Recent Developments in Sterilization Technology

Ed Cappabianca, CEO, EnXray

15 May 2014

Introductions EnXray Limited is a private UK company.

Developing patented low-energy X-ray (LEXR) technology to sterilize material at high speed.

Offering superior solutions to the health care sector, initially focusing on OEM(1) medical device sterilization.

Serious commercial interest from OEM medical device manufacturers, with several reference customers committed.

(1) OEM: Original Equipment Manufacturers. 2

A Brief History

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3000 BC – Egyptians used tar & pitch as antiseptics

1881 – Robert Koch devised the 1st non-pressure steam sterilizer

1940s – ETO developed as sterilant by US military

1950s – Use of plastics in medical devices begins First use of electron beam sterilization

1963 – World’s 1st commercial gamma sterilization facility

1990s – 1st use of High Energy X-Ray sterilization

2014 – LEXR in development

The Sterilization Market

The global sterilization market totalled US$3.8 billion in 2011 (including equipment & consumables).

Sterilization markets include: Medical Devices; Pharmaceuticals; Hospitals; Agriculture; and Food & FMCG Packaging.

Methods: Thermal, Chemical, Radiation & Filtration.

Factors driving adoption: High costs, logistics & environmental issues, particularly in the OEM Medical Device sector.

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A large market with a clear entry point

54%

3%

36%

5% 2%

43%

ETO Other (H2O2, Steam, etc) Gamma electron beam HEXR (high energy x-ray)

Medical Device Sterilization

OEM medical device sterilization: a global market >£1.2 billion. Main methods include:

Ionizing Radiation

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Our technology initially addresses over 40% of the market

Ethylene Oxide (ETO)

Sterilization Methods Compared 1

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Sterilisation type Advantages Disadvantages Steam Fast

Non-toxic Effective air removal key Heat-stable materials only

Dry heat Glassware Depyrogenation

Heat-stable materials only Long processing times

Gamma Good penetration Fast and efficient

Degradation of plastics Third-party sterilisation

Electron beam Lower impact on plastic degradation

Low penetration means uniform density is required

Third-party sterilisation X-ray (high energy) Fast

High penetration May produce radioactive particles in the

device Safety issues due to increased shielding

X-ray (low energy) Point-of-manufacture sterilisation

Rapid turnaround Excellent dose uniformity

Not suitable for dense products or processing of large batches (pallets or totes)

Not yet commercially available Ethylene oxide Suitable for heat and

irradiation-sensitive products Highly flexible

Long cycle times Requires gas ingress and egress Toxic and flammable Third-party sterilisation

Gas plasma Low temperature Non-toxic residuals

Penetration of lumens Unsuitable for absorbent materials

Filtration Suitable for liquid-sensitive products

Higher risk Increased validation and operating controls

Advantages & disadvantages of various methods

Source: “Leave Nothing to Chance”, Medical Device Developments, October 2013.

Sterilization Methods Compared 2

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Cycle time Compliance

Sterilization Logistics Total Health & Safety UDI

Radiation

Gamma 10 – 20 Hours 1 – 3 weeks High High Per pallet

HEXR 2 – 8 hours 1 – 3 weeks High High Per pallet

LEXR <30 seconds None Low None expected Per item

e-beam < 1hour 1 – 3 weeks High Medium Per box

Chemical

ETO 16 – 18 hours 1 – 2 weeks High High Per pallet

NO2 1 – 2 hours None Low High Per box

H2O2 1 – 8 hours n/a n/a High Per box

O3 5 Hours n/a n/a High Per box

Comparison of cycle times & compliance

Source: “Developments in medical device sterilisation technology “, Cleanroom Technology, May 2014.

Traditional X-ray Sterilization Units

Very large footprint machines

Sterilization facilities occupy whole buildings (left) and require thick lead shielding (above)

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Medical devices shipped in large batches to 3rd parties.

Process can take up to 2 weeks or more.

Products are returned to the manufacturer before final sale.

Average annual cost is estimated to be >£120k per company, excluding inventory holding costs.

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Existing methods are time consuming & costly

Sterilization Logistics

Medical Device Manufacturing Companies

Remote Sterilization

Facility

Regulatory Framework

Medical device sterilization is regulated based upon the sterilization method.

ISO 11137 governs ionizing radiation. Based on kGy dosage delivered

ISO 11135 relates specifically to ETO sterilization.

Other chemical methods must define their own standards.

ISO 13485 applies to all sterilization methods, as it forms part of the manufacturing process.

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The regulatory pathway Is clear for ETO & Radiation

What do OEMs want?

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QA & RA Managers “own” Sterilization Responsibility without Direct Control

Any new approach must be fully compliant with existing regs (ISO 11137, ISO 11135, etc)

Beyond that, their Wish List includes: On site & On demand, More Reliable, 100% traceability, No additional HSE compliance issues, Faster, and ideally, Cheaper.

Why now?

