Critical considerations into the new EMA guideline on bioequivalence

Arzneimittel-Forschung/Drug Research

Volumn 61, Issue 4, 2011, Pages 207-220

  Marzo, Antonio ^a   Fontana, Elena ^a  

^a IPAS SA   (Switzerland)

Author keywords

Bioequivalence; Guidelines; Open problems

Indexed keywords

ACETYLSALICYLIC ACID; ALLOPURINOL; AMFEBUTAMONE; AMIODARONE; AMITRIPTYLINE; BETAHISTINE; BROMHEXINE; BUDESONIDE; CARBAMAZEPINE; CHLORPROMAZINE; CIMETIDINE; CLARITHROMYCIN; CODEINE; DIAZEPAM; DICLOFENAC; DILTIAZEM; DOXEPIN; FLUOXETINE; FORMOTEROL; GLIBENCLAMIDE; MESALAZINE; NONSTEROID ANTIINFLAMMATORY AGENT; NORTAMOXIFEN; PIROXICAM; RAMIPRIL; RAMIPRILAT; SIMVASTATIN; TAMOXIFEN; UNINDEXED DRUG; URSODEOXYCHOLIC ACID;

AREA UNDER THE CURVE; BIOASSAY; BIOEQUIVALENCE; DISPERSIBLE TABLET; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE REGIMEN; DRUG FORMULATION; DRUG HALF LIFE; DRUG SOLUBILITY; ENTEROHEPATIC CIRCULATION; EUROPEAN UNION; FOOD AND DRUG ADMINISTRATION; FOOD DRUG INTERACTION; HUMAN; IN VITRO STUDY; PHENOTYPE; PRACTICE GUIDELINE; REVIEW; STEADY STATE; UNITED STATES;

EID: 79955707585     PISSN: 00044172     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-0031-1296190     Document Type: Review

References (106)

