Last week in Part 1 of our series, we presented observations from industry leaders into how they plan for success by installing comprehensive quality management systems and laying down detailed groundwork for an optimized transition to GMP-compliant starting materials and technologies. This week in Part 2 of our series, cell therapy manufacturers present their own perceptions of what constitutes an ideal cell therapy starting material supplier, as well as what can be done on their end to ensure their cell therapy retains consistent quality and potency.
“Consistency and quality of cellular starting material are key components of successful cell therapy development. The cell therapy industry needs to take steps to ensure that product potency is optimized and maintained from the point of donor cell collection all the way to patient administration.”- Dr. Dominic Clarke, Global Head of Cell Therapy at HemaCare
Choosing the Right Starting Material Supplier
In a recent CGTI webinar,  Dr. Sean Kevlahan emphasized the impact of raw materials on the final cell therapy product. Ensuring a sufficient supply of high-quality starting material, especially during scale-up, is always a key concern for cell therapy commercialization.
Marketa Horalkova is the supply chain manager for Sotio, an international biotechnology company which specializes in developing new therapies for cancer and autoimmune disease. As someone directly involved with the purchase of raw materials and services, Dr. Horalkova explains that it’s important to verify the production capacity of the supplier, and determine the shelf-life of the materials they provide. It’s also wise to understand how much lot-to-lot variability to expect, in case you need to over-estimate supply needs to guarantee consistent quality.
“Forecasting (your supply needs) really is crucial, especially for material that can directly influence the quality of your product. You need to be aware of the production capacity of your supplier, in terms of lot size, sourcing time, lot-to-lot variability, and shelf life.”-Dr. Marketa Horalkova, Supply Chain Manager at Sotio
Lisa Fox, co-founder of Broken Lance Biotech Consulting, agrees that the selection of apheresis supplier and qualification of materials is critical. Her company has guided the implementation of GMP manufacturing infrastructure for many cell and gene therapy companies. From her point of view, one of the most effective measures companies can take is to assemble a quality oversight team from the start to act as a liaison between suppliers and cell therapy manufacturers. Companies should make sure that they begin with the appropriate cell quality screening assays in place, and know how much starting material will be needed for those assays.
Manufacturing Site Readiness
Dr. Angel Mendez, Head of Pharmaceutical Development at Takeda, brings up the point that a cell therapy manufacturer should perform audits, and understand what a supplier’s quality control process really is, and exactly what they’re doing to assure the safety and quality of their material. Further, a manufacturer should consider whether “unique” or customized raw material is really necessary. While there can be benefits to utilizing unique material, it also increases risk in terms of availability and assay compatibility.
There is also the question of whether other starting materials are being collected or prepared in the same facility. Dr. Patrick Ginty, who leads Regulatory Affairs at the Cell and Gene Therapy Catapult in the U.K., says that cell therapy companies need to be more aware of cross-contamination risks. He also thinks researchers need to plan for factors related to material supply at their own processing site early in the development process. Understand what your own warehousing capacity is, both for starting materials and finished products, and understand what percentage of your supply order will be used for quality assessment.
“To produce consistent and effective therapies, the industry needs to surmount the difficulties of dealing with an inherently variable living product. Quality management systems should cover not just the product, but factors such as training programs, equipment, methods development, and cold-chain processes.”  Dr. Dominic Clarke, Global Head of Cell Therapy at HemaCare
HemaCare currently provides leukapheresis process development material for 100% of the current FDA-approved immunocellular therapies. Collaborating with pharmaceutical companies on the cutting edge of cell and gene therapy has brought a true understanding of the challenges involved in positioning a cell-based therapeutic for success. Quality oversight must be maintained from start to finish, ideally even before the transition to GMP compliance. Careful planning and attention to detail on the part of both the supplier and the manufacturer will help guarantee the consistent quality on which patients depend.
- Kevlahan S. Planning for Success: Emerging GMP-Grade Raw Materials & Technologies for Cell Therapy. Cell and Gene Therapy Insights: live webinar. Mar 2019. https://insights.bio/cell-and-gene-therapy-insights/emerging-gmp-grade-raw-materials-and-technologies-for-cell-therapy/
- Clarke D., and Taylor, B. Bridging the Gap: Laying the Foundation for Successful Advanced Therapies. European Biopharmaceutical Review. 24-28. April 2019.