Journal Archive

Editorial

Umbilical cord derivatives for intervertebral disc regeneration: advances and challenges

Editorial

Sasha Mikhael, Naimisha Beeravolu & G Rasul Chaudhry

MullerKleinHeckmann

Lower back pain (LBP) is one of the most common causes of morbidity worldwide, found in approximately 80% of the population in their life time. One of the major causative factors of LBP is a damaged intervertebral disc (IVD), which leads to degenerative disc disease (DDD). Recent advances in stem cell research provide promising opportunities to explore cell therapy as an alternative to traditional medicine to treat degenerative diseases such as DDD. As a result, a significant effort is being devoted to develop regenerative cell therapies to repair, regenerate or prevent IVD degeneration.

DOI: 10.18609/cgti.2016.076
Citation: Cell Gene Therapy Insights 2016;2(6), 629-634.

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Commercial Insights

Cell & Gene Therapy Commercial Insight – November 2016

Mark Curtis & Richard Philipson

Providing a critical overview of the sector’s commercial developments – M&As, licensing agreements & collaborations, financial results, IPOs and clinical/regulatory updates, with commentary from our Expert Contributors.

CELL THERAPY:

Atlas Venture and Third Rock launched Magenta Therapeutics with a $50 million series A this past month, perhaps the culmination of a period of renewed interest and activity among industry in the area of stem cell transplant. The company’s mission will be to bring transplant to the masses. While bone marrow transplant has been practiced for more than 50 years, generally it has only been used in instances where the benefit of a cure outweighs the risk of GVHD, which is often fatal. It has predominantly been used as a cure for leukemias and lymphomas. However, transplant has great potential beyond oncology, and many multiples of patients with rare blood disorders and severe autoimmune disorders stand to benefit from a world of transplant without GVHD. Magenta will seek to develop technologies in three areas: patient conditioning, stem cell mobilization and stem cell expansion/modulation; all areas of critical significance to the advancement of transplant, and factors that can help reduce patient mortality. Removing GVHD from the picture with improved matching could make it possible to safely ‘reset’ a patient’s immune system, which means the next generation of transplant technology could be a real threat to in vivo gene therapy in diseases such as Type 1 diabetes, multiple sclerosis, sickle cell anemia and Crohn’s disease.

GENE THERAPY:

This month illustrates the challenges faced by companies developing and commercializing gene therapy products, with uniQure announcing workforce cuts and pipeline prioritization. Nevertheless, the field continues to march forwards with further exciting developments in CRISPR-Cas9, with the announcement of the first clinical trial using this technology in patients with metastatic non-small-cell lung cancer. There is also positive news from AveXis, who have announced that the US Food and Drug Administration (FDA) has accepted the use of natural history data for comparison in its pivotal single arm trial in SMA Type 1. The FDA is notoriously resistant to the use of natural history data, so this is a real achievement!

DOI: 10.18609/cgti.2016.075
Citation: Cell Gene Therapy Insights 2016; 2(6), 635-647.
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Expert Insight

Analytical considerations for cellular therapy manufacturing

Spotlight Article

Expert Insight

Christopher Wiwi

Latest advances in the analytical toolkit

The commercialization of cell-based products presents unique challenges. An evolving regulatory landscape, rapid advances in manufacturing technologies, products with complex mechanisms of action (MOA) and inherent variability in starting cellular material are just a few examples of these challenges. The availability of relevant analytical tools is important in manufacturing and process development, where they are used to control the product and to enable process changes. When considering process changes, cellular therapy manufacturers seek to apply sound engineering principles, develop good process understanding and use meaningful analytical methods for product characterization. The diversity and complex nature of cell therapy products requires an increasingly broad set of analytical tools to assist in this endeavor. Scientists engaged in assay development are challenged to select the most appropriate methods and adapt these assays to a quality environment. Cell and patient variability, multiple MOAs, lack of reference materials and complex analytical methods and instruments underlie some of the technical difficulties. This article discusses the testing strategies used by cell therapy manufacturers throughout the product development lifecycle as well as solutions to commercial challenges such as method validation, automation and potency assay development.

