MODALITY COMPARISONS

There are pros and cons associated with each technology—gamma, e-beam, x-ray, EO—and the
sterilization process varies depending on the medical-related product being sterilized. This section
compares the modalities.

7.1 Suitability to Sterilization of Medical Devices

While all modalities are suitable for sterilization of medical-related products, the chosen modality
depends on a number of product considerations.

Gamma E-beam X-ray EO

Mode of action Ionizing radiation Ionizing radiation Ionizing radiation EO is a
in the form of in the form of a in the form of x- penetrating gas
gamma rays beam of electrons rays generated by
electrons hitting a
target
Medical device Materials are Materials are Materials are Package and all
product compatible with compatible with compatible with parts of product
requirements radiation, radiation, radiation, to be sterilized
penetrate full penetrate boxes penetrate full must be gas
pallets with bulk with bulk pallets with permeable,
density up to 0.40 densities up to densities up to irrespective of
g/cm3 0.25 g/cm3 0.50 g/cm3 density
Material Wide range of Wide range of Wide range of Widest range of
compatibility polymer polymer polymer material
compatibility; compatibility compatibility compatibility
some limitations compared to compared to except for
due to oxidation gamma; some gamma; some moisture and
effects— PTFE limitations due to limitations due to temperature-
and PVC affected oxidation effects oxidation effects sensitive
materials (>30oC
and/or <30% RH)
Largest processing Pallets or boxes Boxes Pallets or boxes Pallets or boxes
unit
Processing Product exposed Product exposed Product exposed Product exposed
to gamma rays for to an e-beam for to x-rays for a to EO gas, at a
a validated period a validated period validated period defined moisture,
of time to achieve of time to achieve of time to achieve pressure and
a desired a desired a desired temperature for a
minimum dose minimum dose minimum dose validated period
Control system Control system Control system of time to achieve
can raise or return can quickly stop can quickly stop the specified SAL
sources from/to and start the and start the
pool manually or source manually source manually
automatically or automatically or automatically
Tolerance for High Low Very high Medium
density variation
Processing time <24 hours typical <8 hours typical
for a typical 45-ft but could process for smaller
tractor trailer small batch batches
(~3,000 ft3) quicker
Processing There is a need to There is a need to
parameters monitor cycle simultaneously
time and product monitor a number
size and density of parameters to
to ensure the ensure that the
prescribed dose is prescribed dose is
achieved delivered (e.g.
beam current,
conveyor speed,
product box size
and weight)
Gamma, E-beam, X-ray(Radiation-
based Sterilization)
Product release In order to release product to market,
parameters the following are required:
 Control of the product
manufacturing processes to
ensure supply of material and
product packaging is
consistent with the validated
radiation process
 A validated processing
configuration in which an
array of dosimeters have been
measured to demonstrate the
relationship between
processing parameters and
minimum and maximum dose
to product and a routine
dosimeter measurement
(validation requirements and
methods are well described in
ISO 11137-1)
 A measurement of routine
dose for a given processing
run, which indicates that a
dose within specification has
been delivered. This
measurement can be made as
soon as the irradiation
process is complete, so there
<24 hours typical 1-7 days typical
but could process
small batch
quicker
There is a need to There is a need to
simultaneously simultaneously
monitor a number monitor a number
of parameters to of parameters to
ensure that the ensure that the
prescribed dose is prescribed dose is
delivered (e.g. delivered (e.g. EO
beam current, concentration,
cycle time, temperature, RH
product size and and exposure
density) time)
EO (Gas-based Sterilization)
In order to release product to market,
the following are required:
 Control of the product
manufacturing processes to
ensure supply of material is
consistent with the validated EO
process
 Compliance of the process
parameters, monitored
independently from the control
function, to the validated
process specification
 Routine monitoring and
independent release of process
using either (1) successful
microbiological sterility tests of
biological indicators of known
“resistance” prescribed by the
ISO standards retrieved from the
sterilization load post-process
and incubated for typically 7
days and/or (2) routine
independent monitoring of
critical parameters (EO and
relative humidity) as
“parametric release”
 And any additional tests that
may be required: bacterial
endotoxin test, product EO
 is no required waiting time residues test and functional
before release product/packaging tests
Gamma E-beam X-ray EO
Pros (specific to  60-year proven  60-year  Highest  90-year
medical devices track record proven track potential proven track
 >40% of the record penetration record
world’s single-  Equivalent to depth in product  EO is
use medical or less  Efficient and compatible
devices are expensive targeted with many
delivery of dose materials that
sterilized using than gamma
 Product holdup cannot
Cobalt-60 for certain
may be smaller tolerate or are
 Simplicity of products
than in a degraded by
monitoring  Product comparable radiation
cycle time and holdup gamma plant sterilization
density (amount of  Ability to
 Ability to product process in large
schedule within the volume
multiple irradiator) quantities
products to be may be  Ability to
processed at smaller than schedule
one time in a multiple
products to be
 Reliability and comparable
processed at
dependability gamma plant
one time
of the radiation  Quickest
source processing
 Ability to times
process in
large volume
quantities
(pallets)

