Update on Transportable and Point of Care Manufacturing

In a presentation by Celeste Frankenfeld Lamm, PhD, Senior Director – Global Quality and Regulatory Chemistry, Manufacturing, and Controls (CMC) Policy and Advocacy – Merck at the 2025 ISPE Annual Meeting & Expo on 27 October, she explored the reasons behind the shift, its implications for patients, and how industry and regulators can collaborate to make it a reality. The speaker presented on behalf of the Transportable/PoC Manufacturing Team within ISPE, focusing on regulatory and technological shifts in pharmaceutical manufacturing.

Navigating the Challenges of Advanced Pharmaceutical Manufacturing

As pharmaceutical manufacturing evolves toward distributed, modular, and PoC models, the promise of greater accessibility and agility comes with a complex set of challenges. These innovative approaches—designed to bring therapies closer to patients and improve supply resiliency—must still meet the highest standards of safety, efficacy, and quality. That’s easier said than done when production moves from traditional large-scale facilities to hospitals, remote clinics, or even mobile units.

As Lamm presented, one of the most pressing issues lies in quality assurance for personalized therapies. PoC manufacturing often involves extremely small batches, sometimes down to an “N of one.” Traditional control strategies—such as extensive release testing and maintaining retained samples—are simply not feasible in these scenarios. To compensate, manufacturers need advanced technologies for real-time monitoring and process automation to ensure compliance with good manufacturing practices (GMP) without adding complexity for operators.

Workforce readiness adds another layer of difficulty. These facilities may be staffed by individuals unfamiliar with GMP requirements, making simplification and automation critical to reduce human error and maintain consistent standards.

Lamm emphasized that regulatory oversight is another major hurdle. Distributed manufacturing, while closer to conventional models, still requires careful oversight to manage risk across multiple sites. The proliferation of manufacturing sites complicates inspections, prompting proposals for risk-based approaches, control sites, and master files to centralize compliance documentation.

Unfortunately, it seems as if regulators are responding at different speeds: the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) leads the way with updated legislation and detailed guidance, introducing concepts like control sites and modular manufacturing pathways. The US Food and Drug Administration (US FDA), while actively exploring advanced manufacturing through its Framework for Regulatory Advanced Manufacturing Evaluation (FRAME) initiative, has yet to issue formal guidance. Meanwhile, the European Medicines Agency (EMA) is in the midst of a multi-year legislative update that includes decentralized manufacturing, but harmonization remains elusive.

And that’s the crux of the global challenge: lack of alignment. Terminology varies (e.g., “distributed” in the US vs “decentralized” in Europe) and definitions of PoC manufacturing differ widely. Aligning this language is essential to ensure clarity and consistency in regulatory expectations.

Without harmonized language and regulatory frameworks, companies face uncertainty when implementing these models across borders. The European Union’s restriction that decentralized sites remain within its borders further limits distributed manufacturing as a global solution. Expanding mutual recognition agreements and reliance mechanisms for inspections and submissions will be essential to unlock the full potential of these technologies.

Lamm has posited that, despite these obstacles, there is reason for optimism. International forums like the International Pharmaceutical Regulators Programme (IPRP) and the Pharmaceutical Inspection Co-operation Scheme (PIC/S) are already discussing harmonization, and there’s growing momentum toward an eventual International Council for Harmonisation of Technical Requirements (ICH) guideline for PoC and distributed manufacturing. Industry collaboration will be key—aligning terminology, quality systems, and training so that regulators encounter familiar, standardized approaches. She added that by working together, industry can create a future where therapies are accessible anywhere, tailored to individual needs, and produced with resilience against shortages.

Global Harmonization Needs

Pharmaceutical manufacturing is undergoing a profound transformation. Traditional large-scale facilities, while foundational, often fail to meet the evolving needs of patients and therapies. Drivers such as personalized medicine, drug shortage concerns, and government interest in domestic production are pushing the industry toward more agile, innovative approaches. The industry’s vision is clear: manufacturing that can move with the patient, medicines tailored to individual needs, and scalable production that prevents shortages.

