Biowaivers detail explanation topic .pdf

Biowaivers detail explanation topic .pdf

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  Biowaivers Dr. Muhammad Usman AssistantProfessor IPS, UVAS, Lahore usman.ips@uvas.edu.pk
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  Introduction • The term“Biowaiver” is applied to regulatory drug approval process when application is approved based on evidences other than in-vivo equivalence testing. • BCS Classification system was introduced by Department of Health and Human Services, US FDA (HHS-FDA) with the aim to grant biowaiver only to SUPACs (Scale Up and Post Approval Changes) but application of biowaiver has been extended to certain orally administered generic products. Dr. Muhammad Usman 2
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  Introduction • A Biowaivermeans that in-vivo Bioavailability or Bioequivalence studies may be waived (NOT considered necessary for product approval). • Only in-vitro testing (Dissolution) is performed instead of conducting expensive and time consuming in-vivo testing. • The major advantage is the simplification and reduction of time required for product approval and availability to market. Dr. Muhammad Usman 3
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  Biowaiver types ofProducts • The FDA will waive the requirement for submission of in vivo evidence demonstrating the bioavailability of the drug product if the product meets one of the following criteria. 1) The drug product is an IV solution and contains the same API combined with same solvent and in same concentration as in the IV solution that was approved (NDA). 2) Topically applied preparation. 3) Solid oral dosage form that is not intended to be absorbed (e.g Antacids, Radiopaque medium etc.) Specific in-vitro studies may be required for example BE of cholestyramine is performed in-vitro by binding of bile acids to the resins. Dr. Muhammad Usman 4
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  Biowaiver types ofProducts 4) Drug product is intended to be administered through inhalation as a gas or vapor and contains the same API in same dosage form as in the product that was approved (NDA). 5) Oral solutions, elixir, syrup, tincture or similar other solubilized form and contain no excipient which can significantly affect the absorption of active ingredient. Dr. Muhammad Usman 5
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  6) Lower strengthof immediate release or extended release products. Dr. Muhammad Usman 6 Biowaiver types of Products A B 1000 mg 1000 mg Bioequivalent 500 mg 500 mg Biowaiver A B 250 mg 250 mg A B
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  BCS Classification Dr. MuhammadUsman 7 High Solubility Low Solubility High Permeability Class-I Class-II Low Permeability Class-III Class-IV Solubility: A drug substance is considered highly soluble when the highest dose strength is soluble in 250 mL or less of aqueous medium over the pH range 1–8. BCS Based Biowaiver
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  • Permeability: To beclassified as highly permeable, a test drug should have an extent of absorption >90% in humans. 1. in vivo intestinal perfusion studies in humans; 2. in vivo or in situ intestinal perfusion studies in animals; 3. in vitro permeation study using excised human or animal intestinal tissues 4. in vitro permeation study across a monolayer of cultured human intestinal cells. • Dissolution: An immediately release drug product is considered rapidly dissolving when not less than 85% of the label amount of drug substance dissolves within 30 minutes using USP Apparatus I at 100 rpm or Apparatus II at 50 rpm in a volume of 900 mL or less in each of the following media: (1) An acidic media such as 0.1 N HCl or simulated gastric fluid without enzymes, (2) A pH 4.5 buffer, (3) A pH 6.8 buffer or simulated intestinal fluid USP without enzymes. Dr. Muhammad Usman 8
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  According to HHS-FDA Dr.Muhammad Usman 9 BCS Based Biowaiver Class I BCS Class According to WHO Class I Class II Class III If > 85% dissolved within 30 minutes at pH 1.2 to 6.8 (75 rpm) If > 85% dissolved within 15 minutes at pH 1.2 to 6.8 (75 rpm) BCS Class
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  Dr. Muhammad Usman10 Other considerations for Biowaiver Rapidly Dissolving Must NOT affect absorption of API Must NOT contain API with Narrow Therapeutic Index Product should not be designed to be absorbed from oral cavity Dissolution Excipients Therapeutic Index Formulation