Pharma&Biotech. ADC Process Transfer from a CMO Perspective: How to Make a Collaboration Successful

Transcription

1 Pharma&Biotech ADC Process Transfer from a CMO Perspective: How to Make a Collaboration Successful

2 Additional Information and Disclaimer Lonza Group Ltd has its headquarters in Basel, Switzerland, and is listed on the SIX Swiss Exchange. It has a secondary listing on the Singapore Exchange Securities Trading Limited ( SGX-ST ). Lonza Group Ltd is not subject to the SGX-ST s continuing listing requirements but remains subject to Rules 217 and 751 of the SGX-ST Listing Manual. Certain matters discussed in this presentation may constitute forward-looking statements. These statements are based on current expectations and estimates of Lonza Group Ltd, although Lonza Group Ltd can give no assurance that these expectations and estimates will be achieved. Investors are cautioned that all forward-looking statements involve risks and uncertainty and are qualified in their entirety. The actual results may differ materially in the future from the forward-looking statements included in this presentation due to various factors. Furthermore, except as otherwise required by law, Lonza Group Ltd disclaims any intention or obligation to update the statements contained in this presentation. 2

3 ADC Process Transfer from a CMO Perspective Tools for a smooth and efficient ADC process transfer and development Overcoming challenges at manufacturing scale The world beyond process development and production 3

4 Tools for a Smooth & Efficient ADC Process Transfer & Development Communication Defined project team CMO Customer Reg. Aff Reg. Aff Eng. R&D R&D Eng. Logistics Project manager QC QC Project manager Logistics Supply chain QA QA Supply chain Production Production Dedicated and experienced project team Standardized project management tools (intra and inter sites) Daily/weekly project updates (time zone) 4

5 Tools for a Smooth & Efficient ADC Process Transfer & Development Communication Knowledge exchange CMO Research report Development report Campaign reports Executed MBRs Process description Analytical methods BFD Customer Unit operations Process parameters (t, T, eq, ) Buffers composition Hold times Stability studies Freeze/Thaw studies Edge of failure (Robustness) Densities Formulation Filters, TFF membrane types Filter sizing data IPC Specifications Raw material quality Alignment of expectations as a first step 5

6 Project Patterns in Our Experience High Degree of process definition Low Fully developed manufacturing process Fully developed lab process Partially developed process No process available Familiarization Familiarization Familiarization Familiarization Process Adaptation Purification Development Conjugation Development Purification Development Process Demonstration Process Demonstration Process Demonstration Process Demonstration Manufacturing Manufacturing Manufacturing Manufacturing Tech Transfer Process Adaption Process Optimization Process Development 6

7 Tools for a Smooth & Efficient ADC Process Transfer & Development Familiarization Reproducing customer's process at milligram-scale: Jacketed glass reactors (1 10 ml) Desalting columns (e.g. NAP-25) Reproducing purification and formulation steps at gram scale Adaption Optimize parameters to increase manufacturing fit Process optimization and Manufacturability Screen and optimize ranges for most influential parameters In process hold time studies TFF membrane selection and sizing TFF parameter optimization Chromatography parameter optimization Filter selection and sizing Equipment contact material compatibility 7

8 Tools for a Smooth & Efficient ADC Process Transfer & Development Process development: Product quality attributes Control over drug-to-antibody ratio (DAR) Minimize aggregation and drug related impurities Manufacturability Process volumes, times, temperatures Organic co-solvents Purification Filter/membrane selection Tools One factor at the time (OFAT) Reagent titrations Time course study Additives screening TFF & chromatography development Design of Experiments (DoE) 8

9 Overcoming Challenges at Manufacturing Scale Process related challenges ADC Purification Containment Cleaning Toxicity related challenges Bioburden control ADC manufacturing Handling CMO internal approach Process transfer Single use New upcoming technologies vs. equipment Equipment related challenges 9

10 Overcoming Challenges at Manufacturing Scale CMO internal approach Standardized transfer procedures Solid documentation Synergy between R&D and production teams Joint and synchronized campaign preparation activities MSAT support 10

11 Overcoming Challenges at Manufacturing Scale Drug linker and ADC toxicity Protect people from the product (Safety) Protect product from people (cgmp requirement) Closed system Isolator Low cleaning limit Efficient validated cleaning process is needed. Prove that the cleaning limit has been reached. Safe handling of highly potent cytotoxics in a biopharmaceutical environment 11

12 Overcoming Challenges at Manufacturing Scale Process related challenges Removal of the unconjugated toxin or payload TFF with hydrophobic payloads is challenging Chromatography New alternative purification techniques Several 0.2 μm filtrations Filter selection vs scale up 12

13 Overcoming Challenges at Manufacturing Scale Equipment related challenges New ADC projects at Lonza New purification techniques Modular set up Mobile equipment Multi purpose facility Until Alternative to product dedicated equipment Equipment selection vs. material compatibility (e.g. organic solvents) Shorter change-over (No cleaning) Higher consumable costs Leachable assessment needed 13

14 The World Beyond Process Development and Production What does a customer expect from a CMO? (apart from basics) R&D : more than R and D An optimized supply chain Support beyond the BDS shipment 14

15 R&D: More than R and D Supplementary Services Manufacturing of bioconjugates to support toxicology studies Batch size up to 4 L Low bioburden and endotoxin levels Certificate of testing from QC team Vial filling (e.g. reference Standard) Crystal M1 filling station from Aseptic Technologies Closed non-gmp fill under aseptic conditions 1 50 ml aliquots in γ-irradiated cyclo-olefin copolymer (COC) closed vials, laser re-sealing of the stopper Process characterization / process design Qualification of reaction parameters Qualification of purification steps Under QA overview Leachable assessments Risk assessment matrix Leachable studies: DP team Phase III & beyond 15

16 A Optimized Supply Chain ADC End-to-End Offering Making key components of drug product within the Lonza network simplifies the supply chain and saves resources in coordinating and tracking activities Antibody fermentation (Slough, UK) Payload synthesis (Visp, Switzerland) Bioconjugation (Visp, Switzerland) DP services (Basel, Switzerland) 16

17 Support Beyond the BDS Shipment CMO can Offer More than just Technical Expertise Regulatory affairs services Strategic support Scientific Advice (briefing book) Agency meeting support Regulatory strategy IMPD/IND - Clinical trials Summarised CMC Response to questions MAA/BLA Module 3.2.S Detailed CMC ectd ready Lifecycle support Tech transfer Scale up Variations Follow on ROW submissions Stability studies (DS, DP) Core project team assigned to follow the product throughout its life Further QC method and process development for resupply campaigns 17

18 Thank you for your Attention Questions? 18 FOOTER MONTH YYYY