STERILE MANUFACTURING TECHNOLOGY
from grade A to grade D, there are various approaches associated
with each grade, from closed to open handling of a sterile product. In a grade A environment, less than one colony forming unit
(CFU) is allowable meaning there is no contamination. The advent
of sealed transfers using SBV has enabled the downgrading of the
external environment as it creates an internal grade A environment
of its own, the benefits of which will be discussed below.
To overcome challenges during high potency and aseptic processing, several techniques have been introduced to manage the
associated risks and provide assurance of product sterility. SBV
uses hydrogen peroxide gas to bio-decontaminate on the two
mating surfaces before product transfer. These valves consist of
two halves, the active (Alpha) unit and the passive (Beta) unit.
Typically, the active unit is attached to the stationary process
equipment, such as a formulation vessel or filling line, and the
passive unit is attached to the mobile container, such as a flexible
bag or rigid intermediate bulk container (IBC).
The two halves of the valve create a sealed chamber by partially docking the two‘butterfly’disc faces. This allows decontamination to take place in a closed environment. The decontamination
media is applied as small droplets, which are dropped onto a hot
plate and vaporized, before being blown into an air stream and
into the sealed space between the passive and active discs. This
happens before the valve docks, which is when the elimination of
viable microorganisms takes place.
Biological indicators holding one million spores are placed inside the chamber as part of the validation process to determine
the appropriate decontamination cycle. The biological indicator
is then removed afterwards and tested to determine the survival
of any spores. If no spores grow, the process has worked and the
unwanted microbes have been killed meaning that the area can
be classified as contaminant-free.
In short, SBV achieves improved sterility assurance by applying the principles of separation and decontamination. Separation
measures protect the critical line before, during and after transfer,
while eliminating manual intervention by minimizing the exposure of the operator to the product/critical area. Decontamination
delivers a validated approach, eliminating reliance on previous
‘spray and hope’ methodologies.
THE BENEFITS OF SBV
Adoption of the technology means that manufacturers can benefit
from a closed handling method that not only achieves the required
sterility assurance level (SAL) and reduces the requirement for
manual intervention, but also offers the opportunity to reduce the
resource associated with cleaning and validating large volume areas.
SBV enables APIs to be processed while ensuring the safety
of the operating environment by maintaining the required Occupational Exposure Limit (OEL), protecting sensitive products and
helping to eliminate cross contamination. The method eliminates
dust in the processing of raw materials and reduces cleaning requirements and associated downtime.
In addition, SBV with integrated bio-decontamination pro-
vides a validated, repeatable 6-log reduction at the point of fill, as
the conditions and the transfer space are consistent, something
that cannot be guaranteed with a traditional spray and wipe ap-
proach. The de-contamination process using the hydrogen per-
oxide gas reduces the spore count so that a ( 10-6) reduction in
microbiological contamination is achieved on the exposed faces
of the valve. This means there is no risk of the final connection
being contaminated. This is a common concern for operators who
are using the wiping approach, as contaminants can come into
contact with the surfaces that have just been de-contaminated,
particularly as operators are intervening.
Processing time varies between six and 30-minutes depend-
ing on the gassing system utilized. This is extremely fast when
compared to a conventional airlock approach to transfer into the
aseptic core, which would typically be in the region of 30 minutes
to one-hour due to the surface area and volume being transport-
ed. This makes the production process more efficient, helping to
maximize product output.
SBV technology also demonstrates improved ergonomics over
alternatives that rely on working alongside barrier isolation. The
sealed system removes the requirement for the use of glove ports
and reduces associated handling issues that can be challenging for
the operator. Significant cost savings can also be realized as valve
technology is as much as three to five times cheaper than isolators,
while ongoing running and maintenance costs are reduced thanks
to the downgrading of the external environment that it supports.
For example, it is less restrictive and time consuming to enter into
a grade D room than a grade A room. As a result, this can speed up
production and is a more cost-effective way to operate.
SBV is now being applied to several applications including
product transfer for non-terminally sterilized products, adding
bulk powder to formulation vessels, as well as direct transfer from
process dryers into immediate containers and then into filling lines.
The development of SBV technology has increased its suitabil-ity for a wide range of industry applications where not only dust
control and containment is a concern but where product flow,
yield and sterility issues are also prominent. As an alternative to
the industry’s current reliance on high classification cleanrooms
and isolators in aseptic manufacturing processes, the adoption
of SBV can not only achieve time and cost savings as the surrounding environment can be downgraded, but it can bring improved sterility assurance and reduced opportunity for operator
introduced contamination. Offering a validated methodology
to transform the way that containment and sterility is achieved
during aseptic processing, SBV is helping to transform operator
safety and the quality of final drug products. CP
CHRISTIAN DUNNE is the global product manager for ChargePoint Technology for the aseptic range of products. Over the past
15 years, Christian has been creating innovative solutions for the
pharmaceutical, biotech, cell therapy and fine chemical industries
in the form of high containment and aseptic process solutions. For the past
four years, Christian has been working with ChargePoint Technology on the
advancement of its split butterfly range of solutions in the aseptic and containment fields, handling high potent/sterile powders and small-scale components, where both product and operator protection are paramount.