations. Unfortunately for prefilled syringes, plungers, as the vial stoppers, are still exposed for long periods
of time in vibrating bowls.
Another risk is operator intervention because humans are always a source of contamination. Equipment manufacturers have the
task of making systems more reliable and reducing the number of steps. One recent trend in the pharma industry is to reduce
the speed of filling equipment in order to minimise short stops. The result is that the output is not so affected thanks to
the elimination of many short stops and the quality is improved.
