Presentation on theme: "Bioequivalence of Topical Products"— Presentation transcript:
1Bioequivalence of Topical Products OGD Research ProgramLawrence Yu,Ph.D.DermatopharmacokineticsAnnette Bunge, Ph.D.Bioequivalence of Topical ProductsJonathan Wilkin, M.D.Q& A
2How to Characterize Similarity? Q1: Qualitative SimilaritySame componentsQ2: Quantitative SimilaritySame amounts of the same componentsQ3: Structural SimilaritySame amounts of the same components arranged in the same wayHow do you measure Q3?What does Q3 similarity imply about bioequivalence?
3Definition of Q3 Structural Similarity Arrangement of matter State of aggregationExample: PolymorphsForm A Form BSame SubstanceQ3 is different?Example: SuspensionA BSame SubstanceQ3 is different?
4What Determines Q3? Equilibrium states Non-equilibrium states Example: solutionQ2 implies Q3Non-equilibrium statesExamples: suspension, cream, ointment, gelDetermined by historyManufacturingStoragePhysical state of starting materials
5How To Measure Q3?Different materials/formulations may require different methodsGeneral featuresParticle/Droplet/Excipient size distributionSpatial arrangement/homogeneityParticle/Droplet/Excipient interactions or crosslinks or surface chemistry
6Semi-Solid Dosage Forms Most topical products are semi-solidsCreamLotionGelOintment...Intermediate between liquid and solidDepending on the measurement, their properties are a mixture of solid and liquid behavior
7Phase Structure and Size Distribution MicroscopyLight scatteringPhase structure/Spatial arrangement of particlesDifferential Scanning Calorimetry (DSC) measurements
8InteractionsInteractions between the components of a semi-solid determine the rheologyParticle attraction or repulsionSurface ChargeExcipients/StabilizersPolymer or gel crosslinking
9Rheology of Semi-Solids Linear ViscoelasticityMaterial response to oscillatory strain combines solid and liquid behaviorStress-Strain Rate RelationViscosity depends on strain rateYield StressStress required to induce flow
10Drug Release From Formulation Diffusion Through MembraneFranz Diffusion Apparatus: To determine the diffusional properties of drugs in various semi-solid formulations through biological membranes or artificial membranes
11Relation of Q3 to Topical Product Performance For topical products rheology mattersSimilar spreadability requires viscosity-shear rate curves and yield stress be the samePhase structure of formulation componentsManufacturing processesDrug release rate from formulationHow is the active ingredient contained in the formulation?
12Q3 Validation How to prove that Q3 determination is valid Characterize complex formulations with particles of excipients and particles of activesResearch ProjectMeasure rheology, phase structure, and drug release ratesFormulations with manufacturing differencesFormulation where generic was superior/(inferior), not equivalent, in a clinical trial
13Topical BE: Q&ADPKWhat type of studies should be conducted to validate the DPK method?
14Topical BE: Q&AQ3What type of data is needed to demonstrate that two products are Q3 equivalent?How should the Q3 concept be validated or demonstrated?Demonstration that we can detect changes in manufacturing processes?Demonstration that we can detect formulations with known differences?Demonstration that phase structures are the same?Demonstration that drug release rates are identical?
15Topical BE: Q&A Bioequivalence for topical products What role should Q3 and DPK play in the demonstration of bioequivalence for topical products?Under what circumstances should Q3 equivalence be sufficient to justify a wavier of in vivo bioequivalence tests?Under what circumstances should Q3 equivalence and a DPK method in healthy subjects be sufficient to determine bioequivalence?