Implementing Automation and Flexible Design for Allogeneic Manufacturing

As novel cell therapies continue to advance through the clinical trial pipeline and to commercialization, manufacturing process optimization and capacity become increasingly important . Two types of cell therapies—autologous and allogeneic—differ significantly in manufacturing approaches (1). Autologous cell therapies are patient-specific and use a patient’s own cells. Allogeneic cell therapies are “off-the-shelf” products that begin with cells from healthy donors or renewable sources, such as induced pluripotent stem cells. Allogeneic approaches can be important for cases in which it’s not feasible to use a patient’s own cells. In addition, allogeneic cell therapies hold promise to improve manufacturing efficiency, reduce manufacturing costs, and improve access for patients.

“Allogeneic cell therapies are attractive because they decouple manufacturing from the individual patient,” explains Ellyn Torosian, executive director, global head of Contract Development and Manufacturing Organization (CDMO) quality at Charles River Laboratories (Charles River). “Donor cells can be expanded, banked, and distributed to many patients, enabling much faster availability, simpler logistics for clinics, and a path to lower cost per treatment at scale.”

Compared with autologous therapies, allogeneic therapies have the potential for lower manufacturing costs, because they are produced in larger batches and there is more flexibility around scheduling the timing of the manufacturing process. CDMOs can create even more efficiency by sharing resources across batches or programs, says Melanie Mansbach, general manager of Catalent's North American Cell Therapy Center of Excellence. Multiple batches could be processed at the same time by overlapping short processing days or by overlapping processing days with hold days. “Sharing [manufacturing space] across batches can be slightly less complex than sharing across programs, but both can be used fairly easily by a CDMO to gain efficiency,” she adds.

How are these manufacturing challenges addressed?

Scientists are still searching for solutions to some of the limitations of allogeneic therapies, such as immunogenicity, but progress is being made. As Bruce Thompson, PhD, chief technology officer at Kincell Bio emphasizes, “Allogeneic therapies are still being refined as we learn more about their ability to evade immune detection and rejection, and [as we] identify correlates of clinical efficacy.”

“As the field continues to identify better genetic engineering elements that increase persistence and durability, the allogeneic modality will become more applicable to a wider range of disease indications,” Dr. Thompson adds.

“Allogeneic approaches raise immune and safety questions and require robust donor screening, potency assays and additional engineering [e.g., gene editing or alternative cell types], but the industry views these [issues] as solvable and worth the upside in scale and access,” Torosian says.

How are flexible manufacturing processes designed?

Balancing flexibility in process design with regulatory requirements is a particular challenge for cellular therapies. “As a product works its way to clinical trials, there needs to be flexibility to make changes to make the process more robust and reliable as more data become available, but there also needs to be structure to the changes so the process still meets GMP [good manufacturing practice] requirements and the final data are tracked and gathered in a way that will support a future biologics license application,” explains Mansbach. She says gap assessment and risk analysis exercises can help de-risk and streamline the process.

“[Complexities of cellular therapies] require flexibility in the process, documentation, and testing requirements to ensure the patient gets a high-quality product but also allow for the variability encountered in these unique modalities as early data and experience are generated,” agrees Dr. Thompson. “Challenges include unique raw materials, many complex measurements of cellular health, cell surface receptors used as a surrogate for a particular cellular attribute or phenotype, and the pressures of cost and timing to get these therapies back to very ill patients,” he explains. Dr. Thompson adds that regulators at FDA have been helpful in providing guidance for “phase-appropriate” approaches to raw materials, manufacturing, and testing for many novel cell therapies.

How does automation reduce risk?

Automation is seen as crucial for successful cell therapy manufacturing at commercial scale, as it helps ensure consistent production (2) . Automated and digital technologies can be used throughout the manufacturing process—in manufacturing unit operations, fill/finish, quality control testing, and in data handling and logistics, for example.

Besides improving consistency from batch to batch, automation impacts the ease with which a particular operation can be completed, which has implications not only for avoiding deviations from the manufacturing batch record, but also for lowering the training barrier for new operators, says Dr. Thompson. As more cell therapies reach later clinical development and commercial stages, production will increase, and more operators will need to train on complex unit operations. “The easier each operational step, the better the success rate, and the greater the opportunity to serve more patients,” he adds.

“As operations scale up, automation of common tests can increase throughput and decrease the requirements for numerous highly trained staff, reducing the time and cost to release these products for clinical and commercial use,” continues Dr. Thompson. He notes that automated software systems enable better quality oversight.

“We see increasing use of automation in the quality control process, both in-line and when assessing critical quality attributes,” agrees Nicholas Dolman, PhD, senior manager of program management, Advanced Therapies Collaborations at Thermo Fisher Scientific. “Fundamentally, automation reduces user error and therefore offers significant advantages to the quality and quantity of therapies being produced.”

