Why Are Cell and Gene Therapy Manufacturers Focused on Buffer Quality?
By Anuj Kale, Technical Sales Lead, and Kate Buggle, Strategic BD Director at Aceto
Cell and gene therapy (CGT) products offer innovative approaches to healthcare and may ultimately change the way diseases are treated and potentially cured. From transplantations to the treatment of chronic conditions, cellular and gene therapies could transform healthcare outcomes, offering new hope to patients and increasing consumer confidence in pharmaceuticals.
With a compound annual growth rate (CAGR) of 39.62%, the global cell and gene therapy market is expected to reach more than$36 billion dollars by 2027. As of 2020, at least 12% of all the candidates in the clinical pipeline and 16% of those in the pre-clinical pipeline are cell and gene therapy products. But due to the frequent nondisclosure of preclinical projects, the actual number of CGT products could be significantly higher.
The commercialization of CGT products, however, is still new. As the field advances, manufacturers will seek increased efficacy, productivity, and safety for their products, while simplifying and optimizing manufacturing processes
Cell Therapy Manufacturing Challenges
Manufacturers of cell therapy products face several challenges due to the instability of living cells. These difficulties tend to apply to source materials as well as to cell therapy end products. They include:
- Limitations in shelf life. Manufacturing processes must occur before the cells expire.
- Maintenance of sterile conditions. Living cells cannot be sterilized. Consequently, manufacturers must maintain an aseptic production environment.
Gene Therapy Manufacturing Challenges
Gene therapy incurs similar challenges during production. With gene therapy, manufacturers manipulate or alter the expression of a human gene for therapeutic indications. Due to the nature of the treatments, manufacturers may face the following difficulties:
- Line clearance issues. As viral vectors, many gene therapy formulations require segregation and line clearance during manufacture. The stickier the product, the more difficult the cleaning.
- Sterility concerns. Some gene therapy products cannot be sterile-filtered. Thus, an aseptic manufacturing environment is frequently necessary.
The Importance of GMP-Grade Buffers
Respecting good manufacturing practices (GMPs) is essential in the production of cell and gene therapy products.
Currently, cell and gene therapy manufacturers are paying close attention to buffer quality. Buffers are necessary at practically every step of the manufacturing process—both upstream and downstream. Manufacturing often includes upstream processes to produce therapeutic biologics, and downstream processes to purify and obtain cell and gene therapy formulations.
Buffer role in Cell & Gene TherapyUpstream Processes
To generate the desired therapeutic characteristics during upstream processing, maintaining the pH of the culture media is critical. The required pH window is often tight, and GMP-grade buffers are indispensable for pH maintenance. Buffers such as TRIS, MES, and Guanidine Hydrochloride not only ensure the safety and efficacy of upstream processes but also compliance with global regulatory requirements.
Buffer role in Cell & Gene Therapy Downstream Processes
Therapeutic biologics require specific conditions to remain stable. As a result, during downstream processing buffers are again utilized to maintain pre-defined purification conditions. GMP-grade buffers such as phosphate, citrate, and acetate buffers maintain the stability of the therapeutic biologics and protect them from co-precipitants.
Meeting Buffering Needs with Custom GMP Buffer Blends
Recently acquired by Aceto, A&C Bio Buffer understands the unique GMP-grade buffer requirements of cell and gene therapy manufacturers for various biopharmaceutical processes. We offer pH-specific, custom GMP buffer blends to suit all the phases of CGT development, clinical trials, and commercial manufacturing.
We use multi-compendial raw materials—meeting USP, EP, BP, and JP monographs— in all our standard and custom blends. We can GMP repack and down-pack liquids and powders in a variety of formats, ranging from 1L to 1,000L bio bags and containers. We also accommodate the additional requirements of low endotoxin and low bioburden for critical biopharmaceutical manufacturing processes, as our processes are designed to curtail contamination from microbiological sources and minimize endotoxins.
As the global trajectory of cell and gene therapies continues to evolve, Aceto is committed to helping cell and gene therapy manufacturers meet growing demands and maintain resiliency.