Biopharmaceuticals as Challenges to the Regulatory System

This thesis explores how regulatory tools and requirements have been able to manage specific safety concerns associated with biopharmaceuticals, including biosimilars. Biopharmaceuticals differ from small molecules in terms of structure and pharmacology. It remains unclear whether current regulatory requirements are best fit to establish the optimal benefit-risk profile of biopharmaceuticals, including biosimilars. While immunogenicity is often regarded as a key concern for biopharmaceuticals, most safety concerns observed for biopharmaceuticals can be attributed to their intended mechanism of action. Despite differences in the nature of safety events our results do not indicate any differences in the sources and timing of regulatory actions of biopharmaceuticals. The added value of various regulatory tools to manage the safety of biopharmaceuticals is hard to ascertain. It is important to gain insight in how regulatory tools and requirements contribute to patient benefit. Better methods should be developed to assess the effects of regulatory tools and requirements.

Results

• Ebbers HC, Al-Temimi E, Moors EH, Mantel-Teeuwisse AK, Schellekens H, Leufkens HGM. Differences between Post-Authorization adverse medicine reactions of biopharmaceuticals and small molecules. In: BioMedicines, 2013. (journal publication)
• Ebbers HC, Crow SA, Vulto AG, Schellekens H. Interchangeability, immunogenicity and biosimilars. In: Nat Biotechnol, 2012; 30(12): 1186-90. (journal publication)
• Ebbers HC, Mantel-Teeuwisse AK, Moors EH, SayedTabatabaei FA, Schellekens H, Leufkens HG. A cohort study exploring determinants of safety-related regulatory actions for biopharmaceuticals. In: Drug Saf, 2012; 35(5): 417-27. (journal publication)
• Ebbers HC, Mantel-Teeuwisse AK, Sayed-Tabatabaei FA, Moors EH, Schellekens H, Leufkens HG. The role of Periodic Safety Update Reports in the safety management of biopharmaceuticals. In: Eur J Clin Pharmacol, 2013; 69(2): 217-26. (journal publication)
• Ebbers HC, Muenzberg M, Schellekens H. The safety of switching between therapeutic proteins. In: Expert Opin Biol Ther, 2012; 12(11): 1473-85. (journal publication)
• Ebbers HC, Pieters T, Leufkens HG, Schellekens H. Effective pharmaceutical regulation needs alignment with doctors. In: Drug Discov Today, 2012; 17(3-4): 100-3. (journal publication)
• Macdougall IC, Roger SD, De Francisco A, Goldsmith DJ, Schellekens H, Ebbers H, Jelkmann W, London G, Casadevall N, Hörl WH, Kemeny DM, Pollock C. Antibody-mediated pure red cell aplasia in chronic kidney disease patients receiving erythropoiesis-stimulating agents: new insights. In: Kidney Int, 2012; 81(8):727-3. (journal publication)
• Ebbers HC, Mantel-Teeuwisse AK, Moors EH, Schellekens H, Leufkens HG. Today's challenges in pharmacovigilance: what can we learn from epoetins? In: Drug Saf, 2011; 34(4): 273-87. (journal publication)