Journal Archive

Editorial

Automation: systems thinking shows the value of manufacturing technology & those who can integrate product & process development

Spotlight Article

Editorial

Automation of cell and gene therapy manufacturing: From vein to vein

David J Williams

The use of the word automation immediately raises a question for a manufacturing engineer – what do the machines do and what do the people do? The answer of course is that the machines do what they do best and the people do what they do best. Significantly, however, this is a systems level question. In this editorial, I am going to use some systems thinking to define one or two critical paths forward for our industry where I think there are opportunities to learn from experiences in both mature and developing manufacturing industries.

DOI: 10.18609/cgti.2017.052
Citation: Cell Gene Therapy Insights 2017;3(8), 597-602.

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Commercial Insights

Cell & Gene Therapy Commercial Insight – September 2017

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:

We saw some activity on the financing front this past month. Juno closed a public financing, raising gross proceeds of over US$300 million, which will give the company the financial power it needs to continue progressing what has become a substantial pipeline, while CAR-T developer, Autolus, closed a series C financing of US$80 million. Adaptimmune came upon some cash as well after GSK exercised its option to an NY-ESO T cell program. Adaptimmune received $48 million in total, which it will channel into other, wholly owned programs, including MAGE-A4, MAGE-A10 and AFP.

GENE THERAPY:

Alnylam’s pipeline update this month shows the perils and challenges of developing treatments that act on something as fundamental as a cell’s protein synthesis machinery. Whilst its RNAi treatment for acute intermittent porphyria (Givosiran) is progressing to Phase 3 in a study agreed with FDA, the news for Fitusiran is less encouraging, with the announcement of a patient death due to an initiating event of cerebral venous sinus thrombosis in its haemophilia A program. The approval by FDA of Biogen’s nusinersen for spinal muscular atrophy last year was an important milestone for RNA therapeutics, but this month’s news shows that the path for these treatments is never straightforward. The news is not all gloomy, as this month sees Agilis Biotherapeutics on the cusp of a BLA for its treatment for AADC deficiency and Dimension Therapeutics crossing the line to get its treatment for OTC deficiency into Phase 1.

DOI: 10.18609/cgti.2017.065
Citation: Cell Gene Therapy Insights 2017; 3(8), 663-676.

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Interview

Understanding the Critical Impact of Logistics on Scale-Up & Commercialization

Innovator Insight

Sam Herbert

Sam Herbert World Courier

Sam Herbert is President of World Courier, a global specialty logistics company and a part of AmerisourceBergen. He leads a business that spans more than 140 company-owned offices in 50-plus countries. Prior to his role as President, Herbert was Chief Operating Officer, responsible for World Courier’s global functions. Before joining World Courier in 2013 as Vice President of Strategy, Herbert was a partner in Oliver Wyman’s Health and Life Sciences practice where he advised some of the world’s leading pharmaceutical, healthcare and pharmaceutical services companies, including AmerisourceBergen. He is based in World Courier’s global headquarters in London. Sam recently contributed to a white paper published by AmerisourceBergen, “Commercializing Cell and Gene Therapies.”

DOI: 10.18609/cgti.2017.067
Citation: Cell Gene Therapy Insights 2017; 3(8), 655-662.
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Perspective

An alternative to patents: can DNA be protected by copyright and design right law?

EXPERT INSIGHT

Beatriz San Martin & Heidi Hurdle

Historically, applications of technology that use DNA have been protected through the patent system. Many of the techniques for isolating and manipulating DNA are now considered to be routine and it has become more difficult to rely on the patent system for protection, particularly in light of recent decisions from the US Supreme Court. This is making it increasingly challenging for diagnostic and biotech companies to obtain investment as they increasingly rely on trade secrets for protection. Other types of intellectual property rights, such as copyright and design right, and the role they may play in protecting DNA have not typically been considered or asserted by owners of technology that use, manipulate or design DNA. In this article, we consider the extent to which DNA sequences and what they code may be protected by UK copyright and design right.

Submitted for review: Apr 21 2017 Published: Oct 19 017
DOI: 10.18609/cgti.2017.062
Citation: Cell Gene Therapy Insights 2017; 3(8), 639-649.
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Expert Insight

Advances in automation for the production of clinical-grade mesenchymal stromal cells: the AUTOSTEM robotic platform

