Journal Archive

Commercial Insights

Cell & Gene Therapy Commercial Insight – November 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:

This past month the FDA made progress in formalizing the development and commercialization of cell therapy and regenerative medicine products in the USA with the release of new guidance describing the regenerative medicine advanced therapy (RMAT) designation and how it relates to other regulatory support mechanisms. The RMAT, which is reserved for therapies that are intended to treat, modify, reverse or cure, serious conditions, will include all of the benefits of the existing breakthrough therapy designation and fast track designation, including discussions on surrogate endpoints. Companies seeking a RMAT designation will only need to show that a therapy has the potential to address an unmet medical need in order to receive support. The policies now in place will no doubt stimulate the development of novel regenerative medicine therapies. What will be critical now is the development of a reimbursement environment conducive to the uptake of these therapies as they make their way to market.

GENE THERAPY:

This month sees plenty of good news in the clinical development arena. Two companies have announced positive progress in their early clinical development programs: Ultragenyx has successfully completed the first cohort of three patients in its Phase 1 study in OTC deficiency, and Abeona has enrolled the first patient with MPS IIIA at its site in Spain, adding to already active sites in the USA and Australia. Ziopharm has released new data showing encouraging median overall survival in patients with recurrent glioblastoma treated with its IL-12-based gene therapy, and AveXis has achieved a notable milestone with the publication in the New England Journal of Medicine of positive clinical data from its ongoing trial in spinal muscular atrophy. There’s also an announcement from BioCanCell that clinical data on its lead product, BC-819, in development for non-muscle invasive bladder cancer, will be presented at the upcoming Genitourinary Cancers Symposium in February 2018.

DOI: 10.18609/cgti.2017.086
Citation: Cell Gene Therapy Insights 2017; 3(10), 891-901.

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Perspective

Points to Consider for Cell Manufacturing Equipment and Components

EXPERT INSIGHT

Sheng Lin-Gibson*, Brain Hanrahan, Sandro Matosevic, Aletta Schnitzler, Jiwen Zhang & Claudia Zylberberg

Advances in manufacturing technologies, as well as early development and adoption of industry-wide standards will contribute to a vibrant industry for cell-based therapeutic products (CTP). A critical aspect is manufacturing equipment that can address specific and unique challenges associated with CTP manufacturing. The move towards fully closed and automated systems heightens the need for integrated and standardized strategies to ensure the manufacturing of CTPs with controlled safety and quality profiles. This paper summarizes key points to consider for cell manufacturing equipment and components. In addition to enabling common baseline understanding for equipment requirements, it is meant to stimulate broader discussions for developing best practices and standards for CTP manufacturing equipment.

Submitted for review: Apr 26 2017 Published: Dec 19 2017
DOI: 10.18609/cgti.2017.079
Citation: Cell Gene Therapy Insights 2017; 3(10), 793-805.
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Expert Insight

Biopreservation Best Practices: A Cornerstone in the Supply Chain of Cell-based Therapies – MSC Model Case Study

Spotlight Article

Case Study

Alireza Abazari, Brian J Hawkins, Dominic M Clarke & Aby J Mathew

Supply Chain Management: PoC considerations, Product Tracking & Data Management

Mesenchymal stromal cells (MSCs) are prime candidates for regenerative medicine and therapeutic applications due to both their potent immunomodulatory function and a unique ability to proliferate and differentiate into a variety of cell lineages. However, the stresses incurred during biopreservation/stability intervals (non-frozen and cryopreserved), including transit to and from the clinic can render MSCs ineffective and potentially unsafe. Challenges related to the formulation, transportation, distribution and delivery of source material (tissue, blood, marrow) and MSC-based products are important and inter-related components of the supply chain and scale-up. Effective biopreservation can optimize the quality of cell/tissue source material and final cell/tissue products, mitigate the adverse effects of interruptions and unforeseen events throughout the supply chain, as well as support the return to function of MSCs following patient administration. Conversely, inadequate environmental controls and biological support throughout the supply chain can limit transportation options, restrict the geographic distribution and reduce the clinical efficacy of MSC-based therapies. Indeed, it is possible that the contradicting reports in the literature on the impact of biopreservation on MSCs may stem from the lack of appropriate biopreservation protocols. Optimized biopreservation considerations are critical components of cell and tissue manufacturing systems, a robust and risk-mitigated supply chain, and are recommended for the commercialization of MSC-based products. This article aims to discuss the importance of Biopreservation Best Practices in the commercialization of MSC-based therapies and the relative benefits and concerns of different supply chain models.