1. Note for guidance: Investigation of bioavailability and bioequivalence. Commission of European Communities, III/54/89-EN Final. December 1991.
2. Note for guidance on the investigation of bioavailability and bioequivalence. EMEA, CPMP/EWP/QWP/1401/98. July 26, 2001.
3. Questions and answers on the bioavailability and bioequivalence guideline. EMEA, CHMP/EWP/40326/2006.
4. Questions and answers: positions on specific questions addressed to the EWP therapeutic subgroup on pharmacokinetics. EMEA, 618604/2008 Rev. 1, July 23, 2009.
5. Guideline on the investigation on bioequivalence. EMEA, CPMP/QWP/EWP/1401/98 Rev. 1. January 20, 2010.
6. Note for guidance on the clinical requirements for locally applied, locally acting products containing known constituents. CPMP/EWP/239/95.
7. Note for guidance: replacement of chlorofluorocarbons (CFCs) in metered dose inhalation products. CPMP/III/ 5378/93-Final.
8. 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). CPMP/ EWP/4151/00 Rev 1.
9. Guideline on the pharmaceutical quality of inhalation and nasal products. EMEA, CHMP/QWP/49313/2005Corr.
10. Guideline on the clinical development of fixed combination medicinal products. CPMP/EWP/240/95 Rev. 1.
11. Note for guidance on modified release oral and transdermal dosage forms: section II. CPMP/EWP/280/96Corr.
12. Guidance for industry: bioavailability and bioequivalence. Studies for orally administered drug products. General considerations. U.S. Department of Health and Human Services, FDA, CDER; March 2003, Revision 1.
13. Guidance for industry: in vivo bioequivalence studies based on population and individual bioequivalence approaches. U.S. Department of Health and Human Services, FDA, CDER; October 1997 BPX.
14. Guidance: oral extended (controlled) release dosage forms: in vivo bioequivalence and in vitro dissolution testing. Dighe SV, Williams RL, editors. FDA; September 1993.
15. Guidance for industry: Extended release oral dosage forms: development, evaluation, and application of in vitro / in vivo correlations. U.S. Department of Health and Human Services, FDA, CDER; September 1997.
16. Guidance for industry. Food-effect bioavailability and fed bioequivalence studies. U.S. Department of Health and Human Services, FDA, CDER; December 2002 BP.
17. Guidance for industry. Waiver of in vivo bioavailability and bioequivalence studies for immediate release solid oral dosage forms containing certain active moieties/active ingredients based on a biopharmaceutics classification system. U.S. Department of Health and Human Services, FDA, CDER; January 1999 BP.
18. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm. Accessed: Sep 2010.
19. Diletti E, Hauschke D, SteiniJans VW. Sample size determinations: extended tables for the multiplicative model and bioequivalence ranges of 0.9 to 1.11 and 0.7 to 1.43. Clin Pharmacol Ther Toxicol. 1992;30:S59-62.
20. Marzo A, Fontana E. How improved sensitivity of bioassays, and terminal half-life of drugs impact on bioequivalence trials. Arzneimittelforschung 2009;59:55-8.
21. Louning PE, Lien EA, Lundgren S, Kvimsland S. Clinical pharmacokinetics of endocrine agents used in advanced breast cancer. Clin Pharmacokinet. 1992;22:327-58.
22. Meisel S, Shamiss A, Rosenthal T. Clinical pharmacokinetics of ramipril. Clin Pharmacokinet. 1994;26:7-15 (Pubitemid 24029184)
23. Marzo A. Crossover design in tamoxifen bioequivalence: a borderline situation. J PharmPharmacol. 1998;50:1433-4. (Pubitemid 29043968)
24. Marzo A. Open questions on bioequivalence: some problems and some solutions. Pharmacol Res. 1999;40:357-68. (Pubitemid 29472064)
25. Marzo A. Bioequivalence behind the scenes. Parm Dev Regul. 2003;1:179-89.
