Navigating the Manufacturing Process and Ensuring the Quality of Regenerative Medicine Therapies Proceedings of a Workshop (2017) / Chapter Skim
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4 Designing Technologies to Meet the Manufacturing Needs of New Regenerative Medicine Therapies
4 Designing Technologies to Meet the Manufacturing Needs of New Regenerative Medicine Therapies
Pages 41-54
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From page 41... ...
• Defining a user requirement specification (URS) is an impor tant part of the process of developing a novel manufacturing device for automation that requires significant vendor input.
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From page 42... ...
Three panelists -- Isabelle Rivière, the director of the cell therapy and cell engineering facility at Memorial Sloan Kettering Cancer Center; Rodney Rietze, the lead of current GMP (cGMP) process automation for cell and gene therapies at Novartis; and Philip Vanek, the general manager of cell therapy technologies at GE Healthcare -- discussed opportunities for new technologies and manufacturing models that could increase efficiency and product quality, and they also considered novel and more precise technologies for in-process and final release testing.
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From page 43... ...
NOTE: CAR = chimeric antigen receptor; CofA = Certificate of Analysis; CRF = controlled rate freezer; CTL = cytotoxic T lymphocyte; MPC = magnetic particle concentrator; NSG = NOD scid gamma; QC = quality control; SCID = severe combined immunodeficiency; TCR = T cell receptor. SOURCES: Isabelle Rivière, National Academies of Sciences, Engineering, and Medicine workshop presentation, June 26, 2017.
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From page 44... ...
One approach the Sloan Kettering team uses to decrease the variability of the incoming apheresis product is to start by selecting cell types that will create a more homogeneous starting material; however, Rivière said, a current limitation is that the product developers have yet to define the active cells within the CD3, CD4, and CD8 populations. While selecting subsets of cells and removing undesirable cell types is important for streamlining the manufacturing process, she said, the limited number and high cost of GMP antibodies used to select the starting material limits the applicability of this approach.
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From page 45... ...
Focusing on analytics in the manufacturing process provides manufacturers with a deep understanding of the process and the opportunity for continual improvement of that process, Rietze said, describing how his group at Novartis went about automating and commercializing the CAR T cell production process that Bruce Levine and his collaborators developed at the University of Pennsylvania. Designing a scalable and robust manufacturing process starts with the science and with understanding the product, how it is produced, and what mechanisms are available to control variability.
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From page 46... ...
When his group was working on the CAR T cell process, Rietze said, they targeted specific unit operations for optimization to generate value and lower risk, and they started rethinking some of the analytics with an eye toward what assays would work best in an automated system. With the device selected, the next step is to think about the manufacturing facility.
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From page 47... ...
The team sent the URS to a number of vendors, selected one, and then moved through the device-manufacturing process, which involved building alpha and beta prototypes and testing them in-house. The final step before the integration of the devices into the manufacturing process was to conduct product characterization studies to determine if the devices changed the product.
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From page 48... ...
People involved in the field should understand that the patients affect the cells they provide, which in turn affects the manufacturing process and the drugs that the patients ultimately receive. SCALING PERSONALIZED CELL THERAPY MANUFACTURING Tool providers, or companies who develop enabling technologies such as bioprocessing equipment for manufacturing cellular therapies, have a different perspective than therapy manufacturers, Vanek said, because they have to be agnostic as to cell type or therapy and instead build platforms with broad applicability.
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From page 49... ...
Market research is key when defining the company's investment priorities, Vanek said, explaining that "it takes years and a huge investment to bring new platforms to the market." While U.S. programs will account for most of the new products, Asian and Pacific counties are expected to grow their cell therapy programs significantly, he said.
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From page 50... ...
SOURCE: Philip Vanek, National Academies of Sciences, Engineering, and Medicine workshop presentation, June 26, 2017.
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From page 51... ...
Toward that end, he said, the company has built and made a significant investment in technologies to power digital connectivity. DISCUSSION During the session panel discussion, speakers and workshop participants highlighted some of the challenges and opportunities for using new technologies and automating processes to enable a robust manufacturing platform for cellular therapies.
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From page 52... ...
Engineers have the ability to unitize a process, gather the available data, and create integrative solutions, a workshop participant noted, and an important part of the tool development process is identifying those areas in the development pathway where current tools are not sufficient and need updating. One of those areas, Vanek said, is the characterization and qualification of starting cells.
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From page 53... ...
Unless the analytics are automated too, there will need to be a huge amount of training and standard operating procedures that will need to be transferred from one center to another. For diseases with a large number of patients, she said, hospitals should focus their efforts on the clinical trials and leave manufacturing to biotechnology or pharmaceutical companies.
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