07 Generic Drugs
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Transcript of 07 Generic Drugs
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Generic Drugs
Dr Wong Tee WeeRegulatory Consultant
Pharmaceuticals & Biologics BranchTherapeutics Products Division
Health Products Regulation Group
Health Sciences Authority
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Singapore’s definition
• Essentially similar to a currently registered
product in Singapore (Reference product,RP)
• Generic drug application don’t require non-clinical and clinical data but must fulfill:
– Generic drug (Test product, TP) is bioequivalent toRP
– Route of administration of TP is same as RP
– Pharmaceutical dosage form of TP is same as RP
– Condition of use of TP is same as RP
Indication, dosing regimen, patient population
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Current requirement
• Bioequivalence (BE) data required for– Oral solid dosage form
– POM
• Request for additional information if deemedappropriate
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Current requirement
• Reference guidelines– ASEAN guideline on the conduct of bioavailability
and bioequivalence studies
– CPMP/EWP/QWP/1401/98 (to be replace with new
version soon)– FDA related guidelines on BE
– WHO guidelines, Technical Report Series
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Bioequivalence
• Pharmaceutical equivalent (PE)
– Similar bioavailability in systemic circulation Similar rate and extent of availability of active
ingredient
– Similar dosage form
– Similar route of administration
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Therapeutic equivalence
• Pharmaceutically equivalent
• Same safety and efficacy profiles afteradministration of the same dose
– BE studies
– Pharmacodynamic study
– Clinical efficacy study
– In vitro study
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BE Study
• Clinical study
– Requirements of GCP, GMP and GLP• Basic consideration
– Minimize variability
– Minimize bias
– GOAL is to compare performance of the 2 products
• Study design
– Single dose, 2-period, crossover
– Healthy volunteers– Subjects receive each formulation once
– Adequate washout
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Study Design
• Cross over
– Intra-subject comparison
– Lower variability
– Fewer subjects required
• Fasted or Fed
– Fasted preferred
– Minimize variability not attributable to formulation
– Better to detect formulation differences
• Fed study design
– Known food effects, e.g. grapefruits– Significant GI effects
– Product labeling restriction
– Conditions, depend on local diet and customs
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Dissolution data
• 3 media: pH 1.2, 4.5 and 6.8
• Individual tablet dissolution data• 12 tablets of each TP and RP
• Mean, range and RSD data of all 12 tablets
• F2 calculation– >50 to show similarity
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Biowaiver
• BE study generally not required for– Solutions
– Solutions for injection
– Powder for reconstitution
– Oral suspension
– Topical product without systemic effects
– Otic and ophthalmic products
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Biowaiver
• Submit justification for biowaiver
• Comparative BA studies required• Request based on:
– Dosage form
– Solubility of active ingredient
– Similar dissolution profiles across 3 pH media– PK profile: bioavailability, linearity
– Clinical consequences
– Width of margin between minimum effective and
minimum toxic plasma concentration– Similarities/ differences between formulations
considered
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Pre-submission
• Strongly encourage
• Discuss acceptability of BE data with HSA• Verify the choice of RP before conducting BE
study
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Checklist
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DR Revision
• No change
• Minor editorial
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SQOS – P9.1 (Chemicals)
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Thank You