Cambridge Healthtech Institute’s Inaugural
CMC Strategies for Antibody-Drug Conjugates
Formulation, Scale-up and Supply Chain Challenges
Part of CHI's Ninth Annual The Bioprocessing Summit
August 24 - 25, 2017 | Westin Copley Place | Boston, MA

The manufacture of antibody-drug conjugates not only involves technical hurdles but also creates challenges in the areas of externalization of manufacturing, supply chain management and new technology considerations. Due to the highly toxic nature of the payload, and the different components that make up an ADC, the regulators are highly concerned about the safety, potency and stability of the product. ADC developers, while busy meeting the stringent challenges of the regulatory requirements, will also need to weigh the pros and cons of out-sourcing vs. in-house production and decide on the best supply chain network.

CHI’s Inaugural CMC Strategies for Antibody-Drug Conjugates invites scientists to share their expertise in the areas of regulatory affairs, analytics, process monitoring, process development and manufacturing, and discuss how they have successfully brought an ADC from development to clinical to commercial manufacturing.

Final Agenda

Thursday, August 24

11:30 am Registration Open

12:15 pm Enjoy Lunch on Your Own

1:15 Dessert Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing

KEYNOTE PRESENTATIONS

1:55 Chairperson’s Remarks

Heidi J. Hoffmann, Ph.D., Senior Director, Supply Chain/CMC, Sutro Biopharma

2:00 Development and Manufacture of a Novel Drug-Linker Enabling High-DAR ADCs

Michael J. Kaufman, Ph.D., Senior Vice President, CMC, Mersana Therapeutics

Recently, Mersana Therapeutics has announced the commencement of clinical trials with XMT-1522, a HER2-directed ADC possessing a DAR of 12–15 while maintaining acceptable PK and drug-like properties in preclinical models. In this talk, the process development and manufacture of Fleximer-based ADCs are discussed, with particular emphasis on unit operations in the manufacturing process that provide control of heterogeneity and promote lot-to-lot consistency.

2:45 Development and Manufacturing of SYD985, a Duocarmycin-Based ADC

Aad van de Leur, MSc, COO, Biopharmaceuticals Development, Synthon Biopharmaceuticals

Synthon is developing SYD985, a Duocarmycin-based ADC which is in Phase I clinical development. To allow clinical studies, a conjugation process was developed. Challenges and different approaches to develop a robust conjugation process will be presented. In addition the implications on facility design to handle larger batch sizes to meet standards for safe, effective and reliable manufacturing will be discussed. Clinical data of our dose escalation study will be presented.

SUPPLY CHAIN MANAGEMENT AND TECH TRANSFER TO CMO

3:15 Best Practices in Externalization of the ADC Supply Chain

Vincent Turula, Director, External Supply, Biotherapeutics Pharmaceutical Sciences, Worldwide R&D, Pfizer, Inc.

3:45 Sponsored Presentation (Opportunity Available)  

4:00 Refreshment Break

4:15 Analytical Testing Strategy for Kadcyla® Cleaning Validation in Support of a Drug Product Transfer to CMO

Lan Dai, Ph.D., QC Associate Scientist, MMTech Analytical Chemistry & Lifecycle Management, Global QC Network, Genentech Inc., A Member of The Roche Group

Cleaning validation bottlenecks manufacturing site transfers. The complexity is increased for ADC products, because in addition to meeting requirements of general TOC tests, the presence of cytotoxic residues must also not exceed a pre-defined Maximum Allowable Carryover level after equipment cleaning. The design of QC testing/validation strategy is focused on linking analytical testing to the cleaning process/facility design and aligned with health authority, the company and the CMO’s compliance practice.

4:45 Sourcing for the Right CMOs and Managing Complex Supply Chain Networks for Antibody Drug Conjugates

Brian Clark, Principal, GMP Operations Consulting

ADC manufacturing involves some of the most complex supply chains in the biopharmaceutical business. This session will review the challenges with, and strategies for, CMO selection for the various components of ADCs. It will also discuss approaches for simplifying and managing these complex networks.

5:15 Close of Day

Friday, August 25

8:00 am Registration Open and Morning Coffee

ANALYTICAL AND FORMULATION STRATEGIES FOR ANTIBODY-DRUG CONJUGATES

8:25 Chairperson’s Remarks

Brian Clark, Principal, GMP Operations Consulting

8:30 Use of Slope Measurement for Concentration and DAR Determination of Antibody-Drug Conjugates

Michael Fleming, MSc, Senior Scientist, Analytical & Pharmaceutical Science, ImmunoGen, Inc.

9:00 Analytical and Characterization Strategies for Pfizer’s Early Stage ADC Development

Verl Sriskanda, Ph.D., Principal Scientist, ARD Biotherapeutics Pharmaceutical Sciences, Pfizer

• Molecular assessment for ADCs
• Early stage analytical characterization road maps for ADCs
• Analytical method development strategies for early stage ADCs

9:30 Developing an Efficient, Robust and Scalable Conjugation Process for a Bispecific ADC

Sanjay Nilapwar, Ph.D., Scientist, Purification Development, MedImmune

10:00 Networking Coffee Break

10:30 Analytical and Process Development of a Lyophilized ADC

Lisa Hardwick, Research Scientist, Baxter Healthcare

While the development of an aqueous solution formulation may be preferred over a lyophilized product, it is useful to initially pursue a dual path and develop drug product formulations for both a sterile solution and a freeze-dried solid presentation, ultimately choosing the most successful candidate for final development. This presentation will provide an overview of the development process, useful analytical development tools, and lyo cycle optimization.

11:00 Critical Quality Attribute Assessment of Antibody-Drug Conjugates: A Case Study

Hangtian Song, Ph.D., Senior Scientist, Bristol-Myers Squibb

11:30 PANEL DISCUSSION: Regulatory Complexity for Registration of an ADC

• Will expectations for information provided for the linker-drug and mAb be the same as for a drug substance? What could be the differences/left out?
• How to set specifications for linker drug assuming the conjugation process will impact the impurities? Should they meet ICH Q3 or should ICH Q3 apply for the DS related to the small molecule compound, but how to measure?
• Taking into account the complex and long lasting supply chain for an ADC, multiple process changes could occur during development of the complete process. How will changes in manufacturing linker-drug or mAb impact qualification status of DS and DP?
• For a CMO it can easily be argued to perform manufacturing in disposable equipment. But what are innovator considerations for in-house manufacture using single-use/disposable equipment vs stainless steel? What were issues they run into, and what is considered to be best practice?
• Is there a need to have a cell based potency assay for a mAb to be used in an ADC process?