Distributed Manufacturing May Open New Doors For Well-Prepared CGT Sponsors

By Life Science Connect Editorial Staff

While cell and gene therapy (CGT) developers have more manufacturing options than ever before, selecting the right manufacturing strategy has become increasingly complex. Driven by thousands of CGT therapies in development worldwide, sponsors can now rent or lease facilities designed for virtually any CGT modality, quickly deploy qualified production equipment, and access a rapidly expanding CDMO market projected to grow from $6.2 billion in 2026 to $27.1 billion by 2033.[i]

Although today’s manufacturing market offers more options than ever, choosing the production model best suited to a program’s clinical and commercial objectives remains challenging. Making the right choice based on program phase, available facilities’ capabilities, and the sponsor’s level of control over the production process has never been more critical.

The importance of sound manufacturing model decisions is further amplified as the FDA considers the feasibility of distributed manufacturing establishments (DMEs). If finalized, this “hub-and-spoke” framework would allow sponsors to register multiple manufacturing sites as a single drug establishment, provided they operate under one management structure, a unified pharmaceutical quality system (PQS), and consistent preapproval inspection standards.[ii]

Program Success Typically Requires A Bespoke Production Model

Manufacturing should be viewed as a strategic decision that extends well beyond capacity. Choices at each stage of development should be guided by how they define and develop a regulatory-ready process, as well as their production strategy, which may comprise some combination of renting or leasing facilities, building in-house, or outsourcing. That strategy will likely evolve as sponsors learn more about the product, process, and patient population.

Therefore, making informed decisions requires understanding the advantages and limitations of every available model, along with enough flexibility to adapt for commercialization. Sponsors should also seek input from private equity or venture capital partners, whose experience can provide valuable perspective on the feasibility and investment risks associated with different manufacturing models.

Regardless of the manufacturing strategy, several elements of production are non-negotiable. First, the facility must be fit for purpose, equipped (and staffed, if applicable) expressly to support the sponsor’s specific process and accommodate its scale-up goals, which minimizes rework and tech transfer disruptions as the program advances. A strong technical fit drives manufacturing success rates, an essential requirement for autologous cell therapies, where patient-to-patient variability cannot be accommodated by altering the production process. Traditional pharmaceutical and biologics can often tolerate less-than-perfect manufacturing success rates; however, for autologous cell therapies, every manufacturing failure represents a patient who may never receive treatment.

Toward this goal, the contracted or constructed facility should be able to consistently produce IND-enabling material from the program’s earliest stages — characterized by a stable, characterized process, qualified raw materials, and a well-defined control strategy. That material should be comparable to the final product’s design and functionality, since its characteristics will inform vital decisions throughout the program, including biodistribution and dose range-finding studies. When non-IND starter material is used for assay development or to generate a CMC package, analytics and CMC challenges often surface later in the program.

Additionally, scrutinize the location and supply chain logistics when choosing a facility of any kind. Cell therapies rely on patient-derived material with limited processing windows or shelf lives. Gene therapy is slightly more forgiving in this respect, but not much. So, production site locations must be conscientiously chosen, and collection and transport to sites where the therapy will be administered must be masterfully coordinated.

Outsource, Build, Or Both?

The choice between in-house and outsourced manufacturing typically depends on whether gaps identified in the sponsor’s existing capabilities can meet the program’s capacity, speed, and cost objectives. In most cases, outsourcing delivers the greatest value during early development. As production volumes increase, sponsors often bring more manufacturing activities in-house to gain greater control over quality, safety, cost, and turnaround time.

Many sponsors ultimately adopt a hybrid model because process knowledge grows with every manufacturing campaign. This approach also fosters transparency between development and manufacturing teams, which is vital because process knowledge informs manufacturing, but lessons learned in manufacturing operations also build process knowledge.

For example, some organizations continue to outsource viral vector manufacturing after their product is approved, iteratively improving the process and smoothing its scaleup before implementing a more optimal version in-house. Further, it is important to maintain comprehensive in-house understanding of quality and regulatory expectations for your product, regardless of where it is manufactured.

A library of advice exists on identifying an ideal outsourcing partner, but the most relevant to revisit here include seeking a CDMO with aptitude in CMC and regulatory affairs. Deficiency in either area means more capital spending to get production off the ground. If early assessments show the therapy aligns with a CDMO's established manufacturing platform or cell line, sponsors should evaluate that opportunity carefully, as it may accelerate development while also enabling future decentralized manufacturing models.

