07 Generic Drugs

7/29/2019 07 Generic Drugs

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All Rights Reserved 2008 Health Sciences Authority | 2

Generic Drugs

Dr Wong Tee WeeRegulatory Consultant

Pharmaceuticals & Biologics BranchTherapeutics Products Division

Health Products Regulation Group

Health Sciences Authority




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




Current requirement

• Bioequivalence (BE) data required for– Oral solid dosage form

– POM

• Request for additional information if deemedappropriate




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




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




Therapeutic equivalence

• Pharmaceutically equivalent

• Same safety and efficacy profiles afteradministration of the same dose

– BE studies

– Pharmacodynamic study

– Clinical efficacy study

– In vitro study




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




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




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




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




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




Pre-submission

• Strongly encourage

• Discuss acceptability of BE data with HSA• Verify the choice of RP before conducting BE

study




Checklist




DR Revision

• No change

• Minor editorial




SQOS – P9.1 (Chemicals)




Thank You

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07 Generic Drugs