Skip to main content

Degree of prescriber’s knowledge about variability in biological drugs “innovators” in manufacturing process



The purpose of the study is to analyse the degree of prescribers’ knowledge about the regulation and variability in manufacturing processes (MP) in bio-drugs “innovators” (BI).


For each selected drugs, the date of authorization by the European Medicines Agency, time elapsed until the first change, total number of changes and annual rate of change (ARC) were recorded. A survey was designed with 4 parts: (a) identifying the BI prescribed; (b) knowledge of the number and ARC of each BI during its MP; (c) knowledge of comparability requirement of BI before or after the MP; (d) evaluating the utility of the information in the survey.


Drugs selected and total number of changes: infliximab (41), adalimumab (20), abatacept (13), golimumab (7), etanercept (18), tocilizumab (6) and certolizumab. All BI had been changed in the MP after their authorisation. The survey was answered by 35 professionals from rheumatology, digestive and dermatology area. They had prescribed one or more drugs included in the survey at least once. Sixty-three percent of prescribers did not know the existence of changes relative to the MP. Thirty-seven percent of prescribers knew of their existence, but not about number or frequency. Fifty-seven percent of prescribers did not know the regulation about the comparability among BI. The rest of them knew it, but 29% related it only to biosimilar drugs. Ninety-four percent of prescribers identified information as useful.


BI present a high ARC during their MP after their commercialization, without any efficacy or safety difficulties. Knowledge of this might increase confidence for biosimilars.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3


  1. European Commission (2013) Lo que debe saber sobre los medicamentos biosimilares. European Commission, Brussels Disponible en:

    Google Scholar 

  2. European Medicines Agency (2014) EMA/940451/2011: EMA Procedural advice for users of the Centralised Procedure for Similar Biological Medicinal Products applications. European Medicines Agency, London Disponible en: pdf

    Google Scholar 

  3. EMEA/CPMP/ICH/5721/03. ICH Topic Q 5 E. Comparability of Biotechnological/Biological Products. Step 5. Note for guidance on biotechnological/biological products subject to changes in their manufacturing process. (CPMP adopted June 2005). Disponible en:

  4. CHMP/437/04 Guideline on Similar Biological Medicinal Products. Disponible en:

  5. Ley 29/2006, de 26 de julio, de garantías y uso racional de los medicamentos y productos sanitarios. Boletín Oficial del Estado, n° 178, (27 de julio de 2006)

  6. Danese S, Fiorino G, Michetti P (2015) Are IBD specialists aware of biosimilar monoclonal antibodies? Results from a survey among ECCO members [Abstract]. En: 9th Congress of ECCO. Copenhagen, Dinamarca

  7. Dorantes CB (2009) Controversias sobre medicamentos biosimilares y su intercambio terapéutico. Farm Hosp 33(4):181–182.

    Article  Google Scholar 

  8. Yoo DH, Hrycaj P, Miranda P, Ramiterre E, Piotrowski M, Shevchuk S, Kovalenko V, Prodanovic N, Abello-Banfi M, Gutierrez-Ureña S, Morales-Olazabal L, Tee M, Jimenez R, Zamani O, Lee SJ, Kim HU, Park W, Müller-Ladner U (2013) A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis 72(10):1613–1620.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. Park W, Hrycaj P, Jeka S, Kovalenko V, Lysenko G, Miranda P, Mikazane H, Gutierrez-Ureña S, Lim MJ, Lee YA, Lee SJ, Kim HU, Yoo DH, Braun J (2013) A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis 72(10):1605–1612.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. AEMPS: Agencia Española de Medicamentos y Productos Sanitarios [Internet]. Ficha técnica de Remsima®. Disponible en:

  11. AEMPS: Agencia Española de Medicamentos y Productos Sanitarios [Internet]. Ficha técnica de Inflectra®. Disponible en:

  12. Kang YS, Moon HH, Lee SE, Lim YJ, Kang HW (2015) Clinical experience of the use of CT-P13, a biosimilar to infliximab in patients with inflammatory bowel disease: a case series. Dig Dis Sci 60(4):951–956.