Automated processes and the use of closed, single-use systems where feasible are helpful for risk mitigation. “Closed, integrated bioreactor platforms that combine activation, transduction, expansion, wash, and harvest in a single instrument (e.g., CliniMACS Prodigy and newer integrated systems) are enabling more reproducible, lower-contamination manufacturing,” says Torosian. Robotics are also being piloted for repetitive tasks to reduce human contamination risk.

Robust process characterization is important to improve product consistency and reduce lot variability. In addition, in-line analytics—collecting real-time process data combined with artificial intelligence models—can detect drift and maintain potency across large batches. “Predictive modeling and real-time analytics are increasingly used to detect deviations and optimize expansion and potency,” Torosian explains.

An important consideration is defining when in the development and commercialization process to move to automated systems, which require time and financial investment, adds Mansbach. “While automation offers consistency, reproducibility, and standardization, it may limit the flexibility needed during early clinical development,” she explains. “Careful consideration is required to determine which systems should be implemented at each phase and in what sequence to reduce risk while not stifling the ability of the program to adjust as a therapy progresses through each phase of clinical manufacturing and into commercialization.”

“Often, processes are developed without automation, as companies are seeking an expeditious path to clinical proof of concept,” adds Dr. Thompson. “Once a therapy has demonstrated clinical safety and efficacy, sponsors will start to consider (or revisit early assessments) how to supply the expected patient population and support a target product profile, inclusive of price and production parameters. Key considerations for introducing automation into the manufacturing process include performance, cost, and ease of production.”

How are manufacturing needs evolving?

One example of a therapy progressing towards potential commercial manufacturing is bemdaneprocel, an investigational allogeneic pluripotent stem cell derived therapy for the treatment of Parkinson’s disease, from Bayer’s subsidiary BlueRock Therapeutics, currently being tested in a Phase III clinical trial (3). Bayer’s Cell Therapy Launch and Manufacturing Facility in Berkeley, California, which opened two years ago, will supply material for late-stage clinical trials and potential commercialization of the therapy (4). The facility, which was the 2025 ISPE Facility of the Year Award category winner for “Social Impact—Unmet Medical Needs,” serves as a bridge between development and commercial manufacturing and meets the need for a platform to develop allogeneic cell therapies, the company said (5).

As companies move through early- and late-stage clinical cell therapy manufacturing and progress into commercial production, CDMOs see their expertise in multiple types of platforms and processes playing a role.

“We expect to see continued growth in our pipeline,” says Torosian. She notes that Charles River’s Memphis, Tenn. facility was designed for GMP production of both autologous and allogeneic cell and gene-modified cell therapies.

Mansbach points to a lack of standardization in allogeneic cell therapy processes as a key reason for emerging biopharma companies to turn to an experienced CDMO. “With allogeneic cell therapies, the manufacturing needs are evolving,” she says. “As was the case with early autologous cell therapies, we are seeing a wide variety of cell types, indications, process equipment, process duration, release methods, and even testing move through the clinical landscape.”

Addressing the question of facility utilization is another reason innovators will engage CDMOs. “Many innovator companies built their own facilities when faced with scale-out questions of managing an autologous supply chain; however, those elements are quite different for allogeneic products,” Dr. Thompson says.

Dr. Thompson further suggests that there will continue to be a place for both autologous and allogeneic therapies in the market. “As we learn more about what makes therapies effective in different populations, we will likely see a clear use case in many indications for allogeneic or autologous production,” he says.

The key, Dr. Thompson notes, will be to identify the correct combination of factors needed to support the target patient population. Ultimately, the curative nature of these cell therapies will continue to attract attention and investment from innovator companies, he concludes.

References

1. Briggs, A. Navigating Cell Therapy Commercial Readiness. Webcast, criver.com (accessed Oct. 3, 2025).
2. Ahsan, T.; Harris, K.; Snowden, A.; et al. The New Standard for CGT Manufacturing: Flexibility and Scalability. Presentation at Cell and Gene Meeting on the Mesa, Oct. 6, 2025.
3. BlueRock Therapeutics. First Parkinson’s Disease Patient Treated in BlueRock’s Pivotal Phase III Trial of Investigational Cell Therapy bemdaneprocel. Press Release. Sept. 22, 2025.
4. Bayer. Bayer Opens First Cell Therapy Manufacturing Facility to Advance Regenerative Medicines on a Global Scale. Press Release. Oct. 10, 2023.
5. ISPE. Meet the 2025 ISPE Facility of the Year Award (FOYA) Category Winner for Social Impact – Unmet Medical Needs: Bayer Healthcare LLC. iSpeak Blog. Oct. 1, 2025.