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ISOLATORS vs
BIOLOGICAL SAFETY CABINETS
Lita Chew
BSc (Pharm), M.Med.Sc(Oncology), BCOP
Pharmacy Manager, National Cancer Centre
Assistant Professor, National University of
Singapore
Learning Objectives
u After attending this discussion, the participants will
be able to
1. Appreciate the differences between an isolator and a
BSC
2. Consider issues related to work practices between an
isolator and a BSC
3. Identify relevant references and tools for incorporating
cabinet(s) into work processes
Sterile Compounding in Pharmacy
u Sterile compounding in hospital and ambulatory
care settings is undergoing changes
Laminar flow technology has been around for >20 years
Recently barrier-isolation technology is becoming available
u Recent guidelines
ASHP Guidelines on Handling Hazardous Drugs
Am J Health-Syst PharmVol 63 Jun 15, 2006
ISOPP Standards of Practice. Safe Handling of Cytotoxics
Pre-publication
u 1980s First available in Europe
u Early1990s Preferred enclosure in UK and Ireland
u Mid1990s Introduced/Used in USA
u Late 1990s Introduced/Used in Singapore
u 2000s Introduced/Used in Thailand & Malaysia
Barrier Isolator Technology
- History of use in pharmacy
Barrier Isolator Technology
u It was developed to remove operator from
the environment in which products are
prepared eliminating source of
contamination
u Enclosed, ventilated controlled
environment (vertical laminar or turbulent
airflow)
u Access is through transfer hatch/
chamber; operation conducted through
fixed-glove access
u Good aseptic technique and support
materials are required
HEPAfilter
Exhaust
Components of a typical isolator
Work Areas
Transfer hatch
HEPA Filters
Exhaust
Gloves Port
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Design main characteristics
u Protection of products
Physical barrier
Permanent enclosure
Transfer devices
(interlocking door)
HEPA filters (Grade A)
u Protection of operators
Physical barrier
Permanent enclosure
Transfer devices
(interlocking door)
Evacuation of air outside
building
Air-flow in Isolator
Specification for a barrier isolators
should include:
u Physical Structure
u Internal environment
u Transfer and Interaction technologies
u Monitoring system
Physical Structure
u Hard shell
Hard Plastic
Plexiglass
Stainless Steel
u Soft shell
Soft Plastic Film
u Best construction is stainless steel
type 316L
Am J Health-Syst PharmVol 57 Feb 15, 2000
Internal Environment
- Typical specs
u All interior surfaces of the isolator are to be
smooth and cleanable, including welds
u Easy access for maintenance
u Both entering and existing air is to be HEPA
filtered. Filters protected during cleaning
u Air introduced will have directional flow. Per
Federal Std 209E, system is capable of
maintaining at least class 100 environment
u Capable of maintaining required pressure
(0.25-1.0 inches of water pressure)
Transfer technologies
u Offers means of introducing materials into
work areas without compromising internal
integrity of system
u Selected based on the level of protection
needed
Simple transfer hatches
Laminar-airflow interfaces
Timed air lock
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Interaction technologies
u Allows operator to interact with the
process or equipment contained in
barrier system
Gloves ports
Half-suits
Interaction technologies
- Gloves ports
u Sleeves-and-gloves
arrangement
u One piece system
Higher integrity but more
expensive
u Two-piece system
Better fit for gloves
Less expensive
Interaction technologies
- Half suits
u Were developed to increase lifting capabilities
and expand areas of reach within work areas.
