February 7, 2023
When cell therapies emerged more than a decade ago, solutions providers considered them more of a small, niche market, and therefore tended to invest resources in other areas. Manufacturers often repurposed tools from other industries for their cell therapy processes. Single-use solutions are examples of the tools that have evolved to meet the unique challenges of these therapies.
Today, demand for specialized single-use production tools, components, expertise, and capabilities continues to grow as innovative cell therapies evolve. Often, organizations begin the cell therapy journey with benchtop-level experiments in the lab. Eventually, drug developers need more suitable containers for the development of a process designed for clinical production. As they scale up or out, many organizations turn to single-use solutions.
However, concerns and misconceptions abound regarding the use of single-use solutions. A poll conducted during a recent Cell & Gene: Live event, Scaling Cell Therapies: Auto vs. Allo, asked participants to rate their most significant concerns associated with single-use solutions (Fig. 1). This article discusses the source of those concerns and ways to overcome them.
#1 Concern — Cell Damage During Processing
During the cell therapy manufacturing process, cell damage can occur if equipment or components are not purpose-built to accommodate the complexities of advanced therapies. One way single-use solutions can decrease cell damage is by using overmolds, a type of connection used in single-use manifolds, because they create seamless transitions between tube sections. This type of manifold decreases cell shear stresses that can be damaging to some cell types and can make scale-up easier.
Harmful leachable substances can also impact cell health. Within process development, production materials and equipment must be vetted for biocompatibility and extractables to mitigate potential risks that can negatively impact therapy safety, efficacy, and potency. Charter Medical, LLC helps manufacturers design systems that minimize processing stresses during therapy production by carefully selecting components and raw materials when designing both standard and custom products for cell therapy applications.
Concern #2 — Particulates
Particulates remain a top concern for cell therapy manufacturers, especially as the industry engages in more clinical trials and commercializes new therapies.
Manufacturers, in turn, expect single-use suppliers to address particulates as early as possible in the supply chain to avoid potential patient harm downstream. Charter Medical embraces this responsibility in three ways:
- Optimizing Operations — The implementation of supportive equipment, environmental controls, process improvements, and training relevant to mitigating particulates during the manufacture of single-use products has been and continues to be an organizational priority.
- Enhancing Monitoring — Charter Medical continues to refine its analytical capabilities to identify and trend particulate challenges, leading to more effective remediation.
- Securing the Supply Chain — Charter Medical has enforced higher standards for incoming raw materials by assessing its supplier base, including supplier audits, or increasing audit frequency as applicable, collaborating to improve the suppliers’ operations, monitoring lot acceptance/rejections, and insourcing select processes to maintain higher quality standards.
Concern #3 — Closed-System Processing & Sterility
Product contamination leads to lost time and scrapped materials. Regaining that product loss requires reformulation — a process that could cost tens if not hundreds of thousands of dollars. The human cost of contamination is even higher because the patient must now wait even longer to receive that potentially lifesaving treatment.
Unfortunately, many cell therapy processes take an “open system” approach to transferring fluids, which places cellular materials at an elevated risk for contamination in an open environment. Pipetting is one of the most common open-system transfer methods. Closed-system processing, enabled by single-use solutions like tubing and bags, aims to ensure and preserve sterility by drastically reducing handling touchpoints. Closed-system designs also maximize space and resources as a cell therapy is scaled up or out. Charter Medical has been developing products tailored to closed systems for more than 20 years.
In addition to the benefits of closed system processing, single-use solutions are pre-sterilized to mitigate contamination even before usage. Charter Medical has validated and uses internal procedures to ensure and verify every single-use product, component, and system has successfully passed through the applicable sterilization process.
Concern #4 — Tubing and Connection Tolerances & Leaking
Only tight, accurate tubing and component connection tolerances can mitigate the potential for leakage during fluid processing. An ill-fitting connection generates a high probability of leakage; added pressure from the pump and operator handling only increases this probability.
To create a single-use assembly design that balances manufacturability and specific process needs, suppliers and customers must collaborate to zero in on the right dimensional tolerances. Together — and as early as possible — they should discuss critical processing needs, such as production equipment, component choice, and materials to ensure manufacturing success.
Further, qualifying these component connections will contribute to continued product quality.
Leakage of single-use bags is a top concern for therapy producers. Ensuring that bags are not filled over their qualified volumes can reduce leakage, especially during freeze/thaw. Charter Medical prioritizes developing and manufacturing quality products with built-in quality controls to ensure consistency from product to product and lot to lot. To ensure our solutions can be used within specific cell therapy manufacturing processes, each container may individually go through in-process testing (e.g., leak testing).
Concern #5 — Other
Participants in the Cell & Gene: Live event had other concerns, including hold-up volume: product that remains in a single-use biocontainer after filling is complete. This is an issue for two reasons. First, bio fluids are expensive to produce, so any volume loss can be costly. Second, any fluid loss could be the difference between treating or not treating a patient, as therapy manufacturers may have a finite amount of starting material due to the nature of the treatment regimen. Charter Medical alleviates those concerns by designing products that minimize hold-up volume and maximize final product volume.
Concern #6 — Ease of Use
Although this was identified by some as a concern, ease of use could be celebrated as one of single-use’s greatest strengths. After all, the biggest benefit of single-use solutions is that they’re designed to reduce process complexities. Single-use solutions have become intuitive tools for therapy manufacturing. In contrast, stainless steel and other reusable technologies have much lengthier, more intensive processes involved to achieve sterilization between batches. They require specific plumbing in many cases, significant manual labor, and large amounts of water, cleaning agents, disinfectants, and/or sterilization agents. Stainless steel technologies also often require testing after use to ensure effective sanitization. The labor and resources required for a changeover procedure from one batch to the next are extensive. Single-use solutions eliminate those arduous steps, requiring fewer operators, equipment, and expertise — all of which reduce process complexities.
Final Thoughts
Implementing single-use solutions into a cell therapy process can be intimidating. With the support of a collaborative, experienced single-use partner, cell therapy manufacturers can confidently design in standard or custom solutions when building a process to reliably scale lifesaving therapies.
Charter Medical includes customers at every step of the process build to help them overcome common concerns with single-use technologies. This collaboration and understanding leads to application-appropriate process designs and single-use solutions that ultimately play a role in shaping the next generation of advanced cell therapies.
Charter Medical employs process specialists, market experts, and engineers with experience across the cell and gene therapy industry, ensuring we truly understand our partners’ concerns and communicate within our organization to effectively implement that feedback into our designs, our internal processes, and our collaborations and communications.
About Charter Medical, LLC
Charter Medical, LLC has more than 30 years’ experience developing and providing specialty single-use products for bioprocessing, advanced therapies, and blood management applications, delivering solutions to the biotechnology and pharmaceutical markets. Our 16,000 square feet of cleanroom space located in Winston-Salem, NC, is ISO 13485:2016 certified and FDA registered, with a focus on designing and supplying single-use solutions for cell growth, frozen storage, and biological fluid handling. Custom product design services are available for clients who need specialized single-use products for biomanufacturing. Our team of engineers will work with you to develop the best solution for your specific requirements. Charter Medical is committed to providing quality products and services with an experienced staff dedicated to exceeding customer expectations from product development to delivery and implementation. At Charter Medical, we work closely with our sister companies, Polyzen, SanaVita Medical, and Secant Group, to provide essential products and services to life science companies. Through integrated research and development activities, we are helping to bring new technologies and therapies to market.
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