• 1
    European Medicines Agency. Scientific guidelines on biosimilar medicines. EMA, London, 2005-2013 [cited 2013 Nov 6]. Available from:
  • 2
    Food and Drug Administration (FDA). Guidance for industry: scientific considerations in demonstrating biosimilarity to a reference product. US Department of Health and Human Services, FDA, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), February 2012 [cited 2014 Mar 5]. Available from:
  • 3
    Australian Therapeutic Goods Administration (TGA). Evaluation of biosimilars. Version 1.0, July 2013 [cited 2014 May 19]. Available from:
  • 4
    RogerSD, GoldsmithD. Biosimilars: it's not as simple as cost alone. J Clin Pharm Ther2008;33:459-464.
  • 5
    Kidney Disease Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl2012;2:279-335.
  • 6
    SchellekensH. Biosimilar therapeutics – what do we need to consider?NDT Plus2009;2(Suppl 1):i27-36.
  • 7
    WeiseM, BielskyMC, DeSmetK, et al. Biosimilars: what clinicians should know. Blood2012;120:5111-5117.
  • 8
    MillerJP, PerryEH, PriceTH, et al. Recovery and safety profiles of marrow and PBSC donors: experience of the National Marrow Donor Program. Biol Blood Marrow Transplant2008;14:29-36.
  • 9
    AnderliniP. Effects and safety of granulocyte colony-stimulating factor in healthy volunteers. Curr Opin Hematol2009;16:35-40.
  • 10
    PulsipherMA, ChitphakdithaiP, MillerJP, et al. Adverse events among 2408 unrelated donors of peripheral blood stem cells: results of a prospective trial from the National Marrow Donor Program. Blood2009;113:3604-3611.
  • 11
    NuamaNM, GokerH, KilicYA, et al. Spontaneous splenic rupture in a healthy allogeneic donor of peripheral-blood stem cell following the administration of granulocyte colony-stimulating factor (g-csf). A case report and review of the literature. Haematologica2006;91:e26-28.
  • 12
    MiuraY, KamiM, YamadaM, et al. Rapid diffuse alveolar hemorrhage associated with all-trans-retinoic acid and filgrastim. Am J Hematol2008;83:683.
  • 13
    GanetskyA, KucharczukC, Del PercioS, et al. Spontaneous subcapsular splenic hematoma associated with filgrastim in a patient undergoing allogeneic hematopoietic stem cell transplantation. Ann Pharmacother2013;47:e22.
  • 14
    NaglerA, Korenstein-IlanA, AmielA, et al. Granulocyte colony-stimulating factor generates epigenetic and genetic alterations in lymphocytes of normal volunteer donors of stem cells. Exp Hematol2004;32:122-130.
  • 15
    BennettCL, EvensAM, AndritsosLA, et al. Haematological malignancies developing in previously healthy individuals who received haematopoietic growth factors: report from the Research on Adverse Drug Events and Reports (RADAR) project. Br J Haematol2006;135:642-650.
  • 16
    LymanGH, DaleDC, WolffDA, et al. Acute myeloid leukemia or myelodysplastic syndrome in randomized controlled clinical trials of cancer chemotherapy with granulocyte colony-stimulating factor: a systematic review. J Clin Oncol2010;28:2914-2924.
  • 17
    Marmier-SavetC, LarosaF, LegrandF, et al. Persistence of lymphocyte function perturbations after granulocyte-colony-stimulating factor mobilization and cytapheresis in normal peripheral blood stem cell donors. Transfusion2010;50:2676-2685.
  • 18
    VokurkaS, KozaV, JungovaA, et al. Haematological malignancies in sibling and unrelated donors of allogeneic peripheral stem cells mobilised with G-CSF filgrastim: a transplant centre and Czech National Marrow Donors Registry experience. Bone Marrow Transplant2012;47:867-868.
  • 19
    HöligK, KramerM, KroschinskyF, et al. Safety and efficacy of hematopoietic stem cell collection from mobilized peripheral blood in unrelated volunteers: 12 years of single-center experience in 3928 donors. Blood2009;114:3757-3763.
