Current regulatory approaches of bioequivalence testing

Expert Opinion on Drug Metabolism and Toxicology

Volumn 8, Issue 8, 2012, Pages 929-942

  Karalis, Vangelis ^a   MacHeras, Panos ^a  

^a NATIONAL AND KAPODISTRIAN UNIVERSITY OF ATHENS   (Greece)

Author keywords

Bioequivalence; Biowaivers; Complex drugs; European Medicines Agency; Food and Drug Administration; Regulatory guidelines; Scaled bioequivalence approach

Indexed keywords

DRUG METABOLITE; GENERIC DRUG; IMMUNOSUPPRESSIVE AGENT; LIPOSOME;

BIOEQUIVALENCE; DRUG ABSORPTION; DRUG EFFICACY; DRUG EXCRETION; DRUG FORMULATION; DRUG HALF LIFE; DRUG METABOLISM; DRUG PENETRATION; DRUG SAFETY; DRUG SCREENING; DRUG SOLUBILITY; ENANTIOMER; FOOD AND DRUG ADMINISTRATION; GASTROINTESTINAL ABSORPTION; ISOMER; MAXIMUM PLASMA CONCENTRATION; MICROEMULSION; PH; PHARMACODYNAMICS; PHARMACOGENOMICS; PRACTICE GUIDELINE; QUALITATIVE ANALYSIS; QUANTITATIVE ANALYSIS; REVIEW; SAMPLE SIZE; STEADY STATE; TIME TO MAXIMUM PLASMA CONCENTRATION; URINARY EXCRETION;

BIOSIMILAR PHARMACEUTICALS; DRUGS, GENERIC; ENDPOINT DETERMINATION; GUIDELINES AS TOPIC; HUMANS; IMMUNOSUPPRESSIVE AGENTS; THERAPEUTIC EQUIVALENCY; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 84864038467     PISSN: 17425255     EISSN: 17447607     Source Type: Journal    
DOI: 10.1517/17425255.2012.690394     Document Type: Review

References (100)

