CASSS Welcome & CGTP Summit 2023 Introduction

Jun 26, 2023 8:30am ‐ Jun 26, 2023 9:00am

Identification: 64044

Comparability assessments are necessary for life cycle management of all biological products, including cell and gene therapies (CGT), and are conducted to ensure that manufacturing changes do not adversely impact product quality, safety, or efficacy.  The complexity and diversity of CGT product modalities can pose considerable challenges to the usual approaches, which are guided by the principles in ICH Q5E.  In this summit, we will discuss a range of CGT modalities and some new concepts in comparability required for certain CGT products.

Session 1: Comparability Considerations for Viral Vector-Based Gene Therapies

Jun 26, 2023 9:00am ‐ Jun 26, 2023 10:40am

Identification: 64050

Viral vector-based gene therapy products are the fastest growing segment of the gene therapy field, with adeno-associated virus (AAV)-based vectors dominating the landscape. The possibility of a one-time injection, and a relatively low-risk safety profile, increased demand for application of AAV-based vectors for the treatment of rare, serious, and life-threatening diseases. As sponsors scale-up and scale-out to meet the increasing demands and implement changes to optimize manufacturing process productivity and performance, it is imperative to effectively design and carry out comparability studies. 

A well thought out comparability study is critical for demonstrating that the product attributes indicative of quality, safety and efficacy are similar pre and post change. Data derived from a robust comparability study also ensures that the preclinical and clinical data derived pre-change can be leveraged for future clinical studies and/or for supporting licensure without the need for repeat studies with post change product to demonstrate comparability. Implementing manufacturing changes to meet the demands of clinical supply and commercialization has presented challenges when evaluating comparability of the pre- and post-change product.  For example, transition from an adherent to a suspension process may increase output while simultaneously impacting process- and product-related impurities. Limitations in the current understanding of how structure impacts function thus limits our ability to know which product quality attributes are important when making manufacturing changes. Inadequate comparability studies can lead to delays and misalignment of the clinical and CMC development and sometimes to the stalling of promising clinical programs. 

This session will include case studies that illustrate the challenges and the strategies used for assessing comparability at different stages of development of viral vector-based gene therapies, and a discussion of the key considerations in the design of comparability studies.

Session Speakers: 

Case Study: Comparability between AAV manufactured by Triple-plasmid transfection/HEK293 and Double-baculovirus/Sf9 Processes 

Garrett Daniels, Prevail Therapeutics

Analytical Comparability – Evolution of Analytical Methods & Case Study for Late-Stage Change

Phillip Ramsey, Sangamo Therapeutics

De-Risking Analytical Comparability for an AAV Manufacturing Process Change in Late Development

Taro Fujimori, Ultragenyx

Assessing Comparability: It’s More Than Just Numbers 

Julia O'Neill, Direxa Consulting

Session 2: Comparability Considerations for Cell-Based Therapies

Jun 26, 2023 1:55pm ‐ Jun 26, 2023 3:10pm

Identification: 59421

Comparability assessments for cell-based therapies are challenging due to complex manufacturing processes, inherent variability of cell starting materials, and evolving understanding of product quality attributes and analytical technologies. Many of these products are made-to-order for a specific patient, and materials are limited for any type of analytical evaluation.  Early generation of the first autologous cell therapy products applied fast-to-market CMC approaches to expedite the delivery of life-saving treatments to patients.

As the focus of the field shifts towards optimized manufacturing, better understanding of CQAs, and superior product performance, well designed comparability strategies can streamline cell therapy product development, reduce the costs of manufacturing, and provide faster access to these important medicines. Limited characterization and understanding of the relationship between the product and its function further complicate the ability to rigorously compare pre- and post-change product. 

In this session, comparability strategies used with commercial and investigational cellular therapy products will be presented as case studies. In addition, industry stakeholders and regulators will engage in discussions to address uncertainties in comparability including planning comparability studies during early and late stages of drug development, and challenges involved in showing clinical relevance. The relevance of the lessons learned to newer generations of autologous and allogeneic CAR-T cell products will be discussed. Discussions will also include gene editing and healthy donor considerations to maximize product and process consistency while ensuring product quality, safety, and efficacy.

Session Speakers:

Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products

Elizabeth Lessey-Morillon, CBER, FDA

Statistical Perspectives on Analytical Comparability Studies for Autologous Cell-based Therapies

Kedar Dave, Bristol-Myers Squibb Company

Challenges and Considerations for Allogeneic CAR T Therapy Comparability Studies 

Mark DiMartino, Allogene Therapeutics

CASSS Welcome & CGTP 2023 Introduction

Jun 27, 2023 8:30am ‐ Jun 27, 2023 9:00am

Identification: 64059

Keynote Presentation

Jun 27, 2023 9:00am ‐ Jun 27, 2023 10:00am

Identification: 64056

Keynote Speaker: 

Gene Therapy Drug Development for Ultra-Rare Disease: Challenges & Opportunities

Becky Schweighardt, Grace Science LLC

Parallel Session 2: Product Quality Testing for Individualized Medicines

Jun 27, 2023 10:45am ‐ Jun 27, 2023 12:20pm

Identification: 64142

With the significant progress in the development of individualized medicines, several issues with respect to their routine quality testing have emerged. As a new batch has to be tested for each patient, an extensive set of quality attributes to be analyzed and elaborate testing methods can be a challenge on both number of samples that are needed and the time that is required for testing. The latter is especially true for verifying the sterility of the drug product. As batches for individualized medicines cannot be stocked and the medical needs often require fast treatment of the patients, standard sterility testing can become the limiting factor for the success of an individualized therapy. In addition, it has to be ensured that the assays will function independent of the patient-specific aspects of the final product. 

