Abstract
Pharmacodynamic (PD) studies can be used to establish bioequivalence of drug products when pharmacokinetic (PK) and in vitro studies are not applicable. Compared with clinical endpoint bioequivalence studies, PD studies are more cost-effective, timesaving, sensitive, less risky, and less complicated. In this chapter, we will discuss PD endpoint-based bioequivalence studies, the general considerations for PD study design and validation, and US Food and Drug Administration (FDA) recommendations for bioequivalence studies of specific drug products. Finally, the other potential PD endpoints reported in literatures for bioequivalence studies will be briefly discussed.
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References
Adams WP, Ahrens RC, Chen ML, Christopher D, Chowdhury BA, Conner DP, Dalby R, Fitzgerald K, Hendeles L, Hickey AJ, Hochhaus G, Laube BL, Lucas P, Lee SL, Lyapustina S, Li B, O’Connor D, Parikh N, Parkins DA, Peri P, Pitcairn GR, Riebe M, Roy P, Shah T, Singh GJ, Sharp SS, Suman JD, Weda M, Woodcock J, Yu L (2010) Demonstrating bioequivalence of locally acting orally inhaled drug products (OIPs): workshop summary report. J Aerosol Med Pulm Drug Deliv 23:1–29
Ahrens RC, Teresi ME, Han SH, Donnell D, Vanden Burgt JA, Lux CR (2001) Asthma stability after oral prednisone: a clinical model for comparing inhaled steroid potency. Am J Respir Crit Care Med 164:1138–1145
CDSCO-India (2005) Guidance for bioavailability and bioequivalence studies. http://cdsco.nic.in/html/be%20guidelines%20draft%20ver10%20march%2016,%2005.pdf
Chen ML, Shah V, Patnaik R, Adams W, Hussain A, Conner D, Mehta M, Malinowski H, Lazor J, Huang SM, Hare D, Lesko L, Sporn D, Williams R (2001) Bioavailability and bioequivalence: an FDA regulatory overview. Pharm Res 18:1645–1650
Creticos PS, Adams WP, Petty BG, Lewis LD, Singh GJ, Khattignavong AP, Molzon JA, Martinez MN, Lietman PS, Williams RL (2002) A methacholine challenge dose-response study for development of a pharmacodynamic bioequivalence methodology for albuterol metered- dose inhalers. J Allergy Clin Immunol 110:713–720
Daley-Yates PT, Parkins DA (2011) Establishing bioequivalence for inhaled drugs; weighing the evidence. Expert Opin Drug Deliv 8:1297–1308
Drent ML, Van Der Veen EA (1993) Lipase inhibition: a novel concept in the treatment of obesity. Int J Obes Relat Metab Disord 17:241–244
EMEA (2000) Note for guidance on the investigation of bioavailability and bioequivalence. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003519.pdf
EMEA (2007) Scientific discussion. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000726/WC500028287.pdf
EMEA (2009) Guideline on the requirements for clinical documentation for orally inhaled products (OIP) including the requirements for demonstration of therapeutic equivalence between two inhaled products for use in the treatment of asthma and chronic obstructive pulmonary disease (COPD) in adults and for use in the treatment of asthma in children and adolescents. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003504.pdf
Evans C, Cipolla D, Chesworth T, Agurell E, Ahrens R, Conner D, Dissanayake S, Dolovich M, Doub W, Fuglsang A, Garcia Arieta A, Golden M, Hermann R, Hochhaus G, Holmes S, Lafferty P, Lyapustina S, Nair P, O’Connor D, Parkins D, Peterson I, Reisner C, Sandell D, Singh GJ, Weda M, Watson P (2012) Equivalence considerations for orally inhaled products for local action-ISAM/IPAC-RS European Workshop report. J Aerosol Med Pulm Drug Deliv 25:117–139
FDA (1995) Guidance for industry-topical dermatologic corticosteroids: in vivo bioequivalence. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070234.pdf
FDA (2000) Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. http://www.fda.gov/downloads/Drugs/…/Guidances/ucm070246.pdf
FDA (2003a) Guidance for industry: bioavailability and bioequivalence studies for nasal aerosols and nasal sprays for local action. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070111.pdf
FDA (2003b) Guidance for industry: exposure-response relationships—study design, data analysis, and regulatory applications. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072109.pdf
FDA (2009) Draft guidance on acarbose. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM170242.pdf
FDA (2010a) Draft guidance on orlistat. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM201268.pdf
FDA (2010b) Guidance for industry-bioequivalence recommendations for specific products. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072872.pdf
FDA (2011a) Draft guidance on enoxaparin sodium. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM277709.pdf
FDA (2011b) Draft guidance on fluticasone propionate. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM244386.pdf
FDA (2011c) Draft guidance on lanthanum carbonate. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM270541.pdf
