Meeting the Challenges of Clinical and Commercial Manufacturing
Cell therapies have the promise and potential to not only treat, but potentially cure disease. Rapid growth in the Cell Therapy industry is driving demand in cellular manufacturing, and with that comes the increased need for quality, scalable components, and products to support the clinical and commercial therapeutic pipeline (1). While a wide variety of ancillary products, including single-use disposables, exist to support the Cell Therapy industry. Many have been designed for other industries and purposes resulting in Cell Therapy manufacturers having to adapt to pre-existing processes (2). Given the critical limitations that come with many autologous cell-based therapies, it is important to provide and implement products that will help to enhance quality, safety, and commercial viability.
Maintaining a Controlled Process
Delivery of cell-based products to the market presents unique risks in regards to the safety and efficacy of the final therapeutic, as well as the inherent challenges experienced throughout the manufacturing process. For cell therapies, a controlled, robust, and reproducible manufacturing.
Many current personalized cell therapies advancing through clinical trials are highly manual in practice and require numerous ancillary components and handling steps. Component modifications within the process can impact both the manufacturing process and also the final product (3, 4).
Ancillary Material Quality for Cell Therapy Applications
The selection and use of ancillary materials is a vital quality component to consider when developing a manufacturing process for cell therapies (3). Depending on the ancillary material and the intended use within the manufacturing process, quality aspects including biocompatibility, extractables and leachables, particulates, or cell recovery/viability may be impacted (3-5). Early implementation of high quality materials with the appropriate components, testing, and supporting validation will help to mitigate potential risks (6). If available, FDA cleared medical devices are generally recommended due to the guarantee of appropriate supporting documentation and qualified, safe materials, thus providing a higher level of assurance (7).
Given that many cell therapies are manufactured in cleanroom facilities, the packaging of ancillary products being introduced into these environments is very important. Packaging supports a number of aspects including physical protection, barrier protection, and handling or use. The packaging materials and configurations of the incoming products are significant considerations. Ideal packaging of the ancillary items entering the cleanroom will enable smooth transfer eliminating the need to perform excess handling and cleaning steps and reduce potential contaminants like particulates entering the production suite and final product.
When processes begin to scale out, as part of late stage multicenter clinical trials across different regions for example, Cell Therapy manufacturers are often challenged with varying regulatory compliance requirements (2, 6). Maintaining consistency of the manufacturing process and materials used is critical. This is important as regulatory requirements for cGMP compliance are not always interchangeable (e.g. components, testing, supporting documentation, availability) and can result in unnecessary delays.
Transfer Sets and Accessory Sets
As medical devices, transfer sets are most commonly associated with traditional blood transfusion applications. The starting material, techniques, and processes from many of the currently researched cell therapies originate from similar clinical settings. Therefore, a wide number of ancillary tools specifically developed to support the blood transfusion industry have been adopted into Cell Therapy manufacturing protocols. Transfer sets, often referred to as accessory tubing sets, are used regularly within this field and have the potential to be used in nearly every step of the manufacturing process, as demonstrated in Figure 1.
These ancillary components are mainly used to transfer fluids or reagents from container to container, and are an especially critical component enabling Cell Therapy production. Given the usage frequency and the consideration that autologous Cell Therapy products are often limited to a single product per intended patient, transfer sets should be selected that provide the right components, performance and quality assurance.
The current range of commercially available transfer sets or accessory sets were not designed for Cell Therapy manufacturing and therefore lack key industry requirements. Incorporation of transfer sets designed to support cell therapies will aid in the implementation of controllable, consistent, and safe cGMP amenable manufacturing procedures.
Charter Medical Cell Therapy Fluid Transfer Sets
Charter Medical has introduced a new family of regulated fluid transfer set devices designed to support Cell Therapy applications. While alternative transfer set products are commonly used, industry deficiencies exist including component quality, testing, packaging, configurations and availability. The new Cell Therapy fluid transfer sets offered by Charter Medical are intended for sterile transfer of cell based products, including whole blood and cell suspensions for transfer from one container to another.
Table 1 outlines some of the specific Cell Therapy manufacturing requirements the new Cell Therapy transfer sets have addressed. In addition to using components not manufactured with DEHP (Bis(2-ethylhexyl) Phthalate), final product designs have been tested and validated to support industry requirements for cell-based compatibility and control of particulate levels. As previously noted, traditional transfer set products were designed for blood transfusion applications where cleanroom manufacturing is not performed. The new CT fluid transfer sets are provided with pouching and packaging specifically suited for cleanroom manufacturing. As medical devices with supportive testing and validation, the quality and availability of these products reduce or eliminate potential challenges faced in the technology transfer procedure. The availability of these units bridge international needs for Cell Therapy manufacturing throughout multiple manufacturing sites and regions.
Charter Medical’s Cell Therapy Fluid Transfer Sets are the only transfer sets designed to support the global quality and manufacturing requirements within the Cell Therapy industry.
About Charter Medical
Charter Medical helps produce safe and effective medicines by designing and manufacturing single-use solutions for Cell Therapy, bioprocessing, blood transfusion and blood filtration markets. Charter Medical is a wholly owned subsidiary of Fenner PLC (LSE:FENR) and operates out of an ISO 13485 certified and FDA registered manufacturing facility in Winston-Salem, NC. To learn more, visit http://www.chartermedical.com.
- 1. Heathman, T et al. The Translation of Cell-Based Therapies: Clinical Landscape and Manufacturing Challenges. Regen. Med. 2015; 10(1): 49-64.
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- 7. Food and Drug Administration Center for Biologics Evaluation and Research (2008). Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs).