Current hurdles to the translation of nanomedicines from bench to the clinic

Abstract

The field of nanomedicine has significantly influenced research areas such as drug delivery, diagnostics, theranostics, and regenerative medicine; however, the further development of this field will face significant challenges at the regulatory level if related guidance remains unclear and unconsolidated. This review describes those features and pathways crucial to the clinical translation of nanomedicine and highlights considerations for early-stage product development. These include identifying those critical quality attributes of the drug product essential for activity and safety, appropriate analytical methods (physical, chemical, biological) for characterization, important process parameters, and adequate pre-clinical models. Additional concerns include the evaluation of batch-to-batch consistency and considerations regarding scaling up that will ensure a successful reproducible manufacturing process. Furthermore, we advise close collaboration with regulatory agencies from the early stages of development to assure an aligned position to accelerate the development of future nanomedicines.

Keywords: Characterization; Manufacturing; Nanomedicine translation; Regulatory framework; Scale-up.

Fig. 1

Approaches for nanomedicine manufacture

Fig. 2

Representation of those critical material attributes (CMA) and critical process parameters (CPP) that cause discrepancy and variability of critical quality attributes (CQAs) during the rational design and production of nanomedicines

Fig. 3

Critical and additional parameters of nanomedicines and corresponding analytical techniques for their characterization (NCL approved techniques are highlighted). LC–MS/MS liquid chromatography–mass spectrometry, FFF field flow fractionation, NMR nuclear magnetic resonance, AUC analytical ultracentrifugation, RS remote sensing, IR infrared, HPLC–UV high-performance liquid chromatography-ultraviolet, Vis-FLD visible-fluorescence detector, ATR-FTIR attenuated total reflection—Fourier transform infrared spectroscopy, NOESY-NMR nuclear Overhauser effect spectroscopy-nuclear magnetic resonance, SANS small angle neutron scattering, SAXS small angle x-ray scattering, FRET fluorescence resonance energy transfer, CD circular dichroism, PT potentiometry, TEM transmission electron microscopy, EM electron microscopy, GC–MS/MS gas chromatography–mass spectrometry, LAL assay limulus amebocyte lysate assay, PCR polymerase chain reaction, AF4-UV asymmetric field flow fractionation-ultraviolet, DLS dynamic light scattering, Cryo-TEM cryogenic transmission electron microscopy, FCS fluorescence correlation spectroscopy, SEC size-exclusion chromatography, PTA particle tracking analysis, Si silicon, Fe iron, Au gold