Cons (specific to  Requires  Not suitable  Technology has  EO process can

medical devices requalification for products limited adoption, leave residuals
suitability) of irradiator that have which means on products
operation after challenging that backup  Toxicity issues
source product facilities may not  Safety issue as
replenishments, geometries be available EO is explosive
which are and localized during  Medical
typically annual regions of maintenance or devices must
(but can vary highdensity other shutdowns be packaged in
from 6 months materials  Few existing gaspermeable
to several years  Inability to products are system
depending process in currently  Cannot
upon palletized validated with penetrate a
format the x-ray liquid
 operational technology.  Has difficulty
need) Switching penetrating
existing products closed valves
to x-ray will
require
revalidation

7.2 Equipment There are comparative differences based on the irradiator design and operation. These
differences are primarily based on relative complexity of the equipment and the simplicity, or lack
thereof, in making repairs.

Gamma E-beam X-ray EO

Number of ~10 (There are <10 (best <3 >10 Varies as
irradiator about 4 or 5 estimate for some contract
manufacturers Cobalt-60 sterilization of sterilization
Worldwide suppliers for healthcare companies make
irradiators.) products) their own EO
chambers
Number of ~200 <75 (best <5 ~65 (best estimate
healthcare estimate for for number of EO
sterilization sterilization of sterilization sites)
facilities worldwide healthcare
(commercial products)
availability)
Penetrating Gamma Electrons, due to The spectrum of Using proper
capability radiation their charge and photons created temperature and
emitted by mass, have a from the x-ray vacuum pressure
Cobalt-60 is used much lower target provides an conditions, EO has
to penetrate product- overall the ability to
pallets up to 120 penetrating penetration penetrate most
cm thick at capability than depth somewhat products and
densities up to either gamma or greater than product
0.4 g/cc in x-ray photons and gamma, assuming packaging—
normal two- can penetrate up an input electron requires
sided operation to approximately energy between 5 breathable
15 cm singlesided and 7 MeV packaging
or 40 cm two-
sided irradiation
at densities up to
0.2 g/cc for
electron energies
up to 10 MeV
System repair Tends to be in  Can vary from  Can vary from Mostly scheduled
downtime (e.g. the order of hours to days hours to days preventative
source/system for hours.  Conveyor  Conveyor maintenance
machine sources; Equipment repair related repair related program often
issues generally items are items are availing of
system for Cobalt- related to generally generally opportunistic
60) conveyor can quick quick downtime
generally be  Accelerator-  Accelerator between batch
repaired quickly. related issues and x-ray processing
Source re- can converter-
loading, sometimes related issues
approximately take days to can
annually, takes repair sometimes
between 24 and take days to
72 hours repair
Reliability and Stable and Stable and Stable and Well maintained
maintenance reliable due to reliable in a daily reliable in a daily chambers and
the use of an production production ancillary
isotope source environment. environment. equipment show
and the Actual Actual stable and reliable
simplicity of the operational operational performance
product handling experience has experience has
system. Actual demonstrated demonstrated
operational ~90% uptime ~90% uptime
experience has
demonstrated
~95% uptime
Pros  The Cobalt-  For low-  X-ray offers Flexible processing
(equipmentrelated) 60 energy density the only limited by
allows homogenous penetration sterilization
processing of materials, advantage of chamber size
totes and ebeam is gamma
carriers up to more efficient  The source of
full pallets of than gamma radiation can
healthcare and x-ray for be turned off,
products this subset of which allows
 No issues processing for easy access
with respect  The source of and repair
to source radiation can  X-ray
reliability be turned off, irradiators
when which allows allow
resuming for easy processing of
operations access and totes and
 Irradiators repair carriers up to
are  The source full pallets of
extremely energy is healthcare
reliable electricity and products
because the does not  Dependent on
source of require the design
radiation material to be conditions, x-
never fails transported ray can
provide the
  Flexibility to opportunity to
“grow” the achieve a
irradiator as better DUR
demand under like-for-
increases like conditions
 Product with gamma.
handling  The source
systems are energy is
easily electricity and
maintained, does not
usually with require the
in-house material to be
resources, transported
with off-
theshelf
components
Cons  Cobalt-60 is  Additional  Potentially  EO is a
(equipmentrelated) radioactive complexity of higher initial carcinogenic
material, equipment capital costs material
which will and process versus gamma  EO is a
require and validation as investment flammable
appropriate when in “full and explosive
management compared to capacity” may material,
at the end of gamma be necessary which will
the life of the processing in initial require
source  Maintenance investment properly
 Historically, outsourcing or  Potential designed and
world supply development longer rate of operated
of Cobalt-60 of technical return of process safety
is dependent staff to investment systems
on the manage and  Equal or  Stringent
availability maintain greater environmental
and equipment complexity of health and
willingness of required equipment safety
nuclear  Need for validation and requirements
reactors that ongoing maintenance for EO sites
are capable replenishment to that of  Many supply
of producing of critical ebeam variables to be
Cobalt-60 components  Need for controlled and
 Cobalt-60 over life of ongoing maintained;
requires equipment replenishment e.g. EO
scheduled  Costly parts of critical supply, steam
reloading due to components supply, N2
that might complexity over life of supply,
require  Reliable and equipment temperature,
downtime high electrical  Maintenance etc.
and some power outsourcing or
 revalidation consumption development  Multiple
efforts required of technical working parts
staff to for complex
manage and preventive
maintain maintenance
equipment schedule
 Reliable and  EO
very high sterilization
electrical facilities are
power more complex
consumption to design and
requirement operate
 Costly parts
due to
complexity
 Need for a
nearby back-
up facility in
case of
lengthy
shutdown for
repair

