Journal Archive

Editorial

Challenges in gene therapy for desminopathies

Editorial

Markus B Heckmann, Hugo A Katus and Oliver J Müller

MullerKleinHeckmann

Desminopathies are diseases linked to mutations in the desmin gene. Although of monogenetic etiology, desminopathies are challenging and very intriguing from a gene therapeutic point of view as pathophysiology varies with different mutations. Animal models mirroring their distinct pathophysiologic mechanisms are still scarce. Recent scientific advances have revealed promising new therapeutic strategies. This editorial highlights the recent gene therapeutic approaches being tested in animal models for the treatment of desminopathies.

DOI: 10.18609/cgti.2016.052
Citation: Cell Gene Therapy Insights 2016;2(4), 403-406.

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Commercial Insights

Cell & Gene Therapy Commercial Insight – October 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:

Organova has been busy for some time now developing 3D bio-printed tissues for use in screening drug candidates. The thesis being that Pharma can save dollars by adopting screens that provide greater ‘predictiveness’. It’s a tough business model. Cellular Dynamics International, now owned by FujiFilm, burnt through a great deal of money in its day trying to persuade Pharma to screen compounds with its cell lines. Organovo upped the ante, though, with its printing platform, creating 3D, multi-cellular aggregates, or ‘organoids’, which more closely resemble real tissue. The company announced a collaboration with Merck in 2015, giving Merck access to its human liver tissue platform for drug development. Now, Organovo has plans to transcend tools into the realm of therapeutics, and will bring its bio-printed tissue into the clinic, initially for liver disease. Ambitious? Absolutely, but it’s a small step towards realizing the big vision of artificial organ replacement.

GENE THERAPY:

This month illustrates the mixed fortunes of companies working in cell and gene therapy. Whilst Spark Therapeutics continues to roll out positive clinical data in the rare eye disease Leber’s congenital amaurosis-2, and Agilis Biotherapeutics announced authorization of a Phase IIb trial in the rare CNS disease aromatic-l-amino acid decarbolylase deficiency, there is less good news from Adverum, which announced a 1-year delay to its alpha-1-antitrypsin deficiency program due to manufacturing issues. Adverum uses a baculovirus-based AAV production system; whilst these systems are scalable, they can present problems with low yields and baculovirus stability. R&D in gene therapy is as healthy as ever, but manufacturing can often prove to be the Achilles heel for the field.

DOI: 10.18609/cgti.2016.053
Citation: Cell Gene Therapy Insights 2016; 2(4), 407-422
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Expert Insight

Manufacturing process development of ATMPs within a regulatory framework for EU clinical trial & marketing authorisation applications

Spotlight Article

Expert Insight

Giulia Detela & Anthony Lodge

PRODUCT & PROCESS UNDERSTANDING

The quality attributes of advanced therapy medicinal products (ATMPs) that correlate with safety and efficacy in patients are determined not only by manufacturing process inputs such as starting and raw materials, but also by how the manufacturing process itself is designed and controlled. To ensure regulatory compliance, the manufacturing process should therefore be developed based on thorough characterization of the ATMP during all stages of process and analytical development; this ensures that the critical quality attributes that correlate with safety and efficacy are identified and that their specifications can be met during routine manufacturing. In the European Union, the regulatory approval of ATMPs for use in patients requires that data demonstrating their quality, safety and efficacy are submitted in dossiers to regulatory agencies for review. Indeed, such dossiers have a specific format that, in the case of quality data in particular, is informative for the manufacturing process development strategy. This manuscript describes how dossier requirements can be implemented into the design of industrialized ATMP manufacturing processes and fulfilled to enable effective regulatory submissions.

Submitted for review: Sep 18 2016 Published: Nov 10 2016
DOI: 10.18609/cgti.2016.056
Citation: Cell Gene Therapy Insights 2016;2(4), 425-452.

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The key to commercial success: process development & logistical considerations for autologous immunotherapies

Spotlight Article

Innovator Insight

Dan H O’Donnell

CELL & GENE THERAPY MANUFACTURING PATHWAY

The success of a cell therapy clinical trial rests on the ability to deliver a viable, potent product. This positive end result is directly attributable to the strategy in place and the supporting processes. A reliable cell therapy logistics strategy is imperative in ensuring your biopharmaceutical products, therapeutic materials and patient biological samples remain viable from the point of manufacture to the final clinical site delivery.

