Overview and Introduction - BEBAC • Consultancy Services for ...

1/6 | Overview & IntroductionDobrodošli!Design and Evaluationof BE StudiesHelmut SchützBEBACConsultancy Services forBioequivalence and Bioavailability Studies1070 Vienna, Austriahelmut.schuetz@bebac.atinformalife sciencesBioequivalence and Bioavailability, Pre-Conference Workshop | Ljubljana, 17 May 2010 1 • 10

1/6 | Overview & IntroductionAnswering the Question:What is Enlightenment?informalife sciences„Enlightenment is man’s emergencefrom his self-imposed immaturity forwhich he himself was responsible.Immaturity and dependence are theinability to use one’s own intellectwithout the direction of another. Oneis responsible for this immaturity anddependence, if its cause is not a lackof intelligence, but a lack of determination and courage tothink without the direction of another. Sapere aude!Have courage to use your own understanding! is thereforethe slogan of Enlightenment.” Immanuel Kant (1784)Bioequivalence and Bioavailability, Pre-Conference Workshop | Ljubljana, 17 May 2010 2 • 10

1/6 | Overview & IntroductionTo bear in Remembrance...Whenever a theory appears to youas the only possible one, take this asa sign that you have neither under-stood the theory nor the problemwhich it was intended to solve.Even though it’s applied sciencewe’re dealin’ with, it still is – science!Karl R. PopperLeslie Z. Benetinformalife sciencesBioequivalence and Bioavailability, Pre-Conference Workshop | Ljubljana, 17 May 2010 3 • 10

1/6 | Overview & IntroductionBioequivalenceMain TopicsSurrogate of clinical equivalence orMeasure of pharmaceutical quality?Types of studiesPharmacokinetic (PK)Pharmacodynamic (PD)Clinical (equivalence and/or safety/efficacy)informalife sciencesBioequivalence and Bioavailability, Pre-Conference Workshop | Ljubljana, 17 May 2010 4 • 10

1/6 | Overview & IntroductionMain TopicsTypes of studies (cont’d)Healthy SubjectsPatientsSingle doseMultiple doseCross-overParallelReference product (another modified releaseformulation, IR, solution)informalife sciencesBioequivalence and Bioavailability, Pre-Conference Workshop | Ljubljana, 17 May 2010 5 • 10

1/6 | Overview & IntroductionMain Topicsinformalife sciencesTypes of studies (cont’d)(PK interaction)Food effectDesign IssuesDose regimenFasted / fed stateType of standard mealsBioanalytics (not GLP!)Parent drug / metabolite(s) / enatiomers / pro-drugsValidation / routine applicationBioequivalence and Bioavailability, Pre-Conference Workshop | Ljubljana, 17 May 2010 6 • 10

1/6 | Overview & IntroductionMain TopicsEthics (GCP!)Dose levels / number of administered dosesNumber / volume of blood samplesDrug and/or adverse effectsClinical performance (GCP!)CRO selectionResponsibilities of sponsor / investigatorAudits / monitoringinformalife sciencesBioequivalence and Bioavailability, Pre-Conference Workshop | Ljubljana, 17 May 2010 7 • 10

1/6 | Overview & IntroductionMain Topicsinformalife sciencesNCA / PK (PD)Sampling scheduleMetrics (AUC, C max ; AUEC, Ae max ,…)Design, methods, evaluationSample sizeEstimation from previous and/or pilot studies,literatureHighly variable drugsBiostatisticsModels & assumptionsProtocol, evaluation, reportBioequivalence and Bioavailability, Pre-Conference Workshop | Ljubljana, 17 May 2010 8 • 10

1/6 | Overview & Introduction‘What if’-scenariosCommon pitfallsMain TopicsProblems in clinical performance – studies ‘on hold’Failure to meet the required performance inbioanalyticsBlind review‘Failed’ studiesDeficiency lettersinformalife sciencesBioequivalence and Bioavailability, Pre-Conference Workshop | Ljubljana, 17 May 2010 9 • 10

1/6 | Overview & IntroductionAnother reminderinformalife sciencesRoseis a roseis a roseis a rose. Gertrude Stein (1913)Guidelinesare guidelinesare guidelines.Henrike Potthast (ca. 2004)In advanced engineering, you expected failure; you learnedas much from failures as from successes – indeed if younever suffered a failure you probably weren’t pushing theenvelope ambitiously enough.Stephen Baxter; Transcendent, Chapter 36 (2006)Bioequivalence and Bioavailability, Pre-Conference Workshop | Ljubljana, 17 May 2010 10 • 10