7.3 Economics Following are some economic guidelines that should be considered when considering
these sterilization modalities. They are intended to provide some overall financial and budgetary
considerations when comparing the technologies.

CAPEX Gamma E-beam X-ray EO

Sterilization Cost of generator Cost of generator Cost of generator Cost of Sterilizers
source Includes Includes Includes Includes pressure
irradiator, pool, accelerator, accelerator, vessels,
installation, IQ beamline, scan beamline, scan preconditioning,
and OQ and initial horn, installation, horn, equipment primary and
loading of Cobalt- IQ and OQ. The cooling system, secondary
60. Production cost of the removable or degassing, air
throughput is accelerator fixed x-ray target, handling,
proportional to strongly depends installation, IQ emission controls
activity of Cobalt- on beam power. and OQ. The cost (catalytic oxidizer
60 loaded in the Production of the accelerator and/or scrubber),
irradiator. Initial throughput is strongly depends gas delivery
loading of isotope proportional to on beam power. systems, gas
may be beam power. It is Production storage, EO
significantly lower possible to throughput is storage, nitrogen
than maximum increase the e- proportional to storage and
capacity of facility beam source beam power. It is delivery systems,
and can be capacity at a later possible to integrally safe
increased over stage by adding increase the x-ray electrics,
 time. Cobalt-60 power modules to source capacity at microbiology
transportation the accelerator or a later stage by laboratory, pallet
needs to be by adding a adding power racking systems
considered and second modules to the and heat
can vary accelerator (if accelerator or by generation boiler
depending upon planned in the adding a second systems.
activity being initial facility accelerator (if
transported, design). planned in the
carriers utilized, initial facility
routes followed design).
and price of fuel.
Treatment of Cost
of Cobalt-60 as
Capital Expense or
OPEX can vary.
Process Conveyor Conveyor Conveyor Transport
management Typically tote or Typically box Typically tote or Systems
pallet conveyors conveyor pallet conveyors A combination of
with an ability to sometimes with automated and
utilize a second automated box manual
conveyor allowing flipping for dual transportation
multiple products side irradiation systems
requiring different
doses to be
processed
Safety Systems Safety Systems The Safety Access Safety Systems
The Safety Access System prevents unauthorized access Gas detection
System prevents into the accelerator room and systems, fire
unauthorized irradiation chamber. Should there be suppression
access into the an authorized intrusion in the systems, damage
irradiation irradiation area, the safety system limitation area,
chamber. Should instantaneously stops the accelerator integrally safe
there be an irradiation. electrical systems
authorized in critical areas.
intrusion in the access controls,
irradiation area, personnel
the safety system monitoring
instantaneously systems and
stops the personal
conveyor and protective
lowers the source equipment.
rack to the
bottom of the
irradiator pool.
Process Control System The Process Control System coordinates all equipment
involved in the treatment process and manages the production orders and
recipes.
 Project Engineering and Management This covers the process design, shielding
calculations, integration service of the process components such as product
handling, treatment quality monitoring, safety or building management.
Dosimetry A dosimetry system for routine production Biological
requirements and qualification needs Indicators
Biological
indicators,
monitoring and
recording devices
with a
microbiological
laboratory
Specific Shielding Shielding Shielding Venting /
Infrastructure Shielding is Shielding is Shielding is Shielding
usually made of usually made of usually made of Explosion venting
concrete. A concrete. A concrete. A systems are
typical foot print typical foot print typical foot print provided in the
for an x-ray or for an e-beam for an x-ray or EO storage and
gamma irradiation system including gamma irradiation sterilizer areas.
system including shielding and system including Shielding can also
shielding and conveyor is about shielding and be made of
conveyor is about 20m x 15m. conveyor is about concrete and/or
25m x 20m. 25m x 20m. steel to form a
damage limitation
area
Irradiation Authorizations including compliance of design Environmental
shielding and safety system according to standards. Authorizations
including federal
and/or local
environmental
permits and
hazardous
materials licenses
Ancillary systems Includes water cooling, compressed air, Ancillary systems
ozone venting, fire prevention Includes emission
controls, boilers,
water cooling,
compressed air,
fire prevention