26. Rusca A, Di Stefano AF, Doig MV, Scarsi C, Perucca E. Relative bioavailability and pharmacokinetics of two oral formulations of docosahexaenoic acid/eicosapentaenoic acid after multiple-dose administration in healthy volunteers. Eur J Clin Pharmacol. 2009;65:503-10.
27. Marzo A, Fibbioli M, Marone C, Cerutti B. The degree of predictivity in pilot studies on six subjects in bioequivalence trials. Pharmacol Res. 2004;49:283-6. (Pubitemid 38064340)
28. Marzo A. Open questions on bioequivalence: an updated reappraisal. Curr Clin Pharmacol. 2007;2:179-89. (Pubitemid 46813425)
29. Fourtillan JB, Bubourg D. Etude pharmacocinétique du piroxicamchez l'homme sain, après administration d'une dose égale à 20 mg par voie orale. Thérapie. 1983;38:163-70. French.
30. Brogden RN, Heel RC, Speight TM, Avery GS. Piroxicam. A reappraisal of its pharmacology and therapeutic efficacy. Drugs. 1984;28:292-323.
31. Marzo A, Reiner V. Open questions on bioequivalence: the case of multiple peak phenomenon. J Pharm Pharmacol. 2004;56:281-2. (Pubitemid 38232760)
32. Reiner V, Reiner A, Reiner G, Conti M. Increased absorption rate of diclofenac from fast acting formulations containing its potassiumsalt. Arzneimittelforschung. 2001;51: 885-90. (Pubitemid 33096108)
33. Chan KH, Mojaverian P, Ziehmer BA, John VA. Application of radiotelemetric technique in evaluating diclofenac sodium absorption after oral administration of various dosage forms in healthy volunteers. Pharm Res. 1990;7: 1026-32. (Pubitemid 20366729)
34. Terhaag B, Gramatte T, Hrdlcka P, Richter K, Feller K. The influence of food on the absorption of diclofenac as a pure substance. Int J Clin Pharmacol Ther Toxicol. 1991;29:418-21.
35. Macià MA, Frias J, Carcas AJ, Guerra P, Valiente R, Lucero ML. Comparative bioavailability of a dispersible formulation of diclofenac and finding of double plasma peaks. Int J Clin Pharmacol Ther. 1995;33:333-9.
36. Bettini R, Giordano F, Donini C, Massimo G, Castellani PL, Colombo P. Swelling force development as a result of hydrate formation in diclofenac sodium or nitrofurantoin tablets. STP Pharma Sci. 2000;10:335-9. (Pubitemid 30654811)
37. Idegami H, Shima K, Tanaka A, Tahara Y, Hirota M, Kumahara Y. Interindividual variation in the absorption of glibenclamide in man. Acta Endocrinol 1986;111:528-32. (Pubitemid 16086320)
38. Balan G, Timmins P, Greene DS, Marathe PH. In-vitro invivo correlation models for glibenclamide after administration of metformin/glibenclamide tablets to healthy human volunteers. J PharmPharmacol. 2000;52:831-8. (Pubitemid 30461916)
39. Parquet M, Metman EH, Raizman A, Rambaud JC, Berthaux N. Bioavailability, gastrointerstinal transit, solubilization and faecal excretion of ursodeoxycholic acid in man. Eur J Clin Invest. 1985;15:171-8. (Pubitemid 16239879)
40. Najib NM, Idkaidek N, Adel A, Admour I, Astigarraga REB, De Nucci G, et al. Pharmacokinetics and bioequivalence evaluation of two simvastatin 40 mg tablets (Simvast and Zocor) in healthy human volunteers. BiopharmDrug Dispos. 2003;24:183-9. (Pubitemid 36939689)
41. Lin JH. Pharmacokinetic and pharmacodynamic properties of histamine H2-receptor antagonists. Clin Pharmacokinet. 1991;20:218-36.
42. Grahnén A, VanBahr C, Lindström B, Rosén A. Bioavailability and pharmacokinetics of cimetidine. Eur J Clin Pharmacol. 1979;16:335-40. (Pubitemid 10212154)
43. Somogyi A, Gugler R. Clinical pharmacokinetics of cimetidine. Clin Pharmacokinet. 1983;8:463-95. (Pubitemid 13023843)
44. Marzo A. Toxicokinetics of endogenous substances: a neglected issue. Arzneimittelforschung. 1996;46:1-10.