1. Sisko A, Truffer C, Keehan S, et al. National health spending projections: The estimated impact of reform through 2019. Health Aff 2010;29:1933-1941
2. Carpenter D, Tobbell DA. Bioequivalence: The regulatory career of a pharmaceutical concept. Bull Hist Med 2011;85:93-131
3. Niazi S. Handbook of bioequivalence testing. 1st edition. Informa Healthcare; NY: 2007
4. Chen ML, Shah VP, Crommelin DJ, et al. Harmonization of regulatory approaches for evaluating therapeutic equivalence and interchangeability of multisource drug products: Workshop summary report. Eur J Pharm Sci 2011;44:506-513
5. Chen ML, Shah VP, Crommelin DJ, et al. Harmonization of regulatory approaches for evaluating therapeutic equivalence and interchangeability of multisource drug products: Workshop summary report. AAPS J 2011;13:556-564
6. European Medicines Agency, Evaluation of Medicines for Human Use, CPMP. Note for guidance on the investigation of bioavailability and bioequivalence. London: 2001
7. European Medicines Agency, Evaluation of Medicines for Human Use, CHMP. Guideline on the investigation of bioequivalence. London: 2010
8. Food and Drug Administration, Center for Drug Evaluation and Research (CDER), bioavailability and bioequivalence studies for orally administered drug products, general considerations. Rockville, MD: 2003
9. Chen ML, Shah V, Patnaik R, et al. Bioavailability and bioequivalence: An FDA regulatory overview. Pharm Res 2001;18:1645-1650
10. Bois F, Tozer T, Hauck W, et al. Bioequivalence: Performance of several measures of extent of absorption. Pharm Res 1993;11:715-722
11. Bois F, Tozer T, Hauck W, et al. Bioequivalence: Performance of several measures of rate of absorption. Pharm Res 1994;11:966-974
12. Chen ML, Lesko LJ, Williams RL. Measures of exposure versus measures of rate and extent of absorption. Clin Pharmacokinet 2001;40:565-572
13. Rescigno A. Bioequivalence. Pharm Res 1992;9:925-928
14. Chinchilli VM, Elswick RK. The multivariate assessment of bioequivalence. J Biopharm Stat 1997;7:113-123
15. Moore J, Flanner H. Mathematical comparison of curves with an emphasis on in vitro dissolution profiles. Pharm Tech 1996;20:64-74
16. Polli JE, McLean AM. Novel direct curve comparison metrics for bioequivalence. Pharm Res 2001;18:734-741
17. Karalis V, Macheras P. Pharmacodynamic considerations in bioequivalence assessment: Comparison of novel and existing metrics. Eur J Pharm Sci 2003;19:45-56
18. Endrenyi L, Tothfalusi L. Without extrapolation, Cmax/AUC is an effective metric in investigations of bioequivalence. Pharm Res 1995;12:937-942
19. Macheras P, Symillides M, Reppas C. An improved intercept method for the assessment of absorption rate in bioequivalence studies. Pharm Res 1996;13:1755-1758
20. Chen ML. An alternative approach for assessment of rate of absorption in bioequivalence studies. Pharm Res 1992;9:1380-1385
21. Macheras P, Symillides M, Reppas C. The cutoff time point of the partial area method for assessment of rate of absorption in bioequivalence studies. Pharm Res 1994;11:831-834
22. Midha KK, Hubbard JW, Rawson MJ et al. The application of partial areas in assessment of rate and extent of absorption in bioequivalence studies of conventional release products: Experimental evidence. Eur J Pharm Sci 1994;2:351-363
23. Reppas C, Lacey LF, Keene ON, et al. Evaluation of different metrics as indirect measures of rate of drug absorption from extended release dosage forms at steady-state. Pharm Res 1995;12:103-107
24. Endrenyi L, Csizmadia F, Tothfalusi L, et al. The duration of measuring partial AUCs for the assessment of bioequivalence. Pharm Res 1998;15:399-404
25. Endrenyi L, Csizmadia F, Tothfalusi L, et al. Metrics comparing simulated early concentration profiles for the determination of bioequivalence. Pharm Res 1998;15:1292-1299
26. Chen ML, Davit B, Lionberger R, et al. Using partial area for evaluation of bioavailability and bioequivalence. Pharm Res 2011;28:1939-1947
27. Tozer TN, Bois FY, Hauck WW, et al. Absorption rate vs. exposure: Which is more useful for bioequivalence testing? Pharm Res 1996;13:453-456
28. Food and Drug Administration, Center for Drug Evaluation and Research (CDER), statistical approaches to establishing bioequivalence. Rockville, MD: 2001
29. Westlake WJ. The design and analysis of comparative blood-level trials. In: SWARBRICK J, editor. Current concepts in the pharmaceutical sciences, dosage form design and bioavailability. Lea and Febiger, Philadelphia 1973. p. 149-79
30. Westlake WJ. Bioavailability and bioequivalence of pharmaceutical formulations. In: PEACE KE, editor. Biopharmaceutical statistics for drug development. Marcel Dekker, Inc.; New York 1988. p. 329-52
31. Schuirmann D. A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J Pharmacokinet Biopharm 1987;15:657-680
32. Hauck WW, Anderson S. Types of bioequivalence and related statistical considerations. Int J Clin Pharmacol Ther Toxicol 1992;30:181-187
33. Schall R, Luus H. On population and individual bioequivalence. Stat Med 1993;12:1109-1124
34. Chinchilli VM. The assessment of individual and population bioequivalence. J Biopharm Stat 1996;6:1-14
35. Anderson S, Hauck W. Consideration of individual bioequivalence. J Pharmacokinet Biopharm 1990;18:259-273
