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INDUSTRIAL GAMMA AND X-RAY: “SAME BUT DIFFERENT”

Author: Philippe Dethier, IBA

Date: April 2016

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Contents Executive summary ................................................................................................................ 4 Industrial irradiation technology overview .......................................................................... 5 X-ray: high energy, high power ................................................................................................ 5 Gamma: processing using Cobalt-60 sources ........................................................................... 6 X-ray vs gamma: technologies compared ............................................................................. 8 Dose uniformity (overdosing effects) ....................................................................................... 8 Penetration properties and optimal product loads (pallet vs. tote processing) .......................... 8 Dose rate, irradiation impact on medical devices ..................................................................... 9 Volume of product being irradiated ........................................................................................ 10 Fixed Co-60 decay costs vs. variable X-ray electricity costs ................................................. 10 Maintenance ........................................................................................................................... 11 Reliability ............................................................................................................................... 11 Safety ...................................................................................................................................... 12 Security ................................................................................................................................... 12 Capacity increases .................................................................................................................. 13 Standards and validation (IQ, OQ, PQ) .................................................................................. 14 X-ray vs. gamma cost comparison.......................................................................................... 14 Gamma and X-ray comparison summary ............................................................................... 18 Why isn’t X-ray taking off faster? ...................................................................................... 19 High product revalidation costs for already validated medical devices .................................. 19 Expanding gamma capacity is still possible and economical ................................................. 19 X-ray is not widely available .................................................................................................. 19 Weak Canadian dollar vs. US dollar ....................................................................................... 19 Industry inertia to existing technologies ................................................................................. 20 Gamma safety and decommissioning cost are partially subsidized ........................................ 20 Obstacles linked to Cobalt-60 logistics are handled by gamma suppliers .............................. 21 When and how will X-ray take off? .................................................................................... 21 If there is a shortage in Co-60 supply or in installed activity ................................................. 21 Should “high-activity sources” become more regulated ......................................................... 21 Irradiation service centers will adopt X-ray first .................................................................... 21 First wave of X-ray systems: E-beam and X-ray dual technology configurations ................. 22 Second wave of X-ray systems: dedicated X-ray configurations ........................................... 22 What would accelerate the development of X-ray? ........................................................... 23 Incentives for two X-ray facilities in target areas ................................................................... 23 Reduce product revalidation barriers when shifting from gamma to X-ray ........................... 23 Incentives to re-validate and migrate EXISTING medical devices to X-ray .......................... 24 Design NEW medical devices for X-ray ................................................................................ 24 FAQ ....................................................................................................................................... 25 Is X-ray a reliable technology? ............................................................................................... 25 Is the X-ray technology available today? ............................................................................... 25 Is gamma a good technology? ................................................................................................ 25 What is the equivalence between X-ray power and gamma activity? .................................... 25 Which is best: X-ray or gamma? ............................................................................................ 25 Will X-ray replace gamma in the future? ............................................................................... 25 Conclusion ............................................................................................................................. 25 About IBA ............................................................................................................................. 26

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Executive summary

When radiation is used to sterilize medical devices, it is generally by gamma

irradiation. Gamma is an irradiation technology based on a radioactive Cobalt-60

source. In 2015, about 440 MCi of Cobalt-60 was in operation worldwide, half of which

is located in the US. This installed activity doubles every 15 years to support the

growth in the disposable medical device supply. Although very reliable and widely

adopted by the industry, gamma presents challenges in terms of supply, transport,

waste disposal and security. Furthermore, in the present international security context,

there is growing international pressure to reduce the world’s dependence on high

activity sources.

Electron beam is an attractive alternative to gamma technology, but due to its limited

penetration properties, substitution is not possible for all products and packaging.

In most cases, X-ray is an ideal alternative to gamma since the flux of photons of both

technologies have similar properties. The main advantage of X-ray systems is that

they are powered by electricity, a source of energy that will remain widely available in

the very long term and increasingly made of renewable energies.

In theory, switching products from gamma to X-ray is very easy and would reduce the

industry’s dependence on Co-60 sources. But practically, many barriers force

manufacturers to keep using Co-60 sources. The main reasons are the high cost

required to revalidate products from gamma to X-ray, the “non-availability” of X-ray

irradiation capacity and the ease to expand capacity of existing Co-60 facilities.

Without any change in Cobalt-60 supply or in regulations, it is expected that use of

Cobalt-60 with pursue its growth and alternative technologies will be adopted at a very

slow pace.

Besides regulation changes, there are several ways to encourage capacity shift from

gamma to X-ray. Potential initiatives include financial support from authorities to build

new X-ray facilities and financial support to revalidate target products to allow a shift

in capacity from gamma to X-ray.

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Industrial irradiation technology overview

Half of single-use medical devices are sterilized with ethylene oxide, another well-

established sterilization method based on a toxic gas. The remaining 50% are

sterilized using irradiation. Most of the single-use medical device sterilization is

performed by Sterilization Service Centers which provide sterilization services to

medical device manufacturers. In addition to Sterilization Service Centers, some large

medical device manufacturers also operate in-house industrial sterilization facilities.

