Events & Insights
For biotechnology companies developing and marketing advanced treatments like CAR-T cell therapies, clinical success is only half the battle. The ultimate operational test is managing the clinical clock, which starts ticking the moment a patient’s cells are collected. For autologous cell therapy CDMOs, managing the total time from the initial cell collection to the infusion back into the patient, or vein-to-vein (V2V) time, is one of the primary keys to success.
Currently, the most significant bottleneck in the V2V cycle is quality control (QC) and lot release processes, as traditional quality and lot release tests routinely take weeks to complete, an unacceptable duration when most cell therapy patients are critically ill and cannot wait for treatment, not to mention the challenges in maintaining cell viability.
Cell therapy lot release is the critical quality assurance process that verifies a cell therapy is safe, sterile, and potent before it is administered. For autologous therapies, it serves as the final gatekeeper to ensure that a treatment meets predefined specifications, preventing the administration of failed or harmful doses.
As mentioned, accelerating lot release is vital and by modernizing testing workflows, cell therapy developers can safely slash V2V times, reduce manufacturing costs, and deliver treatments to bedsides faster. Here are four ways cell therapy CDMOs can accelerate cell therapy lot release.
1. Leverage Rapid Microbiological Methods (RMM)
Traditional sterility tests rely on legacy growth-based methods that require growing microbes in culture dishes to determine whether contamination is present. This process is slow, requiring 14 to 28 days to yield a final, compliant result. For autologous cell therapies, where a single batch of medicine is custom-made for a specific patient, 14 days can easily consume the product’s entire viable shelf life, not to mention the clinical need to rapidly receive the therapeutic for patient treatment.
Utilizing RMMs can include benefits such as:
- Automated Systems: Growth-based automated platforms detect microbial contamination days earlier by continuously monitoring changes in the sample.
- Molecular Tests: Modern techniques like Polymerase Chain Reaction (PCR) copy target DNA to identify hidden mycoplasma bacteria in just hours instead of weeks.
- Rapid Cartridges: For endotoxin testing, cartridge-based automated tools compress testing windows to under 15 minutes.
Adopting these rapid safety testing tools can shave weeks off the lot release timeline, ensuring patients receive healthy cells and keeping their treatment programs on track.
2. Automate Analytics and Data Gating
Manual quality control testing introduces human error, high operator-to-operator variability, and massive data bottlenecks. Automating these analytical workflows removes human variables and standardizes data collection. Options from this automation can include solutions such as:
- Smart Instruments: Instruments such as modern, high-throughput flow cytometers feature premixed test reagents and automated gating software to generate operator-independent results in minutes.
- Multiplexing: Advanced automated immunoassay platforms enable QC teams to simultaneously analyze a therapeutic lot for multiple quality parameters, such as cell identity, viability, purity, and potency, from a single sample.
These approaches both expedite quality control testing and conserve sample material. For autologous therapies, patient material is limited and time is of the essence, making automation and advanced methods even more important.
3. Transition to Real-Time Release Testing (RRT)
A traditional pharmaceutical manufacturing model treats cell production and quality testing as separate, sequential phases. However, real-time release testing (RRT) removes this barrier by integrating manufacturing and testing.
By incorporating process analytical technologies (PAT) to monitor cells as they grow and by creating closed manufacturing systems, operators can continuously check medicine quality. Some approaches to achieve RRT include:
- Enclosed Platforms: Fully enclosed manufacturing platforms perform automated in-process checks, cell washing, and final formulation without exposing cells to external elements.
- Digital Connectivity: Connecting process instruments to digital manufacturing execution systems (MES) and laboratory information management systems (LIMS) enables real-time data transmission, supporting RTT.
Quality assurance teams can review data during the manufacturing run rather than after the batch is finished. The shift to RRT drastically reduces delays in final batch release and boosts facility throughput.
4. Leverage Regulatory Flexibilities and CMC Guidance
The FDA and other global regulators fully recognize that new rules are needed for living, personalized medicines. In response, they have introduced specific chemistry, manufacturing, and controls (CMC) flexibilities designed specifically for the cell therapy sector. Biotech executives and CDMOs can leverage these evolving guidelines to streamline their lot release programs significantly.
- Smart Evaluation: Modern guidelines allow grouping strategies such as bracketing and matrixing that reduce the total number of validation lots a company must test.
- Conditional Release: Agencies permit conditional protocols for ultra-short-shelf-life products, meaning a manufacturer can safely ship a product to the hospital for infusion while longer-term, traditional sterility tests finish incubating in the background.
Engaging early with regulators to secure approval for these flexible analytical strategies reduces potential approval complications and paves the way for a clear pathway to the market.
Kincell Bio’s RTP Facility Expansion is Expediting Lot Release and Expanding QC Testing Capacity
Reducing vein-to-vein time requires a multi-prong strategy, and modernizing lot release is critical to the effort. By adopting rapid microbiological methods, automating analytical steps, shifting toward real-time testing data, and embracing regulatory flexibilities, companies can safely and dramatically reduce their production timelines. Every day saved in the quality control laboratory is a day given back to a patient waiting in a hospital.
To meet this need, Kincell Bio is making significant investments to expand the Research Triangle Park, North Carolina, facility. As part of this effort, we are converting existing space into a dedicated microbiology lab, which will allow us to bring rapid microbial and sterility testing fully in-house, eliminating dependence on outsourcing and accelerating release timelines. The expansion also includes an additional quality lab to increase testing capacity.
Contact us to learn more about how our Research Triangle Park expansion is supporting the expedited release of lots for autologous and allogeneic cell therapies.