Common Land
infrastructure Building
Warehouse
Miscellaneous fences, racks, furniture, forklifts
Local authorizations Building permits, fire department, environmental
regulations such as noise
OPEX Gamma E-beam X-ray EO
Variable costs Operators Operators typically work in shifts. Processing Operators
Costs that are boxes requires more labor compared with pallet processing. Operators typically
proportional to work in shifts.
production Moving materials
into and out of the
Pre Con,
sterilization and
Degas areas,
preparing, placing
and recovering
BI's. The process is
batch based but
requires
continuous
monitoring and
supervision
Power Power Power Power
Consumption Consumption Consumption Consumption EO
Minimal as it is Typical Typical plants operate
only required to accelerators have accelerators have with elevated
raise and lower power power temperatures,
source rack and efficiencies from efficiencies from humidity and air
operate the chiller 20 to 50%. 20 to 50%. handling
for pool Accelerator Accelerator requirements.
power power Power is also
consumption consumption required to draw
stops when stops when vacuums and to
products are not products are not process waste EO
processed. Other processed. Other gas concentrations
power power via an emission
consumption is consumption is control system. All
for office and for office and of these processes
other non- other consume
accelerator nonaccelerator considerable
related related amounts of power.
components. components. X-
Ebeam has ray systems
considerably require
greater demand significantly more
for electricity beam power
than gamma. compared with e-
beam systems for
similar
throughput due
to power losses in
the x-ray
converter.
Conveyor power consumption
Spare Parts Spare Spare Parts Spare parts stock may Spare Parts Spare
parts stock may vary and can be expensive. The parts stock may
vary. Due to the minimum spare parts to store are vary. There are a
simplicity of specialized consumables which greater number of
Cobalt60 require periodic replacements (e.g. support systems
irradiators, spare cathode, tetrodes, klystrons, seals, that require
parts are minimal filters, pipes). Other spare parts may maintenance and
and readily be stored in order to reduce intervention. Spare
available downtime in case of failure. Spare parts required for
compared to parts required for the conveyor are the conveyor are
Accelerator based similar compared with gamma. similar to gamma,
systems. Spare e-beam and x-ray
parts required for but many other
the conveyor are systems require
similar compared routine
with e-beam and maintenance.
x-ray.
Dosimeters BI Testing
Maintenance Maintenance Engineer Someone with Maintenance
Engineer General specialized electronics and mechanics Engineer General
conveyor/electrical background needed for maintaining conveyor/electrical
maintenance an accelerator. Specialized expertise maintenance
background available from the manufacturer may background. The
be required due to equipment amount and
complexity. nature of the
equipment on site
results in high
levels of routine
operational
maintenance
Cobalt-60 Activity Emission Controls
reload Cobalt-60 Emission control
decays by 12.3 % systems require
every year. regular
Therefore, to maintenance and
maintain constant testing.
throughput, Replenishing the
sources should be equipment (e.g.
replenished every oxidizer catalyst or
1-2 years. There is scrubber liquid and
usually a cost for materials) can be
return of depleted significant
sources requiring ongoing
investment
Cobalt-60 Reload Maintenance Service Source Such
Service Exclusive service is usually outsourced to the
 of the cost of equipment supplier and lasts 30 to 50
Cobalt60 and hours per year
transport, a
service may be
provided by the
source provider to
perform the
source reloads.
Reloads usually
last approximately
24 hours per year
Provisions for Provisions for Facility Provisions for
Facility Decommissioning Minimal, depending Facility
Decommissioning on jurisdiction, it may be necessary to Decommissioning
Depending on provide financial assurance for any Minimal
jurisdiction, it may activated components. In many
be necessary to situations, it is probable that no
provide financial induced radioactivity would be
assurance for the present at closure, or that such
disposition of induced radioactivity as may be
Cobalt-60 sources present would have shorter half-lives
in the event that such that the activity would decay
the facility is during the closure time. As such, no
decommissioned. additional cost would be required for
For this paper, it is decommissioning. For this white
assumed that the paper, it is assumed that the facility
facility would not would not remove the shield
remove the shield
or pool
Maintenance service conveyor
Dosimetry technician Microbiologist
Quality Manager
Other power consumption office, warehouse

