Drugs containing nanomaterials: FDA finalizes 2017 guidance with several changes
The FDA on Thursday finalized a draft guidance from 2017 explaining the principles and specific considerations for developing drugs (biologics and gene therapies are excluded) containing nanomaterials, including via abbreviated pathways.
Considerations related to quality, nonclinical, and clinical studies are included in the 29-page final guidance, which also features “two noteworthy changes” from the draft version in response to stakeholder comments, according to the FDA.
“First, the final guidance provides a glossary of terminology to assist in understanding how important terms are used in the document,” the FDA said. The final version now includes definitions for terms like nanoemulsion (“A nanomaterial kinetically stabilized emulsion system, with at least one feature that falls into the size range of 1-1,000 nm”) and “Nanomaterial-associated Drug” (i.e. a drug that’s trapped, bound, encapsulated, or associated with a nanomaterial).
“Second, several revisions were made to reflect FDA’s current thinking with respect to abbreviated applications, including abbreviated new drug applications (ANDAs), for products containing nanomaterials,” the agency said in today’s Federal Register.
On the topic of generics, the final guidance explains how nanomaterials can range from simple nanocrystals, organic nanomaterials (e.g., liposome, polymeric nanoparticle), and inorganic nanomaterials (e.g., gold nanoparticles), to complex integrated nanoparticles (e.g., core-shell, surface modified nanoparticles), and ANDA applicants are “responsible for providing sufficient scientific evidence based on a comprehensive in vivo PK evaluation and in vitro physicochemical characterization to demonstrate bioequivalence between a proposed generic drug and its nanomaterial-containing RLD.
“In addition, for an active ingredient that is a nanomaterial, comprehensive characterization of the RLD [reference listed drug] and understanding of the fundamental chemistry used to form the active ingredient may be needed to demonstrate active ingredient sameness. Current thinking is that any critical structural change in the multiple components of nanomaterial-based products may influence the BE [bioequivalence], pharmacology, and toxicology profiles,” the guidance adds.
But ANDAs referencing oral drugs using nanomaterials to improve bioavailability for poor water-soluble drugs, according to the FDA, need not use that particular nanomaterial or any nanomaterial, but may use alternative strategies to achieve the same BA enhancement, the FDA adds.
In general, however, the guidance notes that a sponsor should evaluate the potential risk(s) associated with drugs containing nanomaterials and should assure: “(1) adequate characterization of the nanomaterial, and (2) adequate understanding of a nanomaterial’s intended use and application, and of how the nanomaterial attributes relate to product quality, safety, and efficacy. ”
In addition to changes in response to comments, the FDA also said that the final guidance document’s discussion regarding over-the-counter monograph drugs has been updated for consistency with the enactment of OTC reform provisions of the Coronavirus Aid, Relief, and Economic Security Act.