The rise of advanced therapy medicinal products (ATMPs) marks a new era in medicine, offering unprecedented possibilities for treating previously intractable diseases. These cutting-edge therapies are transforming the healthcare landscape, bringing hope to patients and driving innovation across the life science industry as personalized treatments.
However, the growth of the ATMP platform also presents unique challenges for developing and manufacturing these complex therapies, including the need for meticulously designed and controlled environments to ensure the safety and quality of the product. Consequently, carefully planned cleanrooms play a vital part in meeting these stringent requirements.
In this article, Matthew Dean, Director of Process Architecture at AES Clean Technology, explores the critical role of cleanrooms in ATMP development and manufacturing, examining the specific challenges these innovative therapies pose throughout cleanroom design. Leveraging his unique insight, Matt highlights the advantages of modular cleanroom solutions and outlines key considerations for ATMP developers embarking on cleanroom projects.
The rapid rise of ATMPs
ATMPs are revolutionizing the way to treat diseases. These cutting-edge therapies, including gene, cell and tissue-engineered therapies, hold immense promise for treating a wide range of diseases, rare genetic disorders, various forms of cancer, neurological conditions and metabolic disorders [1].
The global ATMP market is experiencing remarkable growth, fueled by advancements in methodologies and technologies with an expanded understanding of molecular and cellular biology. In 2023 alone, the market was valued at USD 11.99 billion and projected to reach USD 35.59 billion by 2032, reflecting the rapidly rising demand for these innovative treatments [2].
This surge in ATMP development brings new hope for patients and healthcare providers alike. With thousands of therapies in various stages of development, targeting diverse therapeutic areas, ATMPs are poised to revolutionize how we approach disease treatment and prevention [1].
However, realizing the potential of ATMPs and supporting their rising demand necessitates the development of highly specialized and controlled facilities capable of supporting the complex manufacturing processes and stringent quality standards. Cleanrooms play a key role in ensuring operator and product safety with the adaptability required for these advanced therapies as a core component of these technical facilities.
The unique challenges of ATMP cleanrooms
ATMPs present specific challenges for cleanroom design and operations. As ATMP manufacturing operations often involve intricate processes (often manual steps), sensitive materials and the handling of patient-derived cells or tissues, they demand stringent control over contamination with a focus on containment strategies and room environment conditions. The operational challenges and potential manual processing involved in both autologous and allogeneic cell and gene therapy (C>) production platforms, in particular, introduce special cleanroom design requirements.
- Autologous therapies
As autologous C> treatments are highly personalized, their production relies on harvesting the cells of individual patients for modification and reintroduction. With autologous C> development and manufacturing processes beginning and ending with the patient, ideally, these procedures would take place in a cleanroom environment logistically closer to medical centers, significantly improving the speed-to-patient and product quality. The layouts for these cleanrooms must support patient-specific workflows while minimizing the risk of cross-contamination or mix-ups. This requires meticulous segregation of materials, personnel, processing with rigorous adherence to aseptic techniques and robust quality control measures.
- Allogeneic therapies
Allogeneic therapies, while also developed from human cells, are donor-derived and manipulated to treat groups of patients, subsequently presenting a different set of challenges. The cleanroom infrastructure must enable efficient plus scalable processing and segregation of donor-derived materials, ensuring the safety and integrity of the final product. This necessitates careful integration of the process workflow, proper segregation of flows, alignment on process automation and contamination prevention strategies into the cleanroom design.
In response to these unique challenges posed by ATMP operations, with their intricate processes, vulnerable materials and patient-specific considerations, developers and manufacturers are under rising pressure to ensure their cleanroom facility meets their complex needs.
Cleanroom design to meet the needs of ATMPs
As the field of ATMPs continues to advance, the need for specialized cleanroom facilities is expanding in parallel. However, traditional stick-built cleanrooms, while functional, can present significant drawbacks in the fast-paced and demanding world of ATMP development.
Stick-build cleanroom construction projects can be time-consuming, requiring extensive on-site labor and intricate coordination of various trades (including electricians, HVAC and plumbing contractors) all while needing to ensure meticulous attention to detail. This complexity increases the likelihood of unforeseen delays, cost overruns, potential disruptions to ongoing operations with a stalled product launch.
As a result, modular cleanrooms have been proven as a game-changing solution to address the specific needs of ATMP development and manufacturing while addressing the demand for speed-to-patient. Unlike traditional stick-built construction, modular cleanrooms utilize prefabricated components manufactured in a controlled environment and assembled on-site. This modular approach delivers several key advantages for ATMPs:
- Speed and efficiency
Speed is crucial in the fast-paced world of ATMP development, where getting treatments to patients quickly can significantly improve health outcomes and even save lives. Modular cleanrooms can be constructed and deployed rapidly, accelerating time-to-market for these critical therapies. This streamlined approach eliminates the need to coordinate multiple contractors and trades, significantly reducing complexities and potential delays associated with traditional construction.
By providing a single-source solution for cleanroom design, manufacturing and installation, modular construction allows ATMP developers to focus on their core competencies while ensuring their facilities are delivered with speed and efficiency.
