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The cell and gene therapy field is rapidly advancing as shown by the growing number of clinical trials and regulatory-approved therapies.¹ As the breadth of cell types, technology platforms, and target diseases continues to evolve, so too does the scrutiny of the materials and processes used in the manufacture of the intended cell or gene therapy product.
Beyond the need for specialized tools and tissue-specific protocols, developing safe and effective cell and gene therapies also involves navigating raw material qualification, which can be a challenging process.
This article will answer some key questions on considerations while working with your supplier to select and qualify raw materials for cell or gene therapy manufacturing, and how STEMCELL Technologies can support your cell and gene therapy research and development endeavors.
What Are Raw Materials?
Raw materials are substances used during the manufacture of cell therapy, gene therapy, or tissue-engineered products that are not intended to be part of the final product. Raw materials include cell isolation reagents, culture and cryopreservation media, and disposables, such as plasticware and bioprocessing bags. The term “raw materials” is not globally recognized by regulators and nomenclature varies among regions (for example, raw materials are referred to as “ancillary materials” in North America).
Even though raw materials are not intended to be present in the final product, they can still affect its safety, efficacy, and consistency. Therefore, raw materials need to be carefully scrutinized in terms of their chemical and biological characteristics, as well as their effects on the final cell therapy product. To learn more about this topic, watch this webinar by Lynn Csontos (Vice President, Regulatory Affairs at STEMCELL Technologies) discussing how raw materials can impact your translational research.
What Is Raw Material Qualification and Why Should I Care About It?
“Raw material qualification” refers to the process of establishing the safety, quality, and suitability of a given raw material in the context of your cell or gene therapy manufacturing process. The qualification requirements for a raw material depend on many factors, including the type of raw material, the type of cell or gene therapy or tissue-engineered product being manufactured, and the stage of manufacture in which the raw material is used. Therefore, it is impossible to provide a “one-size-fits-all” qualification program suitable for every situation. Instead, manufacturers must design their own qualification programs using a risk-based approach and an understanding of applicable guidelines and regulations (for example, United States Pharmacopeia chapter <1043> or European Pharmacopoeia chapter 5.2.12).
How Can Manufacturers and Raw Material Suppliers Work Together to Streamline Raw Material Qualification?
While raw material qualification is ultimately the responsibility of the cell therapy manufacturer, it can be made much more efficient through close partnerships with raw material suppliers. Suppliers can assist manufacturers in many ways, such as by providing robust quality documentation, permitting audits of their facilities, notifying manufacturers of changes to a raw material before such changes take effect, preparing and submitting a Master File or a Regulatory Support File (RSF), and providing increased levels of testing or customized reagent formulations. Table 2 in Solomon et al.² provides a clear overview of the respective accountabilities of cell therapy manufacturers and raw material suppliers.
How Can STEMCELL Technologies Support CGT Developers as a Raw Material Supplier?
STEMCELL Technologies provides specialized products, expert educational resources, and custom services for cell and gene therapy developers. Manufactured under a strict quality management system certified to ISO 9001 and ISO 13485, our high-performance, standardized media and reagents can be used to consistently maintain, activate, expand, or differentiate cells for use in cell and gene therapy development and manufacturing. For example, the recently launched GMP ImmunoCult™-XF is a high-performance medium designed for expansion of T cells for use in cell therapy development without the need for serum or serum derivatives.
This medium is also phenol red-free, xeno-free, and free from added cytokines—providing complete flexibility and reproducibility for your workflows. When combined with GMP ImmunoCult™ Human T Cell Activators (CD3/CD28) and (CD3/CD28/CD2), large yields of viable, functional T cells can be generated, without the use of magnetic beads, feeder cells, or antigens. The ImmunoCult™ T cell workflow streamlines T cell therapy development by enabling process standardization and scale-up from discovery through to clinical and commercial manufacturing.
How will your T cells perform with these reagents? Request an introductory offer to try ImmunoCult™-XF medium and ImmunoCult™ Human T Cell Activators in your lab!
Similarly, if you’re working with hematopoietic stem and progenitor cells, or differentiating and maintaining human pluripotent stem cells, you can also explore our GMP StemSpan™-AOF and TeSR™-AOF media, respectively.
Can I Use Products for Clinical Applications If the Label States “For Research Use Only”?
STEMCELL Technologies has a growing portfolio of GMP products; however, we understand that in some cases non-GMP products may be the best fit for your workflow. STEMCELL’s Services for Cell Therapy Program can work with you to identify custom solutions to enable the use of non-GMP products in clinical trials, as illustrated in the case study below:
Recently, a TCR-T cell therapy developer was preparing an Investigational New Drug (IND) application for a cell therapy product manufactured using one of STEMCELL’s non-GMP immune cell expansion media. By following a stringent ancillary material qualification process, the developer identified additional quality and regulatory requirements for the medium. Specifically, they determined that the product formulation would need to be shared with their FDA reviewer and that a human-origin raw material in the product formulation must be sourced according to 21 CFR 640. The developer was put in touch with a Services for Cell Therapy Program Manager, who worked across STEMCELL departments to deliver the required solutions:
- An abbreviated FDA Master File for the T cell expansion medium was put in place for the sponsor to reference.
- Custom product manufacturing runs were arranged using specific raw materials sourced in accordance with 21 CFR 640.
Through the sponsor’s proactive risk assessment and support from the Services for Cell Therapy Program, their IND was cleared by the FDA with no further information required, with several subsequent INDs also gaining clearance.
Customer Testimonial
“During a recent IND submission, we were challenged with a fast-approaching deadline. Our solution-oriented program manager helped us navigate the complex regulatory requirements to support us through our clinical journey by providing quality documentation and customized reagents for use in our clinical trial. By leveraging STEMCELL’s global experience and knowledge, we were able to meet our regulatory commitments and achieve a successful IND filing.”
Senior Manager,
External Manufacturing at a biotechnology company developing TCR-T cell therapies
Got questions? Contact us to begin discussing your specific regulatory or product requirements or explore additional resources that can support you on your CGT research and development journey below:
- Request an introductory offer to try STEMCELL’s cell and gene therapy product offerings in your lab
- Watch this ISCT webinar sponsored by STEMCELL for a step-by-step guide to qualify ancillary materials for clinical use
- Explore this resource page to learn more about qualifying raw materials for cell therapy manufacturing, how we work with you to meet your compliance requirements, and how to access relevant documentation
References
- The Sector Snapshot: December 2023, Alliance for Regenerative Medicine. https://alliancerm.org/sector-snapshot-december-2023/ (accessed Feb 27, 2024).
- Solomon J et al. (2016) Current perspectives on the use of Ancillary Materials for the manufacture of cellular therapies. Cytotherapy 18(1): 1–12.
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