    CAS  Article  PubMed  Google Scholar 

  13. Yoon Suk J, Park DI, Kim YH, Seo PJ, Kim JW, Kang HW (2015) Efficacy and safety of infliximab’s biosimilar (REMSIMA) for IBD [Abstract]. En: 10th Congress of ECCO. Barcelona, España

  14. Gecse K, Farkas K, Lovasz B, Banai J, Bene L, Gasztonyi B et al. (2015) Biosimilar infliximab in inflammatory bowel diseases: first interim results from a prospective observational cohort nationwide [Abstract]. En: 10th Congress of ECCO. Barcelona, España

  15. Sieczkowska J, Banaszkiewicz A, Plocek A, Jarzebicka D, Gawronska A, Toporowska-Kowalska E et al (2015) Assessment of safety and efficacy of biosimilar infliximab in children with Crohn disease: a preliminary report [Abstract]. En: 10th Congress of ECCO. Barcelona, España

  16. Molnar T, Farkas K, Rutka M, Bálint A, Nagy F, Bor R et al (2015) Efficacy of the new infliximab biomarker CT-P13 induction therapy on mucosal healing in ulcerative colitis patients [Abstract]. En: 10th Congress of ECCO. Barcelona, España

  17. Jarzebicka D, Plocek A, Sieczkowska J, Toporowska-Kowalska E, Kierkus J (2015) First observations of the use of biosimilar infliximab for treatment of ulcerative colitis in paediatric population [Abstract]. En: 10th Congress of ECCO. Barcelona, España

  18. Jarzebicka D, Banaszkiewicz A, Plocek A, Sieczkowska J, Gawronska A, Toporowska-Kowalska E et al (2015) Preliminary assessment of efficacy and safety of switching between originator and biosimilar infliximab in paediatric Crohn disease patients [Abstract]. En: 10th Congress of ECCO. Barcelona, España

  19. Kang HW, Lim YJ, Kim JH, Kang Y-S (2015) An experience of anti-TNF biosimilar, CT-P13 use: clinical efficacy, safety and interchangeability in inflammatory bowel disease; a pilot study [Abstract]. En: 9th Congress of ECCO. Copenhagen, Dinamarca

  20. Smolen JS, Choe JY, Prodanovic N, Niebrzydowski J, Staykov I, Dokoupilova E et al (2017) Safety, immunogenicity and efficacy after switching from reference infliximab to biosimilar SB2 compared with continuing reference infliximab and SB2 in patients with rheumatoid arthritis: results of a randomised, double-blind, phase III transition study. Ann Rheum Dis 0:1–7

    Google Scholar 

  21. Guerrero Puente L, Iglesias Flores E, Benítez JM, Medina Medina R, Salgueiro Rodríguez I, Aguilar Melero P, Cárdenas Aranzana MJ, González Fernández R, Manzanares Martin B, García-Sánchez V (2017) Evoution after switching to biosimilar infliximab in inflammatory bowel disease patients in clinical remission. Gastroenterol Hepatol 40(9):595–604.

    Article  PubMed  Google Scholar 

  22. Vergara-Dangond C, Sáez Belló M, Climente Martí M, Llopis Salvia P, Alegre-Sancho JJ (2017) Effectiveness and safety of switching from innovator infliximab to biosimilar CT-P13 in inflammatory rheumatic diseases: a real-world case study. Drugs R D 17(3):481–485.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Komaki Y, Yamada A, Komaki F, Micic D, Ido A, Sakuraba A (2017) Systematic review with meta-analysis: the efficacy and safety of CT-P13, a biosimilar of anti-tumor necrosis factor-α agent (infliximab), in inflammatory bowel diseases. Aliment Pharmacol Ther 45(8):1043–1057.

    CAS  Article  PubMed  Google Scholar 

  24. Gerdes S, Thaçi D, Griffiths CEM, Arenberger P, Poetzl J, Wuerth G, Afonso M, Woehling H (2017) Multiple switches between GP2015, an etanercept biosimilar, with originator product do not impact efficacy, safety and immunogenicity in patients with chronic plaque-type psoriasis: 30-week results from the phase 3, confirmatory EGALITY study. J Eur Acad Dermatol Venereol.

  25. Kay J (2013) Josef S Smolen. Biosimilars to treat inflammatory arthritis: the challenge of proving identity. Ann Rheum Dis 72(10):1589–1593.

    CAS  Article  PubMed  Google Scholar 

  26. Gerrard TL, Gaugh DR, Johnston G (2015) Biosimilars: extrapolation of clinical use to other indications. GaBi J 4(3)

  27. Ismael G, Hegg R, Muehlbauer S, Heinzmann D, Lum B, Kim SB, Pienkowski T, Lichinitser M, Semiglazov V, Melichar B, Jackisch C (2012) Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol 13(9):869–878.

    CAS  Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Lucía Jiménez-Pichardo.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Jiménez-Pichardo, L., Gázquez-Pérez, R. & Sierra-Sánchez, J.F. Degree of prescriber’s knowledge about variability in biological drugs “innovators” in manufacturing process. Eur J Clin Pharmacol 74, 505–511 (2018).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • Biosimilar
  • Variability
  • Rheumatology
  • Dermathology
  • Digestive