Technology transfer and working with a CDMO: challenges and important aspects to consider for an efficient partnership

Prerequisites for a successful tech transfer, typical example of tech transfer – tips, common mistakes, lessons learned

PDA IsraelTechnology Transfer and Working with CMO/CDMOTel Aviv, 4th March 2019

Riccardo Bernasconi, PhDCARBOGEN AMCIS AG

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Brief introduction of Carbogen Amcis – setup and capabilities

Prerequisites for a successful tech transfer – common pitfalls

Example of a tech transfer recently performed at Carbogen Amcis

Lesson learned

Presentation Overview

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CARBOGEN AMCIS – Key Facts

• Over 30 years experience in process development and manufacturing – from early phase to commercial supply

• Global presence – 8 manufacturing sites

• 800 employees

• Swiss CDMO – part of the Dishman Carbogen Amcis Ltd.

• More than 150 complex projects per annum

• 75% of projects are return customers

• Commercial supply into major markets (US, EU, Japan, Australia, Brazil, India,…)

• Highly successful audit history

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Footprint of CARBOGEN AMCIS

• Process development• Full analytical support• Manufacture (from 6 L to 8’000 L)

• High potency• Preparative chromatography• Flow chemistry

• ADCs• Drug product (aseptic filling)

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General assumptions

Prerequisites for a successful tech transfer

• Who owns the IP?

• CDMO philosophy of project management

• Approach to process R&Do Regulatory requirements / regulatory history of the siteo Who has the knowledge

• Factors influencing cost, quality and speedo From RFP to POo It’s not just when the CMO can start, but when the legal paperwork can be signed

• Site visit & site audit

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• Project timelineo Set realistic timelines (both for you and the CDMO)o Ensure the project plan captures all deliverables

Prerequisites for a successful tech transfer

• Define the start date

• Technology transfero Face-to-faceo Technical-to-technicalo Transfer of knowledge (transfer of Scientist)

• Resources / equipment / processes in place to handle challenges

• Communication – when, where and how ofteno Routine project updateso When something goes wrong – define clear communication channels

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Prerequisites for a successful tech transfer

Research Preclinical Phase I Phase II Phase III Market

EARLY STAGEProcess Research and RapidSupply of APIs preparedaccording to non-GMP

LATE STAGEProcess Development

and cGMPManufacture

COMMERCIALProcess Optimisation

COGs OptimizationFDA audited

• Mindset / setup of the CDMO

• Maturity of the project

• Project complexity / challenges

• Short vs. long term expectations

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Prerequisites for a successful tech transfer

• Project management – responsibilities at the CDMO

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Prerequisites for a successful tech transfer

Generate Technology Transfer Plan

Initiate project and transfer information

Change Review

Lab Trialing

Perform Pre-formulation Review

Production and Analysis

Production and Quality Comparison

Technology Transfer Protocol

Technology Transfer in the SOP

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Target: Manufacture of an Antibody Drug Conjugate (ADC)

Starting point: Elementary lab procedure, rudimentary analytical methods

Timeline: 2 years – from process development to multi grams non-GMP batch

Deliverables: - Process development report- Full analytical report- Scale up report- non-GMP material- cGMP material

Successful tech transfer – case study

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Highly potent containment

Successful tech transfer – case study

3x Building block synthesis

Solid phase transformation

Chromatographic separation

Conversion to Payload

Antibody conjugation

Fill and finished formulation

Manchester site

2 steps11 steps6 steps

Neuland site

15 steps

Aarau site Bubendorf site

4 steps

Bubendorf site

1 step

Riom site

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• 39 chemical steps• 5 manufacturing sites involved• 5 developmental teams involved in process implementation, development and

scale-up activities• 24 months from tech transfer to first non-GMP delivery• 12 months scale up and first cGMP campaign• 1 project management

Successful tech transfer – case study

Client

PM

Site 1 Site 2 Site 3 Site 4 Site 5

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Support from the client:

• During tech transfer and process optimizationo Full technical supporto Few experiments performed by the client

• During production and scale-upo Technical and paper support

Successful tech transfer – case study

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Lesson learned

• Project management

• Technical team

• Response rate and responsiveness

• Expectations vs. reality

• Partner vs. supplier

• Saving vs. investment in process development

• Communication, communication and…..communication!

Thank you for your attention!

riccardo.bernasconi@carbogen-amcis.com