36. Hauck W, Anderson S. Individual bioequivalence: What matters to the patient. Stat Med 1991;10:959-960
37. Schall R, Williams R. Towards a practical strategy for assessing individual bioequivalence. J Pharmacokinet Biopharm 1996;24:133-149
38. Patnaik R, Lesko L, Chen ML, et al. Individual bioequivalence: New concepts in the statistical assessment of bioequivalence metrics. Clin Pharmacokinet 1997;33:1-6
39. Midha K, Rawson M, Hubbard J. Individual and average bioequivalence of highly variable drugs and drug products. J Pharm Sci 1997;86:1193-1197
40. Endrenyi L, Amidon G, Midha K, et al. Individual bioequivalence: Attractive in principle, difficult in practice. Pharm Res 1998;15:1321-1325
41. Haidar S, Davit B, Chen ML, et al. Bioequivalence approaches for highly variable drugs and drug products. Pharm Res 2008;15:237-241
42. Haidar S, Makhlouf F, Schuirmann D, et al. Evaluation of a scaling approach for the bioequivalence of highly variable drugs. AAPS J 2008;10:450-454
43. Food and Drug Administration, Office of Generic Drugs, Draft Guidance for Industry on Bioequivalence Recommendations for Progesterone Capsules, Feb2011
44. Shah V, Yacobi A, Barr W, et al. Evaluation of orally administered highly variable drugs and drug formulations. Pharm Res 1996;13:1590-1594
45. Blume H, Elze M, Potthast H, et al. Practical strategies and design advantages in highly variable drug studies: Multiple dose and replicate administration design. In: BLUME H, Midha K, editors. Bio-international 2: Bioavailability, bioequivalence and pharmacokinetic studies. Medpharm Scientific Publishers; Stuttgart: 1995. p. 117-22
46. El-Tahtawy A, Jackson A, Ludden T. Comparison of single and multiple dose pharmacokinetics using clinical bioequivalence data and monte carlo simulations. Pharm Res 1994;11:1330-1336
47. El-Tahtawy A, Jackson A, Ludden T. Evaluation of bioequivalence of highly variable drugs using monte carlo simulations. Part I: Estimation of rate of absorption for single and multiple dose trials using Cmax. Pharm Res 1995;12:1634-1641
48. Jackson A. Prediction of steady-state bioequivalence relationships using single dose data I-linear kinetics. Biopharm Drug Dispos 1987;8:483-496
49. Benet L. Bioavailability and bioequivalence: Definitions and difficulties in acceptance criteria. In: MIDHA KK, Blume HH, editors. Bio-International: Bioavailability, bioequivalence and pharmacokinetics. Medpharm Scientific; Stuttgart: 1995. p. 27-35
50. McGilveray I, Midha K, Skelly J, et al. Consensus report from "Bio-International '89": Issues in the evaluation of bioavailability data. J Pharm Sci 1990;79:945-946
51. Blume H, Midha K. Bio-International '92, Conference on bioavailability, bioequivalence and pharmacokinetic studies. J Pharm Sci 1993;82:1186-1189
52. Van Peer A. Variability and impact on design of bioequivalence studies. Basic Clin Pharmacol Toxicol 2010;106:146-153
53. Tothfalusi L, Endrenyi L, Midha K. Scaling or wider bioequivalence limits for highly variable drugs and for the special case of Cmax. Int J Clin Pharmacol Ther 2003;41:217-225
54. Blume HH, McGilveray IJ, Midha KK. Bio-International 94, conference on bioavailability bioequivalence and pharmacokinetic studies. Eur J Pharm Sci 1995;3:113-124
55. Boddy A, Snikeris F, Kringle R, et al. An approach for widening the bioequivalence acceptance limits in the case of highly variable drugs. Pharm Res 1995;12:1865-1868
56. Tothfalusi L, Endrenyi L. Limits for the scaled average bioequivalence of highly variable drugs and drug products. Pharm Res 2003;20:382-389
57. Karalis V, Symillides M, Macheras P. Novel scaled average bioequivalence limits based on GMR and variability considerations. Pharm Res 2004;21:1933-1942
58. Karalis V, Macheras P, Symillides M. Geometric mean ratio dependent scaled bioequivalence limits with leveling-off properties. Eur J Pharm Sci 2005;26:54-61
59. Kytariolos J, Karalis V, Macheras P, et al. Novel scaled bioequivalence limits with leveling-off properties. Pharm Res 2006;23:2657-2664
60. Karalis V, Symillides M, Macheras P. On the leveling-off properties of the new bioequivalence limits for highly variable drugs of the EMA guideline. Eur J Pharm Sci 2011;44:497-505
61. Karalis V, Symillides M, Macheras P. Bioequivalence of highly variable drugs: A comparison of the newly proposed regulatory approaches by FDA and EMA. Pharm Res 2011;published online 28 December 2011; doi: 10.1007/s11095-011-0651-y
62. Tothfalusi L, Endrenyi L, Arieta AG. Evaluation of bioequivalence for highly variable drugs with scaled average bioequivalence. Clin Pharmacokinet 2009;48:725-743
63. Tothfalusi L, Endrenyi L. Sample sizes for designing bioequivalence studies for highly variable drugs. J Pharm Pharm Sci 2011;15:73-84
64. Karalis V, Symillides M, Macheras P. Comparison of the reference scaled bioequivalence semi-replicate method with other approaches: Focus on human exposure to drugs. Eur J Pharm Sci 2009;38:55-63
65. Midha K, Rawson M, Hubbard J. The Role of metabolites in bioequivalence. Pharm Res 2004;21:1331-1344
66. Midha K, Shah V, Singh G, et al. Conference report: Bio-international 2005. J Pharm Sci 2007;96:747-754
67. Houston JB. Importance of metabolites in bioequivalence. In: Mcgilveray JJ, Dighe SV, French IW, et al. editors. Proceedings bio-international 89: Issues in the evaluation of bioavailability data. Toronto, Canada, 1989. p. 99-100
