Review of GCC Health Minister's Council Bioequivalence Guidelines

This report provides an overview of the bioequivalence guidelines set forth by the Executive Board of the Health Minister’s Council for GCC States. It covers key concepts such as bioavailability, historical cases of bio-inequivalence, and bioequivalence testing procedures based on EMA and FDA guidelines. The report details various study designs, including standard crossover and replicate designs, and specifies criteria for subject selection, sampling times, and primary parameters like AUC, Cmax, and Tmax. It also addresses bioanalytical methodology, bioequivalence criteria based on 90% confidence intervals, and considerations for narrow therapeutic index drugs. Furthermore, the report touches upon the Biopharmaceutics Classification System (BCS) and its role in biowaivers, replacing in vivo BE studies with in vitro dissolution tests. This document is intended to provide a comprehensive understanding of the regulatory framework surrounding bioequivalence within the GCC states.

Executive Board of the
Health Minister’s Council
for GCC Sates
The GCC Guidance for Bioequivalence

 Concept of bioavailability
 Historical cases of bio-inequivalence
 Bioequivalence testing : EMA and FDA
guidelines
 Study designs
 Bioequivalence criteria
 Special issues
OUTLINE

 In essence, a bioequivalence is considered to
be two medicinal products which are made up
of similar active elements. For this to happen,
then they have to be pharmaceutically
equivalent or rather pharmaceutical
alternative and thus their overall ability (rate
and extent) after administering in similar
molar dose that often lie within the
acceptable limits.
 The limits are often set to ensure there is a
comparable Vivo performance.
Introduction

 The idea of bioequivalence Is important
particularly in the application of generic
curative produces.
 The main purpose of coming up with
bioequivalence is for the purpose of
demonstrating equivalence in bio
pharmaceutics value between the general
therapeutic product and a reference
therapeutic produce to allow linking of
preclinical examinations as well as of
clinical trials related with the reference
medical product.

 In essence, this guide tend to focus on the
overall recommendation for bioequivalence
particularly for release formations with a
systematic action.
 Additionally, it ensures that there is a set
relevant criteria where bioavailability
studies is not required.
SCOPE OF THE STUDY

 standard design:
 Randomized
 two-period
 two-sequence
 single dose cross-over design
 alternative designs: parallel design as well
as replicated designs
STUDY DESIGN

2 x 2 CROSS-OVER
DESIGN
R
A
N
D
O
M
IZ
A
TI
O
N
subjects
sequence 1
sequence 2
R
T
W
A
S
H
O
U
T
T
R
period 1 period 2

REPLICATE DESIGN
4-period, 2-sequence, 2-formulation design
R
A
N
D
O
M
I
Z
A
T
I
O
N
subjects
sequence 1
sequence 2
R
T
T
R
period
T R
R T
I II III IV
wash-out

STUDY SUBJECT
 The study involved around 24 healthy
subjects, preferably the non-smoking
 The nonsmoking individuals were ranging
between 18-55 of age as well as 15% of an
reasonable body weight.
 strict inclusion/exclusion criteria
 patients, if the investigative active
substance is identified to posses severe
impacts deliberated intolerable for those
healthy volunteers
 subjects could belong to either sex

 SAMPLING TIMES
“The sampling schedule should
include frequent sampling around the
predicted tmax to provide a reliable
estimate of peak exposure. In
particular, the sampling schedule
should be planned to avoid Cmax being
the first point of the concentration-
time curve.”

SAMPLING TIMES
“The sampling schedule should also cover the plasma
concentration time curve long enough to provide a
reliable estimate of the extent of exposure which is
achieved if AUC0-t covers at least 80% of AUC0-.
At least 3 to 4 samples are during the terminal log-
linear phase in order to reliably estimate the terminal
rate constant, which is needed for a reliable estimate
of AUC0-.”
At least 3 to 4 samples are during the terminal log-
linear phase in order to reliably estimate the terminal
rate constant, which is needed for a reliable estimate
of AUC0-.”