In this session, we will discuss key challenges and opportunities with respect to product quality testing for Individualized medicines to enable the successful development of such therapies.

Session Speakers:

USP Evolving Position on Use of Rapid Microbial Methods

Huiping Tu, United States Pharmacopeia 

Defining Microbial Control Strategies for Cell-free and Cell-based Individualized ATMP's

Friedrich von Witzingerode, Genentech, a Member of the Roche Group

Delivering Next Generation Cell Therapy Manufacturing Faster without Compromising Quality

Scott Nichols, Kite, A Gilead Company

Additional Panelists:

Elvira Argus, CBER, FDA

Bryan Silvey, A2 Biotherapeutics, Inc. 

Parallel Session 1: CMC Challenges with Ultra Rare Diseases

Jun 27, 2023 10:45am ‐ Jun 27, 2023 12:20pm

Identification: 64137

Bringing treatment to those afflicted with an ultra-rare disease is complex. These products are encumbered with challenges ranging from high development costs with a limited ROI, to issues with executing and interpreting clinical trials with unusually small patient populations. Furthermore, the cost to generate the quantities of product required to support an approvable CMC package can be prohibitive for many organizations. 

This session will address ways in which companies have tackled the CMC and regulatory challenges when bringing these life changing therapies to patients in need.

Session Speakers:

Manufacturing Challenges Limiting the Access to ATMPs 

Ralf Altenburger, F. Hoffmann-La Roche Ltd.

Development of a Single Patient CRISPR Therapeutic 

Richard Horgan, Cure Rare Disease

Additional Panelists:

Emmanuel Adu-Gyamfi, CBER, FDA

Becky Schweighardt, Grace Science LLC

Technical Seminar presented by MilliporeSigma

Jun 27, 2023 12:45pm ‐ Jun 27, 2023 1:45pm

Identification: 64140

Ensuring the Virus Safety Profile of Your Product - Expectations and Recommendations From the Latest Update to ICH Q5A

Rebecca Bova, MilliporeSigma

Kathryn Martin Remington, MilliporeSigma

Parallel Session 4: Considerations for CGTP Delivery Device Development

Jun 27, 2023 2:20pm ‐ Jun 27, 2023 3:55pm

Identification: 64143

Many cell and gene therapy products use special delivery devices. Generally, there are two approaches for development and commercialization. 1: specify a device brand in the label to be used with the cell or gene therapy products. Under this approach, the sponsor is developing a drug/device combination product, need to navigate complex, often rather different, regulatory pathways in different countries, regions. 2: not to specify a brand but only describe device characteristics so that end users can source the device on their own to the defined characteristics. Under this approach, the sponsor needs to consider data required to support drug compatibility with potentially a class of device products. The US FDA has issued a guidance in 2019 on CGTP delivery devices. In the EU, regulatory requirements differ between integral, non-integral co-packaged, or not co-packaged (e.g. referenced) medical devices. In addition, distinct legislative frameworks for medicinal products and medical devices require joint input of respective experts. 

This session will use case studies to explore and discuss each approach, share lessons learned during early and late stage CGTP development on managing regulatory procedures, overcoming regulatory hurdles.

Session Speakers:

The Regulatory Interface of ATMPs and Medical Devices in Europe 

Ilona Reischl, Austrian Medicines and Medical Devices Agency

U.S. FDA’s Perspective on Delivery Devices Used to Administer Cell and Gene Therapy Products 

Laura Ricles, CBER, FDA

What Device Engineers Can Teach You About CGTP Delivery Devices 

Saran Baskaran, AstraZeneca
Samir Shah, AstraZeneca

Parallel Session 3: Lifecycle Approaches to Potency Assay Selection

Jun 27, 2023 2:20pm ‐ Jun 27, 2023 3:55pm

Identification: 64144

Potency testing is a critical part of the assessment and release of cell therapy products. These functional assays provide quantitative assessments of the biological activity of a cell or gene therapy product that are associated with that product’s in vivo mechanism(s) of action (MOA). Current state-of-the-art analytical methods still rely mainly on in vitro assays including immune-assays, cell-based proliferation, cytokine release as well as cytotoxicity assays and involve complex technology such as flow cytometry. In some cases, these assays may lack the required robustness, simplicity, sensitivity and/or throughput required to function well in the QC GMP environment.   In other cases these assays reflect an average measurement that represents the entirety of a sample and do not provide information regarding the function associated with individual cell phenotypes. Next generation potency assays are needed which are easy to use, robust and provide a more comprehensive evaluation of the quality attributes of the Drug Substance (i.e. Viral Vector, plasmid) and Drug Product.   

This session will involve case studies highlighting innovative approaches being used to develop potency assays in support of programs from early phase to late phase and commercialization. Assay design strategies focused on reflecting a cell therapy product’s complex MOA, while balancing this with attributes that are important for a method to function effectively to perform QC release and stability testing will also be included. Points to consider for critical reagents used to support potency assays for cell/gene products as well as viral vector will also be discussed.

Session Speakers:

Rethink the Potency Paradigm for Gene Therapy Products 

Xiaohui Lu, Ultragenyx

Success Story: Luxturna Potency Assay Development to Validation 

Ravindra Kumar, Spark Therapeutics

Unleashing the Power: Assessing CAR T Cell Therapy Potency and Maximizing Life Cycle Management 

Seema Bansal, Bristol-Myers Squibb

Additional Panelists:

Andrew Byrnes, CBER, FDA