  • 20
    MüllerMM, BialleckH, BomkeB, et al. Safety and efficacy of healthy volunteer stem cell mobilization with filgrastim G-CSF and mobilized stem cell apheresis: results of a prospective longitudinal 5-year follow-up study. Vox Sang2013;104:46-54.
  • 21
    European Group for Blood and Marrow Transplantation (EBMT). Position statement: biosimilar granulocyte-colony stimulating factor (G-CSF) for stem cell mobilization in related and unrelated donors. 2009 [cited 2014 Feb 27]. Available from:
  • 22
    ShawBE, ConferDL, HwangWY, et al. Concerns about the use of biosimilar granulocyte colony-stimulating factors for the mobilization of stem cells in normal donors: position of the World Marrow Donor Association. Haematologica2011;96:942-947.
  • 23
    GastlG, GeisslerD, GeisslerK, et al. Austrian Society of Hematology and Oncology position on biosimilars. Mag Eur Med Oncol2009;4:232-233.
  • 24
    BarosiG, BosiA, AbbracchioMP, et al. Key concepts and critical issues on epoetin and filgrastim biosimilars. A position paper from the Italian Society of Hematology, Italian Society of Experimental Hematology, and Italian Group for Bone Marrow Transplantation. Haematologica2011;96:937-942.
  • 25
    Japan Society for Hematopoietic Cell Transplantation. Position statement of the Japan Society for Hematopoietic Cell Transplantation regarding the use of biosimilar granulocyte-colony stimulating factors for the mobilization of hematopoietic stem cells in healthy donors. April 2013 [cited 2014 Feb 18]. Available from:
  • 26
    GascónP, FuhrU, SörgelF, et al. Development of a new G-CSF product based on biosimilarity assessment. Ann Oncol2010;21:1419-1429.
  • 27
    LubenauH, SveikataA, GumbreviciusG, et al. Bioequivalence of two recombinant granulocyte colony-stimulating factor products after subcutaneous injection in healthy volunteers. Int J Clin Pharmacol Ther2009;47:275-282.
  • 28
    LubenauH, BiasP, MalyAK, et al. Pharmacokinetic and pharmacodynamic profile of new biosimilar filgrastim XM02 equivalent to marketed filgrastim Neupogen: single-blind, randomized, crossover trial. BioDrugs2009;23:43-51.
  • 29
    delGiglioA, EniuA, Ganea-MotanD, et al. XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy. BMC Cancer2008;8:332.
  • 30
    EngertA, delGiglioA, BiasP, et al. Incidence of febrile neutropenia and myelotoxicity of chemotherapy: a meta-analysis of biosimilar G-CSF studies in breast cancer, lung cancer, and non-Hodgkin's lymphoma. Onkologie2009;32:599-604.
  • 31
    GatzemeierU, CiuleanuT, DediuM, et al. XM02, the first biosimilar G-CSF, is safe and effective in reducing the duration of severe neutropenia and incidence of febrile neutropenia in patients with small cell or non-small cell lung cancer receiving platinum-based chemotherapy. J Thorac Oncol2009;4:736-740.
  • 32
    WallerCF. Critical appraisal of biosimilarfilgrastim (Nivestim®) for febrile and chemotherapy-induced neutropenia. Biosimilars2012;2:1-11.
  • 33
    SchiestlM, StanglerT, TorellaC, et al. Acceptable changes in quality attributes of glycosylated biopharmaceuticals. Nat Biotechnol2011;29:310-312.
  • 34
    LefrèreF, BrignierAC, ElieC, et al. First experience of autologous peripheral blood stem cell mobilization with biosimilar granulocyte colony-stimulating factor. Adv Ther2011;28:304-310.
  • 35
    MankoJ, Walter-CroneckA, JawniakD, et al. A clinical comparison of the efficacy and safety of biosimilar G-CSF and originator G-CSF in haematopoietic stem cell mobilization. Pharmacol Rep2014;66:239-242.
