Work Item
ASTM WK76861

New Practice for In vivo analysis of nanoparticle-mediated physiological changes accompanying hypersensitivity reactions

1. Scope

This practice covers the rationale, features, units, definitions and technical execution of the porcine model of complement activation-related pseudoallergy (CARPA), an in vivo test enabling sensitive and quantitative assessment of non-IgE-mediated Type I (pseudoallergic) hypersensitivity reactions (HSRs) caused by i.v. administered nanoparticulate drugs and agents, commonly referred to as nanomedicines (NMs).




Severe manifestations of NM-induced HSRs (also known as infusion, or anaphytlactoid reactions), are usually rare (occur in less than 5% of patients), but occasional deaths (0.1%) still can occur. Despite decades of research showing that the incidence of such HSRs depends on both drug and patient features, it is largely unknown why some NMs and patients are prone to these reactions and why others are not. For this reason, assessing the reactogencity of NMs in an animal model of reactive, i.e. hypersensitive people, is an important preventive measure. Pigs provide such a model as injection of small amounts of reactogenic NMs in pigs can quantitatively reproduce some of the human symptoms of severe HSRs. These include, but not limited to systemic and pulmonary hemodynamic changes (hypo or hypertension), cardiac and pulmonary dysfunction, blood cell alterations, rises of inflammatory mediators in blood. As an acute disease model (i.e., hypersensitivity to reactogenic NMs) the porcine test enables preclinical evaluation of nanomedicine safety, in particular, the risk of anaphylactoid reactions to HSRs to NMs potentially observed in hypersensitive individuals.

The title and scope are in draft form and are under development within this ASTM Committee.


Developed by Subcommittee: E56.03

Committee: E56

Staff Manager: Frank McConnell

Work Item Status

Date Initiated: 05-10-2021

Technical Contact: Marina Dobrovolskaia

Item: 002

Ballot: E56.03 (21-02)

Status: Negative Votes Need Resolution