Advanced therapy medicinal products (ATMPs) are transforming disease treatment, helping improve patients’ lives worldwide. These therapies—including cell and gene therapies (CGTs)—have the potential to treat a variety of currently untreatable diseases, from rare genetic diseases to cancers, metabolic disorders, and neurological conditions^.1 

The global ATMP market is rapidly expanding, fueled by innovations in methodologies and technologies and a growing knowledge of molecular and cellular biology. Valued at $14.6 billion in 2024, the ATMP segment is on track to reach $35.6 billion by 2032.²

There are now thousands of CGTs and other ATMPs in various stages of development, targeting diverse therapeutic areas, all set to revolutionize healthcare.¹

Nevertheless, ATMPs’ complex manufacturing processes and stringent quality standards demand specialized infrastructures, with cleanrooms capable of ensuring sterile integrity during their production. 

This article explores the crucial role of cleanrooms in ATMP development and manufacturing, examines the specific challenges ATMPs pose in cleanroom design, and highlights the benefits of modular cleanroom solutions for ATMPs. 

ATMPs pose unique cleanroom design challenges

The development and manufacturing of ATMPs frequently involves complex procedures, delicate materials, and the handling of patient-derived cells or tissues. As a result, ATMPs present unique challenges for cleanroom design and operation, demanding stringent control over contamination and environmental conditions. These must be overcome if ATMPs are to fulfill their potential in transforming patients’ lives. 

Autologous CGT treatments are incredibly personalized, as their production relies on harvesting the cells of individual patients before they are modified and reintroduced. These cleanrooms must support patient-specific workflows while minimizing the risk of contamination or mix-ups through meticulous segregation of materials and processes, rigorous adherence to aseptic techniques, and robust quality control measures. The cost of manufacturing a CGT for a single patient also means it is essential that cleanroom processes are designed optimally to ensure they can accommodate personalized workflows for each patient and ensure no contamination occurs.

Conversely, allogeneic therapies are donor-derived and manipulated to treat groups of patients. Cleanrooms for allogeneic therapies must enable efficient and scalable processing and segregation of donor-derived materials, ensuring the safety and integrity of the final product. This necessitates careful consideration of workflow design, environmental control, and contamination prevention strategies.

Due to these unique challenges, developers and manufacturers are under rising pressure to ensure their cleanroom designs meet these complex processing and regulatory needs. Additionally, to maintain proper control and transport of patient materials, these facilities must be situated near population centers or networks affiliated with major national and regional healthcare systems.

Meeting ATMP cleanroom needs

Traditional stick-built cleanrooms—using steel-studded structures covered in gypsum wallboard—have limitations that can be problematic in the fast-paced ATMP development environment.

These cleanroom projects require extensive on-site labor and intricate coordination of various trades, including electricians, heating, ventilation and air-conditioning (HVAC) technicians, and plumbers. The meticulous attention to detail required for these projects increases the possibility of unforeseen delays, cost overruns, and potential disruptions to ongoing operations, making them time-consuming and complex.

One option to address and circumvent the issues posed by traditional cleanrooms is to leverage modular technologies for ATMP facilities. Unlike stick-built, this modular approach utilizes prefabricated component-based architectural and environmental systems that are assembled and configured on-site to meet diverse manufacturing demands. This modular strategy, which has matured over the past two decades, can adapt to virtually any facility configuration horizontally and vertically. This allows it to protect the development process and accommodate even the most challenging host-building locations.

The benefits of modularity

The flexibility of the modular cleanroom approach offers multiple benefits, not just for manufacturers and patients. These benefits include:

• Faster patient access to approved treatments: Speed is everything in ATMP drug development. Getting treatments to patients quickly can drastically improve health outcomes and save lives. With their rapid construction and deployment, modular cleanrooms can accelerate the time-to-market for these essential therapies. This streamlined approach eliminates the need to juggle multiple contractors and trades, significantly reducing complexities and potential delays often associated with traditional construction methods. Furthermore, modular construction empowers ATMP developers to concentrate on their core competencies while ensuring their facilities are delivered quickly and efficiently by providing a single-source solution that encompasses cleanroom design, manufacturing, and installation.
• Improved patient safety and regulatory compliance: A modular cleanroom system enhances ATMPs by promoting standardized procedures and workflows through replication. Its consistent design improves training and staffing efficiency due to uniform critical operations and systems. While not directly improving ATMPs, modular cleanrooms mitigate risk through reliable performance and predictable outcomes. They also create sustainable environments for treatment processing and quality-compliant platforms, enabling expansion to meet future demands.
• Minimized integration challenges: The modular approach’s adaptability is vital for ATMPs, which are developed in diverse settings like academic research labs, hospitals, and dedicated manufacturing facilities. This approach ensures cleanrooms can be seamlessly incorporated into existing infrastructure or new purpose-built facilities, minimizing disruption and maximizing efficiency. 
• Modular cleanroom technologies allow designers to leverage the configurability of purpose-built architectural components and high-performance environmental systems. These components are precisely manufactured in a controlled factory environment and then deployed at the project site to bring the facility to life. The modular approach can accommodate various facility layouts and configurations, addressing the challenges of different host building locations.
• Streamlined installation schedules: Modularity also helps reduce the time needed for installation and lends an element of assembly precision that traditional methods cannot accommodate. Although cleanroom modules encompassing an entire 3D space have been implemented, the ideal modular solution refers to a pre-engineered component-based cleanroom implemented as a comprehensive, integrated system with guaranteed performance. 
• Greater adaptability to meet future ATMP manufacturing needs: Modular cleanrooms’ adaptability makes them easily reconfigurable and expandable to keep pace with evolving processes and emerging therapies. This flexibility is essential in a dynamic segment like the ATMP space, where future needs and advancements must be accommodated.
• Optimized cost and operational efficiency: Modular cleanrooms streamline the construction process and minimize on-site complexities, reducing capital expenses and ongoing operational costs. This contributes to long-term financial sustainability and improved ATMP development and commercial viability for manufacturing.  Additionally, modular cleanrooms support scalability by reducing the operational risks associated with ATMP manufacturing.

