The authors survey nanotechnology platforms that aim not only to transport drugs, but to modulate immunity, direct regeneration and enable precision intervention at the cellular level. They range from cell-hitchhiking nanoparticles, biomimetic multivalent vaccines and implantable immunotherapy depots to high-loading polymeric micelles, organ-targeted gene and RNA carriers, and bio-hybrid extracellular vesicle and mitochondrial therapies.
That complexity has consequences for manufacturing. As nanomedicines expand in molecular complexity, the authors write, robust manufacturing and purposeful quality frameworks are essential to ensure reproducibility, safety and a scalable clinical supply. In her section on manufacturing, Meeuswissen covers a phase-appropriate CMC roadmap, quality by design, scale-up and purification.
Why complexity raises the bar for manufacturing
Nanomedicine pipelines traditionally encapsulated small molecules. Nowadays, they increasingly also incorporate peptides, proteins, plasmid DNA, mRNA and oligonucleotides into diverse nanoparticle architectures. This rise in structural and functional complexity demands coordinated chemistry, manufacturing and controls (CMC) strategies that unify process design with analytical development.
A phase-appropriate CMC roadmap
A phase-appropriate CMC roadmap de-risks translation by defining unit operations, control strategies and analytical requirements from early development through clinical manufacturing. A typical progression:
- 1. Process implementation
- 2. Development and scale-up
- 3. Demonstration batches to support toxicology and stability studies
- 4. GMP clinical manufacturing, guided by validated quality control and stability programs
How quality by design builds quality into nanomedicine
Quality by design (QbD) provides a structured pathway to embed quality directly into nanomedicine. Citing ICH Q8(R2), Q9(R1) and Q10, the sequence is:
- 1. Establish a quality target product profile (QTPP).
- 2. Identify critical quality attributes (CQAs).
- 3. Link these CQAs to critical process parameters (CPPs) through risk assessment and experimental mapping.
Common CQAs include particle size distribution, composition, impurity profile and microbiological attributes. CPPs that influence them include mixing intensity, solvent ratios, temperature, flow conditions and downstream purification. By defining how these CPPs influence CQAs, QbD frameworks reduce late-stage failure risk and limit the need for costly bridging studies.
Scaling up: batch or flow
Scalability is equally central to clinical readiness. Translating milliliter-scale research processes into multi-liter manufacturing requires selection of appropriate batch or flow modalities, each governed by unique self-assembly and mass-transfer constraints. Among the sources the authors cite is Ardena’s whitepaper on flow manufacturing for nanomedicines. Flow-based systems, for example, exert strong influence on lipid and polymer nanoparticle formation.
The foundation for clinical-grade nanomedicine
Taken together, QbD principles, scalable unit operations and advanced analytical characterization provide the foundation needed to reliably produce clinical-grade nanomedicine suited for increasingly complex therapeutic applications. These manufacturing and quality frameworks complete the perspective by connecting scientific innovation to the infrastructure required for successful clinical translation of nanomedicine.
The authors conclude on the same theme: the future landscape of nano- and micro-devices will be shaped by platforms that are multifunctional, self-modulating and organ-specific, with manufacturability and regulatory readiness embedded from inception.
This article is based on the review “Nanomedicine beyond carriers: devices, cells & living therapeutics” (Biomedical Microdevices, 2026), which you can read in full on Springer Nature.
Subject Matter Experts
Silvie Meeuwissen
Director Process R&D and Manufacturing Nanomedicines
Silvie Meeuwissen is Director Process R&D and Manufacturing Nanomedicines at Ardena Oss. She specializes in nanomedicine process development and pharmaceutical manufacturing, supporting the development of innovative precision medicine-based therapies. Since joining Ardena in 2013, Silvie has played a key role in the establishment and growth of Ardena’s nanomedicine services. In 2023, she became Director Process R&D and Manufacturing Nanomedicines, leading the department’s efforts in process development and manufacturing activities supporting advanced therapeutic programs. Silvie studied Organic Chemistry and obtained her PhD in Bio-organic Chemistry from Radboud University.
Frequently asked questions
Quality by design (QbD) is a structured pathway to embed quality directly into nanomedicine. It begins with establishing a quality target product profile (QTPP), identifying critical quality attributes (CQAs), and linking these to critical process parameters (CPPs) through risk assessment and experimental mapping. By defining how CPPs influence CQAs, QbD frameworks reduce late-stage failure risk and limit the need for costly bridging studies.
A phase-appropriate CMC roadmap defines unit operations, control strategies and analytical requirements from early development through clinical manufacturing. In doing so, it de-risks translation.
Common CQAs include particle size distribution, composition, impurity profile and microbiological attributes.