There is probably more than 80% of the industrial irradiation capacity is dedicated to

sterilization of disposable or single-use medical devices such as lab ware, gloves,

masks, stents, implants, blood tubing, etc. The typical average density for these

medical devices varies between 0.1 and 0.2 gr/cc. The remaining 20% of the capacity

is allocated to polymer crosslinking, packaging, pharmaceuticals, cosmetics and food.

There are three main industrial irradiation technologies: gamma (based on Cobalt-60

radioactive sources) which counts for about 80% of radiation capacity installed

worldwide; electron beam which counts for about 20% of the total radiation capacity

installed; and X-ray which has started to gain a foothold in the irradiation market.

X-ray: high energy, high power

The first commercial dedicated X-ray facility started operations in Hawaii in 2000 for

the phytosanitary treatment of fresh fruit and vegetables shipped to the US mainland.

In 2001, a second facility opened near Philadelphia, USA. It is currently being used for

the decontamination of mail by the US Postal Service1. The third large-scale system

was built in Switzerland in 2010 and is mainly used for sterilization services.

Since 2010, several E-beam systems have been built with an option to provide X-ray

irradiation services. Several of these “dual technology” E-beam and X-ray facilities

have been installed in Austria, Spain and the US.

While the beam of photons coming from an X-ray or gamma source is very similar, the

way these photons are generated is very different.

An X-ray system is basically an electron beam system where a tantalum target

converts the beam of electrons into a ray of photons (bremsstrahlung effect).

1 The Anthrax Attacks on the United States Postal Service: Sanitizing the Mail, 2001, Marshall R. Cleland, IBA

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Figure 1: An X-ray system is an electron beam system where the beam of electrons is converted into X-ray by a target.

X-ray systems have a directive beam of photons that allows the flux to be concentrated

in the direction of the product, optimizing the photon capture rate.

Gamma: processing using Cobalt-60 sources

In 2015 there was about 440 MCi installed in the world, with half of this capacity

installed in large facilities in the US. There are close to 180 gamma irradiators

worldwide2.

Figure 2: Half of the Co-60 activity is in the US concentrated in large facilities.

Cobalt-60 loses 12.3% of its activity per year. In order to keep the same throughput

(or capacity), gamma facilities must regularly reload their irradiators with “fresh” new

Cobalt-60. The natural loss of activity of Cobalt-60 is called “decay.” This natural decay

causes a constant change of the source activity and forces gamma users to regularly

2 GIPA Comparison of Cobalt-60 Gamma and X-ray Technologies Fact Sheet 2014

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assess the actual site activity and adapt the product processing time accordingly in

order for products to receive the expected dose levels.

The global natural decay can be easily calculated by taking 12.3% of the installed base

of 440 MCi in 2015 representing ~54 MCi of Cobalt-60 per year (figure for 2015). The

additional capacity required to support the growth of the single-use medical device

market is estimated at 4.4% of the installed base of 440 MCi representing ~19 MCi of

Co-60 per year. The total global yearly Cobalt-60 demand is therefore about 73 MCi

(for 2015).

This 4.4% growth will double the Co-60 activity globally installed and shipped every

15 years.

Figure 3: Projections show a 4.4% yearly increase for installed and transported Co-60.

There are about 40 reactors producing Cobalt-60 globally in eight countries. Canada

and Russia are the biggest producing countries, responsible for more than 80% of

global Cobalt-60 production.

Gamma has a so-called “isotropic” radiation which means that photons are irradiating

in all directions. For that reason, the volume of products surrounding the source must

be maximum.

In order to capture as many photons as possible generated by the decay of Co-60

source, products must be positioned in close proximity of each other, horizontally and

vertically. Depending on the configuration of the products and of the source, the

portion of energy that is actually absorbed by the product may reach about 40% in the

best case but can also be as low as 15%, for example in pallet irradiators with an

overlapping source.

0

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2006

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(MCi

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Projected installed Co-60 activity (Mci)

020406080

100120140160

2006

2009

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Ship

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Projected Co-60 demand worldwide (MCi) Additional Co-60 for growth

Co-60 to replace decay

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X-ray vs gamma: technologies compared

Dose uniformity (overdosing effects)

Irradiation does not deliver a single dose within a product but a gradient of doses. In

order to deliver the required sterilizing dose in all parts of the products, some parts of

the product will necessarily absorb higher doses. The ratio between maximum dose

and minimum dose is called Dose Uniformity Ratio (DUR). The DUR is therefore never

lower than 1; the closer the DUR is to 1, the less overdosing.

The dose in excess should be minimum for the quality of the product and also

represents a waste of energy. The maximum dose that a product can accept is

determined by the device manufacturer during validation studies. In recent years, the

trend has been towards lower maximum doses in order to better preserve the quality

of the devices, especially in the rapidly growing sector of drug-device combined

products. In a number of instances, X-ray is the only possible option.

Figure 4: X-ray allows reducing by a factor of 2 the overdosing effect when treating pallets.

Penetration properties and optimal product loads (pallet vs. tote processing)

X-rays higher energy photons are more penetrating than gamma rays from Cobalt-60.

One of the consequences is that there is no need to reduce the size of the load on a

pallet or to create gaps in order to improve the dose uniformity as it is done for gamma

to remain within the specified dose range when the volume or the density is too high.

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Figure 5: The superior penetration properties of X-ray allow for increases in the product loads sterilized.