u Disadvantages:
Difficulty in cleaning
Difficulty in entering and exiting
Hygiene issues with multiple users
Monitoring system
u Used to determined that workstation is
operating within the design parameters
Gauges with visual readouts
Alarm/Alert system
The many looks of ISOLATORS Optional Features
u Inner doors released by foot
switches
u Sliding transfer chamber tray
u Adjustable height
u CCTV monitoring system
u Easy Change Cuff Ring System
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Important things to consider in
selecting barrier isolator:
u Vendor support
Servicing and maintenance
Installation without disruption in existing areas
u Durability
Materials of construction
u Functionality
Size
Ergonomics
Movement of materials in/out of workstation
Heat load and noise level
Lighting
Ease of cleaning and disinfecting work areas
Ability to change systemto meet future needs
u Cost
Capital cost/Cost of set up
Operating cost (disposable items and maintenance)
Productivity
u Remember to ask for a list of references and follow
up with calls or site visits
Important things to consider in
selecting barrier isolator:
Biological Safety Cabinets
u Biological safety cabinets (BSC) are designed to
provide three types of protection:
Personnel protection from material inside the cabinet
Protection for the material inside of the cabinet
Protection for the environment fromthe material inside of
the cabinet
u There are three types of BSCs, Class I, II, and III
u Class I Cabinets
are designed to provide personnel and environmental
protection only.
product inside the cabinet is not protected and thus
subject to contamination.
Biological Safety Cabinets
u Class II Cabinets
Class II cabinets meet requirements
for the protection of personnel,
product and the environment.
There are four types of Class II
cabinets (A, B1, B2, and B3), each
differentiated according to the method
by which air volumes are recirculated
or exhausted.
Biological Safety Cabinets
u Class II, Type A Cabinets
Not vented
u Class II, type B1 Cabinets
must be vented; 30% of the air is exhausted from the
cabinet while 70% is recirculatedback into the room.
u Class II, type B2 Cabinets
must be totally exhausted; 100% of the air from the cabinet
is exhausted through a dedicated duct.
u Class II, type B3 Cabinets
must be vented; 70% of the air is exhausted from the
cabinet while 30% is recirculated.
Biological Safety Cabinets
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u Class III Cabinets
are designed to provide maximum
protection to the worker and the
environment.
Sometimes called Class III glove boxes,
these units are gas-tight enclosures with a
non-opening view window.
Intake air is filtered through a HEPA filter,
and exhaust air passes through two
HEPA filters before being exhausted to
the outdoors.
Biological Safety Cabinets
Recommendations:
u National Institute for Occupational Safety and Health
(NIOSH)
u American Society of Health-System Pharmacists (ASHP)
u International Society of Oncology Pharmacy Practitioners
(ISOPP)
When sterile hazardous drugs are being compounded, use one of the
following ventilated cabinets:
Class II BSC (Type B2 is preferred)
Class III BSC
Isolators intended for asepsis and containment (aseptic
containment isolators) [NSF/ANSI 2002; PDA 2001]
Comparison of Definitions
for the BSC III and Isolator
u Class III BSC is a unidirectional laminar airflow cabinet where the
front is closed by a window fitted with sleeves and gloves to allow
the manipulation inside the cabinet.
u operates usually in a negative air pressure.
u Pass through hatches are used. One hatch is used for entry and one
for the exit of the finished product and waste.
u A manual decontamination process (different fromsterilisation) is
usually performed in the pass through before materials enter the
cabinet. The cabinet is NOT sterile and is NOT sterilized. For
cleaning and decontamination of the cabinet, the window of the
cabinet may be opened periodically.
I SOPP Standardsof PracticeSafeHandlingof Cytotoxics
u Isolator, on the other hand, is a totally enclosed system
running usually in positive air pressure with turbulent
airflow and which is sterilized by gas sterilization.
u Products and preparation devices are introduced into the
isolator using pass throughswhich are always sterilized.
