Manufacturing cell and gene therapies present numerous challenges, in part due to the personalized nature of these therapies, manual processes, and needless to say, costs. George White, General Manager – Product Management, Cell & Gene Therapy at Cytiva discusses key manufacturing challenges, advances being made for commercial manufacture, and how bioprocessing production technology can be leveraged to streamline processes. –KB @font-face {font-family:”Cambria Math”; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:roman; mso-font-pitch:variable; mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face {font-family:Calibri; panose-1:2 15 5 2 2 2 4 3 2 4; mso-font-charset:0; mso-generic-font-family:swiss; mso-font-pitch:variable; mso-font-signature:-536859905 -1073697537 9 0 511 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-unhide:no; mso-style-qformat:yes; mso-style-parent:””; margin-top:0in; margin-right:0in; margin-bottom:8.0pt; margin-left:0in; line-height:107%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:”Calibri”,sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:Calibri; mso-fareast-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:”Times New Roman”; mso-bidi-theme-font:minor-bidi;}.MsoChpDefault {mso-style-type:export-only; mso-default-props:yes; font-size:11.0pt; mso-ansi-font-size:11.0pt; mso-bidi-font-size:11.0pt; font-family:”Calibri”,sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:Calibri; mso-fareast-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:”Times New Roman”; mso-bidi-theme-font:minor-bidi;}.MsoPapDefault {mso-style-type:export-only; margin-bottom:8.0pt; line-height:107%;}div.WordSection1 {page:WordSection1;}
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Contract Pharma: What are some of the key manufacturing challenges for cell and gene therapies?

George White: The fundamental challenge to manufacturing cell and gene therapies is cost. The process is currently very reliant on manual labor which includes a lot of process monitoring. With cell therapies specifically, each drug product is unique and requires a great deal of effort to ensure quality and an effective end result.
 
Automating some parts of the process will be vital. Digitizing records, connecting different instruments, and using big data tools and analytics will help drive down the cost of production, while increasing access to these lifesaving therapies.
 
CP: What can cell and gene therapy learn from bio processing?

GW: An advantage of bioprocessing is that every step of their process is standardized across platforms and systems. The bioprocessing production technology and systems were created specifically for bioprocessing. Moving to purpose-built manufacturing equipment for the cell and gene therapy industry is required to streamline the process and lower barriers to entry for these treatments.
 
Additionally, bioprocessing utilizes automated systems and tools which can oversee and regulate an entire production process. An automated system handling the production allows the highly trained scientists to oversee the process rather than monitor every step.
 
CP: We’re seeing a lot of industry investment in cell and gene therapy manufacturing centers. What advances are being made for the commercial manufacture of these therapies?

GW: In addition to investment in automation and digital tools such as our Chronicle Software, we are working to optimize the logistics and delivery of cell therapies. One of the challenges in cell therapy manufacturing is the need to maintain cryogenic temperatures during transportation between clinical collection and treatment sites. Traditional cryogenic shipping methods use liquid nitrogen dry shippers which requires labor intensive preparations, careful handling and a rigid logistics schedule to ensure the shipper maintains cryogenic temperature during transit.
 
To address the challenges around shipping and logistics, cryobiologists at Cytiva created the VIA Capsule System, the first liquid nitrogen-free cryogenic shipping system. It plugs into standard electric socket to maintain ultra-cold temperatures, making shipments more cost-effective and sustainable. Additionally, this technology removes some of the complexities that the use of liquid nitrogen necessitates, ultimately improving the overall safety and sustainability of cell and gene therapy logistics.
 
CP: How can the process be made more cost effective?
 
GW: Reducing the number of “high-touch” areas within the manufacturing process that require highly skilled technicians and automating them will be the main driver of efficiency. By taking some of the human element out of the manufacturing process, we can lower the cost of the therapy and use their skills to increase viability and market access. Production will always need skilled scientists to oversee and direct operations but minimizing the aspects that are prone to human errors will be key.
 
Currently, cell and gene therapy manufacturing is semi-automated. This involves self-contained systems that are directed by a human operator, but who is not directly manipulating any materials. We will need a continued push toward fully self-contained units of manufacturing to make the process as cost effective as possible.
 
CP: What are the concerns?

GW: Outside of the high cost of manufacturing cell and gene therapies, there are industry-wide concerns about maintaining the quality of end products. Given that cell and gene therapies are currently used in extenuating circumstances or potentially as a final life-saving measure, the consequence of the therapy’s use is extremely high. Manufacturers need to ensure that the therapies that are returned to patients are without contamination or issue. This is another area that automation could be used to ensure proper records and standards are maintained throughout the process.

Another consideration in maintaining quality product is in simplifying the logistics involved in sample collection and therapy distribution. Here, the VIA Capsule system helps by providing continuous cryogenic storage temperatures, giving providers the flexibility to collect or deliver treatment when best suits the patient and not be burdened by timing the refills of liquid nitrogen. By removing the need to refill the container, we can maintain a single chain of identity from the manufacturer to the patient’s bedside, further minimizing sources of contamination and human error.