As nanomedicines such as liposomes, nucleic acid lipid nanoparticles including mRNA-LNPs, polymeric micelles, and nanocrystals continue to advance rapidly, drug delivery has entered the era of nano-engineering.
The efficacy and safety of these products are fundamentally determined by their nanoscale structural attributes. Particle size, morphology, surface chemistry, drug loading efficiency, and structural stability together form a unique nano-fingerprint of the product.
Milestone Pharma understands the full-chain challenges involved in nanomedicine development, from early-stage research to regulatory filing.
Leveraging our FDA-audited cGMP-compliant laboratory and advanced characterization technology platforms, Milestone Pharma provides full-lifecycle nanoparticle characterization and quality research services covering formulation, process, structure, stability, and comparability. We precisely characterize critical quality attributes such as particle size distribution, particle concentration, drug loading and release, and surface properties, molecular weight, aggregation, delivering systematic and reliable data to support nanomedicines from concept to clinical development and from product development to global registration.
01 Core Characterization Requirements under Global Regulatory Convergence
Major global regulatory agencies have reached a scientific consensus that nanomedicines must undergo systematic physicochemical characterization.
China NMPA:
The Technical Guideline for Quality Control Research of Nanomedicines (Trial) emphasizes comprehensive studies of particle size distribution, particle concentration, encapsulation efficiency, Zeta potential, and structural integrity.
U.S. FDA:
According to the guidance on drug products, including biological products, that contain nanomaterials, a thorough understanding of nanoscale attributes is required as the basis for safety and efficacy evaluation.
European EMA:
The reflection paper on nanotechnology-based medicinal products systematically outlines in-depth expectations for nanomedicine characterization.
United States Pharmacopeia (USP):
General Chapter <1153> provides a methodological framework, while the emerging draft Chapter <1155> establishes a new reference model for the characterization of complex nanocolloidal products.
Core Principle:
A multidimensional physicochemical characterization strategy is essential to demonstrate comprehensive product understanding and to establish critical quality attributes associated with process parameters and product performance.
02 Our Solution: A Full-Dimensional Characterization System Based on Orthogonal Methods
Core Technology Platform Overview
Our analytical system covers the complete chain from macroscopic physical properties to microscopic chemical states.
1. Physical Properties and Primary Morphology Analysis
Target Attributes:
Particle size distribution, particle concentration, Zeta potential, and primary morphology.
Core Technology Portfolio:
Dynamic light scattering (DLS), nanoparticle tracking analysis (NTA) / tunable resistive pulse sensing (TRPS), electrophoretic light scattering (ELS), and atomic force microscopy (AFM).
2. Advanced Structure and Absolute Molecular Weight Analysis
Target Attributes:
High-resolution morphology, internal structure, crystallinity, absolute molecular weight, and molecular weight distribution.
Core Technology Portfolio:
Cryogenic transmission electron microscopy (Cryo-TEM), small-angle X-ray scattering (SAXS), X-ray diffraction (XRD), asymmetrical flow field-flow fractionation coupled with multi-angle light scattering and DLS (AF4-MALS-DLS), and analytical ultracentrifugation (AUC).
3. Drug Loading, Release, and Surface Functionality Analysis
Target Attributes:
Encapsulation efficiency, drug loading, in vitro release kinetics, and surface chemical modification.
Core Technology Portfolio:
Analytical ultracentrifugation (AUC), dialysis / ultrafiltration coupled with HPLC, nuclear magnetic resonance such as ³¹P-NMR, electron paramagnetic resonance (EPR), and X-ray photoelectron spectroscopy (XPS).
4. Composition and Stability In-Depth Analysis
Target Attributes:
Lipid / polymer composition, degradation products, phase transition behavior, and elemental analysis.
Core Technology Portfolio:
Liquid chromatography–high-resolution mass spectrometry (LC-HRMS), micro differential scanning calorimetry (mDSC), inductively coupled plasma mass spectrometry (ICP-MS), and thermogravimetric analysis (TGA).
Featured Technologies
AF4-MALS-DLS:
AF4-MALS-DLS enables gentle, high-resolution separation of complex formulations such as liposomes, lipid nanoparticles, and polymeric micelles. It simultaneously provides absolute molecular weight, hydrodynamic radius, and particle concentration, making it a powerful tool for analyzing aggregates and subpopulation distributions.
AUC:
As an absolute method without a stationary phase, AUC can accurately determine molecular weight, sedimentation coefficient, and density under near-physiological conditions. It is one of the gold-standard techniques for verifying drug loading efficiency and detecting trace aggregates.
Cryo-TEM:
Cryo-TEM allows direct visualization of nanoparticle morphology and internal structure in a near-native hydrated state, providing direct evidence for lipid bilayers, LNP cores, and other nanoscale architectures.
SAXS:
SAXS provides in-solution, non-destructive statistical information on average particle size, shape, and internal electron density distribution. It serves as an ideal complement to imaging-based techniques.
03 A Service System Covering the Full Drug Development Lifecycle
Milestone Pharma’s nanoparticle characterization and quality research services go beyond data generation. We serve as a scientific extension of our clients’ R&D teams.
1. Formulation and Process Development Support
We help establish quantitative relationships between critical process parameters and CQAs, guiding formulation optimization and process finalization in line with the principles of Quality by Design.
2. Stability and Comparability Studies
We monitor structural evolution trends of nanomedicines under storage conditions and provide comprehensive comparability characterization reports to support process changes, scale-up, and generic product development.
3. Method Development and Validation
We develop and validate highly discriminating, product-specific analytical methods to ensure that critical quality changes affecting product performance can be effectively detected.
4. Regulatory Filing Strategy Consulting
Based on our in-depth understanding of global regulatory guidelines, we provide professional consulting on submission pathways and CMC documentation for complex nanomedicines, including mRNA-LNPs and ADC-related systems.
04 Milestone Pharma’s Core Strengths
Scientific and Regulatory Expertise:
Our advanced instrumentation platforms are integrated with strong regulatory insight, helping ensure that study designs and data packages meet the expectations of regulatory authorities in China, the United States, and Europe.
Systematic Orthogonal Characterization Capability:
We do not deliver isolated datasets. Instead, we apply orthogonal technology combinations to build a robust and reliable scientific portrait of nanomedicine products.
End-to-End Project Support:
From study design to report generation, we provide one-stop services with transparent and efficient communication throughout the project lifecycle.
Rigorous Quality and Compliance System:
Our laboratory operates in accordance with cGMP requirements, with data management aligned with international compliance expectations such as FDA 21 CFR Part 11, supporting the global use of generated data.
05 Conclusion
From Doxil® to Onpattro®, the development history of nanomedicines has shown that precise structural understanding and controllable manufacturing are fundamental to clinical success.
As global regulatory expectations continue to increase, systematic characterization has become essential.
With an integrated characterization platform and an experienced scientific team, Milestone Pharma supports pharmaceutical companies in:
• Establishing robust quality control strategies
• Overcoming scientific challenges in global regulatory filing
Only by achieving precise insight and control at the nanoscale can the full therapeutic potential of innovative therapies be safely and effectively delivered to patients.
