Cambridge Healthtech Institute ’s 3rd Annual

Cell Therapy CMC and Analytics

August 13-14, 2018


To ensure the quality, safety and rapid production of cell therapies, companies must keep on top of their CMC and analytical strateigies. However, cell-based therapies are extremely complex to analysis with high variability.

Cambridge Healthtech Institute’s Cell Therapy CMC and Analytics meeting focuses on the technical and regulatory requirements needed to advance the analysis, quality and development of cell therapies with in-depth case studies and regulatory feedback on 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 13

8:00 am Short Course Registration Open and Morning Coffee


9:00 - 11:30 Recommended Short Course*

SC4A: Lessons Learned from the First 17 ATMPs Submitted to the EMA

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

* Separate registration required.

11:30 Main Conference Registration Open

REGULATORY REQUIREMENTS

1:00 pm Chairperson’s Opening Remarks

Fouad Atouf, PhD, Vice President, Global Biologics, USP

1:10 Cell Therapy Product Manufacturing Considerations

Bernadette_KeaneBernadette Keane, PhD, Principal, Keane Consultancy

Cell therapies are substantially more complex than small molecule or biological approaches to medicine. This complexity poses challenges for both academic groups and companies developing cell therapies, as well as for regulators seeking to oversee this growing area of medicine. In this interactive session, we will discuss some of the common challenges and lessons learned along the way and explore how collaborations between industry and the regulators can help lead to successful translation and commercialization of cell therapies.

1:45 Regulatory Aspects of Manufacturing and Control of Genetically Modified Cells

Matthias_RennerMatthias Renner, PhD, Scientist, Federal Institute for Vaccines and Biomedicines, Paul Ehrlich Institute

In respect to manufacturing and quality control, genetically modified cells are considered to be most complex medicinal products. Regulatory aspects considering the fundamental steps in manufacturing and control of these medicinal products will be presented, and the regulatory framework for these products which are classified in the EU as advanced therapy medicinal products and are regulated centrally by the European Commission and the European Medicines Agency will be given.

2:15 Standards and Best Practices Applicable for Advanced Therapies

Foud_AtoufFouad Atouf, PhD, Vice President, Global Biologics, USP

Qualification of raw materials used in the manufacturing of cellular therapies, requires the use of risk assessment strategies to categorize the critical components of a manufacturing process. In addition to cell culture supplements, excipients and other formulation’s components must meet the required quality to ensure consistency in manufacturing and subsequently the quality and safety of finished cell therapy products. This presentation will discuss the critical strategies facing the development of cell therapies as per USP recommendations.

2:45 Refreshment Break

CMC STRATEGIES FOR CELL THERAPIES

3:15 FDA’s CMC Review of a Cell Therapeutics

William_LeeWilliam Lee, PhD, Vice President, Regulatory Affairs, Cato Research

This talk will focus on two case studies. The first case study will discuss FDA’s CMC issues with a stem cell therapy that were raised at a pre-IND meeting. The second case study will discuss FDA’s CMC questions for an investigational cell therapy during the pre-IND meeting and then subsequently during the IND 30-day review after initial IND submission.


3:45 PANEL DISCUSSION: Regulatory and CMC Strategies for Cell Therapies

  • Most common questions asked by companies/ regulators
  • Lessons learnt from recently approved products
  • Challenges around gene-edited cell therapies
  • Preparing for IND – What are the priorities, preclinical packages?

Moderator:

Fouad Atouf, PhD, Vice President, Global Biologics, USP

Panelists:

Bernadette Keane, PhD, Principal, Keane Consultancy

Matthias Renner, PhD, Scientist, Federal Institute for Vaccines and Biomedicines, Paul Ehrlich Institute

4:15 Sponsored Presentation (Opportunity Available)

4:30 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.

