Table 2.

Cumulative CQAs for general types of nanomedicine according to different regulatory bodies

Critical parameter	Health Canada [49] (nanomaterial)	FDA [42] (nanopharmaceuticals)	DBT [50] (nanopharmaceuticals)
Composition Entrapment efficacy Drug loading	• Composition • Identity	• Chemical composition • Assay of drug substance	• Complete description of individual component(s) [e.g., API, nanocarrier material (single/multiphase) surface functional groups, contrast agents (theranostic), excipients, targeting ligands, etc.] • Encapsulation efficiency, loaded versus free drug content, with standard deviation • Percentage of drug loading with standard deviation
Size	• Particle size/size distribution	• Average particle size • Particle size distribution (PSD) (description of d10, d50, d90, or polydispersity; modality) • Particle concentration	• Nano-size range by number and/or intensity distribution, average size and polydispersion index, percentage of particle under each distribution with standard deviation • Molecular weight (drug and nanomaterials)
Morphology	• Morphology	• General shape and morphology (aspect ratio) • Coating properties, including how coatings are bound to the nanomaterial • Porosity (if it relates to a function, e.g., capacity to load a drug)	• Shape, surface texture information • State of drug (API) in nanomaterial (chemically conjugated/loaded/complexed with the nanocarrier)
Stability	• Agglomeration/aggregation (or other properties) • Chemical reactivity	• Stability, both physical (e.g., aggregation and agglomeration or separation) and chemical • Particle concentration • Distribution of any drug substance associated with the nanomaterial and free in solution (e.g., surface bound or liposome encapsulated versus free drug substance)	• Colloidal stability information for injections (06 batches)
Structure Surface Nomenclature General properties	• Structural integrity • Surface area/chemistry/charge/structure/shape • Surface-to-volume ratio • Water solubility/dispersibility • Electrical/mechanical/optical properties	• Structural attributes that relate to function (e.g., lamellarity, core–shell structure) • Surface properties (e.g., surface area, surface charge, chemical reactivity, ligands, hydrophobicity, and roughness) • Crystal form	• Empirical formula (drug and nanomaterials) • Chemical name, structure, crystal structure of drug and nanomaterial(s) • Surface charge with standard deviation (zeta potential) • Mechanical integrity/Properties (as applicable) • Viscosity (wherever applicable) • Average pH (wherever applicable) • Osmolality (wherever applicable) • Solubility/dispersion information (for injectable product)
Impurities	• Purity	• Impurities	• Residual solvent content as per ICH guidelines
Sterility Apyrogenicity	---	• Sterility, endotoxin levels, and pyrogenicity	• Endotoxin/microbial load level for parental nanoformulations • Sterilization protocols/methods/stability post sterilization (as applicable)
Drug release	---	• In vitro release	---
Other	• Descriptions of the methods used to assign these determinations • Catalytic or photo-catalytic activity	• Biodegradability of the nanomaterials and their constituents • Compatibility of the nanomaterial relevant to in-use conditions	• Scalable GMP process description of the nanopharmaceutical preparation • Waste disposal method