If the CDMO helps develop the production process, the sponsor must take steps to protect its IP, because the more successful the program, the more the CDMO incorporates that IP into its platform. Conversely, if an initial assessment indicates the sponsor’s therapy fits a CDMO’s proprietary platform or cell line, it is prudent to explore the possibility, since it can create decentralized, point-of-care manufacturing opportunities. Still, sponsors licensing a CDMO capsid should be aware of, and discuss with their financiers, the downstream spending implications of using a proprietary platform or cell line.

As production scales, sponsors should also revisit pricing with their CDMO to reflect the efficiencies gained through higher manufacturing volumes. Pricing models such as suite fees or a batch-success agreements can help preserve both product quality and partnership value as programs mature.

Why Rent Or Lease A Facility?

Choosing between leasing and building is an early capital allocation decision that balances lower upfront investment against reduced operational control. Although the capital costs of building become justified when manufacturing grows to commercial volumes, leasing generally carries less financial risk, since commercialization is never guaranteed. Leasing is also well suited to small-scale production programs, with lengthy pauses between development phases.

As for the facility itself, investigate whether it is designed to support commercial processes for a multi-product pipeline. A commercial-ready facility will have stringent safety and environmental controls, as well as established supply chains, in place. If the assessment identifies shortcomings in any area, sponsors can explore whether the facility can add those controls or capabilities (at its own cost), or whether the space simply has been designed to support academic or single-product programs. Ultimately, facilities with a strong safety, regulatory, and operational foundations should be capable of supporting virtually any product they were designed to manufacture.

Prepare For Distributed Manufacturing

Distributed manufacturing increases production flexibility but also introduces significant logistical complexity. Strong project management is the cornerstone of this model, orchestrating everything from collection and delivery of materials to the development of robust analytical methods. Fragmentation is distributed manufacturing’s key risk, so having a capable individual who can hold all of the pieces together and ensure every team delivers as promised is imperative.

Compelling all manufacturing sites and partners to adhere to the same standards, ensuring consistent production regardless of location, is likely distributed manufacturing’s most significant operational challenge. Every participating site must operate from a single source of truth for the manufacturing process, analytical methods, vectors, and all subsequent process changes.

Process harmonization is critical, too, because the same unit operation can often be performed in multiple ways. Sponsors must control or eliminate that variability to the extent possible, as well as clearly define which changes are acceptable at the site level and which require global control. Preventing product drift is crucial in CGT, so mechanisms must be established to detect any such drift early via centralized technical ownership and monitoring.

Additionally, different manufacturing sites may be subject to regional requirements, with the differences exacerbated by patient material variability. As noted above, the line differentiating acceptable, site-only changes and more in-depth global process changes must be crystal clear. Sponsors should establish systems that identify and monitor site-specific trends, even when results remain within specification. Those insights are essential for demonstrating comparability as programs evolve. Given the ever-evolving nature of CGT, comparability is essentially measured on a variable scale, rather than a stable one, so tracking and measurement demand precise controls.

New Approaches, Similar Priorities And Standards

Regardless of the manufacturing model —or combination of models — successful programs prioritize CMC excellence and the development of a repeatable, scalable process. Digital infrastructure also plays an essential role by supporting comparability, facilitating tech transfer, and enabling consistent manufacturing across traditional or distributed networks. In either scenario, working toward a process that is scalable and trainable enables a high manufacturing success rate and supports comparability between facilities. To learn more, contact the authors and watch the webinar, “Making Distributed Manufacturing Work Beyond Theory.”

About The Experts

Sugu Patro is Senior Vice President of Global Cell Therapy Process Development at Kite, leading T-cell and viral vector process design, analytics, clinical manufacturing, tech transfer, and CMC strategy. He has helped advance Kite’s capabilities over six years. Previously, he was Vice President of Cell Therapy CMC Strategy at Juno Therapeutics/Celgene and spent over 20 years at Amgen in senior roles. He has supported 15 product launches and holds a Ph.D. and M.S. in Biochemical Engineering from RPI.

 

Emily Moran is a global biologics and advanced therapy executive, and is the Founder of 3 Little Birds Consulting, LLC, where she helps various organizations navigate CMC complexities, operational growth, Build design, and advancing therapies toward clinical and commercial stages. With deep technical operations expertise in CMC, Emily has supported leaders through clinic-to-commercial transitions, M&A integrations, and fundraising phases. She is known for helping companies build durable, scalable processes that support both regulatory readiness and business milestones.