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Pharmacogenomic information in drug labels: European Medicines Agency perspective

The Pharmacogenomics Journal volume 15, pages 201–210 (2015)Cite this article

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Abstract

Pharmacogenomics (PGx) has a growing impact on healthcare and constitutes one of the major pillars of personalised medicine. For the purpose of improved individualised drug treatment, there is an increasing effort to develop drugs suitable for specific subpopulations and to incorporate pharmacogenomic drug labels in existing and novel medicines. Here, we review the pharmacogenomic drug labels of all 517 medicinal products centrally approved in the European Union (EU) since the establishment of the European Medicines Agency in 1995. We identified all pharmacogenomic-related information mentioned in the product labels and classified it according to its main effect and function on drug treatment, that is, metabolism, transport and pharmacodynamics, and according to the place of the respective section of the Summary of Product Characteristics (SmPC). The labels are preferentially present in drugs having antineoplastic properties. We find that the number of drugs with pharmacogenomic labels in EU increases now steadily and that it will be an important task for the future to refine the legislation on how this information should be utilised for improvement of drug therapy.

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References

  1. Vijverberg SJ, Pieters T, Cornel MC . Ethical and social issues in pharmacogenomics testing. Curr Pharm Des 2010; 16: 245–252.

    Article  CAS  Google Scholar 

  2. Freuh FW . Real-world clinical effectiveness, regulatory transparency, and payer coverage: Three ingredients for translating pharmacogenomics into clinical practice. Pharmacogenomics 2010; 11: 657–660.

    Article  Google Scholar 

  3. Trent RJ . Pathology practice and pharmacogenomics. Pharmacogenomics 2010; 11: 105–111.

    Article  Google Scholar 

  4. ICH Topic E15 Definitions for Genomic Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding Categories http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002880.pdf.

  5. Wilke RA, Lin DW, Roden DM, Watkins DM, Flockhart DM, Zineh I et al. Identifying genetic risk factors for serious adverse drug reactions: current progress and challenges. Nat Rev Drug Discov 2007; 6: 904–916.

    Article  CAS  Google Scholar 

  6. Eichelbaum M, Ingelman-Sundberg M, Evans WE . Pharmacogenomics and individualized drug therapy. Annu Rev Med 2005; 57: 119–137.

    Article  Google Scholar 

  7. EMA: Guideline on the Use of Pharmacogenetic Methodologies in the Pharmacokinetic Evaluation of Medicinal Products http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/02/WC500121954.pdf.

  8. Maliepaard M, Nofziger C, Papaluca M, Zineh I, Uyama Y, Prasad K et al. Pharmacogenetics in the evaluation of new drugs: a multiregional regulatory perspective. Nat Rev Drug Discov 2013; 12: 103–115.

    Article  CAS  Google Scholar 

  9. Concept Paper on Key Aspects for the Use of Pharmacogenomic Methodologies in the Pharmacovigilance Evaluation of Medicinal Products; (Guideline will be published January 2014) http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/01/WC500120775.pdf.

  10. European Medicines Agency, Committee for Human Medicinal Products Reflection Paper on Pharmacogenomic Samples, Testing and Data Handling. The Agency: London (UK), 2007 Report No.: EMEA/CHMP/PGxWP/201914/2006.

  11. European Medicines Agency, Committee for Human Medicinal Products Reflection Paper on Pharmacogenomics in Oncology (draft). The Agency: London (UK), 2008 Report No. EMEA/CHMP/PGxWP/128435/2006.

  12. European Medicines Agency, Committee for Human Medicinal Products Reflection Paper on Methodological Issues with Pharmacogenomic Biomarkers in Relation to Clinical Development and Patient Selection (Draft). The Agency: London (UK), 2011 Report No. EMA/446337/2011.

  13. European Medicines Agency, Committee for Human Medicinal Products Reflection Paper on Co-development of Pharmacogenomic Biomarkers and Assays in the Context of Drug Development (Draft). London: European Medicines Agency.

  14. EMA Qualification of Novel Methodologies for Medicine Development http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000319.jsp&mid=WC0b01ac0580022bb0.

  15. Innovation Task Force (ITF) at the European Medicines Agency (EMA) http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000334.jsp&mid=WC0b01ac05800ba1d9 Emerging Science at the EMA http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/general/general_content_000339.jsp&mid=WC0b01ac05800baed8.

  16. EMA Scientific Advice Procedure http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000049.jsp&mid=WC0b01ac05800229b9.

  17. Pignatti F, Ehmann F, Hemmings R, Jonsson B, Nuebling M, Papaluca-Amati M et al. Cancer drug development and the evolving regulatory framework for companion diagnostics in the European Union. Clin Cancer Res 2014; 20: 1458–1468.

    Article  CAS  Google Scholar 

  18. European Medicines Agency Workshop on Pharmacogenomics: from Science to Clinical Care http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/events/2012/04/event_detail_000559.jsp&mid=WC0b01ac058004d5c3.

  19. EC Guideline on Summary of Product Characteristics (SmPC) http://ec.europa.eu/health/files/eudralex/vol-2/c/smpc_guideline_rev2_en.pdf.

  20. European Commission “GUIDELINE ON SUMMARY OF PRODUCT CHARACTERISTICS (SmPC)” http://ec.europa.eu/health/files/eudralex/vol-2/c/smpc_guideline_rev2_en.pdf.