Accelerating Cell Therapy Development

Moderator: Fouad Atouf, PhD, Vice President, Global Biologics, USP

Matthias Renner, PhD, Scientist, Federal Institute for Vaccines and Biomedicines, Paul Ehrlich Institute

Bernadette Keane, PhD, Principal, Keane Consultancy

  • Most common questions asked by companies/ regulators
  • Lessons learnt from recently approved products
  • Challenges around gene-edited cell therapies
  • Preparing for IND – What are the priorities, preclinical packages?
  • “Reverse translation” to improve manufacturing and development outcomes
  • CAR Ts in combination with other agents – CMC implications

Commercial Manufacturing of Gene-Modified Cell Therapies: The Challenges Ahead

Moderator: Michael D. Jacobson, PhD., Managing Partner, Cambridge Biostrategy Associates

  • What are the most important problems that need to be solved over the next 3-5 years for this industry to thrive?
  • What key innovations would you like to see that you believe would be transformative?
  • How low do COGS need to go, and how (and when) will we get there?
  • How automated and integrated will cell therapy manufacturing become over the next 5-10 years? What parts of the workflow are most ripe for integration, and which are not?

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

7:00 End of Day

Tuesday, August 14

7:30 am Registration Open and Morning Coffee

CELL COUNTING AND PRODUCT CHARACTERIZATION

7:55 Chairperson’s Remarks

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

8:00 Tools and Strategies to Improve Confidence in Cell Counting Measurements

Laura_PierceLaura Pierce, PhD, Biomedical Engineer, Biosystems and Biomaterials Division, Biomaterials Group, NIST

Cell count, a routinely performed fundamental measurement in the biosciences, underpins key decisions in the manufacturing, commercialization, and release of cell-based therapies. The industry seeks tools to gain greater confidence in cell counting measurements. NIST, in collaboration with industry and other government agencies, is developing strategies to provide fit-for-purpose measurement assurance for cell counting, in the forms of written standards, experimental designs, and control materials.

8:30 Towards Rigor and Reproducibility in Single Cell Analytics for Therapeutic Cell Products

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

Cell characterization occurs at multiple checkpoints of the manufacturing process and is particularly important at product release. In contrast to bulk analysis, single cell analysis offers detailed information about the composition of therapeutic cell products. Flow cytometry provides rapid analysis of millions of cells for up to 30 cellular parameters, simultaneously measured on individual cells, but it can also be difficult, unreliable and expensive. Existing expertise and new developments are applied for successful integration in cell therapy.

9:00 Assays in Purification of Targeted Cell Populations

Patricia Rogers, Manager, Cell Sorting Capability, Broad Institute of MIT and Harvard

Cell purification of targeted populations is necessary when specific populations are needed for downstream applications. Instrumentation needed in order to purify cell populations is often complicated and hard to standardize. Also, there is biological variation between samples that needs to be accounted for. This presentation will focus on understanding the key areas for variation and developing tools to standardize each part of the assay in order to provide reproducible results.

9:30 Developing 21st Century Rapid Sterility Testing for Cell-Based Therapies

Jacqueline Wolfrum, PhD, Associate Director, Biomanufacturing Program (BioMAN), Center for Biomedical Innovation, Massachusetts Institute of Technology

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

POTENCY, AUTOMATED ANALYTICS AND RAPID RELEASE

10:30 Potency Assay Development and Qualification for B-Thalassemia and Sickle Cell Disease Autologous Gene Therapy Drug Products

Ilya_ShestopalovIlya Shestopalov, PhD, Senior Scientist, Cellular Process Characterization and Analytics, bluebird bio

Quantitative potency assays were developed to demonstrate correction of b-thalassemia and sickle cell disease properties in an in vitro cell culture system. Potency was found to be specific to the beta-globin lentiviral vector and dependent on transduction efficiency of the autologous gene therapy drug product, demonstrating ability to reject sub-functional drug products. Considerations for assay development, qualification results, and redundancy to transduction efficiency methods will be discussed.

11:00 Product Release towards Rapid Quality Control

Sadik_KassimSadik Kassim, PhD, Vice President, Process and Analytical Development, Mustang Bio, Inc.