7.4 Environment Industrial irradiator facilities, regardless of modality, operate in compliance with local
regulations concerning occupational exposure to staff and there is no difference in the regulatory limits
for occupational exposure among the modalities. If the facilities are designed, constructed and operated
in accordance with the existing international standard on irradiator design, there should be no dose to
personnel during operations. Environmental impacts from industrial irradiation facility activities have
few differences from other light industrial operations. Therefore, rather than attempting to include all
environmental impacts, only those environmental impacts that may be encountered are included in this
section. Specific areas of environmental concern for industrial irradiators include electrical power
consumption and subsequent greenhouse gas production, effluence (the production of ozone from
radiolysis of air during irradiations), transportation impacts (see Section 3.8), and CO2 generation which
is covered in the next sub-section.
 Gamma E-beam X-ray EO
Electrical power Comparable to Electricity Electricity Electrical
consumption other light requirements are requirements are requirements are
industrial greater than significantly typical for an
operations gamma or other greater than industrial
light industries ebeam and EO operation
and other light involving pumps,
industrial conveyors, etc.
operations
Effluence Small amounts of Small amounts of Small amounts of Exhaust EO gases
ozone produced ozone produced ozone produced must be treated
to acceptable and
safe limits

CO2 Generation

E-beam
A typical 80 kW electron accelerator (which is
equivalent to a Cobalt-60 facility in the range of 5
to 6 MCi) would result in between approximately
1,500,000 lbs and 2,700,000 lbs of CO2
generation (the amount of CO2 generated is
proportional to the electrical power generated).
Estimated outcome if all Cobalt-60 irradiators
were converted to 10MeV accelerators: The
estimated amount of Cobalt-60 in the US is 150
MCi. Converting all Cobalt-60 irradiators to 10-
MeV accelerators would increase the annual CO2
emissions in the US by approximately 57,000,000
lbs (28,500 tons).
X-ray
Based on the assumption that approximately 450
kW of x-ray equates to approximately 4.0 MCi of
Cobalt-60 and 7,884 operational hours per
annum, the annual power requirement is
approximately 7,100,000 kW-h. This annual
power requirement produces between 8,600,000
and 15,400,000 lbs CO2.
Estimated outcome if all Cobalt-60 irradiators
were converted to x-ray accelerators: The
estimated amount of Cobalt-60 in the US is 150
MCi. Converting all Cobalt-60 irradiators to x-ray
accelerators would increase the annual CO2
emissions in the US by approximately
450,000,000 lbs (225,000 tons).