  • 36
    CzerwT, KruzelT, Sadus-WojciechowskaM, et al. Comparison of two formulations of filgrastim, Neupogen (Amgen) and Zarzio (Sandoz), used to accelerate neutrophil recovery after autologous peripheral blood stem cell transplantation. Bone Marrow Transplant2012;47(Suppl 1):S316 (P872).
  • 37
    IanottoJC, TempesculA, YanX, et al. Experience (1 year) of G-CSF biosimilars in PBSCT for lymphoma and myeloma patients. Bone Marrow Transplant2012;47:874-876.
  • 38
    KotwicaK, CiochM, WachM, et al. Biosimilar G-CSF is effective in reducing the duration of neutropenia after autologous bone marrow transplantation. Bone Marrow Transplant2012;47(Suppl 1):S316 (P873).
  • 39
    GopcsaL, RemenyiP, AdamkovichN, et al. Experiences of autologous peripheral blood stem cell mobilization and engraftment after autologous stem cell transplantation with “biosimilar” filgrastim (Zarzio®, Sandoz, granulocyte colony-stimulating factor). Bone Marrow Transplant2013;48(Suppl 2):S114 (P519).
  • 40
    LefrèreF, RibeilJA, TurnerM, et al. Biosimilar compared with originator filgrastim for related-donor allogeneic stem cell mobilisation: a prospective-historical control study. Presented at the 55th Annual Meeting of the American Society of Haematology (ASH), New Orleans, LA, USA, December 7-10, 2013.
  • 41
    OstuniA, MorcianoMR, MeleA, et al. Zarzio plus chemotherapy as peripheral blood stem cell mobilization strategy in patients with haematological diseases candidated to autologous stem cell transplantation. Bone Marrow Transplant2013;48(Suppl 2):S120 (P529).
  • 42
    PublicoverA, RichardsonDS, DaviesA, et al. Use of a biosimilar granulocyte colony-stimulating factor for peripheral blood stem cell mobilization: an analysis of mobilization and engraftment. Br J Haematol2013;162:107-111.
  • 43
    UddinS, RussellP, AgrawalS. Use of biosimilar G-CSF compared with lenograstim in autologous haematopoietic stem cell transplant and in sibling allogeneic transplant. Presented at the 55th Annual Meeting of the American Society of Haematology (ASH), New Orleans, LA, USA, December 7-10, 2013.
  • 44
    YafourN, BrahimiM, OsmaniS, et al. Biosimilar G-CSF (filgrastim) is effective for peripheral blood stem cell mobilization and non-cryopreserved autologous transplantation. Transfus Clin Biol2013;20:502-504.
  • 45
    ZabalzaA, SanchezP, AnteloM, et al. Safety and efficacy of a G-CSF biosimilar (Zarzio®) for haematopoietic progenitor cell mobilization in patients with haematological malignancies. Bone Marrow Transplant2013;48(Suppl 2):S112 (P515).
  • 46
    AzarN, ChoquetS, GarnierA, et al. Use of a biosimilar G-CSF in allogeneic stem cell mobilisation. Bone Marrow Transplant2012;47(Suppl 1):S316 (P727).
  • 47
    AnteloM, ZabalzaA, SanchezP, et al. Safety and efficacy of a G-CSF biosimilar (Zarzio®) for haematopoietic progenitor cell mobilization in allogeneic healthy donors. Bone Marrow Transplant2013;48(Suppl 2):S102 (P491).
  • 48
    SchmittM, XuX, HilgendorfI, et al. Mobilization of PBSC for allogeneic transplantation by the use of the G-CSF biosimilar XM02 in healthy donors. Bone Marrow Transplant2013;48:922-925.
  • 49
    BeckerP, BrauningerS, BialleckH, et al. Biosimilar filgrastim mobilizes haematopoietic stem cells in healthy volunteer donors with expected efficiency and typical acute adverse effects: interim results of a post-authorization safety study. Bone Marrow Transplant2013;48(Suppl 2):S28 (O177).
  • 50
    McCamishM, WoollettG. The continuum of comparability extends to biosimilarity: how much is enough and what clinical data are necessary?Clin Pharmacol Ther2013;93:315-317.
