BIOEQUIVALENCE: HEALTH, COMMERCIAL AND POLITICAL IMPLICATIONS OF THIS TECHNICAL TOOL
Main Article Content
Keywords
Bioequivalence, pharmacokinetics, generic substitution, Limitations, implications
Abstract
Bioequivalence (BE) is a clinical-pharmacological research method that has acquired great relevance in most of the countries due to its health, commercial, and political importance. Some regulatory agencies require routine BE for all products registered in their national territory, while others opt for policies that require this study only for certain products. The truth is that even today there are current debates about its definition, its clinical relevance and the level of requirements that each country must ask to those companies that aim to register a new product.
The objective of this paper is to provide different perspectives on the concept of bioequivalent drugs, establish what are the advantages or disadvantages of adopting different policies on BE, identify the interests associated with this concept and clarify its real importance for public health.
References
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14. Chow, S.-C., & Liu, J.-P. Design and Analysis of Bioavailability and Bioequivalence Studies (2nd ed.). CRC Press,1999. https://doi.org/10.1201/9781420002027
15. Upendra C. Galgatte, Vijay R. Jamdade, Pravin P. Aute, Pravin D. (2014). Study on requirements of bioequivalence for registration of pharmaceutical products in USA, Europe and Canada, Saudi Pharmaceutical Journal 2014; 22-5 391-402.
16. Asian Guideline for the Conduct Bioavailability & Bioequivalence Studies. Pharmaceutical Formulation Design 2004;20:5-10.
17. Health Canada. Conduct and Analysis of Bioavailability and Bioequivalence Studies: Part A: Oral Dosage Formulations Used for Systemic Effects (1992); Part B: Oral Modified Release Formulations (1996); Report C: Report on Bioavailability of Oral Dosage Formulations, Not in Modified Release Form, or Drugs Used for Systemic Effects, Having Complicated or Variable Pharmacokinetics (1992). Health Products and Food Branch Guidence Document. 1992-1996. Available from: http://www.hc.sc.gc.ca
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19. García-Arieta A.. The failure to show bioequivalence is not evidence against generics. Br J Clin Pharmacol.200; 70(3) 452-3.
20. Borgheini G. The bioequivalence and therapeutic efficacy of generic versus brand-name psychoactive drugs. Clin Ther.2003; 25(6) 1578-92.
21. Rheinstein PH. Therapeutic inequivalence (1990). Drug Safety.5 (Suppl 1):114–119.
22. Schall R, Endrenyi L. Bioequivalence: tried and tested. Cardiovasc J Afr.2010; 21(2) : 69-71.
23. Barret JS, Batra V, Chow A, Cook J, Gould AL, Heller A. et al. Pharma perspective on population and individual bioequivalence. J Clin Pharmacol. 2000; 40:561–570.
24. Haas JS, Phillips KA, Gerstenberger EP, Seger AC. Potential savings from substituting generic drugs for brand-name drugs: medical expenditure panel survey, 1997-2000. Ann. Intern. Med. 2005; 142:891–897. doi: 10.7326/0003-4819-142-11-200506070-00006.
25. Heinze G. Potential savings in prescription drug costs for hypertension, hyperlipidemia, and diabetes mellitus by equivalent drug substitution in Austria: a nationwide cohort study. Appl. Health Econ. Health Policy.;2015; 13:193–205. doi: 10.1007/s40258-014-0143-4.
26. Banahan BF, Kolassa EM. (1997) A physician survey on generic drugs and substitution of critical dose medications. Arch. Intern. Med. 157:2080–2088. doi: 10.1001/archinte.1997.00440390066010
27. Kjoenniksen I, Lindbaek M, Granas AG. Patients’ attitudes towards and experiences of generic drug substitution in Norway. Pharm. World Sci. 2006; 28: 284–289. doi: 10.1007/s11096-006-9043-5.
28. Riner B. (2017) “No generics, Doctor!” The perspective of general practitioners in two French regions. BMC Health Serv. Res. 2017; 17:707. doi: 10.1186/s12913-017-2682-5.
29. Huic M, Vrhovac B, Macolic-Sarinic V, Francetic I, Bakran I, Giljanovic S. How safe are bioequivalence studies in healthy volunteers? Therapie.1996; 51(4) 410-3.
