Bringing you the latest cutting-edge research and commentary in bioscience.

Cell & Gene Therapy Insights

Cell & Gene Therapy Insights

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Journal

Welcome to the latest issue of Cell and Gene Therapy Insights – the open access, peer-reviewed publication that brings you the latest insight and commentary from leading experts from academia and industry.

Interview

Critical considerations & common mistakes in early-phase CMC development

Spotlight Article

Interview

Jason Carstens

Cell Therapy Quality/ CMC & Analytics

DR JASON CARSTENS has over 20 years of process development, GMP manufacturing, and CMC project management experience in the biotech industry. Dr Carstens is currently the Chief Operating Officer and a Principal Consultant at Pluristyx, Inc., an advanced therapy tools and service company that he co-founded which serves customers in the rapidly growing field of regenerative medicine and cellular therapies. Pluristyx has a line of pluripotent stem cell-based products and also offers contract development, manufacturing, and consulting services. Prior to Pluristyx, Dr Carstens was VP of Manufacturing and Development at Nohla Therapeutics, a Seattle-based cell therapy company developing clinical products from hematopoietic stem cells. Dr Carstens also spent 5 years as the Director of Cell Therapy Process Development and Manufacturing at the Fred Hutchinson Cancer Research Center in Seattle. While at Fred Hutch, he worked on a variety of autologous and allogenic cell and gene therapy products including CAR T cells, TIL, antigen specific T cells, hematopoietic stem cells, and B cells for use in human clinical trials. Dr Carstens also spent 13 years at CMC Biologics, a contract development and manufacturing organization, where he was responsible for cell line and cell culture process development supporting manufacture, transfer, and scale-up of more than 50 unique recombinant proteins, antibodies and biosimilars. Dr Carstens also has an appointment at the University of Washington as an Affiliate Associate Professor. He earned his PhD in Chemical Engineering from the University of California at Berkeley and a BS in Chemical Engineering from the University of Washington.

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European regulator’s perspective: best practice & future directions in cell therapy CMC

Spotlight Article

Interview

Margarida Menezes Ferreira

Cell Therapy Quality/ CMC & Analytics

MARGARIDA MENEZES FERREIRA graduated in Biology at the Faculty of Sciences of the University of Lisbon. She did her PhD in Medical Biochemistry at the Aix-Marseille II University in France in 1981 and did postgraduate research in molecular endocrinology at the National Institutes of Health, USA, until 1984. She published several research papers in peer-reviewed journals. She has worked at INFARMED since January 1996, the Portuguese Regulatory Authority for Medicines and Health Products developing and supervising the installation of the Biologics, Biotechnology and Microbiology Departments for the National Laboratory for the Control of Medicines and Health Products and coordinating its implementation until 2001. From 1999 to 2001 she also directed the National Control Laboratory for Medicines and Heath Products (OMCL). Since 1999 she has been an appointed member for the Biologics Working Party at the European Medicines Agency (EMA). She has participated in the drafting of European guidance and scientific advice on biological medicinal products including biotechnological and biosimilars as well as gene- and cell-based therapies. She was member of the Cell Products Working Party until its closure and participated intensely in the construction of the regulatory framework and quality guidance for cell based medicinal products. Since 2009 she has been the Portuguese member at the Committee for Advanced Therapies. She lectures on regulatory framework for Biotechnology and Advanced Therapy Medicinal Products at the Faculty of Pharmacy from the University of Lisbon and in several postgraduate courses at the University of Coimbra and University of Aveiro as well as at the Instituto Superior Técnico /University of Lisbon and at the PhD program MIT-Portugal and Harvard-Portugal. She acted as a consultant expert for the building analytical capacity for laboratory control in the pharmaceutical sector in 2001 at Cape Verde for the World Bank and in 2005 at Angola with the European Commission. Since 1998 she has been a member of the National Vaccination Commission.

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Next steps in MSC cell therapy characterization

Spotlight Article

Interview

Bruce Bunnell

Cell Therapy Quality/ CMC & Analytics

Bruce Bunnell PhD is the Director of the Tulane Center for Stem Cell Research and Regenerative Medicine and Professor in the Department of Pharmacology in the Tulane University School of Medicine. In addition, he holds the Aron Family Regents Distinguished Chair in Gene Therapy. Dr. Bunnell obtained his PhD in Microbiology from the University of Alabama at Birmingham School of Medicine. He then pursued Postdoctoral Fellowship research at the Howard Hughes Medical Institute in the School of Medicine at the University of Michigan and the National Human Genome Research Institute at the National Institutes of Health in Bethesda, MD. Dr. Bunnell was an Assistant Professor at the Nationwide Children’s Hospital Research Institute, part of the Ohio State University School of Medicine prior to joining the faculty at Tulane University in 2002. Dr. Bunnell’s research program is focused on both the basic science and translational applications of adult stem cells isolated from the bone marrow and adipose tissue. Dr. Bunnell investigates the use of mesenchymal stem cells isolated from the bone marrow or adipose tissue as a therapeutic intervention for both Multiple Sclerosis (MS) wound injury, lung injury and bone repair. He is currently working towards a human clinical trial for the treatment of MS with these cells. He has served as a reviewer of stem cell, regenerative medicine and tissue engineering grants for the National Institutes of Health, Department of Defense and several state funded programs including Maryland, New York, Virginia and Pennsylvania. He has also served on grant review panels for several foreign countries including Denmark, Ireland, Germany and Spain. Dr. Bunnell serves as an Editorial Board Member for several journals, including Stem Cells, BMC Genomics, and Regenerative Medicine. He has recently ended a term as a member of the NIH TAG study section.

