introducing explora one - rigshospitalet

Siemens Healthcare Molecular Imaging

Introducing

Explora One

Xavier Battle, Ph.D.

General Manager

Siemens Cyclotron &

Chemistry Solutions

Copyright © Siemens AG 2011. All rights reserved.


PET Imaging

One of the fastest growing tests

30% procedure growth

(Source IMV report of average US PET growth per year in the recent 7 years; 0.248 millions in 2001 to 1.521 millions in 2008 )


PET.CT Scanner

Time Magazine Invention of the Year 2000


FDG PET

The very first winning combination


Oncology syngo®.via Symbia.net

Cardiology Clinical Solutions

Biomarkers

Inveon™

Customer Care

Symbia S Symbia E Symbia T c.cam mMR

Biograph™ Symbia™

Eclipse™

Preclinical

PETNET Explora™

Preclinical Imaging Solutions PET

SPECT CT Multimodality Inveon Research Workplace

General NM

TruePoint mCT mCT 20 Excel

Siemens Molecular Imaging

Product overview

Neurology


Explora One

One Integration. Infinite Possibilities.

Introducing Explora One

The Choice for PETNET Solutions

A wide offering through partnership


Introducing

Explora One

Martin Cordell, Ph.D.

Product Manager

Siemens Cyclotron &

Chemistry Solutions



Explora One


system for 18F PET

imaging

biomarker

production

One


Explora One


One Easy,

Integrated

Workflow

One System,

Infinite

Possibilities


Web UI Aids

cGMP

Efficient Connectivity

Browser-based user interface for remote operation, monitoring and troubleshooting

Rapid diagnostics to maximize uptime with Siemens Remote Service

Simplified Quality Compliance

Simplified audit tracking with tiered individual user accounts with password protection

Disposable cassettes reduces user error and minimizes cleaning validation process

Easy Workflow

Reduced interaction for easy setup, minimizing user errors

Integrated user interface provides increased production reliability

Intuitive UI, simpler to learn

Equipment Integration

Integrated synthesis, purification and reformulation

One mini-cell

Lower total equipment cost

Lower maintenance costs

Equipment

Integration

Simplified Quality

Compliance

Efficient

Connectivity

Easy

Workflow

Explora One

One Easy, Integrated Workflow


One Easy, Integrated Workflow

Equipment integration

Additional cassette

manifold for further

processing, e.g.,

reformulation

HPLC drawer for

HPLC purification

Primary cassette

manifold for synthesis

and cartridge

purification


Explora One


One Easy,

Integrated

Workflow

One System,

Infinite

Possibilities


Wider Variety Switch easily

Day 3

Day 2

Day 1

Create new sequences

` Flexible Production Sequences

Allows end users to create new production sequences to expand offerings and share with colleagues

Utilize and/or improve production sequences shared by colleagues

Imaging Biomarker Variety

Wide range of imaging biomarker production sequences to meet demand for variety of PET applications

Multiple consumable suppliers drives competitive pricing

Currently >8 imaging biomarkers are available

Flexible Imaging Biomarker Production

Comprehensive integrated production system supports complex imaging biomarker synthesis processes

Cassette-based disposable fluid pathway allows users to switch easily between imaging biomarkers

Flexible

Production

Sequence

Imaging

Biomarker

Variety

Flexible Imaging

Biomarker

Production

Divisional Sales Meeting Imaging & IT 2009

Explora One

One System, Infinite Possibilities


Explora One


One Easy,

Integrated

Workflow

One System,

Infinite

Possibilities


Explora One One Integration. Infinite Possibilities.



Siemens Explora One:

The Choice for PETNET

Solutions James Cook

Vice President,

PETNET Global Sales



Divisional Sales Meeting Imaging & IT 2009 The choice for PETNET Solutions


Future

Perspective Amyloid*

Ramp-up

Business

Environment

* Amyloid imaging biomarker production


PETNET Solutions

Delivering molecular imaging biomarkers

The SafetyNetTM guarantees reliable delivery of molecular biomarkers to hospitals, clinics and research facilities

Albany Cleveland Houston Los Angeles Phoenix Spokane International Locations

Albuquerque Columbia Indianapolis Louisville Pittsburgh St. Louis Korea

Atlanta Dallas Irvine Minneapolis Portland Tampa United Kingdom

Baltimore Denver I Jacksonville Nashville Raleigh Durham Tulsa Australia

Birmingham Denver II Kansas City New Orleans Sacramento Winston Salem Spain

Boston Detroit Knoxville Omaha San Antonio France

Chicago Ft Lauderdale Las Vegas Palo Alto San Diego India

Cincinnati Hackensack Little Rock Philadelphia Seattle


PETNET Solutions

Delivering molecular imaging biomarkers

Complete radiopharmaceutical

value chain encompassing

discovery, clinical trials and

manufacturing and distribution

Largest global cyclotron-

equipped radiopharmaceutical

manufacturing and distribution

network

Standardized equipment and

processes provides consistent

production of

radiopharmaceuticals at

all sites throughout the world



PETNET Solutions

Clinical non-proprietary imaging biomarkers

Sodium fluoride F 18

(18F NaF)