- Flexibility and adaptability
The modular approach can accommodate various facility layouts and configurations, addressing challenges posed by different host building types. This adaptability is particularly crucial for ATMPs, which are often developed in diverse settings, ranging from academic scale research labs in conjunction with hospitals to industrial manufacturing facilities. Whether integrating cleanrooms into existing infrastructure or constructing new purpose-built facilities, the modular approach ensures that cleanrooms can be seamlessly incorporated, minimizing disruption and maximizing efficiency.
The modular nature of these cleanrooms also allows for efficient reconfiguration and expansion of rooms as processes evolve or new therapies emerge. This adaptability to process operations is essential in the rapidly evolving and dynamic ATMP landscape and the flexibility is key to accommodating future needs and advancements in technology.
- Compliance and safety
Modular cleanrooms are designed and constructed to meet or exceed stringent regulatory requirements, ensuring the safety and quality of ATMPs. They also promote standardization and consistency across facilities, ensuring the seamless tech transfer across different facilities and teams. This is especially beneficial for organizations with multiple locations or those collaborating with partners or contract manufacturers. By utilizing standardized modular components and designs, companies can ensure consistency in their ATMP production processes, regardless of location, contributing to greater efficiency, reduced risk and improved product quality.
- Cost-effectiveness and operational efficiency
Modular cleanrooms offer significant capital expense control and ongoing operational benefits, contributing to the long-term financial sustainability of ATMP development and manufacturing.
By streamlining the construction process and minimizing on-site complexities, modular cleanrooms also reduce the operational risks associated with ATMP manufacturing, contributing to improved commercial viability and scalability.
Preparing for ATMP cleanroom project success
Realizing the benefits that modular cleanrooms can provide for the expanding ATMP market relies on developers and manufacturers having a project plan that carefully considers the technical and regulatory aspects of cleanroom design. This plan must also encompass the logistical, operational and compliance aspects of ATMP manufacturing, ensuring that the facility supports the unique needs of these advanced therapies. There are a number of key steps that ATMP producers must follow when developing this plan to ensure project success and the timely delivery of these life-saving treatments to patients:
- Forecast product supply and demand
A crucial first step is to thoroughly assess the anticipated demand for the ATMP and align the cleanroom facility’s capacity accordingly. This involves understanding the current market size and forecasting future needs, considering factors such as patient population, clinical trial outcomes and potential market expansion. Accurately forecasting demand ensures that the cleanroom facility can accommodate both current and future production needs, avoiding costly bottlenecks or delays in getting therapies to patients.
- Determine make vs. buy
ATMP developers and manufacturers must carefully evaluate whether to produce the product in-house, outsource production or consider dividing operations to a contract manufacturing organization (CMO). In-house cleanroom facilities enable drug developers to cultivate internal process knowledge and more effectively protect intellectual property. ATMPs generally require smaller production footprints than other sterile drug manufacturing, meaning building these facilities in-house could be within reach even for developers in early lifecycle capital investment.
- Know the process
Developing a comprehensive understanding of the intricacies of the process and how they translate to cleanroom requirements is essential. This includes mapping out the process and ensuring a thorough understanding of the parameters and restrictions of each component. This detailed assessment will help ATMP developers and manufacturers identify the most suitable approach for their specific needs.
- Strategize a commercialization plan
The route from bench to patient might be longer if drug developers and manufacturers do not plan ahead. Minimally, a commercialization plan will guide them from Phase 2 through product launch. Ideally, a robust plan will include the ongoing support of clinical pipeline drug product candidates. They should define their regulatory strategy from the outset and tie their product vision with flexible planning to be sure they can supply their product to market.
- Select a host facility carefully
Pharmaceutical developers and manufacturers must dream big while practicing effective due diligence, considering the practical concerns of host facility candidates, including utilities, infrastructure and patient supply distribution proximity. ATMP producers should know their footprint needs and potential to expand or scale their facilities.
- Expect growth
Change is inevitable in the dynamic ATMP landscape. Designing a cleanroom with flexibility in mind is essential to accommodate potential future expansions and maintain adaptability as needs evolve.
- Anticipate advancements
ATMP technologies and treatments are constantly evolving. Future-proofing the facility by planning for adaptability ensures the cleanroom can keep pace with advancements in technology and treatment modalities.
By carefully considering these factors, ATMP developers can lay the foundation for a successful cleanroom project that meets their specific needs now and in the future, accelerating the delivery of these life-saving therapies to patients.
Powering the future of ATMPs with the right cleanroom design
As the field of ATMPs continues its rapid evolution, modular cleanrooms have emerged as a critical enabler of innovation and progress. By providing a flexible, efficient and compliant solution for the development and manufacture of these advanced therapies, modular cleanrooms are accelerating the delivery of life-saving treatments to patients in need.
Looking ahead, the role of modular cleanrooms in the ATMP space is only set to expand. As the industry continues to innovate and push the boundaries of personalized medicine, modular cleanrooms will remain an integral aspect of this journey, providing the infrastructure and flexibility needed to bring these transformative therapies to market. By partnering with a cleanroom vendor embracing modular solutions, ATMP developers and manufacturers can confidently navigate the challenges of this rapidly evolving field and accelerate the delivery of life-saving treatments.
References:
- American Society of Gene & Cell Therapy. (2024). Gene, Cell, and RNA Therapy Landscape Q3 2024 Report. https://www.asgct.org/publications/landscape-report
- https://straitsresearch.com/report/advanced-therapy-medicinal-products-market