Spotlight Article

Expert Insight

Jelena Ochs, Frank Barry, Robert Schmitt & J Mary Murphy

Automation of Cell and Gene Therapy Manufacturing: From Vein to Vein

Stem cell-based therapies are a central element of regenerative medicine and provide new treatment modalities for chronic and life-threatening conditions. Mesenchymal stem/stromal cells (MSCs) represent an important technology in regenerative medicine, although less developed with respect to clinical translation than hematopoietic stem cells (HSCs). MSC therapies may be based on the potential of the cells to differentiate to mesenchymal lineages or on their paracrine effects on host tissue. Both autologous and allogeneic applications are possible, the latter enabled by the low immunogenicity of the cells. Although stem cell therapy holds much promise for the treatment of chronic and debilitating diseases, there are still many obstacles to be overcome. In addition to the compelling need to generate strong and unambiguous clinical evidence, there are major technical gaps that must be filled. Chief among these is the development of manufacturing platforms for cell products that are efficient, cost effective and reproducible. Automated, robotic and closed production systems will provide the most efficient manufacturing strategy. Here we describe advances in automation for the clinical-scale production of MSCs and challenges associated with translating from lab-scale to automated large-scale manufacturing processes.

Submitted for review: Oct 3 2017 Published: Nov 21 2017
DOI: 10.18609/cgti.2017.073
Citation: Cell Gene Therapy Insights 2017; 3(8), 739-748.
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Benefits of automation for pluripotent stem cell therapies, disease modeling & drug discovery

Spotlight Article

Expert Insight

Maciej S Daniszewski, Alice Pébay & Duncan E Crombie

Automation of Cell and Gene Therapy Manufacturing: From Vein to Vein

Pluripotent stem cells show much promise for cellular therapies, drug discovery and disease modeling. There are a number of challenges involved in the culture of pluripotent stem cells to increase the scale of stem cell culture for such applications. Automated processes may prove beneficial in improving consistency and scalability of culture systems for better therapeutic and disease modeling outcomes.

Submitted for review: Jun 27 2017 Published: Oct 27 2017
DOI: 10.18609/cgti.2017.056
Citation: Cell Gene Therapy Insights 2017; 3(8), 613-621.
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The Evolving Role of Automation in CAR-T Cell Commercialization

Spotlight Article

Podcast Interview

Andrew Kaiser

Automation of cell and gene therapy manufacturing: From vein to vein

 
Dr Andrew Kaiser Miltenyi Biotec

Andrew Kaiser joined Miltenyi Biotec’s R&D in 2012, where he heads a team that focuses on developing tools and technologies for clinical applications of adoptive cell therapy and more specifically the automation of gene-modified T cell manufacturing. During his PhD, he focused on translational research of dendritic cell maturation for vaccines at IDM Pharma and at the Cochin Institute in Paris, France. As post-doc, he aimed to further cancer immunotherapy using gene-modified T cells at the Surgery Branch of the NCL, Bethesda, USA and later at the Netherlands Cancer Institute in Amsterdam. Dr. Kaiser is also the scientific coordinator of a Horizon 2020 European consortium called CARAT, that aims to integrate innovative cell manufacturing tools and enabling technologies into a new comprehensive platform that will facilitate the safe, automated, and cost-effective manufacture of gene-engineered T-cells.

DOI: 10.18609/cgti.2017.070
Citation: Cell Gene Therapy Insights 2017; 3(8), 677-681.
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Automation in the translation of an autologous cell therapy from lab to commercial scale

Spotlight Article

Interview

Rodney Rietze

Automation of cell and gene therapy manufacturing: From vein to vein

 

Dr. Rodney Rietze is a Senior Research Investigator in the Exploratory Immuno-Oncology group at the Novartis Institutes for Biomedical Research (Cambridge, MA), developing novel bioprocesses and enabling technologies for the manufacture of next generation CAR-T therapeutics. This work is a continuation of his role at Novartis Pharmaceutical’s Cell and Gene Therapy Unit, where he led the Automation Network that supported the manufacturing process and analytics for KymriahTM, the first FDA-approved personalized CAR-T cell therapy. Before joining Novartis, Dr. Rietze was a Senior Director at TxCell S.A., where he developed the process/analytics for OvasaveTM, an antigen-specific type 1 regulatory T cell-based autologous drug product in clinical trials for the treatment of inflammatory bowel disease. Prior to TxCell, he was a Senior Principal Scientist at Pfizer Regenerative Medicine where he led teams in discovery and early clinical development of small both molecule and cell-based therapeutics for neural, cardiovascular and auto-immune indications. Preceding his transition to industry, Dr. Rietze was a founding member of the Queensland Brain Institute (Brisbane, Australia) and Head of the Neural Stem Cell and Aging Laboratory. His work on the purification of an adult mammalian NSC, and subsequent discovery of the pathway that activates endogenous NSCs spurred the development of several compounds that are currently in clinical trials.

