Design and evaluation of bioequivalence

Design and evaluation of bioequivalence

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  DESIGN AND EVALUATIONOF BIOEQUIVALENCE STUDY Presented By P. NAGA CHANDRIKA, M. Pharm Research Scholar, Department of pharmaceutics, Geethanjali College of Pharmacy, Hyd
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  ELEMENTS OF STUDYPROTOCOL  Title  Study objective  Study design  Study population  Clinical procedures  Ethical considerations  Data analysis  Drug accountability  Appendix
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  Study Objective  Tocompare the drug bioavailability from test and reference product is not statistically different  Same molar concentration  Same route of administration
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  Study designs Fasting Study Overnight fasting atleast 10 hours before drug administration  4 hours fasting should be continued after dosing  No other medication should be given for atleast 1 week prior to study Food Intervention Study  Food + oral drug product Affect bioavailability of drug  High fat and high calorie diet given to subjects 30 min before dosing
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  STUDY DESIGN Two periodcross over design Latin square cross over design Replicate cross over design Balance incomplete block design Parallel group design
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  Two period crossover design  2 Formulations  2 Groups Latin Square Crossover Design  3 formulations  Each formulation administered only once to each subject Period 1 Period 2 Sequence 1 Test Reference Sequence 2 Reference Test Subjects Period 1 Period 2 Period 3 1 A B C 2 B C A 3 C A B
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  Replicate crossover design Four period  Two sequence  Two formulation Parallel Group Design  Two separate groups  Drugs – long elimination half life Period 1 Period 2 Period 3 Period 4 Sequence 1 T R T R Sequence 2 R T R T Test product Reference 1 2 3 4 Subjects 5 6 7 8 9 10 11 12
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   Balanced IncompleteBlock design  Pilot study Subjects Period 1 Period 2 1 A B 2 A C 3 A D 4 B A 5 B C 6 B D 7 C A 8 C B 9 C D 10 D A 11 D B 12 D C
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  Multiple Dose study Cmax : Maximum Drug concentration  Cmin : Drug concentration at the end of dosing interval  Degree of fluctuation: (Cmax – Cmin) / Cmax  Swing: (Cmax – Cmin) / Cmin
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  Drug products Reference product RLD  Innovators or original manufacturers brand name product  Fully approved NDA Test product  Generic product
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  Sample collection Schedule 3 points during absorption phase  3 to 4 at Tmax  4 points during elimination phase
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  Subject Selection  Healthyadult volunteers  Age 18-45 years  Drug use intended in elders (age ≥ 60 years)  Women – pregnancy test prior to first dose of study Selection of number of subjects: Pilot studies Previous studies Published data
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  Exclusion criteria  Chronicdiseases  HIV positive  Jaundice in past 6 months  Psychiatric illness  Participated in BABE studies in past 3 months
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  IRB • Safeguardsrights and welfare of human rights IRB Members • Professionals • Lay persons with clinical expertise as well as sensitivity to ethical issues Institutional Review Board
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  Parameters to bemeasured  Pharmacokinetic parameters to be measured are  Cmax  Tmax  AUC Statistical Evaluation  Cmax, AUC analysed using ANOVA  Tmax analysed by non parametric methods  Geometric mean of Cmax t , Cmax r  Geometric mean ratio Cmax t/ Cmax r  Calculate 90% confidence interval of geometric mean ratio of Cmax
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  To Establish BE The calculated 90% confidence interval for Cmax and AUC should fall within the range 80-125% (Range of bioequivalence)  Non parametric data 90% confidence interval for Tmax should lie with in clinical acceptable range
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  THANK YOU