This is why products are typically treated using X-ray for 2 cubic meter pallets and

thinner 1 cubic meter metallic containers (totes) with gamma source.

Dose rate, irradiation impact on medical devices

Ideally, medical devices should be designed taking into account the target sterilization

technology, selecting compatible polymers as early as possible in the design stage.

Irradiation in general may have an impact on the product’s molecular structure leading

to a change in the polymer functional properties unless special formulations for

irradiation are used. Today, many papers are available describing the impact of

irradiation on most commonly used polymers in medical device manufacturing.

The dose rate is the quantity of radiation absorbed per unit time. The shorter the time

required to deliver a dose, the higher the dose rate.

X-ray and gamma have very different irradiation processes. X-ray systems deliver the

dose to products when they are in front of the X-ray target. For gamma processes,

products receive their dose from the time they enter the irradiation chamber until the

time they leave it. The maximum gamma dose rate is observed when products are in

front of the rack source (perpendicular to the rack) and the minimum dose rate is

observed when products are further away from the Co-60 sources. Consequently,

gamma irradiation of a container is the result of a succession of different dose rates

when for X-ray it is the result of a constant and much higher dose rate

A key parameter to consider when comparing dose rates for both technologies is the

irradiation time. For gamma, irradiation time is the total duration that products receive

dose while turning around the source. For X-ray, irradiation time is the time the

products receive the dose in front of the X-ray target. Since dose rate is proportional

to source power, comparisons of X-ray and gamma dose rates must be done on

equivalent throughput systems.

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Gamma average dose rates are estimated at 10 kGy/h for a 3 MCi gamma site3. For

a similar X-ray system of about 372 kW beam power, the average dose rate during

irradiation time is approximately 60 kGy/h.

When comparing both technologies, the much higher dose rate of X-ray leads to a

drastic reduction in exposure time (six times faster), resulting in significantly fewer

denaturing effects on products after irradiation such as odor generation, material

stability, and color change. It is also observed that there is a reduced effect of ozone-

induced oxidation in the product4. Such reduced chemical effects on polymers result

from the fact that the X-ray dose rate is much higher than gamma, reducing the product

exposure time and preventing some of the chemical reactions from occurring.

All products (and their packaging) currently treated with gamma can be treated with

X-ray. The superior penetration of X-ray over gamma also makes it possible to treat a

broader range of products, including those now considered too sensitive, too large or

too dense to be gamma irradiated.

Volume of product being irradiated

In gamma irradiators dedicated to medical sterilization, products travel in several

parallel paths around the source in order to make optimum use of the available

radiation. The radiation that passed through the previous line of irradiation containers

is thus captured in the next line. However, the quantity of radiation that emerges from

the previous line depends on the density of the product that are in this line.

As a consequence these irradiators are best suited for large batches of identical

products. Switching to products of different densities requires a flushing of the

irradiation room during which phantom products are irradiated before the next batch

is introduced. This results in a significant waste of time and decayed Cobalt-60.

X-ray systems offer far more flexibility since the volume being irradiated (under the

beam only) is only one or two containers and the beam characteristics can be instantly

adjusted for the next containers in order to take into account differences in density or

required dose.

Fixed Co-60 decay costs vs. variable X-ray electricity costs

Since gamma continuously emits and loses activity, for economic reasons it is

mandatory to operate as close as possible to 24/24 7/7. Whenever a gamma facility is

idle, the emitted radiation is wasted. Therefore Co-60-related expense cannot be

adjusted to the actual requirement and constitutes a fixed costs.

X-ray systems, on the other hand, can be turned off when they are not needed. Modern

X-ray systems feature a modular power design that allows their capacity to be

increased when needed. The ability to stop the X-ray system allows for the flexible

management of short-term unplanned production peaks. It also allows for optimized

production by scheduling treatment during target time slots to benefit from lower-cost

labor or lower-cost electricity. Therefore X-ray electricity-related costs are variable

costs proportional to production load.

3 Gamma Irradiators for Radiation Processing – International Atomic Energy Agency 4 Synergy Health Information Sheet – “The sterilization specialists”

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Maintenance

Both technologies have similar maintenance activities on common infrastructure

(conveying systems, control software, building, etc.) The main differences are in

maintenance of the gamma source and the X-ray generator.

X-ray systems usually plan between 30 and 50 hours of planned preventive

maintenance per year. During this preventive maintenance, typical tasks performed

include cleaning, preventively replacing consumables, and others. Since maintenance

is usually performed during the day, production can be recovered during the night

using higher power for faster processing time, so therefore it has no impact on

customer schedules.

Gamma facilities also require weekly, monthly and bi-annual maintenance activities.

Licensing authorities also require a number of safety tests and inspections at a

predetermined frequency.

Replenishment of Cobalt-60 can also be considered as maintenance activity (though

financially it is often treated as a capital expenditure). Typically it takes place once a

year. Adding, moving or removing the source elements on the source rack usually

takes a full day in commercial facilities, during which no processing can take place. As

the new source configuration may affect dose distribution, the replenishment must also

be followed by a new operational qualification exercise and sometimes, depending on

the results a new performance qualification for the products of the customers. These

exercises can take up to several days.

