Cambridge Healthtech Institute’s 4th Annual

Cell Therapy CMC and Analytics

Improve Product and Process Analysis and Characterization

August 12-13, 2019


To ensure the safe and rapid production of cell-based therapies, companies must develop well-characterized processes and products in line with regulatory expectations.

Cambridge Healthtech Institute’s Cell Therapy CMC and Analytics conference focuses on the technical and regulatory requirements needed to advance the analysis, quality control and characterization of cell-based therapies with unpublished, in-depth case studies and regulatory feedback on regulatory and CMC development, product release, assay development and validation, flow cytometry, target product profiles, critical quality attributes, critical process parameters, and product release.

Final Agenda

Monday, August 12

7:30 am Short Course Registration Open and Morning Coffee

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8:30-11:00 Recommended Short Course*

SC3: Quality Considerations for Gene Therapy Viral Vectors


Christopher Bravery, PhD, Consulting Regulatory Scientist, Consulting on Advanced Biologicals Ltd.

Gene therapy viral vectors are complex biological medicinal products which pose a number of challenges with respect to quality and overall adventitious agent safety. Firstly, they are large complex viral particles which must be designed to be replication incompetent. Secondly, as the product is a suspension of viral particles, application of traditional viral reduction and elimination steps is not possible, so control of materials and the process become more important. This course outlines the testing expected to address these fundamental features and ensure a safe product of suitable quality is released.

11:00 Main Conference Registration Open


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12:30 pm Chairperson’s Opening Remarks

NEW: Robert Allen, PhD,. Principal, Dark Horse Consulting

12:40 KEYNOTE PRESENTATION: Challenges and Opportunities in Cell Therapy CMC

RoyKrishnendu_RoyKrishnendu Roy, PhD, The Robert A. Milton Chair and Professor, Biomedical Engineering; Director, Marcus Center for Cell Therapy Characterization Manufacturing (MC3M), Georgia Tech

In this presentation, I will outline, using specific exemplars, how investment in identifying critical quality attributes (CQAs) and development of new technologies for in-line, rapid quality measurements would be critical for the field to move forward. I will also discuss how automation, especially flexible-adaptive automation, and an industry-wide focus on developing pre-competitive standards will be key to our success in cell therapy CMC.

1:10 Roadmap to Successful Commercialization of Cell and Gene Therapy Products Bridging the GAP

Heidaran_MoMo Heidaran, PhD, Vice President, Technical, PAREXEL Consulting, Former FDA Reviewer

Cell and gene therapy products include a diverse array of very complex products which are intended to treat, modify or even cure many life threatening conditions. The opportunities are tremendous, but the challenges are equally complex. Ultimately successful commercialization of cell and gene therapy products requires a multi-disciplinary approach, one that fully integrates patient needs and product knowledge with the capability to commercially manufacture these complex products consistently.

1:40 Standards and Control Strategies for Characterization of Cell Therapy Products

Sarkar_SumonaSumona Sarkar, PhD, Biomedical Engineer, Biosystems and Biomaterials Division, Biomaterials Group, NIST

Several standards are under development to establish high quality analytical methods for characterizing cellular therapeutic products. A draft standard is under development in ISO TC 276: Biotechnology to address general characterization of human cells for therapeutic applications, addressing topics including analytical method development programs, assay matrices, assay quality control, and critical quality attributes. Here we describe these efforts and a general framework for developing fit-for-purpose analytical methods for cell characterization.

2:10 Refreshment Break

2:30 Starting and Raw Material Quality for Successful Scale-up of Clinical and Commercial Manufacturing

Clarke_DominicDominic Clarke, PhD, ISCT Process & Product Committee Co-Chair and Global Head, Cell Therapy, HemaCare

Consistency of the starting source material is a vital component to ensuring the success of cell and gene therapies. As allogeneic therapies transition to multiregional clinical trials, navigating the potential regulatory barriers for access and use of the starting material presents its own set of challenges. It is important to understand as early as possible the quality and level of compliance (e.g. cGMP) required globally.

