Analysis of Immunogenicity Data in the Product Information of Biological Drugs: A Need to Report Immunogenicity Data Systematically

Abstract

Objective: To evaluate whether the current case-by-case practice leads to sufficient reporting of immunogenicity-related information in the Summary of Product Characteristics (SmPCs) of biological products approved in the European market.Methods: Immunogenicity-related information was identified and extracted from a group of 73 biological drugs that complied with drug-selection criteria. Afterwards, thirteen dichotomous questions were proposed to evaluate whether any issues are being commonly neglected.Results: Most SmPCs (92%) do not have any recommendations on how to report immunogenicity-related adverse drug reactions by patients or healthcare professionals. Furthermore, 80% of SmPCs do not identify the assay used to assess the reported immunogenicity rates, while 81% do not address the possible impact of immunogenicity on their drug's pharmacokinetics. It was also identified that a group factor (i.e. older drugs' SmPCs) could be influencing how/which issues were being addressed by newerdrugs SmPCs. To transform SmPCs into useful tools when an immunogenic response occurs, a proposal on how to report immunogenicity-related information in the SmPCs of biological products is advanced. This tool can be used by patients, healthcare professionals, regulators and businesses to evaluate the information of SmPCs. Conclusions:Based on these results, a case-by-case strategy does not yield enough reporting across products and thus immunogenicity-related information should be reported in a systematic way. Further guidance about reporting immunogenicity-related information is required, else SmPCs will not be the basis of information for healthcare professionals on how to use a biological product safely and effectively.

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

“…Previous perspectives on immunogenicity in comparison with the findings in the present study Borrega et al 20 investigated the Summary of Product Characteristics of 72 biological products approved by the European Medicines Agency (EMA). They found that 81% of the products do not address the potential impact of immunogenicity on pharmacokinetics.…”

“…Borrega et al 20 . investigated the Summary of Product Characteristics of 72 biological products approved by the European Medicines Agency (EMA).…”

“…They found that 81% of the products do not address the potential impact of immunogenicity on pharmacokinetics. Considering the heterogeneity of the information presented across these biological drugs, Borrega et al 20 suggested that the standardization of the immunogenicity data is necessary for reporting associated product information. Wang et al 21 reviewed the prescribing information and the FDA's clinical pharmacology review of 121 biological products approved by the FDA before February 2015.…”

Biosimilars: An Opportunity to Update the Product Information of Biological Drugs Regarding their Immunogenicity

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Running Heading: Biosimilars as an opportunity to update the Product Information of biological drugs One of the greatest theoretical clinical concerns regarding the development of biosimilars has been that post-translational protein modifications, even while antigen binding remains essentially unaltered, might result in detrimental immunogenicity. We recently demonstrated [1] that the Summary of Product Characteristics (SmPCs) of biological drugs, approved by the European Medicines Agency (EMA), are very heterogeneous regarding the issues related to immunogenicity that are addressed within these documents.A complementary analysis, using the methodology advanced in [1], to the EMA's documents "Procedural steps taken and scientific information after the authorisation" shows that 57% (30/69) of the biological drugs that have been authorized prior to 2012 did not update their SmPC at least once when it comes to information related to unwanted immunogenicity. These are surprising results given the advancements that have been seen in the field of immunogenicity assessment [2], namely in the development of more

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“…A complementary analysis, using the methodology advanced in [1], to the EMA's documents "Procedural steps taken and scientific information after the authorisation" shows that 57% (30/69) of the biological drugs that have been authorized prior to 2012 did not update their SmPC at least once when it comes to information related to unwanted immunogenicity. These are surprising results given the advancements that have been seen in the field of immunogenicity assessment [2], namely in the development of more…”