Submitted for review: Nov 4 2016 Published: Dec 20 2016
DOI: 10.18609/cgti.2016.071

Citation: Cell Gene Therapy Insights 2016;2(6),651-661.
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Understanding and managing sources of variability in cell measurements

Spotlight Article

Expert Insight

Sheng Lin-Gibson, Sumona Sarkar, John Elliott, Anne Plant

Latest advances in the analytical toolkit

Analytical methods are essential for establishing the quality attributes of cell-based products and for monitoring key steps during their production process. They also underpin the development of new cell therapy products (CTPs) by providing insight into biological mechanisms of action and facilitating the research and development that advances manufacturing. Strategies to improve measurement assurance and standards for cell therapy products have increasingly been recognized for their critical roles in streamlining efforts in R&D, translation, and regulatory submissions. Various forums have been created to develop, coordinate, and disseminate industry best practices and experiences in measurement technologies and assay development. Discussions are underway within various standards development organizations to develop standards to ensure quality, improve manufacturing consistency, and provide measurement confidence for cell-based products. In this review, we examine the role of measurement assurance strategies to identify, minimize, and/or monitor sources of variability encountered in measurement processes associated with the discovery and manufacturing of CTPs.

Submitted for review: Nov 10 2016 Published: Dec 20 2016
DOI: 10.18609/cgti.2016.073

Citation: Cell Gene Therapy Insights 2016;2(6),663-673.
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Product characterization: the evolving analytical toolkit

Spotlight Article

Innovator Insight

Latest advances in the analytical toolkit

Dr Behnam A. Baghbaderani

Behnam-Baghbaderani

Dr Baghbaderani is the head of Cell Therapy Development, Emerging Technologies at Lonza. He has over 13 years of experience in stem cells engineering and bioprocessing. Dr. Baghbaderani holds a PhD degree in Biomedical Engineering from the University of Calgary (Calgary, Canada), where he developed bioreactor protocols for large-scale expansion of human neural stem cells for clinical applications. He completed nearly three years postdoctoral program including a two-year postdoctoral fellowship at the National Institutes of Health (NIH) / National Institute of Neurological Disorders and Stroke (NINDS). His postdoctoral research at the NIH focused on generation of human induced pluripotent stem cells, bioprocessing of both human embryonic stem cells and iPSCs and controlled differentiation into neuronal lineage. Since joining Lonza in 2011, he has been working on developing new technologies and manufacturing processes around human pluripotent stem cells. As the head of CT Development, Dr. Baghbaderani is currently leading the process development and bioassay services, focusing on the development of cGMP compliant processes and cell characterization assays for different cell therapy applications.

DOI: 10.18609/cgti.2016.072
Citation: Cell Gene Therapy Insights 2016; 2(6), 675-681.
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Requirement for smart in-process control systems to deliver cell therapy processes fit for the 21st century

Spotlight Article

Expert Insight

Damian Marshall, Stephen Ward & Marc-Olivier Baradez

Latest advances in the analytical toolkit

The cell therapy field continues to experience significant growth with an increasing number of therapies approaching commercialization and over 535 products currently undergoing phase II and III clinical trials [1]. This focus towards commercialization is leading cell therapy innovators to increasingly look at technologies which can support improved product monitoring, allow more controlled processing and increased consistency during manufacturing. These needs are similar to those experienced in conventional bioprocessing where approaches such as quality by design (QbD) are increasingly being applied to achieve enhanced control of therapeutic products such as monoclonal antibodies. QbD incorporates prior product knowledge with the use of statistically designed experiments, risk analysis and knowledge management. The intent of QbD is to develop sufficient understanding of the product to ensure robustness and consistency in the manufacture process. As the cell therapy field continues to mature it is timely to look at how learnings and technologies from related fields can be used to expedite the development of modern cell therapy manufacturing strategies.

DOI: 10.18609/cgti.2016.074
Citation: Cell Gene Therapy Insights 2016;2(6),683-689.

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