Elucidating the Impact of Immunogenicity Assessment Postapproval: A Targeted Analysis of Immunogenicity Postmarketing Requirements and Commitments

Abstract

Insufficient availability of data to evaluate immunogenicity incidence or clinical impact during regulatory review could require further evaluation postapproval. Through a keyword search of all postmarketing requirements and commitments (PMRs/PMCs) associated with products with their original US Food and Drug Administration (FDA) approvals between 2009 and 2018, we identified products that had PMRs/PMCs established to address concerns or uncertainty related to immunogenicity. Of the 113 relevant products, 50% had an immunogenicity‐related PMR/PMC; of these, 68% were related to developing immunogenicity assays and 48% requested an assessment of clinical impact. Fifty‐five percent of the products with a fulfilled PMR/PMC had a change in the immunogenicity information in their labeling immediately following fulfillment. This work highlights that there are often unknowns associated with immunogenicity incidence and/or impact at the time of approval. Earlier regulatory discussions on immunogenicity assessments in premarket development could improve the understanding and communication of the risk/benefit profile and reduce the need for some immunogenicity PMRs/PMCs.

Evaluation of atezolizumab immunogenicity: Clinical pharmacology (part 1)

“…On the other hand, ADA can impact safety without impacting exposure through offtarget effects. 12 A concept often overlooked is the association of baseline prognostic factors with treatment-emergent ADA development. We will describe the importance of prognostic factors that can potentially increase the chance of developing treatment-emergent ADA.…”

“…Furthermore, as shown in atezolizumab immunogenicity‐efficacy analyses (part 2 of this article series), neutralizing ADA did not lead to clinically relevant impact on efficacy. On the other hand, ADA can impact safety without impacting exposure through off‐target effects 12 …”

Toxicity Evaluation of Long-Term Topical Application of Recombinant Human Keratinocyte Growth Factor-2 Eye Drops on Macaca Fascicularis

“…Immunogenicity testing plays an essential role in verifying the non-clinical safety of therapeutic protein drugs, and it is used to determine the incidence, titer, duration, and neutralization 4) \( 1) _( 1) \( 1) _( 1) \( 1) _( 1) \( 1) _( 1 ability of anti-drug antibodies (Guinn et al, 2021). In this study, the anti-rhKGF-2 antibodies were only detected in animals no.…”

Investigation of Factors Associated With Immunogenicity Labeling Updates and Characteristics of Biologics License Applications

“…12 Therefore, postapproval surveillance is essential to reveal the evolving risk profile. [10][11][12]15 Moreover, concerns have been raised regarding the limited information displayed in labeling documents, which may impede appropriate patient management by clinicians, such as the employment of correct dosing strategies and awareness of situations requiring discontinuation of therapies. 6 The aim of this study is to characterize the evolution of immunogenicity information available in the FDA labeling documents in terms of both incidence/prevalence and the potential consequences thereof.…”

“…Evaluation of immunogenicity is a vital issue during the entire life cycle of the products 2,10–12,15 . Because of strict inclusion and exclusion criteria as well as the limited observation period, the immunogenicity information collected from clinical trials may not be generalizable in a real‐world setting 12 .…”