The FDA released a draft guidance for the development of drugs that use nanomaterials, stating the importance of describing and analyzing nanomaterials and their attributes in a product’s finished form.
The guidance suggests drugmakers include a description of the nanomaterials in the product, covering size, charge, composition, complexation and morphology, in order to ensure consistent quality. The agency also suggested that functionality be included.
Only nanomaterial properties that could affect a product’s performance, safety or quality should be defined, alongside potential risks posed from any changes. A nanomaterial of a different size or shape could be seen as a batch consistency issue if it affects the quality, efficacy or safety of the product.
The agency should be consulted if a common excipient is modified to be a nanomaterial or to be a part of one, the guidance said.
The guidance mentioned that the quality, efficacy and safety of products containing nanomaterials can be sensitive to the production environment and manufacturing process — recommending that environmental controls be established in the early development stages, to avoid cross-contamination.
In addition, carriers consisting of nanomaterials that are missing, empty or have incomplete surface coatings could be considered an impurity, and require quantifying.
The guidance also suggested developers assessing a product’s stability should consider potential factors that could affect a product’s performance — including, but not limited to:
- Changes to particle and size distribution
- Changes to particle morphology
- Self-association (including agglomeration or aggregation)
- Change in surface charge (e.g. zeta potential)
- Changes in dissolution/release rate of active ingredient
- Drug leakage from a nanomaterial carrier
- Degradation of particle (e.g. removal or exchange of surface ligands)
- Interaction with formulation or container closure (e.g. compatibility, or denaturing of proteins)
- Changes to reconstitution properties of the product
- Changes in the solid state (e.g. crystal structure)