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Clinical significance of bioequivalence and biowaivers
PRESENTED BY:
P. Reddy Swetha
M.Pharm. I year 2019
(Pharmaceutics)
Guide:
Prof . R. NAGARAJU
Institute of Pharmaceutical Technology,
Sri Padmavati Mahila Visvavidyalayam
( Women’s University)
Tirupati. A.P

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contents
 Introduction
 Clinical significance of B E studies
 What is Biowaivers?
 Applicationsof Biowaivers
 Limitationsof Biowaivers
 Conclusion
 References

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introduction
Bioequivalence
Definition :
“It is relative term which denotes that the drug
substance in two or more identical dosage forms, reaches
the circulation at the same relative rate & to same relative
extent i.e., their plasma concentration time profiles will be
identical without significant statistical differences”.

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Clinical significance of bioequivalence studies
 Bioequivalence of different formulations of the same drug substance
involves equivalence with respect to the rate and extent of systemic
absorption.
 Generally two formulations whose rate and extent of absorption
differ by 20% or less are considered bioequivalent.
An equivalent clinical response should be obtained from the
comparision dosage form if the plasma drug concentration remain
above MEC for appropriate interval and don’t reach the MTC.

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Reasons for bioequivalence study
 To prove that Generic Drug Products
are bioequivalent to innovators/marketed
drug product (Reference Listed Drugs).
 Change in formulations i.e., from
capsule to tablets.
 To determine the efficacy and safety
from the bioequivalence data.

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Bioequivalence studies are conductedif there is:
 A risk of bio- in- equivalence and/or.
 A risk of pharmacotherapeutics failure or diminished clinical safe .
 In vivo bioequivalence studies and in vitro dissolution testing
recommended to applicants intending to submit (INDs) ,(NDAs)
&(ANDAs) for conventional and extended release dosage forms
administered orally.

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Biowaivers
 The term biowaiver is applied to a regulatory drug approval
process when the dossier(application) is approved based on
evidence of equivalence other than through in vivo equivalence
testing.
A biowaiver has been regarded as an official approval of the waiver
for conducting a bioequivalence study and to boost the drug
development process.

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No biowaiver for:
 Locally applied, systemically acting products.
 Non- oral immediate release forms with systemic action.
 Modified release products.
 Transdermal products.

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REQUIREMENTS FOR A BIOWAIVER STUDY
include regulatory authorities like FDA and WHO.
a) Dissolution Test in 3 different media which are:
Buffer pH 1.2, simulated gastric fluid (SGF) without enzymes or 0.1N
HCl .
Buffer pH 4.5, 6.8 or simulated intestinal fluid (SIF) without
enzymes, all in 900 ml and at 37°C .

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b) 12 samples in each media, paddle rotating at 50 rpm or basket at
100 rpm .
c) Sampling times are 10, 15, 20, 30, 45 and 60 minutes.
d) The profiles of the test and reference products must be similar in
all three media.
e) The products are similar if the similarity factor f2 ≥ 50 and both
products show ≥ 85% dissolution in 15 min

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APPLICATIONSOF BCS IN BIOWAIVER OF DRUG
. Biowaiver means to obtain waive off for carrying out
expensiveand time-consuming BA and BE studies.
 BCS provides biowaiver for Class I, II and III drug with some
specifications.
 The USFDA BCS guidance recommends for biowaiver if the drug
substance is highly soluble and highly permeable (Classdrugs) or an
immediate release drug product.

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Limitation of BCS
BCS based biowaiver are not applicable for the following:
i. Narrow therapeutic range drug products.
ii. BCS based biowaivers have limited application for the class II
drugs and not applicable for class III.

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iii. Dosage form meant for absorption in the oral cavity e.g.
sublingual or buccal tablets.
iv. Effects of food, absorptive transporters, efflux transporters, and
routes of elimination (renal/biliary) were important determinants
ofoverall drug absorption and bioavailability for immediate release
oral dosage forms, which are not considered in BCS.

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conclusion
 Bioequivalence studies are performed to compare the
bioavailability of the generic drug product to the brand name
product.
 Granting biowaivers under systems such as the BCS,
eliminates unnecessary drug exposures to healthy subjects &
provides economic relief, while maintaing the high public health
standard for therapeutic equivalence.

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