30. Zintzaras E. Statistical aspects of bioequivalence testing between two medicinal products. European journal of drug metabolism and pharmacokinetics. 2005; 30(1-2) 41–46. https://doi.org/10.1007/BF03226406
31. Gupta, R., Shah, N. D., & Ross, J. S. Generic Drugs in the United States: Policies to Address Pricing and Competition. Clinical pharmacology and therapeutics 2019; 105 (2):329–337. https://doi.org/10.1002/cpt.1314
32. Koonrungsesomboon, N., Potikanond, S., Na Takuathung, M., Nimlamool, W., & Karbwang, J. Informational needs for participation in bioequivalence studies: the perspectives of experienced volunteers. European journal of clinical pharmacology 2019; 75 (11): 1575–1582. https://doi.org/10.1007/s00228-019-02738-6
33. Karakunnel, J. J., Bui, N., Palaniappan, L., Schmidt, K. T., Mahaffey, K. W., Morrison, B., Figg, W. D., & Kummar, S . Reviewing the role of healthy volunteer studies in drug development. Journal of translational medicine 2018; 16(1) 336. https://doi.org/10.1186/s12967-018-1710-5
34. Van Gelder T., Gabardi, S. Methods, strengths, weaknesses, and limitations of bioequivalence tests with special regard to immunosuppressive drugs (2013). Transplant international: official journal of the European Society for Organ Transplantation. 2013; 26(8) 771–777. https://doi.org/10.1111/tri.12074.
2. WHO. Technical Report Series Nº 863. Expert Committee on Specifications for pharmaceutical preparations. 34 th Report. Geneva,1996.
3. WHO. Guidance on the selection of comparator pharmaceutical products for equivalence assessment of interchangeable multisource (generic) products (2015). In: WHO Expert Committee on Specifications for Pharmaceutical Preparations: forty-ninth report. Geneva: World Health Organization: 2015: Annex 8 (WHO Technical Report Series, No. 992).
4. ANMAT. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica. National Administration of Drugs, Food and Medical Technology (2023). Biopharmaceutical Classification System: Available at: http://www.anmat.gov.ar/webanmat/legislacion/medicamentos/ disposicion_ anmat_758-2009.pdf Accessed August 23rd, 2023.
5. United States Food and Drug Administration. Draft Guidance for Industry. Bioequivalence studies with pharmaco-kinetic endpoints for drugs submitted under an ANDA. (IDRAC N° 173244): URL https://cortellis.thomsonreuterslifesciences.com/ngg/report/ri/regulatory/173244.
6. Langguth P, Fricker G, Wunderli-Allenspach H. EMA versus US-FDA regulatory requirements
7. regarding bioequivalence of orally administered generics (2004). Biopharmazie., 79-162, 165-286.
8. European Commission. Guidelines on the details of the various categories of variations, on the operation of the procedures laid down in Chapters II, IIa, III and IV of Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products and on the documentation to be submitted pursuant to those procedures (2013/C 223/01). (IDRAC N° 163692): URL https://cortellis.thomsonreuterslifesciences.com/ngg/ report/ri/regulatory/163692 Accessed Ocxtober 23rd, 2023.
9. Committee for Medicinal Products for Human Use. Guideline on the investigation of bioequivalence. CPMP/EWP/QWP/1401/98 Rev.1/Corr, 2010. (IDRAC N°120848): URL https://cortellis.thomsonreuterslifesciences.com/ngg/report/ri/regulatory/120848 Accessed August 23rd, 2023.
10. Yu LX. Quality and bioequivalence standards for narrow therapeutic index drugs. GP. Fall Technical Workshop, 2011. URL http://www.fda.gov/downloads/Drugs/DevelopmentApproval Process/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/UCM292676.pdf August 21rd, 2023.
11. Purich E. In: Bioavailability/Bioequivalence Regulations: An FDA Perspective in Drug Absorption and Disposition: Statistical Considerations. Albert KS, editor. American Pharmaceutical Association, Academy of Pharmaceutical Sciences; Washington, DC: 1980. pp. 115–137.
12. FDA. Guidance on Bioavailability and Bioequivalence Studies for Orally Administrated Drug Products – General Considerations. Center for Drug Evaluation and Research, the US Food and Drug Administration; Rockville, Maryland, USA: 2003.
13. Chen KW, Li G, Chow SC A note on sample size determination for bioequivalence studies with higher-order crossover designs. Journal of Pharmacokinetics and Biopharmaceutics. 1997;25 753–765.
14. Chow, S.-C., & Liu, J.-P. Design and Analysis of Bioavailability and Bioequivalence Studies (2nd ed.). CRC Press,1999. https://doi.org/10.1201/9781420002027
15. Upendra C. Galgatte, Vijay R. Jamdade, Pravin P. Aute, Pravin D. (2014). Study on requirements of bioequivalence for registration of pharmaceutical products in USA, Europe and Canada, Saudi Pharmaceutical Journal 2014; 22-5 391-402.
16. Asian Guideline for the Conduct Bioavailability & Bioequivalence Studies. Pharmaceutical Formulation Design 2004;20:5-10.
17. Health Canada. Conduct and Analysis of Bioavailability and Bioequivalence Studies: Part A: Oral Dosage Formulations Used for Systemic Effects (1992); Part B: Oral Modified Release Formulations (1996); Report C: Report on Bioavailability of Oral Dosage Formulations, Not in Modified Release Form, or Drugs Used for Systemic Effects, Having Complicated or Variable Pharmacokinetics (1992). Health Products and Food Branch Guidence Document. 1992-1996. Available from: http://www.hc.sc.gc.ca
18. HCNA. Argentinian National Congress. Law N° 25.649 of generic medicines. Available from: https://www.argentina.gob.ar/ normativa/nacional/ley-25649-77881. ACCESSED October 21rd, 2023
19. García-Arieta A.. The failure to show bioequivalence is not evidence against generics. Br J Clin Pharmacol.200; 70(3) 452-3.
