Cell therapy is still a relatively new form of treatment. As such, not that many cell therapies have successfully reached commercialization. Meeting FDA requirements at each phase of the clinical trial process, balancing the need for scalability and sustainability with production costs, and other challenges make the road to commercializing cell therapy long and difficult.
Yet, by studying the path taken by the few cell therapies that have achieved commercialization—whether they’re autologous or allogeneic—and learning from both their successes and their missteps, it is possible to identify a few common considerations which may be useful to your preparation for commercializing cell therapy.
1. Development by Design (DbD)
Development by Design, or DbD, provides a structured framework for manufacturing development leading to commercial manufacturing that will viably support the value proposition for a cell therapy product. 
The DbD framework calls for the consideration of quality, scalability, sustainability, and cost of goods during each phase of product development for the cell therapy:
- Quality. The critical quality attributes (CQAs) of the final product must be prioritized—and DbD processes recognizes the threat that the manual, open, and human-dependent nature of many process steps poses to meeting CQAs. Automation, integration, closed-system design, and compliance with current good manufacturing practices are considered key tactics for achieving consistently high product quality.
- Scalability. Migrating from clinical scale (tens or hundreds of patient doses per year) to the commercial scale where thousands or tens of thousands of doses per year are necessary presents new risks to quality when many lots are in progress at the same time for patient-specific products (scale-out) or when a much larger process is implemented for allogeneic products (scale-up). These risks must be assessed and mitigated to help ensure any product impact is acceptably low.
- Sustainability.Even if quality and scale needs are met, there is the risk of significant disruption to ongoing manufacture of the cell therapy over the duration of its lifecycle. Limitations on critical raw materials and related tools and technologies from single-source supplies, shortages of manufacturing facilities and personnel challenges must all be considered to ready the supply chain for commercialization.
- Cost of Goods (COGs).
Cell therapy has a relatively high cost of goods compared to traditional pharmaceutical products. As processes mature, COGs can dramatically impact the commercial viability of the cell therapy Addressing other elements of DbD may positively or negatively impact COGs and thus all elements must be considered together.
Analyzing a cell therapy early in clinical testing through the lens of Development by Design can help smooth out the transition between different phases of clinical trials by creating a development roadmap for manufacturing that is well ahead of late stage trials and commercialization where addressing elements of DbD can present substantial product comparability risk and therefore be very costly and time consuming.
2. Automation
Automation is becoming increasingly important in both clinical and commercial cell therapy production. As automation tools become more sophisticated, they can be used to replicate many processes that once required manual processing.
A key advantage of automation is reduced variability in intermediate and final product CQAs. Machines don’t get tired or distracted—they also don’t suffer from repetitive motion stress disorder. Additionally, automation reduces labor costs and eliminates risk of human error which can be very costly to recover from, if at all.
Batch results become highly reproducible, reducing waste in the manufacturing process.
3. Closed Systems
Virtually all of today’s cell therapy products in development are manufactured in high grade cleanrooms in order to mitigate the risk of microbial contamination during the open, manual processing steps that are required. Eliminating these open steps using closed processing systems replaces reliance on aseptic technique of humans operating in a clean but tedious environment with a design that inherently prevents ingress of contaminants.
Additionally, implementation of a closed system for all processing steps enables the possibility of concurrent adjacent processing of multiple patient lots and the elimination of the need for high grade cleanrooms, both resulting in significantly reduced costs for facility infrastructure as well as labor.
4. Cryopreservation
A critical aspect of any cell therapy’s distribution method is how that therapy is stored. If a therapy is no longer functional by the time it reaches the patient, then it might as well not exist.
Typically, the living cells that comprise a cell therapy will significantly deteriorate within a few days or less. One option for the storage and distribution of perishable cell therapies is the use of cryopreservation.
By preserving cell products through freezing for long-term storage and shipment, the viable period of the therapy can be greatly extended, to weeks, months, or even years. This can provide several potential advantages, including:
- Much more time for long-distance transport of products
- Products can be held until all release testing is complete, which can be up to several weeks.
- Products can be held in the event of a need to delay patient treatment
- Products can be subdivided and held for multiple patient treatments over time.
Switching from a fresh to a cryopreserved product is often easier said than done. Substantial development is typically required to establish a method that acceptably minimizes damage caused by freezing and thawing of the cells. Also, products that are supplied frozen to treatment sites must go through more preparation steps prior to patient administration and can add risk to the final quality of the product as it is delivered to the patient.
5. Outsourcing Cell Therapy Manufacturing
Bringing a cell therapy from clinical trials to commercialization is very difficult—so much so that only a few cell therapies have successfully achieved FDA approval for commercial manufacturing.
One thing that cell therapy development teams must do to better prepare their product for commercialization is to focus on current Good Manufacturing Practices (cGMP) in early clinical trial phases.
Some components of cGMP to become familiar with include:
- Training of manufacturing personnel
- Internal and external auditing of processes and controls
- Change and document controls
- Corrective and Preventative Action (CAPA) for deviations
- Validation of processes/procedures
- Material, equipment, and facility controls
Building the infrastructure required of cGMP-compliant cell therapy manufacturing is difficult and expensive. It takes considerable time and labor to set up the facilities needed, establish compliant practices, and create supply chains to ensure smooth production. This is where outsourcing the actual manufacturing of cell therapies can prove to be effective.
By outsourcing manufacturing to a third party who has extensive experience with meeting the requirements of cGMP, cell therapy developers can overcome production challenges such as maintaining sanitary production facilities or finding trained and experienced lab facility personnel.
PCT is the service platform of Hitachi Chemical Advanced Therapeutics Solutions, which has years of experience in overcoming cell therapy commercialization challenges for all kinds of clients—from independent academic research facilities to the cell therapy development units of major pharmaceutical companies. We have manufactured over 20,000 products for over a hundred clients.
We have the experience, the knowledge, the facilities, and the processes to help your cell therapy reach commercialization. Contact us today to speak with an expert.