Reliability

When analyzing system reliability, a key difference should be made between planned

outages (maintenance, Cobalt-60 loading, etc.) and unplanned downtime (mechanical

problems with conveying systems or Cobalt-60 rack handling, accelerator failures,

etc.) Production schedules take planned outages into consideration while unplanned

outages create high stress on customer schedules.

It is recognized by irradiation facility users that most of the reliability issues originate

from mechanical components in the product conveying systems. Irradiation sources

(gamma, electron beam or X-ray accelerator) do not rely on moving mechanical parts,

which explains why they are responsible for only a small part of overall unplanned

downtime.

The emission of gamma radiation by Cobalt-60 is a natural phenomenon that is not

subject to any breakdown. The worst possible problem is a jamming of the source

rack, when its path down to the safe position in the storage pool is obstructed.

Fortunately this is a rare occurrence but when it happens it is impossible to access the

irradiation area for weeks or for months and the heat that the source generate can

even cause the destruction by fire of the equipment inside the irradiation room. The

latest reported case took place near Kuala Lumpur, Malaysia, in 2014.

In terms of reliability, an X-ray system does not differ from an E-beam system. The

only difference between both systems is a passive X-ray converter placed at the exit

of the electron scan horn. This passive X-ray converter is a very basic piece of metal

which has no impact on the reliability of the system. Therefore, X-ray systems are as

reliable as the electron beam systems in use at most of the largest Sterilization Service

Providers, operating reliably 24/24 for decades with availabilities higher than 97%.

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Some accelerator systems such as the Rhodotron are designed with built-in

redundancy. For example radio frequency (RF) systems can be made redundant

which would cover about 35% of typical unplanned issues. Additionally, after a

planned or unplanned downtime, whatever the cause, X-ray systems may increase

their beam power, allowing them to catch up on unprocessed “buffered” products. This

makes X-ray systems an excellent fit for “just in time” manufacturing required by

industrial users.

In summary, while gamma and X-ray are very different technologies, both have very

similar reliability performances, with most of the downtime caused by mechanical

issues relating to product conveying systems.

Safety

High power and high energy X-ray systems and large-size gamma irradiators require

similar shielding with thick-walled concrete vaults. For both technologies, the safety is

based on the impossibility to enter the irradiation room when the facility is operating

and processing products, and on the impossibility to have irradiation emitted in the

irradiation area when personnel is present. Fail-safe systems ensure that the facility

returns to the safe mode in case of fault or abnormal event. However, while the risk of

irradiation is totally annihilated when the X-ray system is turned off, the risk of

personnel exposure is never nil in gamma irradiators since it is impossible to stop the

emission of ionizing radiation.

Security

For more than a decade, the global terrorist threat has made transportation of Cobalt-

60 increasingly difficult and costly, with shipment delays and denials frequently

occurring. Recently, national authorities have also turned their attention to the various

security measures that operators of irradiators should implement to prevent malicious

use of the radioactive sources. The International Basic Safety Standards for Protection

against Ionizing Radiation and for the Safety of Radiation Sources5 describes how

gamma sources shall be kept secure so as to prevent theft or damage and to prevent

any unauthorized person from carrying out any forbidden action.

As the threats have increased, various governments wish to speed up the study of the

feasibility of alternatives. The US government listed sixteen radionuclides as those of

principal concern when considering the problems they could cause if used in a

Radiological Dispersion Device (RDD). Cobalt-60 is one of them6. At the 2014

International Atomic Energy Agency (IAEA) General Conference, the US announced

that they had committed to work jointly with France, the Netherlands, and Germany to

establish a roadmap of actions over the next two years to, among others, support

alternatives for radioactive sources. Subsequently, other states such as the United

Kingdom and the Netherlands have endorsed this effort and France has drafted—and

circulated—a proposed joint statement or “gift basket” supporting alternatives to

5 International Basic Safety Standards for Protection Against Ionizing Radiation and for the Safety of Radiation Sources, Safety Series No. 115, IAEA 6 US Nuclear Regulatory Commission, “The 2010 Radiation Source Protection and Security Task Force Report, Report to the President and the U.S. Congress Under Public Law 109-58, The Energy Policy Act of 2005,” US Nuclear Regulatory Commission, Washington, DC, August 11, 2010

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radioactive sources to governments participating in the 2016 Nuclear Security Summit

in Washington DC 7.

These developments increasingly make X-ray sterilization appear as the sterilization

method of the future, even if gamma irradiation will remain needed for a number of

years.

Capacity increases

During the first years of operation, sterilization facilities contain a fraction of the total

quantity of Cobalt-60 that they can hold. It usually takes several years for the market

to grow to the point where the facility is used at maximum capacity.

For gamma facilities, between two Co-60 replenishments, the throughput of a capacity

is fixed. If it is too high for the demand, the Cobalt-60 decay in excess is wasted. If the

capacity is too low, it is not possible to rapidly adjust it since it takes months to have

Cobalt-60 delivered. In fact the quantity of Cobalt-60 in an irradiator is only

occasionally right for the demand.

Capacity adjustments are very different with X-ray systems. Modern X-ray

accelerators are built with a modular design, so operators can acquire an initial system

with low power and add power modules to increase capacity when and if needed. Such

X-ray power increases can be done within hours if no hardware change is required.

