CRITERIA
US FDA ISP - CHILE
AGE (YEARS) 18 YEARS or older 18 and 55 years
BMI 18.5 to 30
both sexes is generally preferred
SEX BOTH SEXES unless there is a specific reason to
exclude by sex.
SMOKING Not specified preference to non-smokers
MINIMUM SAMPLE
12 12
SIZE
The pilot study is carried out in a
small number of
Pilot study
volunteers and is prior to carrying
out the bioequivalence study itself.
Parent drug and active metobolite
under following conditions:
1) For Produrg
active metabolite,
2) When the concentration of
PARENT DRUG Parent compound.
unmetobolized drug is too low,
/METABOLITE Primary Metabolite
3) measurement of an analyte (drug
or metabolite) carries the risk of
making a type I error (consumer
risk) forstay at a 5% confidence
level
1) IR (within a time period of up to
2 times the median treatment
Removal due to
Tmax value)
Emesis
2) MR (within the therapeutic
dosage range)
recommended
to use appropriate statistical
programs, such as R®, or
Sample size estimate bibliographical references ("On
simple size calculation in
bioequivalence trials", Chow and
Liu, 2001).
Substitution or
not recommended
Repacement
For potency selection, the
equivalent molar dose of both the
study product and the
reference product should be used.
Generally, the marketed potency
with the highest
sensitivity to BE assessment should
be administered as a single dose.
This normally
corresponds to the highest power
marketed. It can use a larger dose
(for example, greater than a unit
statistical power dose) if analytical difficulties arise.
In
this case, the total single dose
should not exceed the maximum
daily dose of the dosage
regimen. In other situations, a study
performed at a lower power may be
considered
acceptable if the power is selected
for safety reasons or if the drug is
highly soluble and
the pharmacokinetics are linear in
the therapeutic range.
type I error
Gap between the
studies
Clinical status
Clinical laboratory
tests
Clinical laboratory
test validity
Electrocardiogram
UDS and pregnancy
test
fasting condition
hospitalization of the
research subjects
sampling schedule
Statistical parameter
PK study model
Design
Washout period
Diet
dosing at fed
condition
AGENCIES
COFEPRIS EMA ANVISA NMPA
18 to 55 years 18 YEARS or older 18 YEARS or older 18 YEARS or older
18.5 to 27
BOTH SEXES (The selection of a
single gender of research subjects
to participate in a study must be Either Sex Either Sex BOTH SEXES
justified)
Preferable to Include Preferable to Include Preferable to Include
Not specified
non-smokers non-smokers non-smokers
18 or 24 in the Absence
must not be less than 12 12 Typically 18 to 24
of ISCV data
not less than 8 research
volunteers piolet study must be
Replicate design
Parent compount. Parent compound.
Parent compound. Parent compound.
For Produrg Primary Active
Metabolite Primary Metabolite
active metabolite Metabolite
1) IR( period of time between 0
and 2 times the tmax)
2) MR(occurs within the
therapeutic dosing range)
obtained from the CV%
intrasubject pharmacokinetic
parameter (Cmax, AUC0-t or
AUC0-ÿ) with greater variability,
which in turn must be obtained
from the CME obtained at
ANADEVA; This information can
be obtained from a pilot study or
from internationally recognized
scientific literature
not permitted
should not be less than 80%,
less than or equal to 5%.
3 months
no history of hypersensitivity or
allergies to the drug under study
1) General urine examination,
2) Blood chemistry that evaluates
liver function, kidney function,
lipids and fasting glucose
3) Complete blood count with
differential count
4) presence of hepatitis B and C,
HIV and VDRL
Maximium 3 months
validity for 3 months (unless
pathology reported in that study
yes during screening
Medications administered orally
should be ingested with 250 mL
of water
at least 10 h before
administration
for at least 2 hours after
administration
one night prior to the start of the
study
frequent sampling around the
expected tmax value to provide a
reliable estimate of Cmax and
must be planned to avoid the first
sampling time corresponding to
Cmax, in such a way that it allows
80% to be characterized. AUC
(minimum 4 t1/2 elimination,
with at least four samples during
the log-terminal phase to obtain
the elimination rate constant)
except for truncated studies.
AUC0-t, AUC0-ÿ, Cmax, tmax, Ke
and the estimated t½ in the
terminal phase
(For truncated sampling periods
AUC0-72, Ke and t½)
(modified release, the TMR must
also be reported)
(Steady State study AUC0-tau,
Cmaxee, Cminee , tmaxee)
(urinary excretion data, Aet and
Rmax)
non-compartmental method
1) crossover design,
2) Crossover or parallel designs
with sampling truncated to a
minimum of 72 h for drugs with a
long halflife.
3)For immediate release drugs
with long elimination half-life (>
24 h),perform truncated AUC
studies, obtaining samples for a
minimum of 72 h.
4) Replicated designs for drugs
with high variability (intrasubject
CV% greater than or equal to
30%).
5) William's designs to compare
more than two formulations
6)Designs to carry out the
bioequivalence study in more
than one stage
7)Multiple dose designs until
reaching steady state.
at least seven half-lives of the
drug
need to be identical between
period
30 minutes after intake of food
TPD TGA WHO ASEAN
18-55, INCLUSIVE 18 YEARS or older 18-55 YEARS 18-55 YEARS
BOTH SEXES Either Sex Both sexes Either sex
Preferable to Include Preferable to Include Preferable to Include
Prefers Non-Smokers
non-smokers non-smokers non-smokers
12 12 12 12
Parent compound.
Parent compound. Parent compound. Parent compound.
Prodrug
Primary Active Primary Active Primary Active
Primary Active
Metabolite Metabolite Metabolite
Metabolite
PMDA (JAPAN) GCC
NOT SPECIFIED 18-55 YEARS
NOT SPECIFIED Either sex
NOT SPECIFIED Prefers Non-Smokers
12
Parent compound. Parent compound.
Primary Active Primary Active
Metabolite Metabolite
