New Center Marks Aggressive Push into CGMP Manufacturing of Cell and Gene Therapies

The past year has seen an aggressive push to close the gap between demand for and capacity to produce cell and gene therapies. Kite and Novartis have both built new facilities in the United States and Europe. Contract development and manufacturing organizations (CDMOs), such as Fujifilm Diosynth Biotechnologies, Lonza, and WuXi Biologics, have been expanding manufacturing capacity to meet explosive growth in demand for clinical supplies of new therapies. At this point, however, a gap still exists between demand and current good manufacturing practices (CGMP)-scale production capacity. Scientists may wait up to 18 months, experts say, for the products they need for clinical research (i.e., customized cells and viral vectors that meet cGMP requirements). 

Partners in a new collaborative center plan to address this gap head on. On Nov. 25, 2019, Harvard University, the Massachusetts Institute of Technology, CDMOs and technology vendors such as Fujifilm Diosynth, GE Healthcare Life Sciences, and MilliporeSigma, and local teaching hospitals disclosed plans to establish a new center in the Boston area for developing and manufacturing cell and gene therapies. The $50-million Center for Advanced Biological Innovation and Manufacturing aims to accelerate innovation in immunotherapy, cell therapies, gene editing, and other technologies, with the goal of broadening access to new therapies. The Center will foster collaborative innovation in both manufacturing processes and drug development and is expected to be incorporated in 2020 as an independent non-profit corporation.

“This new center aims to accelerate developments in immunotherapy, cell and gene therapies, and other technologies that will have an impact on  human health. Its overall mission is to catalyze the development of transformative and advanced therapeutics by shortening the time between clinical research and application. With more than 1000 clinical trials underway for cell and gene therapies, we need to develop better solutions and no one organization can do it alone,” Emmanuel Ligner, president and CEO of GE Healthcare Life Sciences commented to Pharmaceutical Technology on November 26. “The full potential of the regenerative medicine industry can only be realized if we collaborate to improve access, quality, and accelerate innovation,” he said. 

Modular, adaptable design aims to increase agility

The new facility will offer partners access to a new CGMP manufacturing facility at favorable pricing, reducing the wait and cost for researchers at universities, hospitals, and start-ups. Plans call for the facility building to feature a modular design, to make it easier for partners to adapt quickly to changes in technology, as improved methods continue to be developed for gene manipulation, gene editing, oligonucleotides, peptides, and other new methods and discoveries.  

Currently, the Center’s design is envisioned to include a shared collaborative space as well as eight cleanrooms for production of cell and viral vector products and raw materials for Phase I or Phase II clinical trials. It will also provide a platform for training and workforce development in a field that faces a critical need for people with diverse, specialized skills. GE Healthcare Life Sciences will be sharing technologies and expertise in biomanufacturing with members, said Ligner, who emphasized the importance of collaborating, and sharing and managing collective knowledge and best practices. “Given how rapidly the industry is growing, consortiums such as this one are vital to advancing the industry because they provide [stakeholders] opportunities to learn from one another and build off one another’s advances,” he said.               

Ligner also pointed out the need for continuous improvement in workforce training, an area that GE has been emphasizing recently in initiatives including a collaboration with Ireland’s National Institute of Bioprocessing Research and Training. “It’s an exciting time in the cell and gene therapy industry, with more than 1000 regenerative medicine clinical trials taking place globally,” he said. “In addition to bringing together leading life-sciences organizations to advance clinical research, one of the most exciting and valuable aspects of this partnership will be the workforce training and development. While we work to get novel therapeutics to patients faster, we must also train and develop the right talent to continue building and advancing the industry,” he said.

CDMOs scale up

CDMOs have been expanding CGMP capacity for cell and gene therapies. Fujifilm recently invested nearly $119 million (13 billion yen) in gene therapy alone, including an expansion of its Center of Excellence in College Station, Texas. The company will be adding new laboratories for upstream, downstream, and analytical development, which are expected to start up in the fall of 2021. The company is also expanding CGMP manufacturing capacity with the addition of new cleanrooms and eight new 500/2000L single use bioreactors. Fujifilm began to offer clinical and commercial gene therapy fill/finish services early in 2019, and expects to complete the first stage of its CGMP expansion in College Station by the Spring of 2021. 

In 2018, Lonza expanded capacity with a Center of Excellence in Houston including a fill/finish suite and capacity for developing viral vectors for cell and gene therapies, while WuXi AppTec expanded Phase I GMP manufacturing capacity for cell and gene therapy at its San Diego facility.

Building a new logistics and IT infrastructure

As efforts to speed manufacturing and clinical development expand, the industry is also working to develop a new infrastructure to support these efforts. Given the diverse stakeholders involved in cell and gene therapies and personalized medicine, the approaches to information technology, data management, and logistics that have worked for so long in the small-molecule and traditional biopharmaceuticals areas will no longer work for autologous and allogeneic cell and gene therapies.  

In 2019, alliances have started up to streamline data management and access, to improve the transmission of data from patient collection points to manufacturing, and to patients at the point of use.  IT companies, including the manufacturing execution systems (MES) provider Werum, are working on new data platforms, while TrakCel and Vineti are collaborating with CDMOs, logistics companies, and clinical partners in “vein-to-vein” programs designed to develop standardized approaches to data management and to improve risk management and supply chain transparency.

Cryoport, which launched a vein-to-vein program with Vineti and Lonza on November 5, introduced a dedicated fleet of specialty shippers for cell and gene therapies on Dec. 2, 2019, including a validated cleaning program designed to eliminate cross-contamination by reducing contaminants by 99.9999%. According to the company’s Chief Commercial Officer, Mark Sawicki, one of the most challenging aspects of working within this new space has been dealing with the complexity and variability of its supply chain. This is particularly true for autologous therapies, where the origin of the supply is not some distributor but patients themselves. “As a result, [developers are often] extending instrumentation and processes that have been used for single patient production to large-scale manufacturing in a commercial manufacturing environment. The interconnectivity and optimization of workflow isn’t there yet,” Sawicki said, in a recent interview with Pharmaceutical Technology and BioPharm International. 

Working to address the need for interconnectivity on the data management level is Vineti, an IT company dedicated to the cell and gene therapy market, which grew out of GE’s Venture Capital business. The idea for the company came after noticing the challenges that a regenerative medicine pioneer faced back in 2012, as it pushed manual methods to their limits to handle a much more complex workflow and deliver a new innovative therapy during the clinical trial phase. “There was a real need to extend GMP into clinical work and to scale out supply chain solutions,” cofounder and CEO Amy Du Ross told Pharmaceutical Technology.   

Vineti started up formally in 2015 to focus on the need to integrate the development, manufacturing, and logistics systems that innovative therapies required, and to ensure the chain of custody of the product. “It’s not about workarounds, but building for purpose,” Du Ross said.  The company is currently working with leading CDMOs and innovator companies in the cell and gene therapy space and with Cryoport and other logistics providers. 

References 

https://www.harvard.edu/media-relations/new-center-for-innovating-and-manufacturing-next-generation-medicines-planned-for

http://www.pharmtech.com/ge-healthcare-partner-nibrt-biopharma-education-program

https://www.fujifilm.com/news/n191114.html

https://www.lonza.com/about-lonza/media-center/news/Tensid/2019-11-05-14-47-English.aspx

https://www.lonza.com/about-lonza/media-center/news/Tensid/2018-02-14-06-00-English.aspx

https://www.cphi-online.com/wuxi-apptec-expands-site-in-california-for-news075747.html