Home
This Title All WIREs
WIREs RSS Feed
How to cite this WIREs title:
WIREs Nanomed Nanobiotechnol
Impact Factor: 6.14

Nonclinical regulatory immunotoxicity testing of nanomedicinal products: Proposed strategy and possible pitfalls

Full article on Wiley Online Library:   HTML PDF

Can't access this content? Tell your librarian.

Abstract Various nanomedicinal products (NMPs) have been reported to induce an adverse immune response, which may be related to their tendency to accumulate in or target cells of the immune system. Therefore, before their market authorization, NMPs should be thoroughly evaluated for their immunotoxic potential. Nonclinical regulatory immunotoxicity testing of nonbiological medicinal products, including NMPs, is currently performed by following the guideline S8 “Immunotoxicity Studies for Human Pharmaceuticals” of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). However, this guideline does not cover all the immunotoxicity endpoints reported for NMPs in the literature, such as complement activation related pseudo allergy, hypersensitivity and immunosuppression. In addition, ICH‐S8 does not provide any nanospecific testing considerations, which is important given their tendency to interfere with many commonly used toxicity assays. We therefore propose a nonclinical regulatory immunotoxicity assessment strategy, which considers the immunotoxicity endpoints currently missing in the ICH‐S8. We also list the known pitfalls related to the testing of NMPs and how to tackle them. Next to defining the relevant physicochemical and pharmacokinetic properties of the NMP and its intended use, the proposed strategy includes an in vitro assay battery addressing various relevant immunotoxicity endpoints. A weight of evidence evaluation of this information can be used to shape the type and design of further in vivo investigations. The final outcome of the immunotoxicity assessment can be included in the overall risk assessment of the NMP and provide alerts for relevant endpoints to address during clinical investigation. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials
Flow diagram of current regulatory immunotoxicity evaluation of nonbiological pharmaceuticals. Adapted from guideline ICH‐S8
[ Normal View | Magnified View ]
Proposed paradigm for preclinical testing of inflammasome activation after administration of nanomedicinal products
[ Normal View | Magnified View ]
Proposed paradigm for preclinical testing of effects on macrophage function after administration of nanomedicinal products
[ Normal View | Magnified View ]
Proposed paradigm for preclinical testing for CARPA induction by nanomedicinal products, modified from the suggested paradigm by Szebeni and Storm (2015)
[ Normal View | Magnified View ]
Proposed regulatory immunotoxicity evaluation strategy of nanomedicinal products
[ Normal View | Magnified View ]

Browse by Topic

Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials
Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

The latest WIREs articles in your inbox

Sign Up for Article Alerts