Analysis of Immunogenicity Data in the Product Information of Biological Drugs: A Need to Report Immunogenicity Data Systematically
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The aim of this analysis was to evaluate whether the current unsystematic assessment leads to sufficient reporting of immunogenicity-related information in the Summary of Product Characteristics (SmPCs) of biological products approved in the European market.
Immunogenicity-related information was identified and extracted from a group of 72 biological drugs that complied with drug-selection criteria. Afterwards, 12 dichotomous questions were proposed to evaluate whether any issues are being commonly neglected.
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 newer drugs’ 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 decision tree should contribute towards increasing the quality and transparency of the immunogenicity-related information being reported in the SmPCs, thus leading to better informed medical decisions.
Based on these results, an unsystematic assessment 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, otherwise SmPCs will not be the basis of information for healthcare professionals on how to use a biological product safely and effectively.
We express our gratitude to Carlos Araújo for providing his time by evaluating, together with RB, SmPCs difficult to appraise.
Compliance with ethical standards
No sources of funding were used to support the writing of this research article.
Conflict of interest
PT has received research grants or has been an invited speaker and advisor for AbbVie, Biogen, Celgene, Fresenius Kabi, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB. JG has received research grants or has been an invited speaker and advisor for Biogen, Astra-Zeneca, Pfizer, Sandoz, Novartis and Hikma. RB and JPC have no conflicts of interest to declare.
All authors meet the journal’s criteria for authorship. All authors have contributed to the work and approve the presented findings.
- 4.European Medicines Agency. EMEA/CHMP/BMWP/14327/2006-Guideline on Immunogenicity assessment of therapeutic proteins. Available at: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-immunogenicity-assessment-therapeutic-proteins-revision-1_en.pdf. Accessed Mar 2019.
- 6.European Medicines Agency. EMEA/CHMP/BMWP/101695/2006-Guideline on comparability after a change in the manufacturing process-non-clinical and clinical issues. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-comparability-biotechnology-derived-medicinal-products-after-change-manufacturing-process_en.pdf. Accessed Mar 2019.
- 7.European Medicines Agency. EMA/168402/2014- Guideline on good pharmacovigilance practices (GVP) product- or population-specific considerations II: Biological medicinal products. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-good-pharmacovigilance-practices-gvp-product-population-specific-considerations-ii_en-0.pdf Accessed Mar 2019.
- 13.European Medicines Agency. A Guideline on Summary of Product Characteristics (SmPC). https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-2/c/smpc_guideline_rev2_en.pdf. Accessed Mar 2019.
- 23.Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). Labeling for Biosimilar Products Guidance for Industry. Available at: https://www.fda.gov/media/96894/download. Accessed Aug 2019.
- 26.European Medicines Agency. Mixtard Summary of Product Characteristics. https://www.ema.europa.eu/en/documents/product-information/mixtard-epar-product-information_en.pdf. Accessed Mar 2019.
- 27.European Medicines Agency. Protaphane Summary of Product Characteristics. https://www.ema.europa.eu/en/documents/product-information/protaphane-epar-product-information_en.pdf Accessed Mar 2019.
- 28.European Medicines Agency. Actraphane Summary of Product Characteristics. https://www.ema.europa.eu/en/documents/product-information/actraphane-epar-product-information_en.pdf Accessed Mar 2019.
- 29.European Medicines Agency. Actrapid summary of product characteristics. https://www.ema.europa.eu/en/documents/product-information/actrapid-epar-product-information_en.pdf Accessed Mar 2019.
- 30.European Medicines Agency. Insulatard Summary of Product Characteristics. https://www.ema.europa.eu/en/documents/product-information/insulatard-epar-product-information_en.pdf Accessed Mar 2019.
- 32.European Medicines Agency. Summary of product characteristics (SmPC)- What is it and what does it contain? https://www.ema.europa.eu/en/documents/presentation/presentation-summary-product-characteristics-what-it-what-does-it-contain_en.pdf. Accessed Apr 2019.