Advanced Manufacturing And CDMOs Are Rewriting The CGT Cost Equation

By Fahimeh Mirakhori, M.Sc., Ph.D.

Advanced therapy medicinal products (ATMPs), especially cell and gene therapies (CGTs), are among the most revolutionary medical breakthroughs of our era. Yet despite their clinical promise, their benefits remain out of reach for many patients due to the complexity, cost, and limitations of traditional manufacturing methods.

Addressing these barriers demands a shift toward highly automated, precision-driven platforms and global outsourcing models that can enable wider access and long-term sustainability.  

Modern CGT manufacturing diverges sharply from traditional biologics. Unlike mass-produced vaccines or monoclonal antibodies, many CGTs, especially autologous treatments, must be tailored to the individual patient. This highly personalized approach has historically required manual, labor-intensive steps conducted in isolated, paper-based environments. The result is a process prone to variability, delays, and high production costs.^{1, 2}

Today, advances in equipment design, sensor technology, and computational platforms are reshaping CGT manufacturing. Automated, closed, and single-use equipment allows end-to-end production within a single device or unit of operation. These advances streamline critical steps, from initial cell isolation through genome editing and expansion to final formulation and packaging. In some instances, fully automated platforms have demonstrated a significant reduction in batch-to-batch variability and operator error, yielding higher and more reproducible product quality while drastically reducing the demands for highly trained staff and costly cleanroom facilities.^{3, 4}

Outsourced manufacturing has emerged as an essential component of CGT commercialization. CDMOs enable smaller biotech firms and academic institutions to access highly sophisticated manufacturing capabilities that would be cost-prohibitive to build in-house. By partnering with CDMOs, therapy developers can focus their internal resources on clinical advancement and pipeline expansion, relying on established platforms and expertise to manage production and quality controls. Importantly, CDMOs play a pivotal role in global access.

Regional manufacturing hubs enable localized manufacturing closer to patient populations, reduce reliance on long and fragile global supply chains, and optimize pricing strategies aligned with regional economic realities. By fostering regional hubs, the CGT sector can reduce its carbon footprint, mitigate bottlenecks related to transportation and cold‑chain storage, and ensure more rapid access to treatments for underserved patient groups.

Selecting a manufacturing model for ATMPs/CGTs, whether in-house, CDMO-based, or decentralized, requires balancing cost efficiency, quality, scalability, risk management, digital readiness, pricing, and patient access. Centralized models may offer economies of scale for large patient populations. At the same time, decentralized approaches provide rapid local access, shorten vein-to-vein time, and reduce or eliminate the need for cryopreservation. Cost considerations include minimizing up-front infrastructure investment and optimizing operational expenses through the use of automation and digital platforms.^{5, 6} Flexibility and speed to market depend on a partner’s ability to adapt to clinical demands and use automated, in-line testing. Effective chain-of-custody and risk management systems ensure transparency and minimize delays associated with transportation and logistics. Ultimately, success hinges on technological readiness for automation, a robust digital infrastructure, alignment with value-based pricing models, and the capacity to meet evolving global regulatory standards (Table 1).

Table 1: Established Matrix for Evaluating CDMO/CROs (based on industry best practices; ICHQ9-10, BCPI, ISPE & PDA Good Distribution Practice guidelines, and EMA regulation EC No. 1394/2007).

Criteria	Importance for ATMP/CGT Development
Scalability and local access	Enables rapid patient access and global market coverage.
Cost optimization	Reduces up-front investment, operational expenses, and waste.
Quality control and compliance	Supports rapid release and robust patient outcomes.
Flexibility and speed to market	Supports quick clinical trial advancement and commercialization.
Risk management and traceability	Provides end-to-end oversight and robust quality guarantees.
Technology compatibility, digital readiness	Supports automated platforms, PAT, and digital integration, etc.

 

Advanced Technologies Driving Cost Reduction

In autologous cell therapy, traditional economies of scale do not apply, making cost-effective manufacturing especially challenging. To address this, new approaches are focusing on reducing three primary cost drivers: processing, reagents, and quality control.^7-10

While advances have already been made in lowering reagent expenses, a significant opportunity lies in automating and streamlining quality control. Integrated multi-omics platforms can enable rapid, cost-effective release testing, reducing turnaround times and providing deeper insights into critical quality attributes that directly correlate with patient outcomes. Such platforms can operate within centralized or decentralized settings and, when combined with digital monitoring tools, enable end-to-end visibility throughout the manufacturing process. By doing so, these advances have the potential to transform autologous therapy production, making it more accessible, cost-efficient, and aligned with patient needs.

Smart CGT manufacturing increasingly depends on advanced technologies that can both reduce cost and support scalability:

• Automated bioreactors and modular units: These platforms enable end-to-end production in a fully enclosed, single-use environment, significantly reducing the risk of contamination and ensuring batch-to-batch consistency. Modular bioreactors can be deployed flexibly across facilities and adapted quickly for new treatments.
• Continuous processing and In vivo editing: The shift from traditional batch manufacturing to continuous processing improves yield and efficiency. In vivo genome editing platforms further bypass the expensive ex vivo steps altogether, making treatments viable for larger patient populations.
• AI and machine learning for optimization: AI-enhanced platforms can analyze massive data sets generated throughout CGT production, facilitating predictive analytics and precision quality control. By identifying variability trends and automating process adjustments, AI improves batch reliability and reduces waste, yielding lower cost of goods across the manufacturing pipeline.
• Real‑time monitoring and PAT tools: Process analytical technologies (PAT) enable in-line and at-line monitoring of critical process parameters (CPPs), reducing batch failures and delays. These advances enable tighter process controls and a shift toward a fully digital manufacturing paradigm, akin to an Industry 4.0 approach. This precision allows for improved resource utilization and greater scalability.