Reaping the benefits of modularity for ATMPs

To fully take advantage of modular cleanrooms within the expanding ATMP sector, developers and manufacturers should create a project plan that addresses the technical and regulatory requirements of cleanroom design while also incorporating the logistical, operational, and commercial considerations specific to ATMP manufacturing. This comprehensive approach will ensure that the facility effectively supports the unique needs of these advanced therapies.

To craft an effective project plan for a new cleanroom, ATMP developers should ask some crucial questions regarding their specific needs: 

Question 1: What is the anticipated demand for ATMP? 

Effectively forecasting product supply and demand can help determine the capacity required for the new cleanroom facility. The cleanroom facility must meet current and future production requirements, with minimal risk of expensive bottlenecks or delays in delivering therapies to patients. This necessitates understanding the present market size and predicting future requirements, considering elements such as patient population, clinical trial results, and potential market expansion. 

Question 2: Will the product be manufactured in-house or outsourced? 

Developers and manufacturers must weigh the benefits of producing ATMPs in-house or outsourcing to a contract manufacturing organization. Outsourcing can allow access to ready-made cleanroom capacity, accelerating commercialization, provided the facility has the specific equipment needed for the ATMP in question. With in-house production, drug developers can cultivate internal process knowledge and more effectively protect intellectual property. Compared to traditional drug manufacturing, the smaller production footprints required for ATMPs may make building these facilities in-house feasible, even for developers in early lifecycle capital investment.

Question 3: What are the specifics of the manufacturing process for the ATMP? 

ATMP developers and manufacturers need to deeply understand the process and how it relates to cleanroom requirements before they design their new facility. This involves mapping the process and understanding the needs and restrictions of each component. This will allow them to determine the best approach for their specific needs.

Question 4: Is there a commercialization plan that the cleanroom needs to support? 

Drug developers and manufacturers should have a robust commercialization plan that supports clinical pipeline drug product candidates and aligns product vision with flexible planning to ensure successful market supply. This plan should be a comprehensive guide through the project, from Phase 2 to product launch. It should also define its regulatory strategy, ensuring it can efficiently bring its product from bench to patient. The final cleanroom should be designed to meet the needs outlined in this commercialization plan. 

Question 5: How can the cleanroom be futureproofed? 

Change is inevitable, especially in the ATMP space. Designing a cleanroom with flexibility in mind is essential to accommodate potential future expansions and maintain adaptability as needs evolve. The host facility must be carefully selected to ensure it has the footprint and potential to expand or scale as needed. Designing the modular cleanroom with adaptability in mind can ensure the cleanroom can keep pace with advancements in technology and treatment modalities.

Considering these questions can give ATMP developers the expertise they need to ensure a successful cleanroom project that meets their current and future needs. This will accelerate the delivery of life-saving therapies to patients.

Time to harness alternative approaches to cleanroom design for ATMPs

Commercializing ATMP drug products requires substantial resources, including many experienced staff and tens of thousands of hours. To expedite the delivery of treatments to patients, it is crucial to prioritize and implement a comprehensive facility execution plan as early as possible.

Modular approaches to cleanroom deployment offer significant advantages in terms of capital expense control and ongoing operational benefits that align with market objectives. These modular cleanroom facilities will play a pivotal role in ensuring the safe and effective delivery of ATMP therapies in the future. Collaborating with a cleanroom vendor specializing in modular solutions empowers ATMP developers and manufacturers to overcome the challenges of this rapidly evolving field and accelerate the delivery of life-saving treatments.

References

1. American Society of Gene & Cell Therapy. (2024). Gene, Cell, and RNA Therapy Landscape Q3 2024 Report. https://www.asgct.org/publications/landscape-report 
2. https://straitsresearch.com/report/advanced-therapy-medicinal-products-market

Karen Winterbottom is architectural design manager at AES Clean Technology, a modular cleanroom facilities provider for high-performance manufacturing customers engaging in clinical research through commercial manufacturing, addressing unmet medical needs in areas such as immunotherapy, diabetes, cancer, and various other debilitating conditions. For more information about AES Clean Technology, please visit www.aesclean.com.