3:00 Integration of Multiplexed Analytics for Cell Therapy Process Optimization

Anna Brown, Associate Director, Process & Analytical Development, Unum Therapeutics

The use of autologous patient cells as starting material provide increased variability compared to traditional cell manufacturing raw materials. In addition, monitoring of multiple cellular product attributes is required to understand the impact of process changes on product quality. In order to optimize Unum’s cell therapy manufacturing process, Unum has developed a powerful integrated high throughput platform around multiplexed cell analytics to enable the rapid testing of process conditions.

3:30 Are Cell Therapy Standards the Right Approach?

Christopher Bravery, PhD, Consulting Regulatory Scientist, Consulting on Advanced Biologicals, Ltd.

3:45 Session Break

3:55 Plenary Keynote Session View details

5:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing 

6:30 End of Day

Tuesday, August 13

7:30 am Registration Open and Morning Coffee


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7:55 Chairperson’s Remarks

Christopher Bravery, PhD, Consulting Regulatory Scientist, Consulting on Advanced Biologicals, Ltd.

8:00 Flow Cytometry Assay Validation: O, the Places You’ll Go

Hulspas_RuudRuud Hulspas, PhD, Independent Consultant, Cellular Technologies Bioconsulting, LLC

Flow cytometry is used for cell characterization for release therapeutic cell products and in patient follow-up studies. Measurements involve a wide range of variables demanding validation of instrumentation and methodology to guarantee quality of the results. Although official guidance documents on validation of this method are lacking, helpful information can be found in recommendation papers. This presentation will provide an overview with accompanying footnotes about assay validation in flow cytometry.

8:30 Cytof/Mass Cytometry Analytics for CAR T Drug Products – Opportunities and Challenges

Kleinsteuber_KatjaKatja Kleinsteuber, PhD, Scientist II, Cellular Analytics, Bluebird Bio

Cell-based gene therapy drug products are a heterogeneous mixture of phenotypically and functionally distinct cells. Phenotypic analysis requires tools that efficiently deconvolute cellular subpopulations of these drug products. Here, we present the application of mass cytometry (CyTOF), a single-cell multiplex technology measuring up to 40 protein targets, to reliably quantify the phenotypic composition of autologous CD34 and CAR T drug products. We also summarize strategies to overcome common challenges inherent to this technology.

9:00 Analytical Method Transfers to Enable Technology Transfer to Manufacturing Sites at Various Stages of Development

Junzia_WangJunxia Wang, PhD, Director, Analytical Development, Mustang Bio, Inc..

Analytical method transfers to internal and external testing sites are required by health authorities to ensure both quality of clinical materials provided to patients, and effective testing during registrational stability studies. The different approaches to meet these regulatory requirements, factors such as early and late stage of process development, complexity of the control strategy, prior experience from recent analytical transfers to support a cellular therapy drug product manufacturing process will be provided.

9:30 Selected Poster Presentation: Development of a B Cell Flow Cytometric Method Intended for the Characterization of Incoming Patient Apheresis Materials

Michelle Tseng, PhD., Associate Director, Analytical Operations, Process Development at Kite, A Gilead Company

9:40 Selected Poster Presentation II: Applying High Throughput Particle Characterization Methods to Assess the Relative Titer and Physical Stability of Viral Vectors

Lydia Shih, PhD., Senior Associate Scientist, Biologics Drug Product Development, Gilead Sciences

9:45 Coffee Break in the Exhibit Hall with Poster Viewing


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10:30 Machine Learning-Guided Product Development

Wilkinson_DanielDaniel Wilkinson, PhD, Scientist, Computational Biology, Bluerock Therapeutics

As cell therapy manufacture scales to meet market demand it will be necessary to implement in-process controls and analytics to optimize product purity and safety. Using a combination of single cell RNA sequencing and machine learning techniques it is possible to define a molecular process signature that reflects cell phenotype and overall process health. This phenotypic signature may then be assessed as part of a statistical process control-guided manufacturing paradigm.

11:00 Assay Development Strategies for Cell Therapy Product Characterization

Keightley_AngelaAngela Keightley, PhD, Director, Assay Development, Bluerock Therapeutics

Product characterization is key to successful cell therapy development and analytical methods are essential tools throughout the product development lifecycle. But how do we identify critical analytics in early stage process development that can be leveraged to develop robust downstream quality control tests? Examples will illustrate how bioinformatics data have been successfully used to develop robust release assays for monitoring cellular impurities.

