Report of the AAPS Guidance Forum on the FDA Draft Guidance for Industry: "Drug Products, Including Biological Products, that Contain Nanomaterials"

Abstract

To guide developers of innovative and generic drug products that contain nanomaterials, the U.S. Food and Drug Administration issued the draft guidance for industry titled: "Drug Products, Including Biological Products, that Contain Nanomaterials" in December 2017. During the AAPS Guidance Forum on September 11, 2018, participants from industry, academia, and regulatory bodies discussed this draft guidance in an open setting. Two questions raised by the AAPS membership were discussed in more detail: what is the appropriate regulatory pathway for approval of drug products containing nanomaterials, and how to determine critical quality attributes (CQAs) for nanomaterials? During the meeting, clarification was provided on how the new FDA center-led guidance relates to older, specific nanomaterial class, or specific product-related guidances. The lively discussions concluded with some clear observations and recommendations: (I) Important lessons can be learned from how CQAs were determined for, e.g., biologics. (II) Publication of ongoing scientific discussions on strategies and studies determining CQAs of drug products containing nanomaterials will significantly strengthen the science base on this topic. Furthermore, (III) alignment on a global level on how to address new questions regarding nanomedicine development protocols will add to efficient development and approval of these much needed candidate nanomedicines (innovative and generic). Public meetings such as the AAPS Guidance Forum may serve as the place to have these discussions.

Fig. 1

Distribution of nanomaterials use in drug products from 1973 to 2015. Breakdown of the types of nanomaterials used in drug products. The nanotechnology terminologies do not represent any implication for CDER drug product labeling and were used only to describe/interpret the type of nanomaterials in identified drug products for the purpose of this analysis (adapted from 4)

Fig. 2

Example on how FDA guidances on the same general subject relate to each other

Fig. 3

The complex drug landscape (illustrative). Drug products are positioned on the basis of the challenge to assess pharmaceutical equivalence (PE) and bioequivalence (BE) of two drug products (i.e., the reference product and its generic version). Conventional low-molecular-weight drugs that can be fully characterized are shown in orange; demonstration of PE and BE is relatively simple. Biologics are shown in green, NBCDs are shown in blue, and other complex drugs are shown in gray. Albumin-bound nanoparticles and low-molecular-weight heparins are blue with a green outline (classification of these drugs varies across the globe). Adapted from Hussaarts et al. (10)