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Optimizing quality & compliance for cord blood-derived cells

Spotlight Article

Interview

Roger Horton & Christopher Leonforte

Cell Therapy Quality/ CMC & Analytics

ROGER HORTON was trained in Biochemistry and cancer immunology and obtained a PhD in 2006. He previously worked in academia and then at Cancer Research UK before joining Anthony Nolan in 2007. Roger is the ANCTC Cord Blood Bank operational manager, and works to provide cord transplants globally for patients in need in conjunction with operations in London head office and the team at ANCTC. He is currently in training to be a FACT inspector and has been the HTA’s designated individual for ANCTC since 2016.
CHRISTOPHER LEONFORTE is scientist-turned-manager who trained in Biochemisty in 2009 and completed an MSc in Biomedical Science in 2017. He has worked at the Anthony Nolan charity since 2010 and is passionate about the work that it does. Chris is the Cord Blood Bank processing and quality control manager. He oversees the processing, testing and storage of the cord blood. Chris works with an excellent team to maintain the bank’s FACT-Netcord accreditation and HTA license and he has completed training to be a FACT Netcord Inspector.

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Perspective

An Academic Model for Cell & Gene Therapy Asset Development

Spotlight Article

Perspective

David DiGiusto

Cell Therapy Quality/ CMC & Analytics

New treatments for neoplastic, infectious and monogenic diseases employing cell and/or gene therapy modalities are at the forefront of modern medicine. Many of these treatments are initially discovered in academic research centers and require significant development prior to out-licensing for commercial development and regulatory approval. Over the past 20 years, numerous academic institutions have elected to build infrastructure to perform the required early translational science and clinical testing “in house” before seeking a commercial partner. Product development requires careful planning and management to realize the full benefit of what is often a significant financial investment. Multiple stakeholders participate in this process and outcomes depend heavily on the vision, planning and financial commitment of the institution. Described here are common considerations and practices for creating a sustainable cell and gene therapy asset development program at an academic institution.

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Expert Insight

Standards Landscape in Cell Counting: Implications for Cell & Gene Therapy

Spotlight Article

Expert Insight

Sumona Sarkar, Laura Pierce, Sheng Lin-Gibson & Steven P Lund

Cell Therapy Quality/ CMC & Analytics

Recent advances in the fields of cell and gene therapy and regenerative medicine have increased the need for a standardized approach to cell counting. International efforts in the development of documentary standards as well as workshops which include input from device manufacturers, regulators, researchers and manufacturing organizations have sought to increase confidence in cell count measurements. Improving comparability between methods, enabling fit-for-purpose method selection, and facilitating the translation of cell counting measurements between stages of product development are critical for the success of cell and gene therapy products. Here, we describe recent efforts in the area of standards development for cell counting and outline a technical approach for the comparison and selection of cell counting methods in the absence of reference materials. These standards and approaches offer strategies for the development and implementation of counting methods that are fit-for-purpose to address the broad needs of cell and gene therapy and regenerative medicine.

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Using Machine Learning for Critical Quality Attribute Discovery in Cell Therapy Manufacture

Spotlight Article

Expert Insight

Dan Charles Wilkinson Jr & Stefan Irion

Cell Therapy Quality/ CMC & Analytics

Stem cell-derived cellular therapies are currently entering clinical trials for several degenerative diseases. For these therapies to be commercially viable, it is necessary for manufacturing to be adapted to commercial scale. Though, before bioreactors and multi-layered flasks are capable of producing hundreds and thousands of clinical doses, it is important to examine the assays and criteria for assessing a cell therapy’s safety and potency. Unlike molecular drugs, a stem cell-derived therapy comprises processed, living material consisting of millions of individual cells. The potency of the therapy is not simply related to a molecular formula, or confined to a single biological molecule; it depends on the complex cellular machinery, and more often than not, on the dynamic interplay between different cellular populations. Further, cell therapies may change or differentiate during the multistep process of transplantation, integration and maturation. The complexity of this multifaceted process must therefore be reflected in the quality control mechanisms employed during manufacture, especially as scaling and good manufacturing practice (GMP) adaptation may lead to unforeseen permutations. FDA, under the Process Analytic Technology framework, has prescribed that manufacturers adopt a set of Critical Quality Attributes (CQAs) that can be assessed during manufacture under a Quality by Design process regime [1,2]. With the aid of Machine Learning (ML) techniques, discovery of new CQAs is now possible for cell therapies. ML offers a set of mathematical mechanisms for discovery and prediction that would allow for the distillation and online evaluation of QCAs from large, traditionally unwieldy data sets. When coupled with a comprehensive data collection program guided by statistical design of experiments (DOE) methodology, these newly discovered CQAs may be assessed and implemented in GMP manufacture using a statistical process control (SPC) program to ensure process reliability and fidelity. In this article we outline three techniques that, when combined with ML, can help define CQAs of a cell therapy manufacturing process.

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How to Reduce the Vein to Vein Timeframe Through Efficient, Accelerated QC & Release Testing

Spotlight Article

Expert Insight

Adrian P Gee

Cell Therapy Quality/ CMC & Analytics

An issue associated with certain types of cellular therapies is the ability to manufacture and test the cell product within the timeframe available to treat the patients. Some products, such as extensively expanded cells, require prolonged manufacturing and manipulation ex vivo, with the result that the intended recipient’s disease may have progressed by the time the product is available, and they are no longer eligible for the treatment. To a lesser extent, the time required to release test the product can cause delays to administration and may require use of two-stage testing, with provisions to deal with failing results obtained after the product has been administered. This article discusses strategies that can be used to reduce manufacturing and release testing delays using state of the art techniques that can accelerate product availability. It focuses on products being used under Investigational New Drug (USA)/Investigational Medicinal Product (EU) approvals.

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