Automated, decentralized manufacturing combined with cloud-based data management and advanced in-process and QC testing can speed up product release and enable the treatment of more patients.

The advances in manufacturing platforms and outsourcing strategies must be matched by pricing and reimbursement models that reflect their potential for reducing cost and expanding access. Value-based pricing, which ties the cost of treatments to clinical outcomes, can help mitigate the financial risk associated with these highly complex treatments. Risk-sharing agreements, milestone payments, and tiered pricing enable payers and developers to balance up-front costs with long-term benefits for patients and healthcare systems (Table 2). For example, a therapy that demonstrates long-term benefits or disease‑modification can justify a higher up-front investment if structured with milestone payments contingent upon clinical outcomes. Meanwhile, tiered pricing enables global suppliers to adjust their cost structures for low- and middle-income countries, making treatments viable across diverse economic landscapes.

Table 2: Examples of value-based strategies for policy reforms for ATMPs/CGTs.

Framework	Description	Primary Benefit
Outcome-based payment models	Tie therapy costs to clinical outcomes, such as milestone payments based on biomarker improvements or hospitalization reductions.	Aligns payment with actual patient outcomes.
Risk-sharing agreements	Developers refund part of therapy costs if outcomes (e.g., motor function in SMA) are not achieved after a set period.	Reduces payer risk for expensive therapies.
Global access subsidy programs	Collaborative programs to subsidize gene therapy in LMICs, with adherence to value-based pricing and cost transparency.	Expands access in low-resource settings.
Adaptive regulatory pathways with conditional pricing	Allow early market access with provisional pricing, contingent upon confirmatory real-world effectiveness data.	Encourages early access while validating effectiveness.
Tiered p models	Set therapy prices based on country income level or healthcare infrastructure, ensuring affordability across markets.	Supports global equity in gene therapy pricing.
Centralized value assessment and pricing benchmarks	Establish pricing benchmarks via national/regional authorities using CETs and societal value (e.g., expanded ICER frameworks).	Promotes pricing transparency and consistency.
Manufacturing innovation incentives	Provide grants or tax credits for adopting cost-saving manufacturing technologies like in vivo gene editing or automation.	Incentivizes scalable cost-reducing innovation.
Real-world evidence integration platforms	Use real-world evidence for post-market surveillance, adaptive pricing, and ongoing validation of therapy value.	Enables adaptive pricing based on real-world impact.

 

Sustainability And Scalability Through Outsourced Manufacturing

The future of CGT and ATMP manufacturing rests upon a collaborative approach that combines global outsourcing capabilities, localized production hubs, and advanced digital manufacturing platforms.^7-10 The benefits of this shift extend beyond cost reduction:

• Resilient supply chains: By decentralizing production across regional hubs, therapy developers can mitigate global supply constraints and respond to localized clinical needs.
• Expanded market reach: Lowering the cost of goods and reducing reliance on centralized facilities allow CGTs to reach patient populations that were previously inaccessible due to cost constraints.
• Enhanced quality and consistency: Automation and digital process controls enable manufacturers to maintain higher quality standards across global production sites, providing greater reliability and patient safety.

With advances such as automated continuous end-to-end platforms, AI-driven optimization, and in vivo genome editing technologies, CGTs can evolve from rare treatments into global therapeutic platforms. CDMOs and regional manufacturing hubs will serve as the backbone of this transition, reducing barriers related to cost, access, and supply chain resilience.

Advanced manufacturing and outsourcing have emerged as pivotal forces reshaping the global CGT and biologics landscape. By leveraging state-of-the-art technologies, digital platforms, and collaborative manufacturing hubs, the sector can overcome longstanding constraints related to cost and scalability. These advances, coupled with innovative pricing and reimbursement models, have the potential to redefine access, making life-changing treatments available to patients regardless of their geographical location or socioeconomic status.

In this new era of CGT manufacturing, precision automation, global outsourcing, and digitalization are more than operational advances; they are the foundation for a truly patient-centric global bio‑innovation ecosystem. Through this paradigm shift, CGTs can fulfill their promise to revolutionize medicine for all.

References:

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8. Andrew Sinclair DP, Yuki Abe, Rob Noel. Evolution and Uptake of Bioprocess Economic Modelling https://www.bioprocessintl.com/sponsored-content/evolution-and-uptake-of-bioprocess-economic-modelling: BioProcess International; 2022 [Accessed December 2024].
9. Beachy S.H., Alper J., and Drewry M. Emerging Technologies and Innovation in Manufacturing Regenerative Medicine Therapies. Proceedings of a Workshop—in Brief.   National Academies Press (U.S.); 2024 Feb 16. ISBN-10: 0-309-71584-9
10. Pinto, E., Lione, L., Compagnone, M. et al. From ex vivo to in vivo chimeric antigen T cells manufacturing: new horizons for CAR T-cell based therapy. J Transl Med 23, 10 (2025). https://doi.org/10.1186/s12967-024-06052

About The Author:

Fahimeh Mirakhori, MSc., PhD., PMP, is a professional strategist with 17-plus years of experience in life sciences and biotechnology. She is a consultant and educator who addresses scientific, technical, and regulatory challenges in cell and gene therapy (CGT), genome editing, regenerative medicine, and biologics product development. She has held diverse roles in the industry and academic settings, acquiring broad experience across various therapeutic modalities. Her expertise includes autologous and allogeneic engineered cell therapeutics (CAR-T, CAR-NK, iPSCs), viral vectors (AAV, LVV), process and analytical development, and regulatory CMC.