Module 9 2024

03/09/2024

Towards Harmonisation of Immunoassays?

Wadhwa M, Mytych DT, Bird C, Barger T, Dougall T, Han H, Rigsby P, Kromminga A, Thorpe R; Participants of the Study.

WHO/BS/2022.2430 ENGLISH ONLY

Establishment of the first WHO Erythropoietin antibody reference panel: Report of an international collaborative study .

EXPERT COMMITTEE ON BIOLOGICAL STANDARDIZATION Geneva, 24 to 28 October 2022 Proposed 1st WHO International Reference Panel for Infliximab anti-drug antibodies

J Immunol Methods. 2016 Aug;435:32-42. doi: 10.1016/j.jim.2016.05.005.

Wadhwa M, Subramanyam M, Goelz S, Goyal J, Jethwa V, Jones W, Files JG, Kramer D, Bird C, Dilger P, Tovey M, Lallemand C, Thorpe R.

Meenu Wadhwa, Isabelle Cludts, Eleanor Atkinson, Peter Rigsby

Use of a standardized MxA protein measurement-based assay for validation of assays for the assessment of neutralizing antibodies against interferon- β.

J Interferon Cytokine Res. 2013 Nov;33(11):660-71. doi: 10.1089/jir.2012.0079.

The Organisation for Professionals in Regulatory Affairs

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Reporting of Data

Regulatory expectations for immunogenicity assessment have evolved considerably over the past 2 decades.

Reporting of data should include (list not exhaustive):

rationale for choice of methods and sequence of testing

assays validation data

assays results - ADA incidence, titres, neutralising capacity of the antibodies

kinetic of ADA response (onset & duration - transient/persistent, presence of ADA after treatment)

impact of ADA on PK, PD, efficacy, safety; clinical relevance

Meeting regulatory expectations for ADA assessment can be a bioanalytical challenge (e.g., assay sensitivity, drug tolerance). Full assay validation packages are submitted for licence application (BLA) / marketing authorisation application (MAA) - methods not deemed validated until regulators review and agree.

The Organisation for Professionals in Regulatory Affairs

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