As “living drugs”, cell therapies pose unique analytical characterization challenges; these challenges extend from the research bench to the cGMP manufacturing setting. This talk will review common analytical methods for cell therapies, specifically CAR T- and TCR-based therapies, with a specific emphasis on the limitations of current methods and the move towards automated analytical methods.


11:30 PANEL DISCUSSION: Automation in Analytics and Manufacturing

  • Rapid release testing strategies – purity, rapid sterility testing, what does it mean? Which tests are necessary, which are not?
  • Automated/semi-automated analytics – regulatory considerations, options, issues
  • Adventitious agent testing

Moderator:

Rodney Rietz, PhD, Senior Investigator, Exploratory Immuno-Oncology, Novartis

Panelists:

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

Sadik Kassim, PhD, Vice President, Process and Analytical Development, Mustang Bio, Inc.

Jacqueline Wolfrum, PhD, Associate Director, Biomanufacturing Program (BioMAN), Center for Biomedical Innovation, Massachusetts Institute of Technology

12:00 pm Single Cell Proteomics for Evaluating Function & Clinical Utility in Cell Therapy

Sean_MackaySean Mackay, CEO, IsoPlexis

By capturing 40+ secreted proteins per single cell, thousands of cells at at time, researchers can determine the functional activity and strength of immune cells and cellular products. Using the IsoCode technology to define T-cell functional strength, Kite Pharma has used their pre-infusion product to predict objective response to CAR-T therapy. Isocode technology has also provided biomarker correlates to objective response in checkpoint inhibitor therapy - both from TILs and PBMC.

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

1:15 Dessert Refreshment Break in the Exhibit Hall with Poster Viewing

COMPARABILITY, STABILITY AND VECTOR ANALYSIS

1:55 Chairperson’s Remarks

Scott R. Burger, MD, Principal, Advanced Cell & Gene Therapy, LLC

2:00 Assessment of Comparability of a Gene Therapy Drug Product after Manufacturing Site and Process Changes

Stephen_DuguayStephen J. Duguay, PhD, Director, Cellular Process Characterization and Analytics, bluebird bio

Manufacturing site changes and process improvements were implemented during clinical evaluation of an autologous cell-based gene therapy. A risk based approach was used to rank the potential impact of the changes to product quality, safety and efficacy. Statistical evaluation of study results included equivalence testing, quality ranges and qualitative comparisons. The study design, results and conclusions will be discussed.


2:30 In vitro Product Characterization and Stability Studies of CAR T Cell Therapies

Carlotta_PeticoneCarlotta Peticone, PhD, Senior Scientist I, Process Development, Autolus


3:00 How Much Information Do I Need to Present for the Vector of My Genetically Modified Cell Product?

Christopher_Bravery_2Christopher Bravery, PhD, Consulting Regulatory Scientist, Consulting on Advanced Biologicals Ltd.

How do regulatory agencies view the vector of a genetically modified cell? Does the vector need to be GMP; from what point in manufacture would this apply? Can I use a drug masterfile? How much information, including data, should I provide in the dossier for clinical trials; will this be different for approval?


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

4:15 Designing Strategies for Data-Driven Product Characterization

Marc-Olivier_BaradezMarc-Olivier Baradez, PhD, Lead Analytical Development Scientist, Cell and Gene Therapy Catapult

In the development of cell therapy products, the ability to characterize the product during its manufacture is becoming as valuable as the ability to control and optimize the process itself. This presentation will explain the current limitations and opportunities associated with such dual product/process characterization, and it will cover the principles behind a suitable data-driven strategy for efficient product/process development in the context of industrialization.

4:45 Big Data Strategies for Cell Therapy Manufacturing

Scott_BurgerScott R. Burger, MD, Principal, Advanced Cell & Gene Therapy, LLC

The quest to retrieve, analyze, and leverage that data has become the new gold rush in life sciences. This presentation will discuss the role of big data in cell therapy process development, real time analytics and commercial scale manufacturing.


5:15 End of Conference


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

SC10B: My Potency Assay Is Quantitative – But Is It Quantitative for Potency?

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

* Separate registration required.


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