11:30 Outcomes of Characterization of CD34-Enriched Gene Therapy Drug Products

ilya_cropIlya Shestopalov, PhD, Senior Scientist, Cellular Process Characterization and Analytics, Bluebird Bio

Cell-based gene therapy drug products require advanced analytical methods to characterize their safety and efficacy. This talk will cover utilization of the CyTOF phenotyping technology to quantify the phenotypic heterogeneity of cellular drug products during a multi-year drug product characterization campaign. The impact of phenotypic composition on in vitro and in vivo function of drug products will be discussed.

12:00 pm Integrated E2E Workflow System for Data- and Knowledge-Driven Process Development

Fitzgerald_AmandaAmanda Fitzgerald, PhD, Senior Scientific Consultant, Biologics, Genedata

We present an E2E system for the development of manufacturing processes for biotherapeutics supporting workflows from post-discovery to commercial manufacturing. The system integrates the development of cell lines, upstream, downstream, formulation processes and analytical tests. Its integration layer with instrument equipment enables automation of laboratory work and the platform’s query and reporting infrastructure enables integrated, informed decision-making throughout the process development workflow and comprehensive learning across different development campaigns and molecules.

12:30 Enjoy Lunch on Your Own

1:15 Cake Break in the Exhibit Hall with Poster Viewing


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1:55 Chairperson’s Remarks

Ruud Hulspas, PhD, Independent Consultant, Cellular Technologies Bioconsulting, LLC

2:00 Advancing Product Characterization for Cell Therapies

Xue_QiongQiong (Chelsea) Xue, PhD, Associate Director, Head Analytical Development, Cell Therapies, Pharmaceutical Sciences, Takeda Pharmaceuticals

CAR T product has complicated composition and MOAs. As a result, analytical development for CAR T therapy has gone beyond traditional CMC focus and assumed responsibilities for product understanding and next generation product design. In this talk, we will review means to advance product analytics for cell therapies.

2:30 Process Validation for Cell-Based Therapies

Bravery_ChristopherChristopher Bravery, PhD, Consulting Regulatory Scientist, Consulting on Advanced Biologicals, Ltd.

Before market approval it is necessary to complete process validation of the commercial process. This can only be undertaken if sufficient process knowledge has been accrued to build on earlier process qualification activities to develop a suitable validation approach. This talk will explore some of the challenges with validation of manufacturing processes for cell-based medicines, and consider the various approaches that can be taken.

3:00 Process Development for MGTA-456 to Support Multi-Center Clinical Distribution in Time-Critical Diseases

Kopesky_PaulPaul Kopesky, PhD, Director, Manufacturing and Supply Chain, Magenta Therapeutics

MGTA-456 is produced by expanding CD34+ cells derived from umbilical cord blood which requires a patient-matched starting material and a tight production timeline to address patient medical need. Ongoing process development for MGTA-456 has produced an efficient, cryo-preserved product to support multi-center clinical development.

3:30 Metabolomics in Stem Cell Therapy Manufacturing

Mantalaris_AthanasiosAthanasios (Sakis) Mantalaris, PhD, Professor, W.H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University

Analysis of the metabolome can be used for the evaluation of pluripotent and multipotent stem cell cultures, affording early detection of physiological changes indiscernible with traditional culture monitoring techniques. Finally, metabolomics can be used for the evaluation of the quality of stem cell differentiation in 2D and 3D biomaterial cultures, providing a sensitive and robust state-of-the-art technology guaranteeing high quality cell therapy manufacturing.

4:00 Refreshment Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)

4:15 - 4:30 Stretch Break

4:45 Breakout Discussions

This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges.

5:45 End of Conference

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6:00-8:30 Recommended Dinner Short Course*

SC10: Phase-Appropriate Analytical and Process Control Strategies


Christine P. Chan, PhD, Principal Scientist, Global Manufacturing Science & Technology, Sanofi

Biotherapeutics are challenging to develop due to complexity of the molecular structure as well as the manufacturing process. The establishment of an integrated control strategy for robust manufacturing is an iterative process based on sound science and quality risk management. In this short course, we will discuss key considerations in evolving the analytical and process control strategies through the course of product development.