Quimica

GUIDELINES FOR
BIOAVAILABILITY &
BIOEQUIVALENCE STUDIES
Central Drugs Standard Control Organization,
Directorate General of Health Services,
Ministry of Health & Family Welfare,
Government of India,
New Delhi.
(March 2005)
These guidelines should be read in conjunction with Schedule Y to the Drugs and
Cosmetic Rules, GCP Guidelines issued by CDSCO, Ministry of Health and
FamilyWelfare, GLP and the Ethical Guidelines for Biomedical research on
human subjects issued by Indian Council of Medical Research. All provisions
described in above documents shall appropriately apply to the conduct of
bioavailability and bioequivalence studies.

Contents
1.

INTRODUCTION

2.

DEFINITIONS

3.

SCOPE OF THE GUIDELINES
3.1.

When bioequivalence studies are necessary andtypes of studies
required
3.1.1. In vivo studies
3.1.2. In vitro studies

3.2.
4.

When bioequivalence studies are not necessary

DESIGN AND CONDUCT OF STUDIES
4.1.

Pharmacokinetic Studies
4.1.1. Study design
4.1.2. Study population
4.1.3. Study conditions
4.1.4. Characteristics to be investigated
4.1.5. Bioanalytical methodology
4.1.6. Statistical evaluation
4.1.7. Specialconsiderations for modified release drug products
i Study parameters
ii Study design
iii Requirements for modified release drug products unlikely
to accumulate
iv Requirements for modified release drug products likely to
accumulate

4.2.

Pharmacodynamic Studies

4.3.

Comparative Clinical Trials

4.4.

In-vitro Studies

5.

DOCUMENTATION

6.

FACILITIES FOR CONDUCTING BA/BESTUDIES

7.

MAINTENANCE OF RECORDS OF BA/BE STUDIES

8.

RETENTION OF BA/BE SAMPLES

9.

SPECIAL TOPICS
9.1. Food effect bioavailability studies
9.2. Long half life drugs

1

9.3. Early Exposure
9.4. Individual and population bioequivalence

2

1. INTRODUCTION
Ensuring uniformity in standards of quality, efficacy and safety of pharmaceutical
products is the fundamentalresponsibility of CDSCO. Reasonable assurance
has to be provided that various products, containing same active ingredients,
marketed by different licensees, are clinically equivalent and interchangeable.
Accordingly, the bioavailability of an active substance from a pharmaceutical
product should be known and reproducible. In most cases, it is cumbersome and
unnecessary to assess this byclinical studies. Bioavailability and bioequivalence
data is therefore required to be furnished with applications for new drugs, as
required under Schedule Y, depending on the type of application being
submitted.
Both bioavailability and bioequivalence focus on the release of a drug substance
from its dosage form and subsequent absorption into the systemic circulation.
For this reason, similarapproaches to measuring bioavailability should generally
be followed in demonstrating bioequivalence.
Bioavailability can be generally documented by a systemic exposure profile
obtained by measuring drug and/or metabolite concentration in the systemic
circulation over time. The systemic exposure profile determined during clinical
trials in the early drug development can serve as a benchmark forsubsequent
BE studies.
Bioequivalence studies should be conducted for the comparison of two medicinal
products containing the same active substance. The studies should provide an
objective means of critically assessing the possibility of alternative use of them.
Two products marketed by different licensees, containing same active
ingredient(s), must be shown to be therapeutically equivalentto one another in
order to be considered interchangeable. Several test methods are available to
assess equivalence, including:
i comparative bioavailability (bioequivalence) studies, in which the active
drug substance or one or more metabolites is measured in an accessible
biological fluid such as plasma, blood or urine
ii comparative pharmacodynamic studies in humans
iii comparative...