45. Marzo A, Rescigno A. Pharmacokinetics of endogenous substances: some problems and some solutions. Eur J Drug Metab Pharmacokinet. 1993;18:77-88. (Pubitemid 23177460)
46. Marzo A, Rescigno A, Arrigoni Martelli E. Some pharmacokinetic considerations about homeostatic equilibrium of endogenous substances. Eur J Drug Metab Pharmacokinet. 1993;18:215-9. (Pubitemid 23264114)
47. Marzo A, Vuksic D, Crivelli F. Bioequivalence of endogenous substances facing homeostatic equilibria: an example with potassium. Pharmacol Res. 2000;42:523-5.
48. Guidance for industry: potassium chloride modified-release tablets and capsules: in vivo bioequivalence and in vitro dissolution testing. U.S. Department of Health and Human Services, CDER; October 2005.
49. Levothyroxine sodium tablets. In vivo pharmacokinetic and bioavailability studies and in vitro dissolution testing. US FDA 3/8/2001.
50. De VitoJM, Kozloski GD, Tonelli AP, Johreson JB. Bioequivalence of oral and injectable levoleucovorin and leucovorin. Clin Pharm. 1993;12:293-9. (Pubitemid 23086247)
51. Rennie D. Thyroid storm. J AmMed Assoc. 1997;277:1238-43.
52. Spigelmaw MK. Bioequivalence of levothyroxine preparations for treatment of hypothyroidism. J Am Med Assoc. 1997;277:1199-200.
53. Eckert CH. Bioequivalence of levothyroxine preparations: industry sponsorship and academic freedom. J Am Med Assoc. 1997;277:1200-1.
54. Dong BJ, Hauck WW, Gambertoglio JG, Gee L, White JR, Bubp JL, et al. Bioequivalence of generic and brand-name levothyroxine products in the treatment of hypothyroidism. J Am Med Assoc. 1997;277:1205-13. (Pubitemid 27172743)
55. Cerutti R, Rivolta G, Cavalieri L, Di Giulio C, Grossi E, Vago T, et al. Bioequivalence of levothyroxine tablets administered in target population in steady state. Pharmacol Res. 1999; 39:193-201. (Pubitemid 29119024)
56. Murphy BEP. Some studies of the protein-binding of steroids and their application to the routine micro- and ultramicro measurement of various steroids in body fluids by competitive protein binding-assay. J Clin Endocrinol Metab. 1967;27:973-90.
57. Scotti A, Bianchini C, Abbiati G, Marzo A. Absorption of calcium administered alone or in fixed combination with vitamin D to healthy volunteers. Arzneimittelforschung. 2001;51:493-500. (Pubitemid 32588931)
58. Chen XY, Zhong DF, Duan JL, Yan BX. LC-MS-MS analysis of 2-pyridylacetic acid, a major metabolite of betahistine: application to a pharmacokinetic study in healthy volunteers. Xenobiotica. 2003;33:1261-71. (Pubitemid 38122247)
59. Murrel GAC, Rapeport WG. Clinical pharmacokinetics of allopurinol. Clin Pharmacokinet. 1986;11:343-53. (Pubitemid 16001689)
60. Latini R, Rognoni G, Kates RE. Clinical pharmacokinetics of amiodarone. Clin Pharmacokinet. 1984;9:136-56. (Pubitemid 14164705)
61. Marzo A, Balant LP. Investigation of xenobiotic metabolism by CYP2D6 and CYP2C19: importance of enantioselective analytical methods. J Chromatogr B. 1996;678:73-92. (Pubitemid 26112622)
62. Marzo P., Scaglione F. Antiplatelet and other non-antiinflammatory activities of acetylsalicylic acid: mechanisms of action, expectations and therapeutic relevance. Intern Med. 2000;8:1-4.
63. Bechgaard E, Nielsen A. Bioavailability of bromhexine tablets and preliminary pharmacokinetics in humans. BiopharmDrug Dispos. 1982;3:377-44.
64. Findlay JWA, Van Wyck Fleet J, Smith PG, Butz RF, Hinton ML, et al. Pharmacokinetics of bupropion, a novel antidepressant agent, following oral administration to healthy subjects. Eur J Clin Pharmacol 1981;21:127-35. (Pubitemid 12239647)
65. Busto U, Bendayan R, Sellers EM. Clinical Pharmacokinetics of non-opiate abused drugs. Clin Pharmacokinet. 1989;16:1-26. (Pubitemid 19047168)