20. Borgheini G. The bioequivalence and therapeutic efficacy of generic versus brand-name psychoactive drugs. Clin Ther.2003; 25(6) 1578-92.
21. Rheinstein PH. Therapeutic inequivalence (1990). Drug Safety.5 (Suppl 1):114–119.
22. Schall R, Endrenyi L. Bioequivalence: tried and tested. Cardiovasc J Afr.2010; 21(2) : 69-71.
23. Barret JS, Batra V, Chow A, Cook J, Gould AL, Heller A. et al. Pharma perspective on population and individual bioequivalence. J Clin Pharmacol. 2000; 40:561–570.
24. Haas JS, Phillips KA, Gerstenberger EP, Seger AC. Potential savings from substituting generic drugs for brand-name drugs: medical expenditure panel survey, 1997-2000. Ann. Intern. Med. 2005; 142:891–897. doi: 10.7326/0003-4819-142-11-200506070-00006.
25. Heinze G. Potential savings in prescription drug costs for hypertension, hyperlipidemia, and diabetes mellitus by equivalent drug substitution in Austria: a nationwide cohort study. Appl. Health Econ. Health Policy.;2015; 13:193–205. doi: 10.1007/s40258-014-0143-4.
26. Banahan BF, Kolassa EM. (1997) A physician survey on generic drugs and substitution of critical dose medications. Arch. Intern. Med. 157:2080–2088. doi: 10.1001/archinte.1997.00440390066010
27. Kjoenniksen I, Lindbaek M, Granas AG. Patients’ attitudes towards and experiences of generic drug substitution in Norway. Pharm. World Sci. 2006; 28: 284–289. doi: 10.1007/s11096-006-9043-5.
28. Riner B. (2017) “No generics, Doctor!” The perspective of general practitioners in two French regions. BMC Health Serv. Res. 2017; 17:707. doi: 10.1186/s12913-017-2682-5.
29. Huic M, Vrhovac B, Macolic-Sarinic V, Francetic I, Bakran I, Giljanovic S. How safe are bioequivalence studies in healthy volunteers? Therapie.1996; 51(4) 410-3.
30. Zintzaras E. Statistical aspects of bioequivalence testing between two medicinal products. European journal of drug metabolism and pharmacokinetics. 2005; 30(1-2) 41–46. https://doi.org/10.1007/BF03226406
31. Gupta, R., Shah, N. D., & Ross, J. S. Generic Drugs in the United States: Policies to Address Pricing and Competition. Clinical pharmacology and therapeutics 2019; 105 (2):329–337. https://doi.org/10.1002/cpt.1314
32. Koonrungsesomboon, N., Potikanond, S., Na Takuathung, M., Nimlamool, W., & Karbwang, J. Informational needs for participation in bioequivalence studies: the perspectives of experienced volunteers. European journal of clinical pharmacology 2019; 75 (11): 1575–1582. https://doi.org/10.1007/s00228-019-02738-6
33. Karakunnel, J. J., Bui, N., Palaniappan, L., Schmidt, K. T., Mahaffey, K. W., Morrison, B., Figg, W. D., & Kummar, S . Reviewing the role of healthy volunteer studies in drug development. Journal of translational medicine 2018; 16(1) 336. https://doi.org/10.1186/s12967-018-1710-5
34. Van Gelder T., Gabardi, S. Methods, strengths, weaknesses, and limitations of bioequivalence tests with special regard to immunosuppressive drugs (2013). Transplant international: official journal of the European Society for Organ Transplantation. 2013; 26(8) 771–777. https://doi.org/10.1111/tri.12074.
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Jan 19, 2024
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How to Cite
Rosa Maria Vera, Marcelo Estrin, & Gustavo H. Marin. (2024). BIOEQUIVALENCE: HEALTH, COMMERCIAL AND POLITICAL IMPLICATIONS OF THIS TECHNICAL TOOL. Journal of Population Therapeutics and Clinical Pharmacology, 31(1), 1044–1053. https://doi.org/10.53555/jptcp.v31i1.3780
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Author Biographies
Rosa Maria Vera
Hospital General de Agudos Dr. Carlos G. Durand, Ambrosetti 750, CABA, Argentina
Marcelo Estrin
Hospital Donación Francisco Santojanni, Departamento de Urgencias, Unidad de Terapia Intensiva, Pilar 950, CABA, Argentina
Gustavo H. Marin
Facultad de Ciencias Médicas Universidad Nacional de La Plata. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET-UNLP-CUFAR) Hospital Elina de la Serna, Calle 8 N° 483, La Plata, Argentina