  21. Siller-Matula JM, Trenk D, Schrör K, Gawaz M, Kristensen SD, Storey RF et al. Response variability to P2Y12 receptor inhibitors: expectations and reality. JACC Cardiovasc Interv 2013; 6: 1111–1128.

    Article  Google Scholar 

  22. Trenk D, Hochholzer W . Genetics of platelet inhibitor treatment. Br J Clin Pharmacol 2014; 77: 642–653.

    Article  CAS  Google Scholar 

  23. Price MJ, Berger PB, Teirstein PS, Tanguay JF, Angiolillo DJ, Spriggs D et al. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 2011; 305: 1097–1105.

    Article  CAS  Google Scholar 

  24. Ziagen SmPC http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000252/WC500050343.pdf.

  25. Hughes S, Hughes A, Brothers C, Spreen W, Thorborn D . CNA106030 Study Team. REDICT-1 (CNA106030): the first powered, prospective trial of pharmacogenetic screening to reduce drug adverse events. Pharm Stat 2008; 7: 121–129.

    Article  Google Scholar 

  26. Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J et al. HLA-B*5701 screening for hypersensitivity to Abacavir. N Engl J Med 2008; 358: 568–579.

    Article  Google Scholar 

  27. Poulin-Costello M, Azoulay L, Van Cutsem E, Peeters M, Siena S, Wolf M . An analysis of the treatment effect of panitumumab on overall survival from a phase 3, randomized, controlled, multicenter trial (20020408) in patients with chemotherapy refractory metastatic colorectal cancer. Target Oncol 2013; 8: 127–136.

    Article  Google Scholar 

  28. Peeters M, Douillard JY, Van Cutsem E, Siena S, Zhang K, Williams R et al. Mutant KRAS codon 12 and 13 alleles in patients with metastatic colorectal cancer: assessment as prognostic and predictive biomarkers of response to panitumumab. J Clin Oncol 2013; 31: 759–765.

    Article  CAS  Google Scholar 

  29. O'Sullivan BP, Freedman SD . Cystic fibrosis. Lancet 2009; 373: 1891–1904.

    Article  Google Scholar 

  30. Van Goor F, Hadida S, Grootenhuis PD, Burton B, Cao D, Neuberger T et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci USA 2009; 106: 18825–18830.

    Article  CAS  Google Scholar 

  31. Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Dřevínek P et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011; 365: 1663–1672.

    Article  CAS  Google Scholar 

  32. Davis PB, Yasothan U, Kirkpatrick P . Ivacaftor. Nat Rev Drug Discov 2012; 11: 349–350.

    Article  CAS  Google Scholar 

  33. Llerena A, Dorado P, Ramírez R, González I, Alvarez M, Peñas-Lledó EM et al. CYP2D6 genotype and debrisoquine hydroxylation phenotype in Cubans and Nicaraguans. Pharmacogenomics J 2012; 12: 176–183.

    Article  CAS  Google Scholar 

  34. Work Plan Pharmacogenomics Working Party 2014 - EMA http://www.ema.europa.eu/docs/en_GB/document_library/Work_programme/2010/01/WC500069713.pdf.

  35. Concept Paper on Good Genomics Biomarker Practices: http://www.ema.europa.eu/ema/doc_index.jsp?curl=pages/includes/document/document_detail.jsp?webContentId=WC500170682&murl=menus/document_library/document_library.jsp&mid=0b01ac058009a3dc.

  36. Revision of the Medical Device Directives http://ec.europa.eu/health/medical-devices/documents/revision/index_en.htm.

  37. Nofziger C, Papaluca M, Terzic A, Waldman S, Paulmichl M . Policies to aid the adoption of personalized medicine. Nat Rev Drug Discov 2014; 13: 159–160.

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. European Medicines Agency, Pharmacogenomics Working Party, London, UK

    F Ehmann, L Caneva & M Papaluca-Amati

  2. Pharmacogenomics Working Party—European Medicines Agency (EMA), London, UK

    K Prasad, M Paulmichl, M Maliepaard & A Llerena

  3. Medicines and Healthcare products Regulatory Agency (MHRA), London, UK

    K Prasad

  4. Paracelsus Medical University, Salzburg, Austria

    M Paulmichl

  5. Medicines Evaluation Board,, Utrecht,, The Netherlands

    M Maliepaard

  6. Radboud University Nijmegen Medical Center,,

    M Maliepaard

  7. Nijmegen,, The Netherlands

    M Maliepaard

  8. Extremadura University Hospital, Faculty of Medicine, Clinical Research Center, Badajoz,, Spain

    A Llerena

  9. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

    M Ingelman-Sundberg

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  1. F Ehmann
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  2. L Caneva
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  3. K Prasad
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  4. M Paulmichl
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  6. A Llerena
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  8. M Papaluca-Amati
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Correspondence to F Ehmann.

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The views expressed in this article are the personal views of the author(s) and may not be understood or quoted as being made on behalf of or reflecting the position of the European Medicines Agency or one of its Committees or Working Parties.

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Ehmann, F., Caneva, L., Prasad, K. et al. Pharmacogenomic information in drug labels: European Medicines Agency perspective. Pharmacogenomics J 15, 201–210 (2015). https://doi.org/10.1038/tpj.2014.86

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