66. Bertilsson L, Tomson T. Clinical pharmacokinetics and pharmacological effects of carbamazepine and carbamazepine-10,11-epoxide. An update. Clin Pharmaokinet. 1986; 11:177-98.
67. Greenblatt DJ, Shader RI, MacLeod SM, Sellers EM. Clinical pharmacokinetics of chlordiazepoxide. Clin Pharmacokinet. 1978;3:381-94. (Pubitemid 9013900)
68. Dahl SG, Strandjord RE. Pharmacokinetics of chlorpromazine after single and chronic dosage. Clin Pharmacol Ther. 1977;21:437-48. (Pubitemid 8093375)
69. Fraschini F, Scaglione F, Demartini G. Clarithromycin clinical pharmacokinetics. Clin Pharmacokinet. 1993;25: 189-204. (Pubitemid 23262170)
70. Quiding H, Anderson P, Bandesson U, Borens LO, Hynning PA. Plasma concentration of codeine and its metabolite, morphine, after single and repeated oral administration. Eur J Clin Pharmacol. 1986;30:673-7. (Pubitemid 16018945)
71. Greenblatt DJ, Allen MD, Harmatz JS, Shader RI. Diazepam disposition determinants. Clin Pharmacol Ther. 1980;27:301-12. (Pubitemid 10063481)
72. Rovei V, Gomeni R, Mitchard M, Lazzibaud J, Blatrix Ch, Thebauld JJ, et al. Pharmacokinetics and metabolism of diltiazem in man. Acta Cardiol. 1980;XXV:35-45. (Pubitemid 10067908)
73. Faulkner RD, Pitts WM, Lee CS, Lewis WA, Fann WE. Multiple-dose doxepin kinetics in depressed patients. Clin Pharmacol Ther. 1983;34:509-15. (Pubitemid 13016983)
74. Keller T, Cambon N, Genevray M, Crivelli F, Crivelli M, Dal Bo L, et al. Bioequivalence study of fluoxetine hydrochloride in healthy volunteers. Arzneimittelforschung. 2005;55:491-7. (Pubitemid 41367747)
75. Greenblatt DJ, Divoll M, Harmatz JS, MacLaughlin DS, Shader RI. Kinetics and clinical effects of flurazepam in young and elderly non insomniacs. Clin Pharmacol Ther. 1981;30:475-86.
76. Radwanski E, Perentesis G, Symchowicz S, Zampaglione N. Single and multiple dose pharmacokinetic evaluation of flutamide in normal geriatric volunteers. J Clin Pharmacol. 1989;29:554-8. (Pubitemid 19179687)
77. Sallee FR, Pollock BG. Clinical pharmacokinetics of imipramine and desipramine. Clin Pharmacokinet. 1990;18:346-64. (Pubitemid 20134542)
78. Marzo A, Treffner E. Gas-liquid chromatographic determination of isosorbide-5-mononitrate derivatized with perfluorinated anhydrides for pharmacokinetic and bioavailability investigations. J Chromatogr. 1985;345:390-5. (Pubitemid 16182536)
79. Robertson DRC, Wood ND, Everest H, Monks K, Waller DG, Renwick AG, et al. The effect of age on the pharmacokinetics of levodopa administered alone and in the presence of carbidopa. Br J Clin Pharmacol. 1989;28:61-9. (Pubitemid 19195666)
80. Osborne R, Joel S, Trew D, Slevin M. Morphine and metabolite behaviour after different routes of morphine administration: demonstration of the importance of the active metabolite morphine-6-glucuronide. Clin Pharmacol Ther. 1990;47:12-9. (Pubitemid 20041204)
81. Bernareggi A. The pharmacokinetic profile of nimesulide in healthy volunteers. Drugs. 1993;46 Suppl I:64-72.
82. Thadani U, Whitsett T. Relationship of pharmacokinetic and pharmacolodynamic properties of the organic nitrates. Clin Pharmacokinet. 1988;15:32-43.
83. Hughes KM, Lang JCT, Lazare R, Gordon D, Stanton SL, Malone-Lee J, et al. Measurement of oxybutynin and its N-desethylmetabolite in plasma, and its application to pharmacokinetic studies in young, elderly and frail elderly volunteers. Xenobiotica. 1992;22:859-69.
84. Verbeeck RK, Blackburn JL, Loewen GR. Clinical pharmacokinetics of non-steroidal anti-inflammatory drugs. Clin Pharmacokinet. 1983;8:297-331. (Pubitemid 13069549)
85. Martindale. The complete drug reference. 13th ed. Sweetman SC, editor. London: Pharmaceutical Press; 2007. p. 1250-1251.