Submitted for review: Aug 30 2017 Published: Dec 15 2017
DOI: 10.18609/cgti.2017.082
Citation: Cell Gene Therapy Insights 2017; 3(10), 853-871.
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Impact of Freeze–Thaw Processes on the Quality of Cells

Spotlight Article

Expert Insight

Allison Hubel

Supply Chain Management: PoC considerations, Product Tracking & Data Management

The unique supply chain involved in the production of cell therapies implies that effective methods of preservation are critical for commercial and clinical application of this form of therapy. Effective methods of preservation enable transportation amongst the different sites (collection, processing and administration), time for completion of safety and quality control testing as well as coordination of the therapy with patient care regimes. The preservation protocol consists of a series of steps (pre-freezing processing, introduction of a cryopreservation solution, freezing, storage, thawing and post-thaw assessment). Errors in each step can reduce post-thaw recovery and cell function. Key scientific concepts are described and resources to help those involved in the development of preservation protocols are provided.

Submitted for review: Aug 30 2017 Published: Dec 15 2017
DOI: 10.18609/cgti.2017.069
Citation: Cell Gene Therapy Insights 2017; 3(10), 807-813.
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Personalized Supply Chains for Cell Therapies

Spotlight Article

Expert Insight

Martin Lamb, Robert E Margolin & Joseph Vitale

Supply Chain Management: PoC considerations, Product Tracking & Data Management

The commercialization of two recent autologous genetically engineered T-cell oncology products was a monumental moment for the cell therapy industry and patients. These market approvals, however, have jointly reinforced the need for technological solutions to maintain the complex supply chains of the industry. These supply chains, which are patient-centric, involve multiple stakeholders, including patients, providers, collection centers, couriers, case managers and the manufacturers, all of which must be orchestrated properly for success. Systems currently used by drug manufacturers, such as enterprise and manufacturing systems, quality management systems and patient management systems, although essential, do not provide the needle-to-needle traceability and precise orchestration of the supply chain. To support the requirements of these unique supply chains, cloud based, configurable platforms called Cell Orchestration Platforms (COP) have been designed to both schedule and manage stakeholders and events while also maintaining chain of identity and custody. COPs are not intended to replace existing core systems but are intended to integrate with them to provide a connected end-to-end view of the supply chain. This article aims to provide insight into the function and implementation strategy for COPs, while also considering their strategic position and connectivity with other adjacent systems within the autologous cell therapy supply chain. Additionally, the article reviews the roles of key supply chain stakeholders and the systems they interact with to ultimately provide a seamless experience for physicians and patients.

Submitted for review: Oct 29 2017 Published: Dec 15 2017
DOI: 10.18609/cgti.2017.081
Citation: Cell Gene Therapy Insights 2017; 3(10), 815-833.
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The Importance of Understanding & Designing Cellular Therapy Supply Chains

Spotlight Article

Expert Insight

Christine Rutherford, Jacqueline Barry, John DM Campbell & Marc Turner

Supply Chain Management: PoC considerations, Product Tracking & Data Management

The objective of this article is to propose a revised conceptual framework for the analysis of the supply chains for cellular therapies that considers first the impact of supply and demand uncertainty on the supply chain pathway, and second the impact of complexity on the physical supply network configuration. We suggest a revised cellular therapeutics supply chain taxonomy that emphasizes the interdependence between product characteristics, supply chain pathway and network configuration, which we hope will facilitate structured thinking around the design of optimal supply chain strategies for different products.