Submitted: Aug 15 2016 Published: Nov 10 2016
DOI: 10.18609/cgti.2016.051

Citation: Cell Gene Therapy Insights 2016; 2(4), 453-461.
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Uncovering the potential of ultra scale-down tools to enable cost-effective “Quality by Design”

Spotlight Article

future leader perspective

Fernanda Masri

PRODUCT & PROCESS UNDERSTANDING

With many cell therapy companies struggling to meet the manufacturing demands of large-scale commercial production, the industry is slowly moving towards implementation of “Quality-by-Design” principles to gain an understanding of the impact of critical process parameters on critical quality attributes of the product. However, this framework needs an upfront investment in time and resources (ideally during the discovery phase) and process and product development, which is not always an option. Ultra scale-down technologies, allow high-throughput experimentation with minimal material, providing an attractive option for cost-effective screening during the discovery phase. Given adequate characterization with respect to large-scale operations, these tools hold the potential to enable process development and application of “Quality-by-Design” principles to various cell manufacturing steps, especially those concerning downstream processing. This article discusses some of the key challenges faced in cell therapy manufacturing, and how ultra scale-down devices may be implemented as tools to address these.

Submitted for review: Sep 5 2016 Published: Nov 10 2016
DOI: 10.18609/cgti.2016.057
Citation: Cell Gene Therapy Insights 2016;2(4), 463-471.

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The evolving role of automation in process development & manufacture of cell & gene-based therapies

Spotlight Article

Expert Insight

Qasim A Rafiq & Robert J Thomas

Automation: migration from manual processes to closed-system automation

The need for automation in cell and gene therapy manufacturing processes is primarily driven by the regulatory requirements for reproducibility, clinical need for consistent, efficacious therapies and commercial constraints of developing scalable, cost-effective processes. Automation has already played a pivotal role in healthcare manufacture, including that of successful vaccine production, however the role of automation continues to evolve and technologies and platforms are now emerging which succeed in expediting efforts in process development, facilitating high-throughput approaches, thereby effectively reducing the cost of development and time to market. Moreover, early integration of automation facilitates process transitions at later stages of clinical development and commercialisation. There is however genuine concern regarding the capital costs of developing an automated solution; a clear strategic decision needs to be made as to what point in the development pathway automation is introduced, and to what extent. Factored into this decision, also, is the nature of any solution, for example a turn-key automated system or a bespoke platform. Ultimately the extent and nature of any approach will depend on our level of process and product understanding; as this improves, we are likely to see a significant shift toward the adoption of automated solutions.

Published: Nov 10 2016
DOI: 10.18609/cgti.2016.058
Citation: Cell Gene Therapy Insights 2016;2(4), 473-479.

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Factors influencing automation decisions in cell & advanced therapy manufacture

Spotlight Article

Innovator Insight

Brian Hanrahan

Brian Hanrahan, Invetech

AUTOMATION: MIGRATION FROM MANUAL PROCESSES TO CLOSED-SYSTEM AUTOMATION

Brian Hanrahan has more than 15 years of product development experience across the biomedical and cell therapy industries. In his current role, Brian is the Manager of Invetech’s Cell Therapy Group in San Diego, CA, USA, helping cell and advanced therapy companies across the globe realize clinical and commercial-scale cGMP manufacturing solutions. Brian has been a key contributor in building Invetech’s cell and advanced therapy capabilities and continues to have a deep involvement in projects ranging from the development of cell separation instruments to single-use, automated cell therapy production systems. Brian has a bachelor’s degree in Applied Science from RMIT University in Australia.

DOI:10.18609/cgti.2016.055
Citation: Cell Gene Therapy Insights 2016; 2(4), 481-487.
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Automation in the context of stem cell production – where are we heading with Industry 4.0?

Spotlight Article

Expert Insight

Michael Kulik*, Jelena Ochs*, Niels König & Robert Schmitt

Automation: migration from manual processes to closed-system automation

As the field of cell and gene therapy continues to progress, the need for cell products for therapeutic application is increasing. In order to meet the demands, novel challenges particularly within the manufacturing of these products need to be overcome. By translating and applying automation solutions from the production industries into cell culture applications, standardized processing procedures can be introduced in order to reduce the variability, which is a critical issue within the manufacturing workflow. Additionally, the Industry 4.0 philosophy offers a variety of concepts for the design of adaptive processes that address the specific challenges in stem cell production. Novel tools such as data tracking, data analysis and machine learning are enabling technologies that will help support the safe manufacturing of effective products for future cell and gene therapies.

Published: Nov 10 2016
DOI: 10.18609/cgti.2016.060
Citation: Cell Gene Therapy Insights 2016; 2(4), 499-506.

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