Cambridge Healthtech Institute’s 2nd Annual
Cell Therapy Bioproduction
Industrializing Cell Therapies
August 3-4, 2015
Part of CHI's 7th Annual The Bioprocessing Summit
August 3-7, 2015 | Westin Copley Place Hotel | Boston, Massachusetts

Continuing the discussions initiated at last year’s Cell Therapy Bioproduction conference and building upon the industry’s increasing knowledge and experience in this field, we have identified the top challenges that scientists and engineers are struggling with, which range from navigating the global regulatory maze to raw material sourcing, cell expansion and optimization to scaling up and manufaturing. 

CHI’s Second Annual Cell Therapy Bioproduction aims to open the communication channels between pharma, academia and vendors by presenting first-hand case studies, practical examples, proven concepts and novel technologies to help provide potential solutions to these challenges.

Monday, August 3

8:00 am Pre-Conference Registration and Morning Coffee

11:30 Main Conference Registration

1:00 pm Chairperson’s Opening Remarks

Anthony Davies, Ph.D., President, Dark Horse Consulting, Inc.

COLD CHAIN, PROCUREMENT AND QUALIFICATION OF RAW MATERIALS & FINISHED PRODUCTS

1:45 Cold Chain Design for Allogeneic Cell Therapies

Brian Murphy, Ph.D., Director, Bioprocess Development, Celgene Cellular Therapies

2:15 Qualification of Raw and Ancillary Materials Used in Cell Therapy Manufacturing

Fouad Atouf, Ph.D., Director, Biologics & Biotechnology, U.S. Pharmacopeial Convention

Raw and ancillary materials are important components used in the manufacturing of cell- and tissue-based products. These materials can have a profound effect on the expansion, differentiation, or activity of the processed cellular components, and can therefore have a significant impact on the finished product quality attributes. Thus, ensuring the quality of a cell- or tissue-based therapeutic requires rigorous evaluation and qualification of the components used in its manufacture.

2:45 Refreshment Break

3:15 Sourcing and Qualification of Starting Materials for Cell Therapy Products

Elizabeth Read, M.D., Principal, EJ Read Consulting LLC.

The cellular starting material becomes an integral part of the living, functional cells that constitute the active drug substance of cell therapy products. This presentation will review the common types of cellular starting materials and cover approaches for their sourcing and qualification. Specific challenges in starting material qualification for patient-specific products (autologous or allogeneic) vs. off-the-shelf allogeneic products (multipotent or pluripotent stem cell-derived) will be addressed.

3:45 Raw Materials in the Manufacture of Advanced Therapies Medicinal Products: Quality Attributes and Quality Assurance

Bernd Leistler, Ph.D., Director, Development & Production, CellGenix GmbH

Regulatory agencies recognize an increasing need for guidance for raw materials used for ATMP production and started developing guidelines that outline risk-mitigation strategies and qualification programs for AM selection. AM manufacturers must ensure critical quality attributes to meet increasing quality and safety concerns. GMP grade and animal-derived component-free materials derived from well-characterized cell banks will reduce qualification and validation efforts of ATMP manufacturers and help to ensure consistency, safety and purity of the ATMP.

4:15 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. Then continue the discussion as you head into the lively exhibit hall for information about the latest technologies.

Chimeric Antigen Receptor (CAR)-T Cells: History, Success, Challenges and Advancement

Moderator: Pranay D. Khare, Ph.D., Independent Consultant

• CAR molecule development and advancement   

Hidden Challenges in Cell Therapy Processing

Moderator: Knut Niss, Ph.D., CMC Team Director, PO&T, Biogen

* Assays needed vs. assays wanted

Regulatory Pathways and Differences in US, Europe and Japan – Opportunities for Accelerating Development

Anthony Davies, Ph.D., President, Dark Horse Consulting, Inc.