FDA (2012) Draft guidance on dalteparin sodium. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM319988.pdf
FDA (2013a) Bioequivalence studies with pharmacokinetic endpoints for drugs submitted under an ANDA. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM377465.pdf
FDA (2013b) Draft guidance on albuterol sulfate. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM346985.pdf
FDA (2013c) Draft guidance on fluticasone propionate; salmeterol xinafoate. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM367643.pdf
Health-Canada (1999) Guidance to establish equivalence or relative potency of safety and efficacy of a second entry short-acting beta2-agonist metered dose inhaler. http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/prodpharma/mdi_bad-eng.pdf
Health-Canada (2011) Data requirements for safety and effectiveness of subsequent market entry inhaled corticosteroid products for use in the treatment of asthma. http://www.hc-sc.gc.ca/dhp-mps/consultation/drug-medic/draft_inhal_ebauche_corticost-eng.php
Jatakanon A, Kharitonov S, Lim S, Barnes PJ (1999) Effect of differing doses of inhaled budesonide on markers of airway inflammation in patients with mild asthma. Thorax 54:108–114
Lee S, Chung JY, Hong KS, Yang SH, Byun SY, Lim HS, Shin SG, Jang IJ, Yu KS (2012) Pharmacodynamic comparison of two formulations of Acarbose 100-mg tablets. J Clin Pharm Ther 37:553–557
Lee S, Raw A, Yu L, Lionberger R, Ya N, Verthelyi D, Rosenberg A, Kozlowski S, Webber K, Woodcock J (2013) Scientific considerations in the review and approval of generic enoxaparin in the United States. Nat Biotechnol 31:220–226
Lehman PA, Franz TJ (2012) Assessing the bioequivalence of topical retinoid products by pharmacodynamic assay. Skin Pharmacol Physiol 25:269–280
Lionberger RA (2008) FDA critical path initiatives: opportunities for generic drug development. AAPS J 10:103–109
Lissy M, Ode M, Roth K (2011) Comparison of the pharmacokinetic and pharmacodynamic profiles of one US-marketed and two European-marketed epoetin alfas: a randomized prospective study. Drugs R D 11:61–75
MacDonald AJ, Parrott N, Jones H, Lave T (2004) Modelling and simulation of pharmacokinetic and pharmacodynamic systems-approaches in drug discovery. In: Beilstein-Institut Workshop, May 24–28, Bozen
Mastan S, Latha TB, Ajay S (2011) The basic regulatory considerations and prospects for conducting bioavailability/bioequivalence (BA/BE) studies—an overview. Comp Eff Res 1:1–25
N’Dri-Stempfer B, Navidi WC, Guy RH, Bunge AL (2009) Improved bioequivalence assessment of topical dermatological drug products using dermatopharmacokinetics. Pharm Res 26:316–328
Navidi W, Hutchinson A, N’Dri-Stempfer B, Bunge A (2008) Determining bioequivalence of topical dermatological drug products by tape-stripping. J Pharmacokinet Pharmacodyn 35:337–348
Saudi-FDA (2005) Bioequivalence requirements guidelines (draft). http://old.sfda.gov.sa/NR/rdonlyres/6A114B70-4201-46EF-B4C7-127FD66D3314/0/BioequivalenceRequirementGuidelines.pdf
Swainston Harrison T, Scott LJ (2004) Lanthanum carbonate. Drugs 64:985–996; discussion 997–998
Swystun VA, Bhagat R, Kalra S, Jennings B, Cockcroft DW (1998) Comparison of 3 different doses of budesonide and placebo on the early asthmatic response to inhaled allergen. J Allergy Clin Immunol 102:363–367
Taylor DA, Jensen MW, Kanabar V, Engelstatter R, Steinijans VW, Barnes PJ, O’Connor BJ (1999) A dose-dependent effect of the novel inhaled corticosteroid ciclesonide on airway responsiveness to adenosine-5′-monophosphate in asthmatic patients. Am J Respir Crit Care Med 160:237–243
Treffel P, Gabard B (1993) Feasibility of measuring the bioavailability of topical ibuprofen in commercial formulations using drug content in epidermis and a methyl nicotinate skin inflammation assay. Skin Pharmacol 6:268–275
WHO (2006) WHO expert committee on specifications for pharmaceutical preparation. Geneva. http://apps.who.int/prequal/info_general/documents/TRS937/WHO_TRS_937_eng.pdf#page = 359
Wiedersberg S, Leopold CS, Guy RH (2008) Bioavailability and bioequivalence of topical glucocorticoids. Eur J Pharm Biopharm 68:453–466
Zhang M, Yang J, Tao L, Li L, Ma P, Fawcett JP (2012) Acarbose bioequivalence: exploration of new pharmacodynamic parameters. AAPS J 14:345–351
Zhi J, Melia AT, Eggers H, Joly R, Patel IH (1995) Review of limited systemic absorption of orlistat, a lipase inhibitor, in healthy human volunteers. J Clin Pharmacol 35:1103–1108
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Zou, P., Yu, L.X. (2014). Pharmacodynamic Endpoint Bioequivalence Studies. In: Yu, L., Li, B. (eds) FDA Bioequivalence Standards. AAPS Advances in the Pharmaceutical Sciences Series, vol 13. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1252-0_9
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DOI: https://doi.org/10.1007/978-1-4939-1252-0_9
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