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The Affordable Care Act (aka Obamacare) 2.3% sales tax since January 2013 Increases economic pressure Applies to any US sales, regardless of manufacturing source

UDI (Unique Device Identification) Initiative Became effective September 2013 Increases regulatory pressure Rolling out over 5 years across most classes of devices

Technology developments in medical device markets, such as 3-D printing will demand new approaches

Our Technology is Different Working with Cambridge Consultants, these are some initial concepts for the prototype device(2) to sterilize OEM medical devices, such as those pictured below, left.

(2) Anticipated “footprint”: 2.5m x 1.5m.

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Comparison of LEXR and HEXR

X-axis shows energy of X-rays generated on a Log scale.

Y-axis indicates the level of energy absorbed by the target in kGy(3).

EnXray is able to deliver the same amount of sterilizing energy because of higher absorption rate of LEXR vs. HEXR.

(3) kGy: Kilogray is the unit of measurement of radiation dosage.

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Our technology delivers equivalent sterilizing energy

Our Initial Prototype

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Circular emitting head , 10 cm in diameter.

EnXray’s scientists produced lab-based prototype that generated LEXRs.

The prototype (at right) was used in a randomized dosage trial.

The trial results were validated by an independent lab, WFC Analytics.

Gas-filled chamber

Demonstrated ability to generate LEXRs

Independent Trial Assessment

Sample 1 Sample 2 Sample 3 Sample 4 Sample 5

Independently verified trial provides initial evidence of LEXR technology.

Irradiation target: Bacillus atrophaeus spore strips,

(a safe equivalent of anthrax).

The results: Demonstrated ability to deliver

LEXRs in increasing dosages, as indicated by color changes in the randomized samples.

Future tests will be conducted under the guidance of our Scientific Advisory Board.

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LEXR delivers ionizing radiation

Our USPs LEXR is ideal for sterilizing most medical grade polymers.

High local absorption enables high dosage / throughput.

LEXRs penetrate up to 10cm in air & several cm of plastic.

Safety profile will allow for easy operation at customer facilities.

On site – eliminates time-consuming & costly logistics.

Affordable compared to existing technologies.

Significant indirect cost savings (inventory holding cost).

Greater traceability reduces product recall risks.

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3rd party sterilization companies’ business models built on maintaining high throughput rates.

Pricing models are based upon large volumes – small orders are uneconomic to process.

EnXray will initially provide a low cost alternative for small batch runs & “rush orders”.

OEM’s QA & RA managers are attracted by the concept.

Competitive Landscape

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Edward Cappabianca– CEO. Over 20 years experience advising & raising capital for early stage technology, medical device and biotechnology companies. Former CEO of a novel anti-infective biotechnology company.

Dr. Sergey Mitko – CSO. Very experienced in both theoretical & experimental physics, with in-depth knowledge of pulsed power electronics and electronic design. Sergey has published about 80 scientific papers and patents.

Dr. Yuri Udalov–CTO. Background as an experimental physicist. He began his career at the P.N. Lebedev Physics Institute, Academy of Sciences in Russia, where he met & worked with Sergey. In 2004, he won the New Venture Prize (established by McKinsey and Dutch Ministry of Economics) for the best start-up business. Yuri has published over 120 articles in peer-reviewed journals & also has several patented inventions.

Dr Siddartha Ghose – Operations Director. Internationally trained bioscience engineer with experience implementing cross-functional operations at technology start-ups. Professional certifications & training including: Project Management (PRINCE2); ISO 13485 internal auditor; & Sterilization.

Founders & Management

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Advisors and Partners SMS Electronics – Outsourced manufacturing.

University of Nottingham Precision Manufacturing Centre

3 UK & 1 European Medical Device Cos – Commercial Development Partners & Reference Customers.

Cambridge Consultants – Technology Development.

Mathys & Squire (Martin MacLean) – Patent Attorneys.

Professor Alan Tallentire – Scientific Advisory Board (founding member) & Regulatory Consultant.

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Summary Medical device sterilization is ripe for innovation and

change.

Cost pressures and increasing regulations will drive adoption of methods that address customer needs.

LEXR offers superior performance in cost & performance.

EnXray’s technology can: ♦ be incorporated into existing production processes, & ♦ augment or replace 3rd party sterilization (ie. Gamma).

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Contact Details EnXray Limited

Ed Cappabianca, CEO Phone: +44 77 11 98 43 45 Email: ecc@enxray.com

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Sterilization of Polymers Most medical-grade polymers used today are well suited to sterilization

using ionizing radiation.

10,000 10,000

1,259 1,259

1,122 1,122 1,122 1,122 1,122

158 251

631 501

631 631

251 631

100

1 10 100 1000 10000

Phenolics Polystyrene

Polyurethane Epoxy

Silicone (filled) Polysulphone

Polyamide ABS MBS

Natural rubber Nitrile rubber

Polyester (PET) Polyethylene

Urea-formaldehyde Polycarbonate

Polyvinyl Chloride (PVC) Polyvinylidene Chloride

Cellulose Acetate

Dosage (kGy)

Radiation Resistance of Common Polymers

Resistance

Typical sterilizing dosage: 25 kGy

Source: A Guide to Designing for Sterilization. 23