 5:15 Discussion Report-Outs

5:30 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:00 End of Day

Tuesday, August 4

7:30 am Registration and Morning Coffee

STRATEGIES FROM CLINIC TO COMMERCIALIZATION

7:55 Chairperson’s Remarks

Pranay D. Khare, Ph.D., Independent Consultant

8:00 Translation of Cell-Based Gene Therapy Product into Clinical Phase II Trial

Ulrike Verzetnitsch, MSc, CTO, apceth GmbH

Treatment options based on genetically modified cells may add alternative therapeutic modalities to medical oncology. The in-house developed investigational medicinal product represented in this case study is a genetically modified mesenchymal-stem-cell-suspension (gmMSC) for IV infusion. The product for clinical Phase I was manufactured inhouse within the established GMP manufacturing capabilities. The Phase I study demonstrated the excellent tolerability of this first-in-man and first-in-class drug and data allowed for continuation in Phase II in Q1/2015.

8:30 Optimization and Clinical Manufacturing of Chimeric Antigen Receptor (CAR) T Cells for Solid Tumors

Pranay D. Khare, Ph.D., Independent Consultant

An optimal production process for the chimeric antigen receptor (CAR) expressing T cells (CAR-T) is required for their success in Adaptive T cell therapy clinical trials. Recently, outstanding results in several clinical trials with CAR-T in acute lymphoid leukemia (ALL) and chronic lymphoid leukemia (CLL]) has been achieved. But limited data and success is observed from solid tumors CAR-T clinical trials. This talk will focus on the optimization process and clinical manufacturing of CAR-T production process for solid tumors.

9:00 Stem Cell Therapy – The Road to Commercialization

Jasmin Kee, Ph.D., Head, Engineering, ReNeuron

Our lead product, CTX, is a therapy for the treatment of patients left disabled by a stroke and for critical limb ischaemia. Both treatments are currently in Phase I and II clinical trials. This presentation will discuss the challenges faced through clinical trials and the strategy to commercialization. Topics will include the use of contract manufacturers versus in-house manufacturing, process scale-up and the use of automation to meet clinical trial needs and future commercial supply.

9:30 Sponsored Presentation (Opportunity Available)

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

SCALING UP AND MANUFACTURING CHALLENGES

10:30 Overcoming Comparability and Scale-Up Challenges in Cell Therapy Production

Robert Deans, Ph.D., EVP, Regenerative Medicine, Athersys, Inc.

Advancing cell therapeutics to commercialization requires adapting early pilot scale clinical manufacturing to a scale meeting commercial expectations. Improvements and scaling cell processing can involve radical shifts in bioreactor format, often moving from 2D planar culturing to microcarrier based bioreactor formats. A case study will be presented for comparability analysis involving MultiStem®, an adherent adult stem cell product, in commercialization for cardiovascular and CNS indications.

11:00 Manufacturing Challenges and Solutions for Autologous Cell Therapies

Knut Niss, Ph.D., CMC Team Director, PO&T, Biogen

Compared to traditional drugs where a bulk of drug substance is produced and dispersed to several individual patients, autologous cell therapy products are derived from the patient’s own cells. With this, a unique manufacturing scenario exists where each patient equals one manufacturing batch. Thus, the commercialization strategy for such products needs to consider several unique issues. This presentation will discuss these issues in detail in light of establishing a large market for an autologous therapy.

11:30 Cell Expansion and Scaling Up in 3D: Implementing an Optimized, Standardized and Fully Automated Operation

Ohad Karnieli, Ph.D., Vice President, Technology & Manufacturing, Pluristem Therapeutics

Technologies are evolving to allow production of cells in large quantities under GMP conditions, nevertheless, the advantage opens new questions and challenges including quality, identity, reproducibility and cost. Bioreactor technology brings to the industry the opportunity to manufacture large quantities of cells in a tightly controlled environment, lowering relatively the COGS and improving quality. However within it there are many unmet challenges. The talk will describe the main challenges and possible solutions for bioreactor 3D culturing.

