India’s cell and gene therapy (CGT) ecosystem is evolving from research-led innovation toward early clinical translation, with increasing participation from academia, biotechnology startups, and biopharma stakeholders. The country is witnessing early commercialization signals, particularly in CAR-T therapies, with indigenous products entering the market and clinical pipelines expanding across oncology and rare diseases.

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The question is no longer whether India can develop advanced therapies but whether it can build manufacturing systems that are scalable, reproducible, and aligned with global regulatory standards. 

Scaling CGT manufacturing in India: a shift to process-driven execution

A central challenge in India’s CGT landscape is the transition from research-scale processes to GMP-compliant manufacturing. CGT products are highly sensitive to process variability, even minor deviations can impact critical quality attributes (CQAs), including potency, purity, and safety.

This necessitates a shift to robust chemistry, manufacturing, and controls (CMC)-driven development, with early integration of process design, control strategies, and analytical frameworks.

Viral vector manufacturing: variability at the core of scale-up challenges

Viral vector-based systems, particularly adeno-associated virus (AAV) and lentiviral vectors, form the backbone of CGT manufacturing workflows. However, their manufacturing continues to be a key constraint globally, and more so in India. 

Current upstream processes rely heavily on transient transfection systems, which are inherently sensitive to variations in plasmid quality, transfection efficiency, and cell health. 

Additionally, India currently has limited, dedicated CGT-focused CDMO infrastructure, particularly for viral vector production, resulting in fragmented capabilities and constrained scale-up pathways.

Addressing this requires a shift towards platform-based, scalable manufacturing approaches that enable consistency across modalities while maintaining flexibility and process control.

Plasmid DNA and cell culture systems: foundational determinants of consistency

Plasmid DNA quality is an often-underestimated factor influencing upstream consistency. Variability in plasmid attributes such as supercoiled content, endotoxin levels, residual impurities, and sequence integrity can potentially affect transfection efficiency and downstream impurity profiles. Early definition of plasmid specifications, combined with access to globally validated production platforms, is critical.

In parallel, continued reliance on adherent cell culture systems limits scalability. Globally, there is a clear shift towards suspension-based systems and stable producer cell lines, enabling higher yields and improved process control. 

Effective scale-up demands integration across cell line development, upstream optimization, and manufacturing.

Downstream processing: enabling yield and purity

Downstream purification remains another major constraint. Traditional approaches such as ultracentrifugation are difficult to scale and offer limited control over critical impurities.

Transitioning to chromatography-based purification improves reproducibility, but requires deeper process understanding, appropriate chromatography media selection, and co-optimization with upstream workflow and analytical strategies.

In AAV manufacturing, the challenge of full versus empty capsid heterogeneity remains particularly significant. A substantial proportion of produced capsids may lack the therapeutic payload, reducing the effective dose and potentially introducing safety risks. Addressing this requires both process improvements and robust analytical methods capable of accurate characterization of capsid composition and related quality attributes.

Analytical characterization: linking process to product 

Analytical capability is emerging as a defining factor of manufacturing maturity. 

Across programs, vector titration and characterization approaches vary widely, with limited harmonization across PCR-based, immunoassay and functional methods.

Analytical frameworks must link critical quality attributes to process parameters and clinical outcomes. Technologies such as next-generation sequencing (NGS), quantitative and digital PCR, and high-resolution mass spectrometry are enabling deeper insights into genome integrity, impurity profiling, and potency assessment. However, instrumentation alone is insufficient, success depends equally on method development, application expertise, and regulatory alignment.

Closed, modular manufacturing: balancing automation with process maturity

Many CGT workflows in India still involve open or semi-open processing, increasing contamination risk and operator dependence. Closed and automated systems offer clear advantages in reproducibility and contamination control. A pragmatic approach involves balancing automation with the flexibility required during early-stage process development.

This is particularly relevant for autologous cell therapies such as CAR-T, where complex, patient-specific workflows demand careful process mapping, standardization, and operator training alongside technology adoption.

Cost vs complexity: process inefficiency as a primary cost driver

Gene-modified cell therapies such as CAR-T in India currently cost in the range of INR 30 – 50 lakh per treatment, depending on indication and clinical setting, limiting broader accessibility despite their clinical promise.

While multiple factors influence the cost of cell and gene therapies, process-related challenges such as low yields, batch failures, prolonged quality control timelines, and extensive in-process testing are widely recognized as important contributors to manufacturing costs. Enhancing process efficiency can therefore play an important role in improving affordability. Optimized cell culture systems, chemically defined media, and high-efficiency transfection technologies can significantly enhance productivity and reduce cost per dose. 

Platform-based approaches and the promise of allogeneic therapies

Moving away from molecule-specific processes to standardized, platform-based manufacturing approaches can improve reproducibility, batch success rates and reduce development timelines. 

Such platforms must be designed as integrated systems where upstream, downstream, and analytical components are co-optimized. Achieving this level of integration requires close collaboration across technology providers, manufacturers and regulatory stakeholders.

Allogeneic approaches offer potential for scalability and cost reduction. However, they introduce additional scientific and regulatory complexities, including immunogenicity and long-term safety considerations, requiring data-driven development strategies.

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Localization and regulatory alignment

Localization of manufacturing, particularly for critical inputs such as plasmid DNA, viral vectors, and raw materials, will be essential for long-term sustainability. However, infrastructure alone is not sufficient, it needs to be accompanied by global-quality systems, validated technologies, and deep application expertise. 

From a regulatory standpoint, India has established foundational frameworks through ICMR, DBT and CDSCO. As CGT products move toward commercialization, there is a growing need for greater clarity and standardization in CMC expectations, analytical validation, and potency assessment. Alignment with global regulatory standards will be critical not only for domestic scale-up but also for enabling participation in the global CGT value chain.

What will define India’s CGT scale-up?

The next phase of CGT growth in India will be defined by the ability to achieve consistency at scale. 

Dedicated collaboration environments that enable hands-on process development and workflow integration play a critical role in advancing manufacturing readiness. By supporting process optimization, technology evaluation, and operator training, these environments help bridge the gap between research-scale development and GMP-compliant manufacturing. They provide controlled settings where workflows can be designed, tested, and refined, enabling greater process understanding, reducing variability, and accelerating readiness for clinical translation.

Ultimately, the transition of CGT from niche therapies to broader clinical adoption will depend not only on scientific innovation, but on the ability to deliver therapies that are consistent, scalable, and economically viable.

Views expressed by: Dr. Prathap Naidu, Business Development Lead – Cell, Molecular Biology & Cell Analysis (Cell & Gene Therapy), Thermo Fisher Scientific

Disclaimer: This article is for educational and informational purposes only and does not constitute regulatory, clinical, medical, legal, or manufacturing advice, and does not promote or endorse any specific product, technology, or service.

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Disclaimer: The views and opinions expressed in this article are solely those of the author and do not necessarily reflect the official policy or views of any organisation. The content is intended for informational and educational purposes only and should not be construed as medical advice.

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