May 28 – 30, 2015, Montréal, Québec The future supply of reactor- produced medical isotopes François Couillard May 28 th, 2015.

May 28 – 30, 2015, Montréal, Québec

The future supply of reactor-produced medical isotopes

François CouillardMay 28th, 2015

Disclosure Statement

May 28 – 30, 2015, Montréal, Québec

I have a financial affiliation with a pharmaceutical company and/or medical device: I own common shares of GE and J&J.

I have no conflicts of interest to disclose.

I have no other financial relationship or advisory role with pharmaceutical or device-making companies, or CME provider.

I will not discuss or describe in my presentation at the meeting the investigational or unlabeled ("off-label") use of a medical device, product, or pharmaceutical that is classified by Health Canada as investigational for the intended use.

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Petten reactor, Nl 1958

BR2 reactor, Bel 1959

Osiris reactor, Fr 1957

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MAPLE reactors

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Overview

• About Tc-99m• Supply chain• What’s the problem?• Mitigation strategies• Cyclotron produced Tc-99m- a game changer?• National and international collaboration

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Tc-99m

• Most widely used nuclear isotope in Nuclear Medicine• 80-85 % of all procedures• 30-40 million exams per year worldwide• Uses:

– Cardiac function– Blood flow– Bone metastases

• Distributed via generators to separate:– Mo-99m half-life: 66 hours– Tc-99m half-life: 6 hours

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Current Tc-99m supply chain

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NRU, Canada

BR2 Bl

HFR, Nl

SAFARI, SA

OPAL, Australia

OSIRIS, Fr

Major Mo-99 producing reactors

Maria, PoLVR-15 CR

A complex world- partial logistics map

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Reactors Mo-99 extraction & purification

Tc-99m Generator manufacturing

HRFMallinckrodt,

NLMaria

IRE,Belgium

Lantheus

Mallinckrodt

ANSTO, Australia

NTP,S.A.

AECL & Nordion

BR2

LVR-15

OSIRIS

NRU

OPAL

SAFARI

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What’s the problem?

Supply:• NRU to stop regular production in 2016*• OSIRIS to stop production end 2015• Other reactors except for OPAL (SA) are old and expected to stop production by

2030.• HEU to LEU conversion• Processing capacity insufficient• Economic viability?

Pricing• Future pricing unknown- concept of « full-cost recovery »

* NRU will be in remain in “hot-standy” mode from Oct. 31 2016 to March 31, 2018

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OECD forecast

April 2014 report :

« clearly, insufficient processing capacity will be a major risk for secure supply in the next 5 years »

• Major economic & technical challenges to convert from HEU to LEU• Likely delay of new projects• Competing agendas in the supply chain • Economic fundamentals sustainable?• Expecting a new forecast by summer 2015

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Potential solutions

Increase Production Capacity• Increase reactor base/capacity + processing

capacity• New Mo-99 producers (LINACS, reactors)• Produce Tc-99m directly with Cyclotrons

Optimize distribution and utilization

Substitute tests with other tracers or modalities

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Major new projectsMajor new Irradiators or increased capacity (2015-2020)

– NortStar Medical Radioisotopes/MURR +Linac (USA)– Nortwest Medical Isotopes (USA)– SHINE (USA)– Coqui Pharma (USA)– Nordion/MURR (USA/Canada)– OPAL (Australia)– Korea– RIAR (Russia)– FRM-II (Germany)– China Advanced RR– Brazil MR– Ra-10 (Argentina)– Jule Horowitz RR (France)

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Major New Projects

Major new processing facilities (2015-2019):– NortStar/Murr (USA)– NortStar (LINAC) (USA)– SHINE (USA)– Northwest – ANSTO– RIAR (Russia)– Maria– Korea– Brazil– Ra-10

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Canadian projects

Project Irradiator Particularities Location

Advanced Cyclotron Systems (ACS)

PET cyclotron Direct production of Tc-99mDistribution similar to PET“local” distribution

EdmontonSherbrooke

(CLS) &PIPE consortium

E-beam accelerator

Production of Mo-99Proprietary generatorsCanada-wide distribution

Saskatoon & Winnipeg

TRIUMF PET cyclotron Direct production of Tc-99mDistribution similar to PET“local” distribution

Vancouver

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Mo-99 production: a new game

Few major suppliers Many smaller players

One technology Many technologies

Global supply chain Global & local

Artificially low prices Full Cost Recovery prices

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A more diverse supply

Cyclotron

Clinic

Clinic

Clinic

Clinic

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Canada: Great innovation- lots of work remaining

• Reliable production• Reliable sourcing of target material (Mo-100)• Manufacturing and recycling of targets• Chemistry• Clinical trials• Regulatory approvals• Distribution model uncertain• Commercial model and infrastructure (incl. costs)• Back-up mechanism

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Current assessment

We need to be in a state a alertness between apathy and panic…

Conditions for success

• Investors with deep pockets and an appetite for risk

• Proven/reliable technology• Secure source of target material• Reliable distribution• Commitment to system-wide funding increase

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What will ensure success?

Information sharing and collaboration

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National & international collaboration

• International: ISRRT, SNMMI, OECD, EANM• Industry (AIPES, CORAR)• Canadian Multi-stakeholder Working Group on

Medical Isotopes (Federal & Provincial Governments, associations, industry)

• CAMRT Tc99m supply Expert Group• CAMRT website resource centre• Canadian Medical Imaging Team (CAMRT, CANM,

CAR…)

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Questions?