12:00 pm Translating Cell Therapies: Academic vs. Industry Model

Alexey Bersenev, Ph.D., Director, Advanced Cell Therapy Lab, Yale University

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Session Break

SCALING UP AND MANUFACTURING CHALLENGES (cont.)

1:55 Chairperson’s Remarks

Robert Deans, Ph.D., EVP, Regenerative Medicine, Athersys, Inc.

2:00 Development Strategies for kSep Single-Use Continuous Centrifuge Processes

Jonathan Rubin, Ph.D., Scientist, API Large Molecules, Janssen Pharmaceuticals

Centrifugation is often employed during downstream processing to clarify or concentrate biologics (e.g. antibodies, vaccines, and cell therapies). Disposable centrifuge technology has greatly reduced preparation/cleaning time and contamination risk. Generally, cell therapy products are concentrated in the centrifuge (retentate), whereas clarified vaccine and antibody products flowthrough the centrifuge (centrate). This talk will give a basic overview of kSep technology and discuss strategies used to develop processes for cell therapy and vaccine products.

2:30 Perfused Bioreactor for the Optimization of Human Stem Cell Culture

Veronique Chotteau, Ph.D., Principal Investigator, Cell Technology Group, School of Biotechnology, KTH, Royal Institute of Technology

We have created small perfusion bioreactors supporting the culture of human stem cells adhering on electrospun nanofiber scaffold of biocompatible and biodegradable polymer in EU project HESUB. The bioreactors are scale-down of a novel 50 mL perfusion bioreactor and are used to develop and optimize perfusion processes of human stem cells. We will review our achievements for the culture of human myogenic progenitors and of human pluripotent stem cells, embryonic and induced.

3:00 Oral Poster Presentation

Scalable Manufacturing Solutions for T-Cell and MSC Cell Therapy Products

Martha S. Rook, Ph.D., Director, Stem Cell Bioprocessing Group, Process Solutions, EMD Millipore Corporation

As more cell therapies progress through clinical testing, current in vitro culture methods are highly manual, cumbersome to scale and have limited options for in-process monitoring and control. We have developed an expansion paradigm that uses a scalable, single-use, stirred tank bioreactor for both T-cell and human mesenchymal stromal/stem cell (hMSC) cultures. Director monitoring for the specific cell characteristics can be implemented at any point during the culture assuring product quality and consistency. In addition, we have evaluated human platelet lysate as a serum alternative for hMSC cultures and demonstrated similar growth performance when compared to FBS containing media. the bioreactor expansion process provides ease of use in handling, in-process monitoring and lower medium volume requirements leading to robust processes and reduced cost of goods.

3:15 Refreshment Break in the Exhibit Hall with Poster Viewing

TOOLS AND TECHNOLOGIES TO ENHANCE CELL CULTURE PROCESSES

4:15 Biologics Data Platform for Tailored Support of Cell Line Development

Christian Bender, Ph.D., Computational Biologist, Global Drug Discovery, Global Biologics, Bayer HealthCare

We have successfully implemented the Biologics Data Platform (BDP) for tailored support of our screening and protein production processes. In the context of our cell line development process, we present the integration of BDP with our automation workstation. We demonstrate the power of using a comprehensive data management platform to track data for cell line clones and fed-batch experiments together with molecule information such as primary sequences and experimental results.

4:45 Portable X-Ray Fluorescence Spectrometer: A Tool for Biopharmaceutical Forensic Investigations

Jessica Mondia, Ph.D., Research Scientist, Biogen Idec, Inc.

A portable X-ray fluorescence (XRF) spectrometer is a small, cheap, easy and fast instrument for multi-elemental analysis. In biopharma, forensic investigations usually refer to determining the root-cause and evaluating the risks associated with deviations from GMP guidelines including batch records, procedures and SOPs. Here we introduce the use of a XRF spectrometer for biopharmaceutical forensic applications as an in-house-portable diagnostic tool to help resolve or guide investigations in a timely fashion.

5:15 Close of Conference