Figure 6: IBA’s new Rhodotron® modular design allows operators to start with a 1-amplifier low power system and increase capacity by installing up to 3 amplifiers.

7 Permanent Risk Reduction: A Roadmap for Replacing High-Risk Radioactive Sources and Materials CNS occasional paper # 23 – July 2015

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Standards and validation (IQ, OQ, PQ)

X-ray and gamma radiation facilities use for the sterilization of healthcare products

must meet the requirements of the same international standard ISO 11137. Their

validation consists of the same 3 steps:

Installation Qualification (IQ): Ensuring equipment is installed as per

manufacturer’s specification.

Operation Qualification (OQ): Ensuring equipment, critical control

equipment and instrumentation are capable of operating within required

parameters.

Performance Qualification (PQ): Demonstrating that sterilizing conditions

are achieved in all parts of sterilization load.

X-ray vs. gamma cost comparison

This chapter aims to provide a fair economical comparison between gamma and X-

ray technologies. The comparison is made by comparing similar system configurations

for equivalent throughput capacities. In this comparison, gamma and 7MeV X-rays are

compared on the basis of a pallet-processing configuration.

Gamma and X-ray systems are compared based on their acquisition cost, their running

costs (Cobalt-60 decay and electricity) and on the throughput of products which can

be processed (includes E-beam to X-ray power loss during conversion).

In order for the cost model to apply to a wide number of situations, X-ray and gamma

cost ranges are compared. The cost range gives a range from a worst case scenario

to a best case scenario.

Assumptions for best and worst case scenarios:

Best

case

Worst

case Assumption

2,5 3 USD: cost of Co-60

1,25 1,1 USD/EUR exchange rate8

0,05 0,09 USD/kWh electricity cost9

0 0,1 USD/Ci: decommissioning provision

25.000 50.000 USD: Co-60 transport costs including extra

transportation fees10

8 IRS historical USD Euro exchange rate 9 US average price for industrial electricity is 7.18 c$/kWh. Source : US Energy Information Administration Electric Power Monthly Data for September 2015 10 GIPA “Typically Asked Questions Regarding Cobalt-60 Shipments” Fact Sheet March 2014

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Other assumptions:

Only technology-specific costs are compared. Costs for items comparable for both technologies (such as building, shielding, conveying systems, scheduling systems, manpower, etc.) are neutral and excluded from the comparison.

The minimum sterilization dose is 25 kGy, yearly production of 8.000 hours and the average density of products is 0,15 gr/cc.

Transport costs for one Cobalt-60 replenishment per year is assumed for gamma.

Gamma and X-ray are compared based on a pallet-processing configuration. Therefore it is assumed that labor required to run both configurations is comparable.

Gamma throughput data (pallet configuration):

o ~4,3 m³/h/MCi (0,15 gr/cc, 20 kGy)11

o = 3,44 m³/h/MCi (0,15 gr/cc, 25 kGy)

X-ray throughput data (pallet configuration):

o 93.000 m³ @ 420 kW (0,15 gr/cc, 25 kGy, 8.000 hours, 7 MeV)12

o = 2,77 m³/h/100kW (of E-beam power converted to X-ray)

o = 3,44 m³/h/124kW (of E-beam power converted to X-ray)

o This data takes into account the power losses in the target during the electron beam to X-ray conversion.

Based on the above data, the equivalency used to compare gamma and X-ray will be 1 MCi of Cobalt-60 is equivalent to 124kW since these sources can treat the same volume of products under similar conditions.

Operational recurrent operational costs to run the source:

o Gamma: 12,3% decay on total installed activity

o X-ray: accelerator electrical efficiency (wall-plug to beam power ratio) improves from 22% to 51% with beam power13

Other X-ray unfavorable assumptions:

o X-ray maintenance cost was included in this financial analysis but cost for gamma-specific maintenances or Co-60 reload services were not taken into account.

o It was not included in the assumptions that X-ray systems can optimize the use of labor or electricity by concentrating production during optimal time slots.

11 Nordion’s Parallel Row Pallet Irradiator brochure 12 IBA’s eXelis® X-ray Sterilization brochure – September 2013 13 IBA Industrial – White Paper – Practical Advantages of the Rhodotron®

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This computation is illustrated in this graph:

Figure 7: X-ray (green) and gamma (blue) cumulated 5-year cost comparison. Gamma is more economical for small volumes, X-ray is more economical for large volumes. The typical breakeven point is around 1.4 MCi.

The conclusions that can be drawn from this comparison are the following:

For a typical situation (in between best and worst case assumptions), the breakeven point where X-ray becomes more economical than gamma is for equivalent facility capacity of 1.4 MCi.

In any case, for equivalent activity levels lower than ~0.9 MCi, gamma technology is more economical than X-ray. This is mainly explained by the fact that amortizing an accelerator requires a minimum volume of products to process.

In any case, for activity levels above ~2.3 MCi, X-ray is more economical than gamma. This is explained by the fact that capacity increases are less expensive for X-ray compared with gamma.