Ammonia N 13

(13N NH3)

Fludeoxyglucose F 18

(18F FDG)

Courtesy University Hospital, Tuebingen, Germany



PETNET Solutions

Clinical proprietary imaging biomarkers



The choice for PETNET solutions


Future


Ramp-up

Business

Environment



PETNET Solutions

Network of manufacturing facilities for Amyloid*

PETNET Solutions

Other distributors

PETNET Solutions and other suppliers

United States Active Production Sites

Atlanta Boston Chicago Dallas Denver Hackensack Houston Jacksonville Los Angeles

Minneapolis Palo Alto Philadelphia Raleigh Saint Louis Seattle Fort Lauderdale Cleveland

New Orleans Pittsburgh San Diego Sacramento

Pending Production Sites Charlottesville Detroit Indianapolis Nashville

Copyright © Siemens AG 2013. All rights reserved. * Amyloid imaging biomarker production – w orkflow produced on Explora GNLC. Based on 2.5 hours normal drive time. Actual time may vary.


PETNET Solutions

Amyloid* ramp-up

Deliver Reliability*

YTD – April 2013

% R

elia

bilit

y

96%

100

95

90

85

80

>1,900

Doses shipped as

of April 2013*

* Data on f ile. Amyloid imaging biomarker production – workflow produced on Explora GNLC.


Preparation

Explora One

The choice for PETNET Solutions

Conventional Complex Workflow for Amyloid*

Critical Steps

Cleaning Bombard Target

Sterile Filtering

Synthesis Purification Final Product

1 2 3 4 5 6 7 8 9 10 11


Reformulation Dispensing Quality Control

Quality Control

Preparation

Simplified

Bombard Target

Sterile Filtering


Final Product

1 2 3 4 5 6 7 8

Dispensing Quality Control

Quality Control

Explora One Easy Workflow for Amyloid*


Separate purification and reformulation modules

Two mini-cells

Higher total equipment cost

Higher maintenance costs


One mini-cell

Lower total equipment cost

Lower maintenance costs

Explora One


Conventional Complex Workflow Explora One Easy Workflow

Critical Steps

Synthesis Purification Reformulation

1 2 3

Simplified

1



Increased user interaction and more user errors

Multiple user interfaces decreases production reliability

Complex to learn

Reduced interaction for easy setup, minimizing user errors

Integrated user interface provides increased production reliability

Intuitive UI, simpler to learn

Explora One


Conventional Complex Workflow Explora One Easy Workflow

Critical Steps

1 2 3

Simplified

1

Synthesis Purification Reformulation Integrated synthesis, purification and reformulation


Amyloid* Ramp-up

Conventional complex workflow – high risk

N2

Mini-Cell 1 Mini-Cell 2 Hot Cell Cri

tic

al S

tep

s

1. Start synthesis process on synthesis module

2. Use synthesis module to push product onto pre-HPLC purification cartridge

3. Switch fluid path from waste to collection vials

4. Pull 4 ml of air to fill HPLC loading loop

5. Collect HPLC fraction containing product

6. Push diluent into HPLC fraction to dilute and mix

7. Switch on nitrogen to push product onto reformulation cartridge

8. Switch fluid path to syringe for wash and elution

9. Push wash fluid through reformulation cartridge

10. Move fluid path from waste to product vial using manipulators in hot cell

11. Push eluent through reformulation cartridge

12. Chase product into product vial by pushing more wash fluid

Synthesis

Software Purification Module

Software

Many manual steps

Many manual steps

7 8 9 10 6

5

4

3

2

1

11

12



Amyloid* Ramp-up

Easy Explora One workflow – simplified

Mini-Cell

Hig

h R

isk

Integrated Control Software

Sim

pli

fie

d

1. Start synthesis process on synthesis module

2. Collect HPLC fraction containing product

2 1




Explora One

The choice for PETNET solutions


Future


Ramp-up

Business

Environment



Explora One

PETNET solutions future perspective

Explora One

Allows PETNET solutions to use the same module to produce many different imaging biomarkers

Open source platform and cassette-based system allows for easy adoption of new synthesis sequences

Benefits

Reduces cost of additional modules and mini-cells

Facilitates expansion to new imaging biomarkers easily for production and distribution

Switch easily

Day 3

Day 2

Day 1


A wide offering through

partnership

Dr. Marco Mueller

Senior Scientist

ABX Advanced

Biochemical Compounds


ABX advanced biochemical compounds

ABX products for Siemens Explora One


[18F]F-FDG Yield 70 % [18F]F-FET Yield 25 %

[18F]F-FMISO Yield 25 % [18F]F-CHOLINE Yield 25 %

[18F]F-NaF Yield 90 % [18F]F-FLT Yield 20 %

[18F]F-FES Yield 20 % [18F]F-SFB Yield 20 %

What is available?