Comparison of Definitions
for the BSC III and Isolator
Practice Issues
u Safety (personnel)
Safety Issues - BSC
u Connor TH, Anderson RW, Sessink PJ et al. Surface contamination with
antineoplastic agents in six cancer treatment centers in Canada and the United
States. AmJ Health-SystPharm. 1999; 56:1427-32.
u Sessink PJ, Boer KA, Scheefhals AP et al. Occupational exposure to antineoplastic
agents at several departments in a hospital: environmental contamination and
excretion of cyclophosphamide and ifosfamide in urine of exposed workers. Int
Arch OccupEnviron Health. 1992; 64:105-12.
u Sessink PJ, Van de Kerkhof MC, Anzion RB et al. Environmental contamination and
assessment of exposure to antineoplastic agents by determination of
cyclophosphamide in urine of exposed pharmacy technicians: is skin absorption
an important exposure route? Arch Environ Health. 1994; 49:165-9.
u Sessink PJ, Wittenhorst BC, Anzion RB et al. Exposure of pharmacy technicians to
antineoplastic agents: reevaluation after additional protective measures. Arch
Environ Health. 1997; 52:240-4.
u Schulz, Heidi; Bigelow, Susan; Dobish, Roxanne1; Chambers, Carole R.
Antineoplastic agent workplace contamination study: the Alberta Cancer Board
Pharmacy perspective. J ournal of Oncology Pharmacy Practice. 2005; 11(3): 101-9
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Safety in BSC - Conclusions
u Studies of surface contamination have discovered
deposits of hazardous drugs within the cabinets, outside
cabinets on the floor in front of the Class, and workplace
counter tops.
u Workers must understand that BSC does not prevent the
generation of contamination within the cabinet and
that the effectiveness BSCsin containing hazardous drug
contamination depends on:
operators use of proper technique
operators work practices
operators housekeeping practices
Safety Issues - Isolators
u Mason HJ, Blair S, Sams C et al. Exposure to antineoplastic drugs in two UK
hospital pharmacy units. Ann OccupHyg. 2005; 49:603-10.
Measurable amounts of cytotoxic drugs were detected on the floors of both units and on
the disposable gloves worn by staff preparing the drugs. There was also evidence in both
units of some very low-level drug absorption from urine measurements, using the most
sensitive analytical technique of platinum analysis.
u Crauste-Manciet S, Sessink PJ, Ferrari S, Jomier JY, Brossard D. Environmental
contamination with cytotoxic drugs in healthcare using positive air pressure
isolators. Ann OccupHyg. 2005Oct;49(7):619-28.
Contamination was routinely found inside the isolators but rarely outside the isolators,
indicating that the isolator technology is offering good protection of the cytotoxic drug
handlers as well as the environment during preparation. On the other hand,
contamination was found on the surfaces of infusion bags and gloves in contact with
infusion bags filled with cytotoxic drugs. Consequently, personal protective equipment is
still recommended during the manipulation and administration of the drugs because of
potentially contaminated drug vials and final products.
Safety in Isolators - Conclusions
u Isolators, like Class II BSCs, do not prevent the generation
of contamination within the cabinet workspace, and their
effectiveness in containing contamination depends on:
operators use of proper technique
operators work practices
operators housekeeping practices
The potential for the spread of hazardous drug contamination
from the pass-through and main chamber of the isolator to
the workroom may be reduced by surface decontamination,
but no wipe-down procedures have been studied.
Appendix ERecommendations for working
in BSCs and isolators. Am J Health-Syst PharmVol 63 Jun 15, 2006
u The use of a Class II or III BSC or isolator must be accompaniedby a
stringent program of work practices, including operator training
and demonstrated competence, contamination reduction, and
decontamination.
Do you place unnecessary items in the work area?
Do you over-crowd work zone?
Do you plan work (needed supplies) ahead?
Do you spray or wipe critical sites?
Do you practice wipe down before placing items in cabinet?
Do you place transport bags in cabinet?
Do you do surface decontaminated for final preparation?
Appendix ERecommendations for working
in BSCs and isolators. Am J Health-Syst PharmVol 63 Jun 15, 2006
u Do you decontaminate work surface before and after compounding?
u Do you decontaminate all surfaces of cabinet at the end of the batch, day,
or shift?
u Do you wipe down the outside of BSC front opening and the floor in front
of the BSC daily?
u Do you seal and then decontaminate surfaces of waste and sharps
containers before removing fromcabinet?
u Do you decontamination after each spill in cabinet?
u Do you seal all contaminated materials (e.g. gauze, wipes, towels, wash
or rinse water) in bags or plastic containers and discard as contaminated
waste?