Identifying the breakeven point in the 0.9 MCi <-> 2.3 MCi range will require positioning each technology in its best/worst case range for each specific situation. For example:

300.000 700.000 1.100.000 1.500.000 1.900.000 2.300.000 2.700.000

5 ye

ar c

umm

ulat

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osts

Gamma equivalent capacity (Ci)

X-ray vs gamma 5 year cost assesment

Gamma Worst case X-ray worst case

Gamma Average X-ray Average

Gamma Best case X-ray Best case

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o The breakeven point in a worst case for both gamma and X-ray is ~1.3 MCi (upper lines)

o The breakeven point in a best case for gamma and X-ray is ~1.7 MCi (lower lines)

When comparing yearly source energy costs (Co-60 decay vs. X-ray electricity power

consumption), X-ray is more economical than gamma.

Figure 8: Comparison between Co-60 decay (blue) and X-ray electricity usage (green).

€ 0

€ 100.000

€ 200.000

€ 300.000

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€ 500.000

€ 600.000

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€ 800.000

€ 900.000

€ 1.000.000

0 500.000 1.000.000 1.500.000 2.000.000 2.500.000 3.000.000

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Facility equivalent capacity (MCi)

Yearly X-ray electrcity costs vs gamma Cobalt decay

Gamma Worst case X-ray worst case

Gamma Best case X-ray Best case

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Gamma and X-ray comparison summary Gamma X-ray

Dose uniformity (overdosing effects) Better DUR

Optimal product load Totes Pallets

Dose rate (irradiation time) ~10 kGy / hour ~60 kGy / hour

Product compatibility and irradiation

impact on products

Lower overdosing ->

more products

compatible

Less denaturing

effects on products

Maintenance and impact on

production Production stop to

reload Co-60

Recover production

outside of

maintenance by

increasing power

Reliability > 97%

> 97%

Recover production

after outage by

increasing power

Safety Non-stop irradiating

Co-60 source

Stop X-ray irradiation

when needed

Capacity increases Co-60 deliveries to

be planned 1-2

years ahead

Instant power

increase available

Main standard ISO 11137 ISO 11137

Typical cost optimal capacity range < 1.4 MCi > 1.4 MCi

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Why isn’t X-ray taking off faster?

Even though X-ray is best suited for replacing gamma sources in some situations, the

natural takeoff is very slow, especially in the US. This section describes some of the

reasons for this slow rate of adoption.

High product revalidation costs for already validated medical devices

Every change to the manufacturing process of a medical device, including sterilization,

must be validated. Such validation proves to notified bodies that the medical device

will perform at least as well under the new manufacturing process. Such device

revalidation requires a lot of human and financial resources to support the functional

product testing and to submit the change request to authorities.

Medical device revalidation must be done for every product migrated to another

sterilization technology. The incentives for medical device manufacturers to move to

an alternative technology are often not high enough to justify investing in such product

revalidation efforts.

In some cases, old medical devices were gamma validated using less strict validation

requirements. Should these devices need to be X-ray revalidated, a full gamma

validation would first be required in order to have a valid basis of comparison.

Expanding gamma capacity is still possible and economical

Global regulations are increasingly strict regarding the construction of gamma

facilities. In the last several years, very few new gamma facilities have been built. But

most existing gamma facilities have available capacity and can load additional Cobalt-

60 or expand their gamma cells to meet the short-term demand.

The natural takeoff of X-ray will therefore only occur when gamma facilities will not

have enough capacity available to meet the demand. X-ray would then be the solution

for providing the additional capacity required by the industry.

X-ray is not widely available

A key obstacle in the natural takeoff of X-ray is the lack of service centers in target

areas.

Today we are in a chicken-and-egg situation where medical device manufacturers

can’t commit to the technology because operational X-ray facilities are not available

(at least two for backup). On the other hand, sterilization service providers don’t invest

in X-ray facilities because they can’t get a firm commitment from medical device

manufacturers to X-ray technology. This leads to market technology inertia.

Weak Canadian dollar vs. US dollar

A vast majority of the Cobalt-60 supplied globally is sold from Canada. Therefore the

evolution of the Canadian dollar has an impact on the global dynamics.

Since 2013, the Canadian dollar (CAD) has dropped compared with the US dollar

(USD). Between 2010 and 2013 the average CAD/USD exchange rate was around

1:1. Between 2013 and 2016, the CAD lost 30% of its value compared with the USD.

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Figure 9 : CAD/USD exchange rate history. The Canadian dollar lost ~30% of its value compared with the US dollar between 2013 and 2016, making Canadian Cobalt-60 very economical for US customers.

This explains why, even if the price of Cobalt-60 is increasing over the years (in CAD),

US Cobalt-60 buyers see the price of Cobalt-60 as very attractive (in USD).

Industry inertia to existing technologies

When possible, medical device manufacturers try to stick to technologies they have

already mastered. Moving to a new technology introduces risk and is therefore not

their preferred option. When possible, the preferred option will be to file a new medical

device as the evolution of an existing validated product allowing for partial validation

efforts.

These natural industry behaviors create inertia where manufacturers stick to

technologies they currently use as much as possible.

Gamma safety and decommissioning cost are partially subsidized

In theory, decommissioning a gamma site should not be a major issue. The company

operating the site must prove that no past incident could lead to water, soil or waste

contamination. The end of life sources must also be shipped to a radioactive waste

storage, this is usually managed by the source supplier. Some times damaged cobalt-

60 sources can contaminate water and surrounding soil as reported by the NRC for a

New Jersey plant in 1982. Such contamination can lead to extensive and costly

cleanup.