86. Krause W, Karras J, Seifert W. Pharmacokinetic of canrenone after oral administration of spironolactone and intravenous injection of canrenoate-k in healthy man. Eur J Clin Pharmacol. 1983;25:449-53. (Pubitemid 14234276)
87. McTavish D, Sorkin EM. Verapamil: an updated review of its phamadynamic and pharmacokinetic properties and therapeutic use in hypertension. Drugs. 1989;38:19-76. (Pubitemid 19203576)
88. Holick MF. The cutaneous photosynthesis of previtamin D3: a unique photoendocrine system. J Invest Dermatol. 1981;77:51-8. (Pubitemid 12229300)
89. Dal Bo L, Mazzucchelli P, Marzo A. Assay of zofenopril and its active metabolite zofenoprilat by liquid chromatography coupled with tandem mass spectrometry. J Chromatogr B. 2000;749:287-94.
90. Marzo A, Dal Bo L, Mazzucchelli P, Ceppi Monti N, Crivelli F, Ismaili S, et al. Pharmacokinetic and pharmacodynamic comparative study of zofenopril and enalapril in healthy volunteers. Arzneimittelforschung. 2002;52:233-42. (Pubitemid 34438220)
91. Thadani U, Whitsett T. Relationship of pharmacokinetic and pharmacodynamic properties of organic nitrates. Clin Pharmacokinet. 1988;15:32-43.
92. Schulz M, Schmoldt A, Donn F, Becker H. The pharmacokinetics of flutamide and its major metabolites after a single oral dose and during chronic treatment. Eur J Clin Pharmacol. 1988;34:633-6.
93. Walter-Sack I, de Vries JX, Kreiner C, Ittensohn A, Stenzhorn G, Voss A, et al. Bioequivalence of allopurinol preparations: to be assayed by parent drug or the active metabolite? Clin Invest. 1993;71:240-6.
94. Garteiz DA, Hook RH, Walker BJ, Okerholm RA. Pharmacokinetics and biotransformation studies of terfenadine in man. Arzneimittelforschung. 1982;32:1185-90. (Pubitemid 12035873)
95. White NJ. Clinical pharmacokinetics of antimalarial drugs. Clin Pharmacokinet. 1985;10:187-215. (Pubitemid 15093446)
96. Mooradian AD. Digitalis: an update of clinical pharmacokinetics, therapeutic monitoring techniques, and treatment recommendations. Clin Pharmacokinet. 1988;15: 165-79.
97. Karbwang J, White NJ. Clinical pharmacokinetics of mefloquine. Clin Pharmacokinet. 1990;19:264-79. (Pubitemid 20283426)
98. Altamura AC,Moro AR, PercudaniM. Clinical pharmacokinetics of fluoxetine. Clin Pharmacokinet. 1994;26:201-14.
99. Bennett WM, Pulliam JP. Cyclosporine nephrotoxicity. Ann Intern Med. 1983;99:851-4. (Pubitemid 14248418)
100. Jacobo E, Schmidt JD, Weinstein SH, Flocks RH. Comparison of flutamide (SCH-13521) and diethylstilbestrol in untreated advanced prostatic cancer. Urology. 1976;8: 213-33.
101. Osborne R, Joel S, Trew D, Slevin M. Morphine and metabolite behaviour after different routes of morphine administration: demonstration of the importance of the active metabolite morphine-6-glucuronide. Clin Pharmacol Ther. 1990;47:12-9. (Pubitemid 20041204)
102. Palareti G, Legnani C. Warfarin withdrawal: pharmacokinetic/ pharmacodynamic considerations. Clin Pharmacokinet. 1996;30:300-13.
103. Pokorny R, Finkel MJ, Robinson WT. Normal volunteers should not be used for bioavailability or bioequivalence studies of clozapine. PharmRes. 1994;11:1221. (Pubitemid 24259868)
104. Meyer MC. United States Food and Drug Administration requirements for approval of generic drug products. J Clin Psychiatry. 2001;62 (Suppl 5):4-9. (Pubitemid 32295157)
105. Marzo A, Balant LP. The bioequivalence: an updated reappraisal addressed to applications of interchangeable multi-source pharmaceutical products. Arzneimittelforschung. 1995;45:109-15.
106. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutical drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. PharmRes. 1995;12:413-20.