This document discusses biowaivers, which allow waiving of clinical bioequivalence studies based on in vitro dissolution testing. It introduces the Biopharmaceutics Classification System (BCS), which categorizes drugs into four classes based on their solubility and permeability. BCS-based biowaivers can be granted for BCS Class 1 and 3 drugs that are highly soluble and highly permeable. The criteria for biowaivers include that the highest dose must dissolve within 15 minutes in pH ranges of 1-7.5. Requirements for biowaiver studies are specified, including dissolution testing in 3 media and establishing similarity between test and reference products. Data to support biowaiver requests must demonstrate high solubility, permeability, and

1. BIOWAIVERS: CRITERIA &
REQUIREMENT
Presented by : Shikha singh
Under the guidance of : Dr. Lalit
Kumar
Department of Pharmaceutics
Registration No. 160617009
ManipalCollegeofPharmaceuticalSciences(MCOPS)

2. CONTENTS
1. Introduction
2. Biopharmaceutics classification 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
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3. INTRODUCTION
• Biowaivers are considered 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
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4. Biopharmaceutics
Classification System (BCS)
ᴥ Dissolution
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
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5. Low permeability
High
Solubility
Low
Solubility
HS/HP
Class I
HS/LP
Class III
LS/HP
Class II
LS/LP
Class IV
High permeability
BCS CHART
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8. It is defined as
 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’
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9.  Biowaivers uses Class 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
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CRITERIA FOR BIOWAIVERS

10. Physiological body pH
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site fasted 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
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11. High solubility
 Highest single 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)
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12. High permeability
• A drug 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
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13. REQUIREMENTS FOR A
BIOWAIVER STUDY
 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
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14.  12 samples in 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
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REQUIREMENTS FOR A
BIOWAIVER STUDY
ManipalCollegeofPharmaceuticalSciences(MCOPS)

15. DATA TO SUPPORT
REQUEST FOR 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
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Example
s
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18. CONCLUSION
• BCS is employed 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
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19. REFERENCES
1. Jennifer dressman and 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
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