In many situations, gamma users do not finance the full cost related to security and

decommissioning. Some federal agencies have the mission to secure gamma

radiation facilities in order to reduce risk linked to management of sealed high activity

sources. Such support includes financing which is an indirect funding for gamma

technology. It is also not mandatory in every country to provision for the

decommissioning of high activity sealed source facilities.

Should gamma users have to finance all costs associated with safety and

decommissioning provisions, the technology would be much less attractive.

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Obstacles linked to Cobalt-60 logistics are handled by gamma suppliers

Management of Cobalt-60 logistics such as transport and waste management is a

complex matter. These challenges could motivate gamma users to adopt alternative

technologies but Cobalt-60 suppliers manage Co-60 logistics globally relieving

customers from these hurdles. The end users therefore do not really suffer from these

hurdles and have no natural incentive to look for alternative technologies.

When and how will X-ray take off?

If there is a shortage in Co-60 supply or in installed activity

As described earlier, expanding gamma capacity is usually not an issue. Gamma

capacity can either be increased by adding Co-60 in existing irradiator source racks

or by expanding existing irradiator with a new one.

There will be a natural motivation to handle growing capacity needs using X-ray when

there will be substantial issues to expand gamma capacity or if there should be a

shortage in Co-60 supply.

Increased cost to procure Co-60 would probably not be enough to change the industry

dynamic since sterilization represents about 3% of the medical device cost and

therefore increases in Co-60 cost would have negligible impact on the final cost of the

medical device.

Should “high-activity sources” become more regulated

There are increasing security concerns that highly radioactive material may be used

to build a so-called “dirty-bombs”. In Mexico, four trucks transporting highly-radioactive

material were stolen since 2013. In 2015 a similar truck load went missing in Iraq.

These missing radioactive sources raise concerns that stolen radioactive material may

be used as a weapon by terrorist organizations.

Cobalt-60 sources are classified as category 1 sources by the IAEA which means they

can pose a very high risk to human health if not managed safely and securely.

For more than a decade, several initiatives were taken to promote alternative

technologies but none led to a stringent regulation.

For example, in 2005 the US Energy Policy Act (EPAct) stressed the importance of

implementing “non-isotopic” alternatives. In 2010 the EPAct task force recommended

supporting a migration from “high risk sources” to alternative technologies.

In 2014, US Senator Feinstein and Senator Alexander submitted a bill (Section 402 of

the 2015 appropriations bill for energy and water development and related agencies)

aiming at discontinuing licensing of high-risk radiological sources (including Co-60) in

less than 15 years.

In 2016 a Nuclear Security Summit (NSS) will be held to decide (among others) to

reduce the global HARS inventory (high-activity radioactive sources).

Should one of these initiatives lead to a stringent regulatory change, X-ray would very

quickly take off as a key “non-isotopic” alternative to gamma industrial processing.

Irradiation service centers will adopt X-ray first

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When a new technology is introduced, only a limited number of products are validated

or compatible with that technology. Therefore, service providers typically invest first

into the new technology since they are best positioned to share the sterilization

capacity among multiple customers. This allows service centers to show a viable

business case with reasonable payback periods.

Once medical device manufacturers have converted enough medical devices to X-ray

through service centers, then investing into their own in-house X-ray sterilization

solution will make economic sense.

First wave of X-ray systems: E-beam and X-ray dual technology configurations

In the short term, a very limited volume of products will be validated on X-ray. Such a

low volume of validated products does not justify the investment into a full large-scale

X-ray facility. Therefore, the X-ray systems which will be built in the short run are dual

E-beam/X-ray systems such as IBA’s Rhodotron® DUO.

Figure 10: IBA's Rhodotron® DUO concept is an economical and optimal 10 MeV E-beam system with 7 or 5 MeV X-ray capabilities.

Business cases of such facilities will mainly be driven by E-beam products, X-ray

sterilization will be a minor contribution to the overall facility revenues.

The X-ray option of the dual technology facility will allow operators to gain experience

in X-ray and to start validating product on X-ray instead of redirecting these products

to gamma operators.

A dual technology E-beam/X-ray facility costs between 10 and 15% more than a

dedicated E-beam facility and the power can be flexibly allocated to E-beam or X-ray

depending on the need.

Second wave of X-ray systems: dedicated X-ray configurations

After dual E-beam/X-ray facilities have converted sufficient medical devices to X-ray,

business cases for X-ray-dedicated facilities will show much shorter return on

investment.

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Figure 11: IBA's eXelis X-ray pallet configuration designed to sterilize industrial pallet loads. The X-ray system is based on a standard electron beam accelerator with an X-ray converter.

Additionally, if gamma capacity reaches maximum capacity in some areas, there will

be a strong drive to deploy X-ray optimized facilities for pallet processing such as IBA’s

eXelis configuration based on a standard Rhodotron® accelerator.

What would accelerate the development of X-ray?

Even though X-ray economics make sense for medium and large volume processing,

the technology is reliable and there is a global push towards non-radioactive energy

sources, X-ray technology could benefit from initiatives to speed up adoption of the

technology. Some of the key initiatives which would help the development of X-ray in

the industry are described in this chapter.

