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Cambridge Healthtech Institute’s Inaugural
Process Development for Novel Biotherapeutic Formats
Part of CHI’s 6th Annual The Bioprocessing Summit
August 20-21, 2014 | Renaissance Boston Waterfront Hotel | Boston, Massachusetts

Producers of biotherapeutic drug products have dedicated considerable effort to optimizing their process development organizations to rapidly advance programs through early IND approval and into phase 1 clinical studies by utilizing standardized platforms for upstream and downstream processing. New manufacturability evaluation steps have helped to identify lead candidates with the most ideal yield and product quality profiles, and improved purification technology is resolving downstream bottlenecks brought on by higher upstream titers.

But as monoclonal antibodies give way to new molecule and product formats, including Fc fusion proteins, bioconjugates, multispecific antibodies and nanobodies, these highly efficient systems of bioprocess development are being challenged. The criteria used to evaluate manufacturability are confronted by scale-up and operational concerns for new production systems and technology. Regulatory agencies may themselves be unfamiliar with new product formats, resulting in uncertainties about how much process development work needs to be done prior to early clinical trials, and traditional ways of evaluating product quality and yield may be different for these new formats.

CHI’s Process Development for Novel Biotherapeutic Formats offers a forum to scientists working in bioprocessing operations of all sizes to learn best practices of how to respond when new molecule or product formats are handed off from R&D into the development organization. You will learn when and how you should consider deviating from established platforms, the upstream and downstream technologies that should be part of your toolkit in this new era, and how to evaluate the impacts of these new programs on product yield and quality.

Day 1 | Day 2 | Short Courses | Download Brochure | Speaker Bios 

Suggested Short Course*

Analytical Strategies for Comparability in Bioprocess Development 

Tuesday, August 19, 6:00 – 8:30 pm

*Separate registration required

Wednesday, August 20

7:00 am Registration and Morning Coffee


8:05 Chairperson’s Remarks

AmardeepBhallaAmardeep Bhalla, Ph.D., Principal Scientist, Pfizer


Process Development in an Era of New Product Formats and Changing Technologies

Steven LangSteven Lang, Ph.D., MBA, Scientific Director, Biologics Research, J&J Biotechnology Center of Excellence

The biotechnology industry has created huge advances in efficiencies through the adoption of platform processes during the last 10 years. New therapeutic formats and technologies will challenge platform processes and many development organizations. Success in the next years will depend on creating intelligent flexibility in multiple platform development processes.

9:00 Rapid Characterization of Recombinant Protein’s CQAs: HMW Species and Particulates Determination Using Novel Technologies at Line during Product Process Development Lifecycle

Nesredin MussaNesredin Mussa, Ph.D., Associate Director, Global Manufacturing and Supply, Bristol-Myers Squibb

9:30 Case Studies of Early Process Development for Multi-Component Vaccines

AmardeepBhallaAmardeep Bhalla, Ph.D., Principal Scientist, Pfizer

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

10:45 Case Study: Development and Manufacturing of a Common Light Chain Bispecific Antibody: MCLA-128

LexBakkerLex Bakker, Ph.D., Chief Development Officer, Merus, The Netherlands

MCLA-128 is an ADCC-enhanced human common light chain bispecific IgG1 antibody targeting HER2 and HER3. MCLA-128 demonstrates potent inhibition of HER2:HER3 heterodimer signaling and robust anti-tumor activity in a trastuzumab-resistant xenograft model. It is produced in CHO cells using low fucose expression technology and Merus’ proprietary CH3 engineering to force bispecific IgG heterodimerization. A robust purification process was developed resulting in ultra pure MCLA-128 at high process yields. MCLA-128 is currently undergoing cGMP manufacturing to allow clinical evaluation in a planned first-in-human phase I study.

11:15 Challenges and Insights in Rapid Process Development for Insourced Biotherapeutics of Varying Formats: A Case Study in Upstream Strategy

BrianDoyleBrian Doyle, Senior Research Associate, Gilead


11:45 High-Throughput Screening of Single Cells Using Droplet Microfluidics

Linas Mazutis, Ph.D., Visiting Scholar, School of Engineering & Applied Sciences, Harvard University

12:15 pm Enjoy Lunch on Your Own

1:30 Session Break


1:55 Chairperson’s Remarks

PraticJaluriaPratik Jaluria, Ph.D., Associate Director, Alexion Pharmaceuticals

2:00 Upstream Process Development for DARTs: Challenges and Opportunities with Novel Antibody-Like Bispecifics

Andrew Snowden, Ph.D., Director, Cell Culture Sciences, Macrogenics, Inc.

DART (Dual Affinity Re-Targeting) molecules are highly modular antibody-like therapeutic proteins in development for the treatment of human diseases in the oncology, antiviral and autoimmune related therapeutic areas. Data will be presented showing that unlike a number of bispecific formats, DARTs possess superior molecular attributes that facilitate the routine development of high-titer processes. Examples will be presented including aspects of CHO production cell line generation and the development of high-titer upstream bioprocesses for this new class of antibody-like bispecifics.

2:30 Cell Culture Process Development for a Novel Bispecific Antibody

BenjaminWangBenjamin Wang, Ph.D., Senior Bioprocess Engineer, Merrimack Pharmaceuticals

Merrimack Pharmaceuticals focuses on the development of therapeutics in the oncology space. Many of Merrimack’s molecules use non-traditional antibody designs including bispecific and single chain variable fragment formats. MM-131 is a novel multispecific molecule which is currently in pre-clinical development. We will describe the cell culture process development of MM-131 which will enable clinical manufacturing for MM-131. The presentation will focus on improvements on the overall yield of the molecule, product quality, and manufacturability.

3:00 Collaboration between Upstream and Downstream to Resolve the Challenges of a Novel, Difficult-to-Express Protein

AlanGilbertAlan Gilbert, Ph.D., Senior Engineer, Cell Culture Development, Biogen Idec

An upstream process was designed to increase titer of a small, but highly positively charged protein. One of the unique challenges with this particular protein was the protein’s adherence to the cell surface. A critical step was identifying a new feed medium additive to increase titer that ultimately interfered with the ability to purify the protein. Extensive collaboration between upstream and downstream was required as a result, and integrating this development debottlenecked the process.

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

4:15 Antibody Cocktails: Resolving Batch-to-Batch Variation and Cell Line Stability

HughRussellHugh H. Russell, Ph.D., Director, Antibody Technologies, Excelimmune

Manufacturing of Antibody Combination Therapeutics (ACTs) requires reproducible antibody stoichiometry during production. The presentation will discuss production of cell lines vs. stable pools and methods of cell line creation. Research demonstrates AAV-based integration is superior to random integration for cell line generation and that stable pools are capable of maintaining a consistent antibody ratio during culture.

4:45 Improve-Ization: Challenges in Re-Development of a Late-Stage Upstream Process

PraticJaluriaPratik Jaluria, Ph.D., Associate Director, Alexion Pharmaceuticals

In developing a new, more productive upstream process for a late-stage therapeutic protein, a number of challenges were encountered. This presentation describes experimental work across multiple scales evaluating process changes designed to retain key product quality metrics while overcoming the limitations in our existing cell culture platform process.

 5:15 Networking Reception in the Exhibit Hall with Poster Viewing 

6:30 End of Day

Day 1 | Day 2 | Short Courses | Download Brochure | Speaker Bios 


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