Section 7: Special Devices
ISOPP Standards of Practice. Safe Handling of Cytotoxics
u To prevent or minimize the possible
contamination during reconstitution and
administration of cytotoxicdrugs
u These special devices may be considered in
3 categories:
a) Devices to protect the handler of the vial/ampoule
b) Devices to protect the operator during preparation
c) Devices to protect the administrator during
administration of the cytotoxicdrug to the patient
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Practice Issues
u Safety (personnel)
staff training > technique > housekeeping >
facility & Equipment
Practice Issues
u Safety (personnel)
u Work flow
Grade B (EC GMP) environment
Facility - BSC
HEPAfilter
Cleanroom
Class 10 000
Anteroom
A
Grade C or D environment
Anteroom Cleanroom
Class 10 000
HEPAfilter
B
HEPAfilter
Exhaust
Isolator room
C
Facility - Isolator
Workflow Issues - Preparation
BSC Isolator
PPE +
Restricted Access
Personnel +
Items (pre & post) +
Restricted hand movement +
Efficiency +
Work area in cabinet +
PPE


Class of Room

Requirements for PPE
ClassD Hair / Beard Covering
Normal ProtectiveClothing
ClassC Hair / Beard Covering
Clothesgripped at wrist with raised
Collar
Clothing must not shed fibresor particles
ClassA/ B Hood or other headcovering
Mask
Sterile, Non-powdered gloves
Sterileor disinfected bootsor overshoes
Sterileclothing which must not shed fibres or particles
Sterileclothing must be capableof retainingparticles
shed by operator

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Workflow Issues - Preparation
BSC Isolator
PPE +
Restricted Access
Personnel +
Items (pre & post) +
Restricted hand movement +
Efficiency +
Work area in cabinet +
Practice Issues
u Safety (personnel)
u Work flow
u Monitoring
Physical
Microbiological
Monitoring - Physical
u Aim is to monitor whether the cabinet is performing
to specification.
BSC Isolator
Integrity of the HEPA filters 6-12 mth 6-12 mth
airflow velocity 3 mthly 3 mthly
air circulation (smoke test) monthly monthly
Leak test ---- monthly
airflow retention(front opening) 3 mthly ----
Pressure differential ---- continuous
particulate 3 mthly 3mthly
Noise 3-6 mthly 3-6 mthly
Light 3-6 mthly 3-6 mthly
Monitoring - Microbiology
u Aim is to ensure quality of environment the
product is exposed during manipulation.
BSC Isolator
Frequency
Passive (settle plates) Daily Daily
Active (air sampler) Monthly Monthly
Practice Issues
u Safety (personnel)
u Work flow
u Monitoring
Physical
Microbiological
It is recommended that the cabinets be left running 24
hours a day, 7 days a week in order to help prevent
microbiological and chemical contamination.
BalancingCOST, SAFETY, EFFICIENCY
Cost
Efficiency
Safety
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Costing & Budget
Set up BSC Isolator
Capital Room
Cabinet
Consumables
Maintenance Room
Cabinet
++++ ++
+ ++
++ +
++
+
++
++
10+ 9+
More expensive
Safety & Efficiency
Set up BSC Isolator
Safety
Efficiency (speed)
workflow
++ +++
++ +
++ +
More desirable
More desirable
Unresolved issues related to current
compounding practice
Exposure risks
needle stick injuries
Surface contamination
Cumulative strain disorders
Prep errors in dosage
Prep errors in drug
Recruitment & Training
PHARMACY STAFF
SAFETY/HEALTH
PATIENT
SAFETY
WORK
ORGANIZATION
Alternative to BSC and Isolators
u State-of-the-art technology coupling robotic,
software design and automated waste
handling system
The Automated Solution The Automated Solution
VDO
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THANK YOU