DOI: 10.18609/cgti.2017.063
Citation: Cell Gene Therapy Insights 2017; 3(8), 607-612.
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Critically Evaluating the Benefits of Automation in Commercial-Scale Manufacture

Spotlight Article

innovator insight

Nina Bauer

Automation of cell and gene therapy manufacturing: From vein to vein

Nina Bauer Lonza Cell Therapy

Nina Bauer leads Lonza’s Autologous Cell Therapy business, with manufacturing sites in the US, Europe and Asia. As part of this role, she is also in charge of establishing novel manufacturing technologies to remove bottlenecks and enable commercially viable services for patient-scale therapies. With more than 12 years’ experience in the Regenerative Medicine sector, Nina has held Business Development roles at the Cell Therapy Catapult (UK), and the University of Edinburgh, and worked as a Life Science Consultant for a wide range of Regenerative Medicine businesses. She holds a PhD in Neuroscience from the University of Oldenburg (GER), an MBA from the University of Edinburgh (UK), and conducted post-doctoral research at the Weizman Institute (ISR), Salk Institute (USA), and the University of Edinburgh (UK).”

DOI: 10.18609/cgti.2017.071
Citation: Cell Gene Therapy Insights 2017; 3(8), 695-700.
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Automated, spinning membrane filtration for preparation of mobilized leukapheresis products for CD34+ cell selection

Spotlight Article

Research Article

Alaina C Schlinker

Automation of Cell and Gene Therapy Manufacturing: From Vein to Vein

CD34+ hematopoietic stem and progenitor cells are used to promote bone marrow reconstitution following cancer treatment and may offer a novel treatment for other indications. Leukapheresis of mobilized peripheral blood (mPB) is a common source of CD34+ cells. Depending on the application, it may be desired to purify the CD34+ cells in the leukapheresis product via immunomagnetic selection. Prior to selection, the leukapheresis product must be washed to remove platelets and unbound paramagnetic beads. When performed manually, these processing steps are time-consuming and operator intensive. This study evaluated the LOVO Cell Processing System (LOVO), a commercially available instrument utilizing spinning membrane filtration, as an automated alternative for preparing mPB leukapheresis products for CD34+ cell selection. The LOVO removed >90% of platelets prior to bead incubation and substantially reduced pre-selection processing time compared to a manual approach. Products prepared using the LOVO had an average 76.2 ± 2.9 % CD34+ cell recovery and 4.72 ± 0.41 log T cell reduction following selection.

Submitted for review: Jun 20 2017 Published: Oct 5 2017
DOI: 10.18609/cgti.2017.059
Citation: Cell Gene Therapy Insights 2017;3(8), 623-637.
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Advances in automated analytical tools for cell therapy manufacturing

Spotlight Article

Interview

Christopher Wiwi

Automation of cell and gene therapy manufacturing: From vein to vein

 
Chris Wiwi

Dr Christopher Wiwi is Director of Cell Therapy Analytical Research & Development in Celgene’s Cell Therapy Development and Operations team, located in Warren, New Jersey. Dr Wiwi leads the analytical development, validation and QC efforts for the advancement of Celgene’s novel cellular therapy candidates from research to clinical and commercial manufacturing. He also serves as Celgene’s CMC lead for the bb2121 program, a promising autologous CAR-T therapy being developed in collaboration with bluebird bio for the treatment of patients with advanced multiple myeloma.

DOI: 10.18609/cgti.2017.064
Citation: Cell Gene Therapy Insights 2017; 3(8), 651-654.
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Automated Manufacturing of Dendritic Cell Therapies: Progress & Challenges

Spotlight Article

Interview

Shashi Murthy

Automation of cell and gene therapy manufacturing: From vein to vein

 

Shashi Murthy is a Professor of Chemical Engineering and the Founding Director of the Michael J and Ann Sherman Center for Engineering Entrepreneurship Education at Northeastern University. He is an expert in the areas of cell separation and automated cell culture and current projects in his lab focus on patient-specific dendritic cell generation and dendritic cell-mediated T-cell expansion for therapeutic use. Prof. Murthy obtained his PhD from the Massachusetts Institute of Technology (MIT) and BSc from Johns Hopkins University. He joined Northeastern in 2005 following a postdoctoral fellowship at the Harvard Medical School and Massachusetts General Hospital. Prof. Murthy is the recipient of the National Science Foundation’s Faculty Early Career Development (CAREER) Award and the Søren Buus Award for Outstanding Research in Engineering at Northeastern University and was elected Fellow of the American Institute for Medical and Biological Engineering (AIMBE) in 2015. He has co-authored over 70 publications and is an inventor on seven issued or pending patents. He co-founded Quad Technologies, which commercialized hydrogels as releasable magnetic beads for cell separation and reagents for cell activation. More recently, Prof. Murthy founded Flaskworks, which is commercializing automated systems for the manufacturing of patient-specific dendritic cells and dendritic cell-stimulated therapeutic T cells.

DOI: 10.18609/cgti.2017.061
Citation: Cell Gene Therapy Insights 2017; 3(8), 603-606.
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