Submitted for review: Nov 11 2017 Published: Dec 18 2017
DOI: 10.18609/cgti.2017.087
Citation: Cell Gene Therapy Insights 2017; 3(10), 873–889.
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Delivering Cell Therapies to Patients: Clinical & Logistical Challenges Past, Present & Future

Spotlight Article

Expert Insight

Miguel Forte and Simon Ellison

Supply Chain Management: PoC considerations, Product Tracking & Data Management

Cell therapies present the opportunity to change the lives of patients with previously untreatable conditions, most recently a child with epidermolysis bullosa [1]. Nevertheless, if they cannot be delivered, both clinically and logistically, then their benefit is irrelevant. Indeed a robust, efficient supply chain can differentiate products and therapies. The traditional pharmaceutical development cycle is 10 years, however Kymriah went from clinical trials to market in 5 years and many innovators are talking about times shorter than this. Therefore, robust delivery systems have to be developed now, as the industry does not have the time for a more organic progression. This paper will investigate the evolution of the industry, identify seven delivery barriers (both logistical and clinical) and suggest strategies to ensure continued industry growth and patient benefit.

Submitted for review: Oct 27 2017 Published: Dec 15 2017
DOI: 10.18609/cgti.2017.083
Citation: Cell Gene Therapy Insights 2017; 3(10), 835-841.
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Supply Chain Management in the Delivery of ATMPs for Trials & as Licensed Medicines

Spotlight Article

Expert Insight

Mark W Lowdell & Owen Bain

Supply Chain Management: PoC considerations, Product Tracking & Data Management

Advanced therapy medicinal products (ATMPs) are, without doubt, the most complex medicines being developed and they come with some unique supply chain problems which are often under-estimated or completely misunderstood. The sheer diversity of ATMPs from relatively simple suspensions of somatic cells for immunotherapy or regenerative medicine to complex combination products of cells on medical device scaffolds prevents a comprehensive analysis of supply chain problems but there are very many issues which are universally important or, at least, common to the majority of ATMPs. Similarly, the regulation of cell and tissue therapies differs across the World and critical considerations in one regulatory domain are sometimes irrelevant in others. The term ATMP is unique to the European Union and incorporates all of the cell, gene and tissue therapies which are being developed. However, there are important distinctions across the World where, for example, a combinatorial ATMP consisting of cells applied to a medical device in the EU is not regulated as a medicine in the USA but remains a medical device. This article will focus on the EU ATMP situation but will comment on how the same issues are dealt with in other jurisdictions.

Submitted for review: Oct 20 2017 Published: Dec 15 2017
DOI: 10.18609/cgti.2017.084
Citation: Cell Gene Therapy Insights 2017; 3(10), 843-851.
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The Evolving CAR-T Therapy Supply Chain: Progress and Challenges

Spotlight Article

Interview

Kimberly Lounds Foster

Supply Chain Management: PoC considerations, Product Tracking & Data Management

 
Kimberly Lounds FosterKimberly Lounds Foster Corporate Vice President and Head of Global Commercial Supply, Celgene, leading an integrated plan to make, source and deliver operations functions for all of Celgene’s commercial therapies including supply chain planning and logistics, internal/external manufacturing, CAR-T supply chain, Manufacturing Science & Technology along with Operations, Process and Analytics functions. Prior to Celgene, Kimberly held the position of Head of Global Supply Chain for Novartis’ Cell & Gene Therapy unit. In this role, she was responsible for building out the commercial and clinical autologous supply chain across 13 countries for CTL019. Kimberly spent over six years at Sandoz where she built the External Supplier Operations function for the North America & LatAm markets following a ‘virtual plant’ model, and managed the Sandoz US supply chain for in-line products, new product launches and US distribution centers. Kimberly holds an M.B.A from The Wharton School, University of Pennsylvania and a B.S. in Chemical Engineering from Northwestern University. Kimberly is married and lives in Morris Plains, NJ.

DOI: 10.18609/cgti.2017.085
Citation: Cell Gene Therapy Insights 2017; 3(10), 903-908.
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