ONCOLOGY
Cytoxic handling:
isolators versus cabinets?
Cytotoxic chemotherapy is synonymous with a narrow therapeutic index, severe adverse effects
for patients and occupational exposure risks for pharmacy and nursing staff
Graham Sewell PhD
MPharm MRSC CChem
MBS CBiol
Leicester School of
Pharmacy, De Montfort
University, Leicester, UK
The majority of cytotoxic drugs are administered
as sterile injections or infusions, which means
asepsis must be maintained during the
preparation and administration of chemotherapy,
particularly because many patients are
immunocompromised. Protecting healthcare staff
from occupational exposure, ensuring sterility of
parenteral chemotherapy and complex clinical
management issues all combine to present
a multidimensional challenge to pharmacy
staff and specialist chemotherapy nurses.
This opinion piece considers the different
technologies used for the preparation of cytotoxic
injections and infusions: pharmaceutical
isolators, Class II cytotoxic cabinets (also
erroneously referred to as vertical laminar flow
cabinets), and closed system transfer devices
(CSTDs). The attributes and limitations of each
technology are considered in terms of the
maintenance of infusion/injection sterility
(protection of the product from the environment),
containment of the cytotoxic medicine
(protection of staff from the product), conserving
the pharmaceutical integrity of the product and
issues around the incorporation of these
technologies into oncology pharmacy practice.
Protection of the product
For simple aseptic manipulations involving
reconstitution of vials, withdrawal of liquid and
dilution to prepare pre-filled syringes or infusion
bags, both the class II cabinet and the isolator
offer critical zone environments corresponding to
EUGMP Grade A. This is conditional upon
maintenance, monitoring, testing and validation
for both types of device, the details of which are
available elsewhere. In theory at least, the Class II
cabinet is more vulnerable to changes in airflow
in the vicinity of the cabinet caused, for example,
by personnel moving around in the aseptic suite. 1
This can disrupt the laminar airflow at the open
face and draw in air from outside the critical
zone. Conversely, a pharmaceutical isolator
should, if properly maintained and validated,
sustain the Grade A environment against such
challenges. The isolator offers potential design
advantages in that materials are introduced into
the critical zone via flushed hatch systems with
interlocking doors. This enables the
implementation of a time delay between the
closing of the outer hatch door and opening of
the inner hatch door to the Grade A work zone,
which, in turn, enforces a minimum contact time
15
HHE 2019 | hospitalhealthcare.com
for surface disinfectants sprayed, or wiped onto
the surface of in-bound materials or packaging to
exert a bactericidal effect. Isolators, either
connected in series or used singly, offer the
potential for gaseous sterilisation of consumables
introduced into the isolator prior to aseptic
manipulation. This approach, which is best
applied to batch-scale preparation for applications
such as dose-banding, requires rigorous validation
and systems to ensure there is no ingress of
sterilising gas (usually powerful oxidising agents)
into the product. The main disadvantage of
isolators when compared with Class II cabinets
is that they are more difficult to clean and to
sanitise internal surfaces. 2
There has been much debate over the use
of positive- or negative-pressure isolators for
cytotoxic manipulation; the former, in theory, is
more likely to maintain the aseptic environment
in the event of a leak in the isolator, but the latter
provides a higher level of operator protection in
the same scenario. Guidance based on a limited
study conducted by the UK Health and Safety
Executive was inconclusive and suggested either
positive or negative isolators were acceptable
providing they were properly maintained and
operated. 3
Unlike isolators and Class II cabinets, which
provide an aseptic environment and containment,
CSTDs provide a closed, sterile fluid path for
aseptic manipulation, with either an expansion
chamber or a filtration system to permit
displacement of air by liquid. In most cases, the
CSTD accesses the drug vial or the infusion bag
via a spike or retractable needle system. When
deployed in a non-aseptic environment there
must be the potential risk of microbial
inoculation into the vial or the infusion. In an
uncontrolled environment the manipulation of
CSTD connectors and docking devices may also
carry a risk of microbiological contamination,
even when sophisticated valve systems are used
to mitigate this risk. Additionally, the integrity
of the seal between the drug vial or infusion bag
septum and the CSTD spike or needle is not only
dependent in the design of the CSTD, but also on
the material and design of the vial septum and
this can vary significantly between
manufacturers.
In recent years, CSTDs have been used for drug
reconstitution in clinical areas outside the
pharmacy, particularly for monoclonal antibodies.
While this practice is undoubtedly an