68. Jackson AJ, Robbie G, Marroum P. Metabolites and bioequivalence: Past and present. Clin Pharmacokinet 2004;43:655-672
69. Karalis V, Macheras P. Examining the role of metabolites in bioequivalence assessment. J Pharm Pharm Sci 2010;13:198-217
70. Welling PG. Influence of food and diet on gastrointestinal drug absorption: A review. J Pharmacokinet Biopharm 1977;5:291-334
71. Olanoff L, Walle T, Cowart T, et al. Food effects on propranolol systemic and oral clearance: Support for a blood flow hypothesis. Clin Pharmacol Ther 1986;40:408-414
72. Gupta S, Benet L. High-fat meals increase the clearance of cyclosporine. Pharm Res 1990;7:46-48
73. Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Guidance for industry food-effect bioavailability and fed bioequivalence studies. 2002
74. European Medicines Agency, Note for guidance on modified release oral and transdermal dosage forms: Section II (pharmacokinetic and clinical evaluation). Committee for Proprietary Medicinal Products (CPMP). CPMP/EWP/280/96 1999
75. European Medicines Agency, CHMP efficacy working party therapeutic subgroup on pharmacokinetics (EWPPK). Questions & answers on the bioavailability and bioequivalence guideline. London: 2006
76. Food and Drug Administration, Guidance for Industry, Immediate Release Solid Oral Dosage Forms Scale-Up and Post-approval Changes: CHEMISTRY, Manufacturing, and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation. 1995
77. Shah V, Tsong Y, Sathe P. In vitro dissolution profile comparison -statistics and analysis of the similarity factor, f2. Pharm Res 1998;15:889-896
78. Amidon G, Lennernas H, Shah V, et al. A theoretical basis for a biopharmaceutic drug classification: The correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995;12:413-420
79. Wu C, Benet LZ. Predicting drug disposition via application of BCS: Transport/ absorption/ elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res 2005;22:11-23
80. Chen ML, Amidon GL, Benet LZ, et al. The BCS, BDDCS, and regulatory guidances. Pharm Res 2011;28:1774-1778
81. Dahan A, Miller JM, Amidon GL. Prediction of solubility and permeability class membership: Provisional BCS classification of the world's top oral drugs. AAPS J 2009;11:740-746
82. Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Guidance for Industry Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System, 2000
83. Custodio J, Wu C, Benet L. Predicting drug disposition, absorption/ elimination/transporter interplay and the role of food on drug absorption. Adv Drug Deliv Rev 2008;60:717-733
84. Benet L. Predicting drug disposition via application of a biopharmaceutics drug disposition classification system. Basic Clin Pharmacol Toxicol 2010;106:162-167
85. Benet LZ, Broccatelli F, Oprea TI. BDDCS applied to over 900 drugs. AAPS J 2011;13:519-547
86. Benet LZ, Amidon GL, Barends DM, et al. The use of BDDCS in classifying the permeability of marketed drugs. Pharm Res 2008;52:483-488
87. Broccatelli F, Cruciani G, Benet LZ, et al. BDDCS class prediction for new molecular entities. Mol Pharm 2012;published online 7 February 2012; doi:10.1021/mp2004302
88. Takagi T, Ramachandran C, Bermejo M, et al. A provisional biopharmaceutical classification of the top 200 oral drug products in the United States, Great Britain, Spain and Japan. Mol Pharm 2006;3:631-643
89. Chen ML, Yu L. The use of drug metabolism for prediction of intestinal permeability. Mol Pharm 2009;6:74-81
90. Morais JA, Lobato Mdo R. The new European Medicines Agency guideline on the investigation of bioequivalence. Basic Clin Pharmacol Toxicol 2010;106:221-225
91. Marzo A, Fontana E. Critical considerations into the new EMA guideline on bioequivalence. Arzneimittel-Forschung 2011;61:207-220
92. Schellekens H, Klinger E, Muhlebach S, et al. The therapeutic equivalence of complex drugs. Regul Toxicol Pharmacol 2011;59:176-183
93. European Medicines Agency, Evaluation of Medicines for Human Use, CHMP. Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: Quality issues. London: 2006
94. European Medicines Agency, Evaluation of Medicines for Human Use, CHMP. Guideline on immunogenicity assessment of biotechnology-derived therapeutic proteins. London: 2007
95. European Medicines Agency, Guidance on similar medicinal products containing recombinant erythropoietins. EMEA/CHMP/BMWP/94526/2005, 2006
96. European Medicines Agency, Guideline on similar biological medicinal products containing monoclonal antibodies, Draft guideline. EMA/CHMP/BMWP/ 403543/2010, 2010
97. Schrempf W, Ziemmsen T. Glatiramer acetate: Mechanisms of action in multiple sclerosis. Autoimmune Rev 2007;6:469-475
98. European Medicines Agency, Committee for Medicinal Products for Human Use, CHMP. Reflection paper on non-clinical studies for generic nanoparticle iron medicinal product applications. EMA/CHMP/SWP/100094/2011, 2011
99. Van Gelder T. European Society for Organ Transplantation Advisory Committee: Recommendations on generic substitution of immunosuppressive drugs. Transpl Int 2011;24:1135-1141
100. European Medicines Agency, Guideline on the use of pharmacogenetic methodologies in the pharmacokinetic evaluation of medicinal products. EMA/CHMP/37646/2009, 2012