Nanoparticle iron medicinal products - Requirements for approval of intended copies of non-biological complex drugs (NBCD) and the importance of clinical comparative studies

Regulatory Toxicology and Pharmacology

Volumn 64, Issue 2, 2012, Pages 324-328

  Borchard, Gerrit ^a   Flühmann, Beat ^b   Mühlebach, Stefan ^b  

^a UNIVERSITY OF GENEVA   (Switzerland)

^b Vifor (International) Inc   (Switzerland)

Author keywords

Bioequivalence; Generic; Iron; Iron sucrose; Nanoparticle; Non biological complex drugs; Similar; Therapeutic equivalence

Indexed keywords

NANOPARTICLE; NEW DRUG; NON BIOLOGICAL COMPLEX DRUG; UNCLASSIFIED DRUG;

ARTICLE; COMPARATIVE EFFECTIVENESS; DRUG APPROVAL; DRUG BIOAVAILABILITY; DRUG CONTROL; DRUG EFFICACY; DRUG MANUFACTURE; DRUG MONITORING; DRUG SAFETY; DRUG SCREENING; DRUG SURVEILLANCE PROGRAM; HUMAN; MOLECULAR WEIGHT; NANOFABRICATION; NONHUMAN; PHYSICAL CHEMISTRY; PRACTICE GUIDELINE; PRIORITY JOURNAL;

ANIMALS; DRUG APPROVAL; DRUGS, GENERIC; FERRIC COMPOUNDS; GLUCARIC ACID; HUMANS; METAL NANOPARTICLES; THERAPEUTIC EQUIVALENCY;

EID: 84868273323     PISSN: 02732300     EISSN: 10960295     Source Type: Journal    
DOI: 10.1016/j.yrtph.2012.08.009     Document Type: Article

References (28)

