FDA Guidance for Industry: Drug Products, Including Biological Products, that Contain Nanomaterials
Summary
Final guidance stating FDA’s current thinking on developing and regulating human drug products (including biologics) when a nanomaterial is present in the finished dosage form. It applies existing regulatory frameworks and uses a case-by-case, risk-based approach—no separate “nanomedicine” pathway.
Key Principles & Scope
Covers products submitted in INDs, NDAs, ANDAs, BLAs, and DMFs where the nanomaterial may be the active or an excipient. The guidance does not consider products composed of naturally occurring biological materials at particle sizes up to ~1 µm (such as many gene therapies or vaccines) to be nanomaterials, unless they also contain deliberately engineered nanomaterial components.
How FDA treats “nanomaterial”
FDA does not set a formal definition but provides ‘points to consider,’ such as whether a material has ≥1 external dimension in the ~1–100 nm range or exhibits dimension-dependent properties (which may extend to ~1 µm).
Key considerations
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CMC/Quality: Provide thorough physicochemical characterization and controls. At minimum report chemical composition, average particle size, PSD (e.g., d10/d50/d90 or PDI), morphology/aspect ratio, and physical/chemical stability; consider additional attributes such as surface area/charge (zeta), coatings, porosity, particle concentration, in-vitro release, crystal form, impurities, sterility/endotoxin, biodegradability. Use complementary, fit-for-purpose methods.
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Nonclinical: Tailor studies to potential ADME/PK differences and method suitability; address modality-specific risks (e.g., immunogenicity where relevant).
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Clinical / BE (where applicable): Design trials to capture possible PK/PD shifts caused by nanomaterials; for ANDAs, additional physicochemical comparisons and, when needed, in vivo BE may be required.