The Mazda Pharma Guide 7th October to 13th October | Page 76

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MACHINERY ARTICLE
pharmaceutical powders and oral solid-dosage
forms. Further, small-scale isolator system for
development work, Containment-Lab, is an
array of modular isolators positioned
sequentially for enclosing relevant operations:
dispensing, wet granulation, fluid bed drying,
sieving, tableting, and coating. Users may
combine, add, or delete isolator modules as
they modify processes. Each module contains a
port for locking one module onto another
without exposure to the ambient environment.
Never at a loss for a vivid analogy,
Agalloco describes isolator-enabled unit
operations in pharmaceutical manufacturing
are descibed as islands” with processors
striving to “ferry product from one island to
another within the archipelago.”
For mid-sized pilot or large
development-scale processes, the Process
Coater-Granulator (GPCG2) system is
available with a designed-in fluid bed
processor. Larger processes and equipment
serve as their own containment systems. The
machine itself is the isolator.”
RABS VS. ISOLATORS : Pharma and
biotech companies employ a myriad of barrier
technologies that lack a rigorous airtight seal to
provide product or operator protection. Most of
these systems rely on air flow to provide
protection, as do many less formal types of
barrier systems found in manufacturing suites
and associated laboratories.
Within a facility, there are multiple
spaces with varying needs for pressurization or
air flow direction control to provide either
containment or isolation Control Systems.
Technologies and equipment create a space
within the space and require their own level of
control within the overall environment . LCS,
which provides air flow control systems for
critical environments in pharmaceutical and
biotech, works with designers at the owner
level to manage air- and temperature-control
systems. Restricted access barrier systems
(RABSs) are another emerging, less costly, and
less rigorous alternative to isolators, which
work well for many processes.
ISPE defines RABSs as a barrier
system with a rigid wall enclosure,
unidirectional airflow providing an ISO 5
environment, glove ports with sterilizable
(preferably sterilizable-in-place) surfaces, and
are typically surrounded by an ISO 7 or lower
environment. ISPE's analysis of RABSs vs.
isolators goes into a great deal of technical
detail. The bottom line is that RABSs provide

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a good deal of protection for products from
operators, but not quite as much as isolators do
since RABSs are not airtight and are not
sterilizable using vaporized hydrogen peroxide.
RABSs are particularly attractive in the
food and beverage industries. Serac
(www.serac.fr), which manufacturers filling
and capping machines, recently launched a
new RABS for aseptic packaging of milk and
drinks in and around sterile areas. Like most
RABSs, Serac's is not hermetically sealed. The
barrier results from positive pressure inside the
enclosure.
Manufacturers believed that they could
save money by installing RABSs instead of
isolators, but savings do not always accrue.
While capital costs are lower for RABS,
operating expenses may be higher. An isolator
has a complete seal with different pressures
inside and out, and can be exhaustively
decontaminated. If you eliminate the seal and
keep gloveports, walls, and transfer
mechanisms, you have a RABS.
Regular readers may recall Agalloco's
analogy for comparing true isolator systems
from what used to be known as barrier systems
or barrier-isolators, a term he loathes. He
likens barrier systems to the different
environments in first class and coach on an
airliner; an isolator system is comparable to the
skin of the plane, which shields passengers
from the harsh outdoor environment.
Though isolators are considered to be
superior, but whether they bring in the proper
return on investment is still doubtful. Some
processes will do fine by employing a less
expensive RABSs installation, which in fact is
likely to increase demand for RABSs. It has
been rumoured that RABSs are pretty good,
and that isolators are too complex and
expensive.
ISOLATORS PLAY A VITAL ROLE
WHEN HUMANS NEED TO HANDLE
PHARMACEUTICALS OR PATHOGENS
: These products are not just used for
screening. Isolators are at the interface between
an aseptic or aseptic/toxic zone and humans.
This is where pathogens are analyzed, trials are
conducted and pharmaceuticals are produced
or filled into containers. Isolators are
essentially small Grade A clean rooms which
comply with GMP/PIC guidelines. They
provide an (aseptic) environment which has
less than one particle with a diameter of 0.5
micrometer in 28.3 cubic feet of air. By way of
comparison, normal unfiltered air has 25,000

particles.
The material and functional
characteristics of every part that is used in the
production of isolators have to comply with
very demanding quality criteria, namely the
extremely stringent requirements of the
pharmaceutical industry. These requirements
are defined on regulatory basis in ISO
standards US and EU Pharmacopeia and FDA
guidelines, etc.
Everything from top-grade stainless
steel, safety glass up to sensors controlled by
PLC according GAMP-IV is strictly high-tech!
They cannot even rely in supplier certificates
but need to perform internal tests on a sample
basis to verify items such as welded-in sheet
metal or software validation.
The hydrogen peroxide (H2O2) based
decontamination system which is first fully
embedded in the process and control flow and
second effectively reduces micro organisms to
the required level of a 10-6 contamination
safety level. This decontamination method has
now become a worldwide standard cited in the
FDA guidelines.
Over- or negative- pressure is
maintained in the isolators depending on the
active ingredient which is being filled.
Negative pressure is used for highly active,
cytotoxic substance such as drugs used to
combat cancer. This ensures that the active
ingredients cannot be released to the outside
even if the clean room area develops a leak.
Overpressure is maintained in the isolator when
aseptic and non-toxic active ingredients are
being handled to prevent microbial
contamination from the outside environment. A
filling line is designed for syringes which are
pre-filled with flue vaccine. Pre-sterilized
syringes are transferred into the clean room
area in sealed tubs, each with 100 pieces.
Electron beams (E-Beam) decontaminate the
surface of up to six tubs per minute transferred
into the filling isolator. A small robot in the
peeling zone of the isolator removes the cover
foil. The vaccine is then filled into the syringes
and sealed in a fraction of a second. When
production is fully up and running, six tubs,
600 syringes will be filled every minute.
More than twelve of these Filling Lines
have been installed in Europe and they will be
in operation for three shifts seven days a week,
processing about five million pre-filled
syringes a week.

THE MAZADA PHARMA GUIDE q
7 October - 13 October 2013