1. Bailie G.R., Horl W.H., Verhof J.J. Differences in spontaneously reported hypersensitivity and serious adverse events for intravenous iron preparations: comparison of Europe and North America. Arzneimittelforschung 2011, 61:267-275.
2. Beshara S., Lundqvist H., Sundin J., Lubberink M., Tolmachev V., Valind S., Antoni G., Langstrom B., Danielson B.G. Pharmacokinetics and red cell utilization of iron(III) hydroxide-sucrose complex in anaemic patients: a study using positron emission tomography. Br. J. Haematol. 1999, 104:296-302.
3. Brissot P., Ropert M., Le Lan C., Loreal O. Non-transferrin bound iron: a key role in iron overload and iron toxicity. Biochim. Biophys. Acta 2012, 1820:403-410.
4. Danielson B.G., Salmonson T., Derendorf H., Geisser P. Pharmacokinetics of iron(III)-hydroxide sucrose complex after a single intravenous dose in healthy volunteers. Arzneimittelforschung 1996, 46:615-621.
5. Dunn L.D., Rahmanto Y.S., Richardson D.R. Iron uptake and metabolism in the new millennium. Trends Cell Biol. 2007, 17:93-100.
6. European Medicines Agency, 2011a. Concept paper on the revision of the guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues. (accessed 22.09.11). http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2011/10/WC500115611.pdf.
7. European Medicines Agency, 2011b. Reflection paper on non-clinical studies for generic nanoparticle iron medicinal product applications., (accessed 17.03.11.). http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2011/04/WC500105048.pdf.
8. Food and Drug Administration, 2012a., (accessed 08.08.12.). http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM297630.pdf.
9. Food and Drug Administration 2012b., accessed August 9, 2012. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291128.pdf.
10. Gaisser A. Sind Eisensucrose similar und Original gleich. Supplement " Der Nephrologe" 2009, 6:1-4.
11. Goldberg L.A. Evaluating therapeutic equivalence. Hospital Pharmacy Europe 2011, 54:53-55.
12. Kudasheva D.S., Lai J., Ulman A., Cowman M.K. Structure of carbohydrate-bound polynuclear iron oxyhydroxide nanoparticles in parenteral formulations. J. Inorg. Biochem. 2004, 98:1757-1769.
13. Lima, B.S., 2011. The EMA replies... Scrip Regulatory Affairs, August 13.
14. Martin-Malo A., Merino A., Carracedo J., Alvarez-Lara M.A., Ojeda R., Soriano S., Crespo R., Ramirez R., Aljama P. Effects of intravenous iron on mononuclear cells during the haemodialysis session. Nephrol. Dial. Transplant. 2011, 10.1093/ndt/gfr711.
15. Medice Arzneimittel Pütter GmbH. 2009. Summary of Product Characteristics (Fachinformation), FerMed®, Germany. Available at:, Accessed 17 Aug 2011. http://www.pharmnet-bund.de/dynamic/de/index.html.
16. Meier T., Schropp P., Pater C., Leoni A.L., Khov-Tran V.V., Elford P. Physicochemical and toxicological characterization of a new generic iron sucrose preparation. Arzneimittelforschung 2011, 61:112-119.
17. Rottembourg J., Kadri A., Leonard E., Dansaert A., Lafuma A. Do two intravenous iron sucrose preparations have the same efficacy?. Nephrol. Dial. Transplant. 2011, 26:3262-3267.
18. Schellekens H., Klinger E., Muhlebach S., Brin J.F., Storm G., Crommelin D.J. The therapeutic equivalence of complex drugs. Regul. Toxicol. Pharmacol. 2011, 59:176-183.
19. Snodin, D., 2011. EMA reflection paper on generic nanoparticle iron products: a case of bias by omission? Scrip Regulatory Affairs, August 11-12.
20. Solomon S.D., Uno H., Lewis E.F., Eckardt K.U., Lin J., Burdmann E.A., de Z.D., Ivanovich P., Levey A.S., Parfrey P., Remuzzi G., Singh A.K., Toto R., Huang F., Rossert J., McMurray J.J., Pfeffer M.A. Erythropoietic response and outcomes in kidney disease and type 2 diabetes. N. Engl. J. Med 2010, 363:1146-1155.
21. Stein J., Dignass A., Chow K.U. Clinical case reports raise doubts about the therapeutic equivalence of an iron sucrose similar preparation compared with iron sucrose originator. Curr. Med. Res. Opin. 2012, 28:241-243.
22. Stein J., Hartmann F., Dignass A.U. Diagnosis and management of iron deficiency anemia in patients with IBD. Nat. Rev. Gastroenterol. Hepatol. 2010, 7:599-610.
23. Toblli J.E., Cao G., Angerosa M., Oliveri L. Differences between original intravenous iron sucrose and iron sucrose similar preparations. Arzneimittelforschung 2009, 59:176-190.
24. Toblli, J.E., Cao, G., Giani, J., Domenici, F., Angerosa, M. 2011. Different effects of European iron sucrose similar preparations and originator iron sucrose on nitrosative stress, apoptosis, oxidative stress, biochemical and inflammatory markers in rats. XLVIII ERA EDTA Congress (abstract SuO028).
25. Toblli, J.E., Cao, G., Oliveri, L., Angerosa, M., 2012. Comparison of oxidative stress and inflammation induced by different intravenous iron sucrose similar preparations in a rat model. Inflamm. Allergy Drug Targets. 66-78.
26. Van Wyck D.B. Labile iron: manifestations and clinical implications. J. Am. Soc. Nephrol. 2004, 15(Suppl. 2):S107-S111.
27. Vifor France SA, 2010. Summary of Product Characteristics (Fachinformation), Venofer®, Germany. Available at, Accessed 17 Aug 2011. http://www.pharmnet-bund.de/dynamic/de/index.html.
28. Wysowski D.K., Swartz L., Borders-Hemphill B.V., Goulding M.R., Dormitzer C. Use of parenteral iron products and serious anaphylactic-type reactions. Am. J. Hematol. 2010, 85:650-654.