Incentives for two X-ray facilities in target areas

The first step in kicking off a new technology is making the technology available. In

the case of industrial sterilization, two facilities are required, within a reasonable

radius, to be each other’s backup. This is a mandatory requirement for most medical

device manufacturers in terms of risk management and business continuity.

In the early days of X-ray, justifying the investment in two X-ray facilities is very

challenging since only a small volume of medical devices are validated. Therefore,

special funding for the first two X-ray facilities would make the business case for X-ray

pioneering companies acceptable. Such funding would give time to service centers to

focus in the first years on converting products to X-ray and then focus on volume

production.

Reduce product revalidation barriers when shifting from gamma to X-ray

Today, revalidation is a major obstacle forcing manufacturers to keep sterilizing using

gamma. In an ideal world, should global notified bodies approve a generic equivalency

between gamma and X-ray sterilization, medical device manufacturers would be free

to select the technology best suited to them. Should such “generic X-ray gamma

equivalence” not be acceptable to notified bodies, revalidation requirements should

be reviewed to focus on a minimal list of key requirements.

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Incentives to re-validate and migrate EXISTING medical devices to X-ray

Providing an incentive for manufacturers to migrate key large volume products to X-

ray is another efficient way to promote the kickoff of X-ray.

Some products, already validated on gamma, may benefit from the advantages of X-

ray such as faster turnaround time, less impact of irradiation on products, lower costs,

etc. Such incentive is a one-time investment per product which would initiate an

“instantaneous” shift of capacity from gamma to X-ray.

Design NEW medical devices for X-ray

Migrating existing medical devices to X-ray sterilization requires revalidating work as

described earlier in this document.

But in the case of new (not yet validated) medical devices, initial validation must take

place anyway, so providing incentives for designing and validating new medical

devices for X-ray doesn’t add costs to the healthcare industry.

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FAQ

Is X-ray a reliable technology?

Yes! An X-ray system is an E-beam system with a passive and reliable converter.

Such systems are operated routinely by most major sterilization service providers with

availability figures higher than 97%.

Is the X-ray technology available today?

Yes! X-ray systems are operational today in Switzerland, Austria, USA and Spain.

Is gamma a good technology?

Yes! Gamma is a good technology for the industry since it’s reliable and simple. But it

has logistical, supply and safety issues linked to radioactive source management.

What is the equivalence between X-ray power and gamma activity?

In a 7 MeV pallet configuration, 1 MCi = ~ 124 kW.

Which is best: X-ray or gamma?

Both technologies have pros and cons. There is no absolute “best” technology, there

is a technology best-suited for a particular situation.

Will X-ray replace gamma in the future?

No. In a first instance, X-ray will share the capacity growth with gamma. Later, large

scale dedicated X-ray facilities will start processing large volumes of medical devices

which will reduce worldwide demand for gamma but X-ray will not replace it. In some

instances, it will never make sense to replace some gamma installations with X-ray,

especially small activity installations.

Conclusion

Gamma and X-ray are very similar fluxes of photons but are produced in different

ways. Both technologies are very reliable and well-suited to industrial irradiation

processes. Assessing which technology is more economical must be evaluated case-

by-case. The main parameters influencing an economical comparison between

gamma and X-ray are the volume of products processed, the price of the source

energy (electricity and Cobalt-60), currency exchange rate and technology-specific

costs (decommissioning, provisioning, Cobalt-60 transport costs, etc.) As a rule of

thumb, the breakeven point where X-ray processing becomes more economical than

gamma is usually between 1.3 and 1.7 MCi.

In theory, switching products from gamma to X-ray is very easy and would reduce the

industry’s dependence on Co-60 sources. But practically, many barriers force

manufacturers to keep using Co-60 sources. The main reasons are the high cost

required to revalidate products from gamma to X-ray, the “non-availability” of X-ray

irradiation capacity and the ease to expand capacity of existing Co-60 facilities.

Without any change in Cobalt-60 supply or in regulations, it is expected that use of

Cobalt-60 with pursue its growth and alternative technologies will not take off.

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Besides regulation changes, there are several ways to encourage capacity shift from

gamma to X-ray. Potential initiatives include financial support from authorities to build

new X-ray facilities and financial support to revalidate target products to allow a shift

in capacity from gamma to X-ray.

About IBA

IBA Industrial is the world leader in electron and proton accelerators for industrial

applications. IBA’s unique E-Beam, X-ray and proton treatment solutions are used

across the world in many different applications such as medical device sterilization,

food pasteurization, wire and cable crosslinking, property enhancement for various

materials, safety and detection, crystal modification, and more.

IBA Industrial supplies turn-key irradiation solutions from site planning and

optimization, engineering and integration of all operational sub-systems to assistance

in operation. Over 250 IBA Industrial accelerators are used in the world today, some

for more than 50 years.

IBA also delivers solutions of unprecedented precision in the fields of cancer diagnosis

and therapy. The company also offers sterilization and ionization solutions to improve

the hygiene and safety of everyday life. IBA, a Belgian company, is listed on the pan

European stock exchange EURONEXT.

For more information about this white paper, contact:

Philippe Dethier

Marketing and Business Development Director

IBA

E-mail: philippe.dethier@iba-group.com

www.iba-industrial.com

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