  • 51
    AbrahamI, TharmarajahS, MacDonaldK. Clinical safety of biosimilar recombinant human granulocyte colony-stimulating factors. Expert Opin Drug Saf2013;12:235-246.
  • 52
    World Marrow Donor Association (WMDA). Donor medical suitability recommendations. 2013 [cited 2014 May 19]. Available from:
  • 53
    Foundation for the Accreditation of Cellular Therapy/Joint Accreditation Committee—ISCT & EBMT (FACT/JACIE). Cellular therapy standards. 2013 [cited 2014 May 19]. Available from:
  • 54
    HöligK. G-CSF in healthy allogeneic stem cell donors. Transfus Med Hemother2013;40:225-235.
  • 55
    PulsipherMA, ChitphakdithaiP, LoganBR, et al. Lower risk of serious adverse events and no increased risk of cancer after PBSC versus bone marrow donation. Blood2014;123:3655-3663.
  • 56
    SchellekensH. When biotech proteins go off-patent. Trends Biotechnol2004;22:406-410.
  • 57
    PollockC, JohnsonDW, HörlWH, et al. Pure red cell aplasia induced by erythropoiesis-stimulating agents. Clin J Am Soc Nephrol2008;3:193-199.
  • 58
    TigueCC, McKoyAM, EvensAM, et al. Granulocyte colony-stimulating factor administration to healthy individuals and persons with chronic neutropenia or cancer: an overview on safety considerations from the Research on Adverse Drug Events and Reports project. Bone Marrow Transplant2007;40:185-192.
  • 59
    FalangaA, MarchettiM, EvangelistaV, et al. Neutrophil activation and hemostatic changes in healthy donors receiving granulocyte colony-stimulating factor. Blood1999;93:2506-2514.
  • 60
    LeBlancR, RoyJ, DemersC, et al. A prospective study of G-CSF effects on hemostasis on allogeneic blood stem cell donors. Bone Marrow Transplant1999;23:991-996.
  • 61
    BonigH, BurdachS, GöbelU, et al. Growth factors and hemostasis: differential effects of GM-CSF and G-CSF on coagulation activation–laboratory and clinical evidence. Ann Hematol2001;80:525-530.
  • 62
    TopcuogluP, AratM, DalvaK, et al. Administration of granulocyte-colony-stimulating factor for allogeneic hematopoietic cell collection may induce the tissue factor-dependent pathway in healthy donors. Bone Marrow Transplant2004;33:171-176.
  • 63
    BáezA, Martín-AntonioB, PiruatJI, et al. The granulocyte colony-stimulating factor produces long-term changes on gene and miRNA expression profiles in CD34+ cells from healthy donors. Haematologica2014;99:243-251.
  • 64
    WinklerIG, BendallLJ, ForristalCE, et al. B-lymphopoiesis is stopped by mobilizing doses of G-CSF and is rescued by overexpression of the anti-apoptotic protein Bcl2. Haematologica2013;98:325-333.
  • 65
    HirschB, OsethL, CainM, et al. Effects of granulocyte-colony stimulating factor on chromosome aneuploidy and replication asynchrony in healthy peripheral blood stem cell donors. Blood2011;118:2602-2608.
  • 66
    SchuettpelzLG, LinkDC. Regulation of hematopoietic stem cell activity by inflammation. Front Immunol2013;4:204.
  • 67
    GascónP, TeschH, VerpoortK, et al. Clinical experience with Zarzio® in Europe: what have we learned?Support Care Cancer2013;21:2925-2932.
  • 68
    BensingerWI, PriceTH, DaleDC, et al. The effects of daily recombinant human granulocyte colony-stimulating factor administration on normal granulocyte donors undergoing leukapheresis. Blood1993;81:1883-1888.
  • 69
    BensingerWI, BucknerCD, RowleyS, et al. Treatment of normal donors with recombinant growth factors for transplantation of allogeneic blood stem cells. Bone Marrow Transplant1996;17(Suppl 2):S19-21.