At the heart of this shift are three emerging models Lamm discussed: distributed manufacturing, which standardizes processes across multiple sites; PoC manufacturing, enabling near-patient production; and transportable manufacturing, using modular units that can operate in remote environments or even Antarctica or space. These models promise accessibility and flexibility, but they also introduce new challenges for quality, safety, and regulatory compliance. Each model offers unique benefits and challenges; for example, distributed fleets minimize tech transfer burdens and maintain consistency, but they may sit across the boundaries of different inspectional authorities. PoC and transportable units enable personalized medicine but raise complex questions around quality systems implementation outside of a traditional GMP facility.

In her presentation, Lamm stated that several companies (that she is not affiliated with) are already pioneering these concepts. Some real-world examples that she discussed were:

• CAR-T Therapy: Germfree and Caring Cross deploy modular cleanrooms for local cell and gene therapy, piloting projects in Brazil to improve access and affordability
• PrivMed® Tablets: Personalized table production that tailors the tablet dose to the individual using precision weighing and digital controls
• BioNTainers® from BioNTech: Modular mRNA vaccine facilities are plug-and-play units enabling rapid pandemic response in underserved areas such as Rwanda. The company is planning for factories in Senegal and South Africa

Germfree and Caring Cross are deploying modular clean rooms for cell and gene therapy, while PrimMed in Europe offers the Paracelsus system for personalized tablets and capsules that can be thought of as a “medication Keurig®.” BioNTech is building modular mRNA vaccine facilities in Rwanda, aiming to expand across Africa and train local operators. These examples illustrate how technology can bring lifesaving and/or personalized treatments closer to patients who previously had limited access.

Beyond terminology, harmonizing regulatory approaches and inspection reliance is critical. As manufacturing shifts to distributed and PoC models, regulators must adopt frameworks that allow for shared oversight and mutual recognition of inspections. This will reduce duplication, streamline compliance, and enable faster deployment of innovative technologies across borders.

Lamm also expressed that there is growing momentum toward the development of an ICH guideline specifically addressing these advanced manufacturing models. Such a guideline would provide a global standard for terminology, quality systems, and regulatory pathways, paving the way for smoother implementation and greater patient access worldwide.

Vision for the Future

The vision for the future of pharmaceutical manufacturing is bold and transformative. Imagine a system where manufacturing moves with the patient—bringing therapies closer to the PoC rather than relying solely on centralized facilities. This approach enables personalized medicine to be accessible anywhere, whether in a hospital, a rural clinic, or even in remote environments.

Personalized medicine is at the heart of this vision. By tailoring treatments to individual needs, industry can improve outcomes and reduce waste, ensuring that patients receive exactly what they need when they need it. To achieve this, manufacturing must become agile, modular, and supported by advanced technologies that simplify processes and maintain quality.

Equally important is scalability. A future-ready manufacturing system must be capable of expanding rapidly to prevent shortages during emergencies, pandemics, or supply chain disruptions. By combining mobility, personalization, and scalability, the industry can create a resilient global network that delivers life-saving therapies wherever they are needed most.

Conclusion

Ensuring safety and efficacy in non-traditional settings requires real-time monitoring, automation, and simplified processes. Inspection complexity is another hurdle, prompting proposals for control sites and master files to oversee networks of manufacturing units. Lamm emphasized that global alignment is critical. Harmonizing language, regulatory approaches, and inspection reliance will pave the way for smoother implementation.

Lamm concluded by adding that the future of pharmaceutical manufacturing is dynamic, decentralized, and patient-focused. “The space is very dynamic now. So, I would encourage all of you to seize that opportunity to work together.”

By embracing advanced technologies and modular approaches, the industry can bring life-saving treatments closer to those who need them, whether in rural clinics, underserved regions, or even space. But innovation alone isn’t enough. Harmonized regulations, shared terminology, and collaborative frameworks are essential to ensure safety, quality, and scalability. The opportunity is now. Industry and regulatory collaboration can pave the way for a global system that delivers personalized medicine, prevents shortages, and transforms healthcare for generations to come.