[18F]F-ACETATE Yield 35 %


COOtBu

NHTrMOMO

NO2

H O

COOtBu

NHTrMOMO

18F

H O

[18F]-, K222

K2CO3

DMSO

110 °C

m-CPBA

MeCN

55 °C

2 3

COOtBu

NHTrMOMO

O

18F

COOH

NH2HO

OH

18F

4 6-[18F]-fluoro-L-DOPA (1) >98% ee

O

H

HCl

50 °C

What is new?

[18F]F-L-Dopa Yield 10 %

• n.c.a method (high specific activity)

• enantiomeric purity 99%

• starting activities up to 10 Ci

• “HPLC cleaning“


Complete solutions:

•Easy to use

•Produced According to ICH Guideline

Q7, Chapter 19

•Cassettes gamma-sterilized

•Precursor, Kit , Cassette,

Sequence


Kit description: valve 1) recovery of O-18water, no changes compared to FDG valve 2) QMA, no changes compared to FDG

valve 3) 7ml acetonitrile, no changes compared to FDG

valve 4) 30 ml syringe, no changes compared to FDG

valve 5) 25mg FLT-Precursor dissolved in 2ml of acetonitrile

valve 6) reactor inlet, no changes compared to FDG valve 7) 3ml syringe with 2,4 ml of 1N NaOH

valve 8) 100 ml waterbag, add 2ml of ethanol before placing

the waterbag valve 9) 20 ml syringe of (10/1) water/ethanol

valve 10) 3 ml syringe with 1,5 ml 2N HCl

valve 11) out to final with pre-conditioned Alumina-N light cartridge, sterile filter with needle and vented filter,

add 3ml of buffer solution to the final vial

valve 12) pre-conditioned cleaning cartridges (PS-H, WAX, HLB) valve 13) tubing for cleaning cartridges

valve 14) 30 ml syringe, no changes compared to FDG

valve 15) no changes compared to FDG


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X X X

V P 1/100 sec 1/10 °C mm mm mm 1/100 bar sec. 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 0 1 2 3 4 5 6 23 8 9 10 11 12 13 14

0 Hooking on the syringes 500 0 92 92 92 -50 0 0 1 0 1 1 1

1 Hooking on the syringes 100 0 92 40 20 -50 128 0 30 184 1 1 1 1 1

2 Hooking on the syringes 500 0 92 40 20 -50 0 0 23 0 1 1 1 1







9 Pressurising final solution 100 0 0 40 20 -40 128 0 30 0 1 1 1 1 1

10 Pressurising waterbag 100 0 0 40 0 -40 128 0 30 184 1 1 1 1 1

11 Depressurising left syringe 2000 0 0 40 0 -80 0 0 1 0 1 1

12 Depressurising left syringe 2000 0 0 40 0 -80 0 0 1 0 1 1 1

13 Depressurising left syringe 2000 0 0 40 0 -80 0 0 1 0 1 1

14 Depressurising left syringe 2000 0 0 40 0 -80 0 0 1 0 1 1 1

15 Rinsing manifolds with acetonitrile 100 0 0 40 0 -35 64 0 120 184 1 1 1

16 Rinsing manifolds with acetonitrile 100 0 0 40 0 -35 0 0 1 0 1 1 1 1


18 Rinsing manifolds with acetonitrile 300 0 0 40 0 -65 0 0 1 0 1 1 1 1

19 Pressurising acetonitrile vial 500 0 0 40 0 -65 0 0 1 0 1 1 1 1






25 Pressurising acetonitrile vial 500 0 0 40 0 -65 0 0 1 0 1 1

26 Pressurising acetonitrile vial 100 0 0 40 0 -65 0 0 1 0 1 1 1

27 Rinsing manifolds with acetonitrile 200 0 0 40 0 -65 0 0 1 0 1 1 1 1 1


29 Rinsing manifolds with acetonitrile 500 0 0 40 0 -65 0 0 1 0 1 1













42 Waiting for operator reply 100 0 0 40 0 -30 10 0 1 42 1 1

43 Recovering the target water 100 0 0 40 0 -20 64 0 180 44 1 1 1

44 Recovering the target water 6000 0 0 40 0 -20 0 0 1 0 1 1 1 1 1 1



47 Recovering the target water 1000 0 0 40 0 -30 0 0 1 0 1 1 1 1 1

48 Recovering the target water 100 0 0 40 0 -30 64 0 180 49 1 1 1 1

49 Transfer of the eluent 500 0 0 40 0 -30 0 0 1 0 1 1 1 1





54 Elution of fluoride 100 0 0 40 0 -5 64 0 180 55 1 1 1 1 1 1

55 Elution of fluoride 1000 0 0 40 0 -5 0 0 1 0 1 1 1

56 Elution of fluoride 500 0 0 40 0 -25 8192 0 120 53 1 1 1 1 1

Transfert->PLCTransfert->PLC

Customized Sequences :


Documents for QA, QC:


How can we help with QC?

Monographs (Pharmeuropa) for FDG, FLT, FMiso, NaF and “FET“

Literature and Posters...



Thank You!