The AAPS Journal

, Volume 18, Issue 4, pp 1039–1046 | Cite as

Implementing the Biopharmaceutics Classification System in Drug Development: Reconciling Similarities, Differences, and Shared Challenges in the EMA and US-FDA-Recommended Approaches

  • J.-M. CardotEmail author
  • A. Garcia Arieta
  • P. Paixao
  • I. Tasevska
  • B. Davit
Regulatory Note


The US-FDA recently posted a draft guideline for industry recommending procedures necessary to obtain a biowaiver for immediate-release oral dosage forms based on the Biopharmaceutics Classification System (BCS). This review compares the present FDA BCS biowaiver approach, with the existing European Medicines Agency (EMA) approach, with an emphasis on similarities, difficulties, and shared challenges. Some specifics of the current EMA BCS guideline are compared with those in the recently published draft US-FDA BCS guideline. In particular, similarities and differences in the EMA versus US-FDA approaches to establishing drug solubility, permeability, dissolution, and formulation suitability for BCS biowaiver are critically reviewed. Several case studies are presented to illustrate the (i) challenges of applying for BCS biowaivers for global registration in the face of differences in the EMA and US-FDA BCS biowaiver criteria, as well as (ii) challenges inherent in applying for BCS class I or III designation and common to both jurisdictions.


BCS biowaiver EMA US-FDA 


  1. 1.
    Amidon GL, Lennerhas H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12:413–20.CrossRefPubMedGoogle Scholar
  2. 2.
    Amidon KS, Langguth P, Lennernäs H, Yu L, Amidon GL. Bioequivalence of oral products and the biopharmaceutics classification system: science regulation and public policy. Clin Pharmacol Ther. 2011;90:467–70. doi: 10.1038/clpt.2011.109.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    European Medicines Agency. CPMP/EWP/QWP/1401/98 Rev. 1 Committee for medicinal products for human use (CHMP) guideline on the investigation of bioequivalence. (2010). Accessed 15 Feb 2016.
  4. 4.
    World Health Organization. WHO Technical Report Series No. 992 Annex 7. Multisource (Generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability. (2015). Accessed 15 Feb 2016.
  5. 5.
    U.S. Food and Drug Administration. Draft guidance for industry waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system.…/Guidances/ucm070246.pdf (2015). Accessed 15 Feb 2016.
  6. 6.
    Cook J. Impact of discordance among regulations for biopharmaceutics classification system based waivers of clinical bioequivalence studies. Dissolution Technol. 2015;22:6–10. doi: 10.14227/DT220215P6.CrossRefGoogle Scholar
  7. 7.
    Davit BM, Kanfer I, Tsang YC, Cardot JM. BCS biowaivers: similarities and differences among EMA FDA and WHO requirements. AAPS J. 2016;4.Google Scholar
  8. 8.
    European Medicines Agency. EMA/618604/2008 Rev. 12 Questions and answers: positions on specific questions posted to the Pharmacokinetics Working Party (PKWP). (2015). Accessed 15 Feb 2016.
  9. 9.
    U.S. Food and Drug Administration. Draft guidance for industry dissolution testing and specification criteria for immediate-release solid oral dosage forms containing BCS class I and class III drugs. (2015). Accessed 15 Feb 2016.
  10. 10.
    European Medicines Agency. EMA/CHMP/736403/2014 Rev 2 compilation of individual product-specific guidance on demonstration of bioequivalence. (2015). Accessed 15 Feb 2016.
  11. 11.
    U.S. Food and Drug Administration. Individual bioequivalence guideline capecitabine (2012). Accessed 15 Feb 2016.
  12. 12.
    United States Pharmacopeaia. <1092> The dissolution procedure: development and validation. In: USP 36. Rockville MD: USP; 2015. p. 735.Google Scholar
  13. 13.
    García-Arieta A. Interactions between active pharmaceutical ingredients and excipients affecting bioavailability: impact on bioequivalence. Eur J Pharm Sci. 2014;65:89–97. doi: 10.1016/ejps.2014.09.004.CrossRefPubMedGoogle Scholar
  14. 14.
    U.S. Food and Drug Administration. Guidance for industry dissolution testing of immediate release solid oral dosage forms. (1997). Accessed 15 Feb 2016.
  15. 15.
    Colón-Useche S, González-Álvarez I, Mangas-Sanjuan V, González-Álvarez M, Pastoriza P, Molina-Martínez I, et al. Investigating the discriminatory power of BCS-biowaiver in vitro methodology to detect bioavailability differences between immediate release products containing a class I drug. Mol Pharm. 2015;12:3167–74. doi: 10.1021/acs.molpharmaceut.5b00076.CrossRefPubMedGoogle Scholar
  16. 16.
    U.S. Food and Drug Administration guidance for industry bioequivalence recommendations for specific products. (2010). Accessed 15 Feb 2016.

Copyright information

© American Association of Pharmaceutical Scientists 2016

Authors and Affiliations

  • J.-M. Cardot
    • 1
    Email author
  • A. Garcia Arieta
    • 2
  • P. Paixao
    • 3
  • I. Tasevska
    • 4
  • B. Davit
    • 5
  1. 1.Faculté de PharmacieUniversité d’Auvergne Laboratoire de Biopharmacie EA 4678Clermont-FerrandFrance
  2. 2.Pharmacokinetics and Generic Medicines, Division of Pharmacology and Clinical Evaluation, Department of Human Use MedicinesAgencia Española de Medicamentos y Productos Sanitarios (AEMPS)MadridSpain
  3. 3.INFARMED—National Authority of Medicines and Health ProductsLisbonPortugal
  4. 4.State Institute for Drug Control (SÚKL)Praha 10Czech Republic
  5. 5.Translational MedicineMerck & Co.KenilworthUSA

Personalised recommendations