The Shift to GMP-Compliant Automation in Cell and Gene Therapy Manufacturing

Cell and gene therapies (CGTs) offer the potential to cure a wide range of life-limiting diseases. Known as Advanced Therapy Medicinal Products (ATMPs) in Europe, these treatments provide one-off interventions that can deliver lifelong benefits. Once confined to academic laboratories, they are now being rapidly commercialised, often using equipment with research-lab roots. As regulatory frameworks evolve, the sector is turning toward automation and closed systems to ensure compliance and product integrity.

Manufacturing challenges

Compared with conventional oral or injectable medicines, ATMPs are significantly more complex to produce. The variability of starting materials, the fragility of living cells as wells as the high number of manual processing steps increase the risk of error and contamination. These products cannot be terminally sterilised, so they must be produced aseptically, leaving no room for contamination from viable or non-viable particulates. In order to minimise these risks and meet Annex 1 requirements, which demand strict control of microbial and particulate contamination, the industry is transitioning away from open manual processes toward automated, closed systems.

What are 'functionally closed systems'

Many current ATMPs use “functionally closed” systems, often involving sterile bag-sets of welded tubes and containers. These can maintain internal sterility while operating in lower-grade cleanrooms, such as Grade C. However, they typically perform a single process - like cell expansion - for much of their operation, leaving valuable equipment under-utilised. From an automation standpoint, this imbalance in process flow, or “Takt time,” drives up the cost of goods and limits throughput. These systems also rely on plastic bag containers that can become brittle when cryopreserved, requiring additional handling and storage precautions. As the sector matures, functionally closed systems are gradually giving way to more robust, GMP-compliant solutions that borrow design principles from traditional aseptic fill-finish equipment. Increasingly, vials made from cryogenic-resistant cyclic olefin polymers (COP/COC) are replacing fragile plastic bags as primary containers.

Closed systems

A true closed system isolates the process within an enclosed environment, often a stainless-steel or soft-wall isolator - to protect both operators and products. Before use, isolators undergo hydrogen peroxide vapour decontamination and maintain positive pressure to prevent airborne contamination.

HEPA-filtered unidirectional airflow “washes” the process area, while transfer ports allow safe material exchange. Continuous monitoring ensures aseptic integrity and isolators can operate in Grade D rooms - offering greater energy efficiency and lower facility costs compared to functionally closed systems.

The trend is clear. As with every pharmaceutical sector over the past century, manual, laboratory-based processes are giving way to automated, GMP-compliant production systems.

Meeting GMP and Annex 1 standards

For equipment manufacturers, this shift demands machinery designed from the ground up to meet stringent GMP and Annex 1 standards. Producers must interpret and implement these guidelines precisely within their User Requirement Specifications (URSs).

3P innovation, with our background in commercial pharmaceutical equipment, integrates these principles into every design stage. Even seemingly minor components, like bolts, require attention: hygienic fasteners are polished, sealed and shaped for cleanability, preventing leaks or glove tears that could compromise aseptic containment. Electrical and software design are equally critical. Components must resist sterilants and maintain strict separation between process and technical zones. Software must comply with 21 CFR Part 11 for electronic records and follow GAMP 5 validation principles to ensure traceability and data integrity.

Designing for compliance and validation

Validation, establishing documented evidence that a system performs as intended, is embedded throughout the equipment lifecycle. Airflow design also plays a role: the “first air” principle requires that HEPA-filtered air reach critical zones without obstruction, verified through CFD modelling and smoke studies. By designing with GMP principles in mind, manufacturers can ensure their systems meet regulatory expectations while delivering efficiency and reliability.

Conclusion

Cell and gene therapy manufacturing is evolving rapidly from manual, research-grade methods to automated, GMP-compliant production. Closed-system automation not only reduces contamination risk but also paves the way for scalable, reliable, and regulatory-ready commercial manufacturing. In this transition, engineering precision, from hygienic design to software validation, is key to realising the curative promise of advanced therapies.