Biowaivers

Biowaivers

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  BIOWAIVERS: CRITERIA & REQUIREMENT Presentedby : Shikha singh Under the guidance of : Dr. Lalit Kumar Department of Pharmaceutics Registration No. 160617009 ManipalCollegeofPharmaceuticalSciences(MCOPS)
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  CONTENTS 1. Introduction 2. Biopharmaceuticsclassification system 3. Bcs-based biowaiver 4. Criteria for biowaivers 5. Requirements for a biowaiver study 6. Data to support request for biowaivers 7. Conclusion 8. References 2 ManipalCollegeofPharmaceuticalSciences(MCOPS)
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  INTRODUCTION • Biowaivers areconsidered as the waivers of clinical bioequivalence studies • Bioequivalence studies are as vital concern in drug development process • Biowaivers eliminates unnecessary exposure of healthy subjects to in- vitro studies • Instead of conducting expensive & time consuming in vivo studies, an in vitro dissolution test could be adopted as the surrogate basis for the decision as to whether the two pharmaceutical products are equivalent 3 ManipalCollegeofPharmaceuticalSciences(MCOPS)
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  Biopharmaceutics Classification System (BCS) ᴥDissolution Drug product  drug substance in solution ᴥ Membrane transport  Drug substance in the system  Dissolution, solubility & intestinal permeability are the 3 major factors that govern the rate & extent of absorption of a drug that is stable in the GI tract 4 ManipalCollegeofPharmaceuticalSciences(MCOPS)
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  Low permeability High Solubility Low Solubility HS/HP Class I HS/LP ClassIII LS/HP Class II LS/LP Class IV High permeability BCS CHART 5 ManipalCollegeofPharmaceuticalSciences(MCOPS)
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  It is definedas  Comparison of test and reference  In vitro instead of in vivo ‘bioequivalence’ testing  Bcs-based Biowaivers are intended only for bioequivalence studies BCS-BASED ‘BIOWAIVER’ 8 ManipalCollegeofPharmaceuticalSciences(MCOPS)
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   Biowaivers usesClass 1 & Class 3 drugs  Drugs should be highly soluble & highly permeable  Highest dose strength should be soluble in 250 ml aqueous solution over a pH of 1-7.5 at 37°C  85% of drug should dissolve within 15 mins at 37°C according to EMA guidelines 9 ManipalCollegeofPharmaceuticalSciences(MCOPS) CRITERIA FOR BIOWAIVERS
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  Physiological body pH 10 sitefasted pH fed pH stomach 1.4 – 2.1 4.3 – 5.4 small intestine: duodenum 4.9 – 6.4 4.2 – 6.1 jejunum 4.4 – 6.6 5.2 – 6.2 ileum 6.5 – 7.4 6.8 – 7.5 large intestine: cecum upper colon lower colon 6.4 6.0 7.5 ManipalCollegeofPharmaceuticalSciences(MCOPS)
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  High solubility  Highestsingle dose is completely soluble in 250 ml or less of aqueous solution at pH 1 - 6.8 (37 °C)  Highest dose recommended by WHO (as recommended by WHO Model List of Essential Medicines) 11 ManipalCollegeofPharmaceuticalSciences(MCOPS)
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  High permeability • Adrug substance is considered HIGHLY PERMEABLE when extent of absorption in humans is determined to be > 85% of an administered dose based on a mass balance determination or in comparison to an intravenous reference dose 12 ManipalCollegeofPharmaceuticalSciences(MCOPS)
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  REQUIREMENTS FOR A BIOWAIVERSTUDY  Dissolution Test in 3 different media (in 900 ml and at 37°C) 1. Buffer pH 1.2 simulated gastric fluid (SGF) without enzymes or 0.1N HCl 2. Buffer pH 4.5 3. Buffer pH 6.8 or simulated intestinal fluid (SIF) without enzymes 13 ManipalCollegeofPharmaceuticalSciences(MCOPS)
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   12 samplesin each media (paddle rotating- 50 rpm/ basket- 100 rpm)  Sampling times are 10, 15, 20, 30, 45 & 60 minutes  Profiles of the test & reference products must be similar in all 3 media  Products are similar if the similarity factor f2 ≥ 50 & both products show ≥ 85% dissolution in 15 min 14 REQUIREMENTS FOR A BIOWAIVER STUDY ManipalCollegeofPharmaceuticalSciences(MCOPS)
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  DATA TO SUPPORT REQUESTFOR BIOWAIVERS  The drug substance for which a waiver is being requested should be highly soluble and highly permeable 1. Highly Solubility 2. Highly Permeability 3. Rapid Dissolution 15 ManipalCollegeofPharmaceuticalSciences(MCOPS)
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  17 Example s ManipalCollegeofPharmaceuticalSciences(MCOPS)
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  CONCLUSION • BCS isemployed to waive in vivo bioequivalence testing (i.e. provide “Biowaivers") for new & generic drugs • Granting Biowaivers under systems such as the BCS, eliminates unnecessary drug exposures to healthy subjects & provides economic relief, while maintaining the high public health standard for therapeutic equivalence 18 ManipalCollegeofPharmaceuticalSciences(MCOPS)
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  REFERENCES 1. Jennifer dressmanand johannes kramer, Pharmaceutical dissolution testing, 3rd edition, Taylor & francis group, page no.251-281 2. Seema rohilla, ankur rohilla, arun nanda, Biowaivers: criteria and requirements, International journal of pharmaceutical & biological archives 2012; 3(4):727-731 3. Dr. Mazen kurdi, Biowaivers: criteria and requirements, MOPH –2015 19 ManipalCollegeofPharmaceuticalSciences(MCOPS)
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