Bioavailability & Bioequivalence Studies- Definitions, Methods of Measurement of BA-BE ,Study Design, Requirement for conducting BA-BE study, Biowaiver, Biosimilar

1. Presented By: Rajashree Ghogare
M Pharm Pharmacology
Assistant Professor at PRCOP, Loni
Bioavailability and Bioequivalence

2. List of content
Definitions
• BA
• BE
Objectives
• Objectives BA
• Objectives of BE
• Methods of
measurements
of BA,BE
• Study Design
Requirement for
conducting BA-Be
study
Biowaiver,
Biosimilar
Scope for Students

3. Definition
• Bioavailability (BA) : Bioavailability refers to the
relative amount of drug from an administered dosage
from which enters the systemic circulation and the rate
at which the drug appears in the systemic circulation.
• Bioequivalence (BE): Bioequivalence of a drug product
is achieved if its extent and rate of absorption are not
statistically significantly different from those of the
reference product when administered at the same
molar dose.

4. • Innovator Drug/Product-Approved as a new
drug
• Generic Drug/Product-Product which have
same API, strength, dosage form, dosage
regimen(Administered by same route),

5. Volunteers/Subjects:
Period
Sequence Washout Period

6. Bioavailability Study

7. Bioavailability (BA)
Types- Absolute / Relative(Comparative)
• ‘’Absolute-’’bioavailability compares one non-
IV route with IV administration.
• "Relative" bioavailability compares one non-
IV route or formulation with another (instead
of using IV route as a reference).

8. Factor affecting on Bioavailability
Pharmaceutical Factor related to
physicochemical
Solubility of Drug,Permeability,particle size…etc
Patient related Factor
Age, Gender, Obesity, Disease condition
Route of administration
Parenteral >Oral>Rectal>Topical

9. Bioavailability Fraction

10. Methods of Bioavailability
Measurement
• Plasma Level-Time
Studies
• Urinary Excretion Studies
PK
(Indirect)
• Acute Pharmacological
response
• Therapeutics Response
PD
(Direct)

11. PK Studies(Indirect method)
1.plasma drug conc profile determination by
using series of sample blood.
2.Urine analysis

12. PD Methods
1.Acute Pharmacological response Methods
2. Therapeutic Response Methods-
• ECG,
• EEG,
• Pupil Diameter
• DRC Graph

13. Bioequivalence Study
IN VIVO
IN VITRO

14. Study Design
• 1.Parallel Design-Each subject will received
one type of formulation.
• Disadvantage-Inter subject variation will be
there.
Group Formulations
Period I Period II
1
A(Test)
A(Test)
2 B (STD) B (STD)

15. 2.Cross Over Design-
Latin Square cross over design
Each subject is administered The Test and STD
formulation.
Group Sequence Formulations
Period I
Washout
Period/Time
Period II
1
AB A(Test)
B (STD)
2 BA B (STD) A(Test)

16. 3.3Period 3Sequence cross over design
Grou
p
Sequence Formulations
Period I
Washout
Period/Time
Period II
Washout
Period/Tim
e
Period III
1 ABC A
B
C
2 BCA B C A
3 CAB C A B

17. 4.4Period 4 sequence cross over design
Gr
ou
p
Sequ
ence Formulations
Period I
Washou
t
Period/T
ime
Perio
d II
Washou
t
Period/
Time
Period III
Washout
Period/Ti
me
Period IV
1 ABCD A
B
C D
2 BCDA B C D A
3 CDAB C D A B
4 DABC D A B C

18. Balanced incomplete block design
Subjects
are
randomly
asigned
Subjects Formulations
Period I Period II
1 A B
2 B A
3 A C
4 C A
5 A D
6 D A
7 B C
8 C B
9 B D
10 D B
11 C D
12 D C

19. Requirement for conducting BA-BE study

20. • Guideline For BA-Be Study-
guidance_doc_BABE_NOC1_1Jan2018.pdf
• Updated list BA-BE dt. 10.06.21.pdf
• CT Rule 2019 23NEW DRUGS AND
CLINICAL TRIALS RULES, 2019.pdf
• GCP inspection Checklist-
GCPInspChecklist16.pdf
• Sugam portal
• AE reporting on time

22. Biowaiver
• A biowaiver is applicable when the drug substance(s) in test
and reference products are identical. A biowaiver may also be
applicable if test and reference products contain different
salts provided that both belong to BCS Class I
• must contain the same active and inactive ingredients (Q1) in
the same dosage form and concentration (Q2) and have the
same pH and physico-chemical characteristics (Q3) as an
approved
• In vitro preferred than In vivo
• Amlodipine is classified according to BCS as a Class I drug
therefore qualifies for biowaiver.

23. Biosimilar
• A biosimilar is a biological medicine highly
similar to another already approved biological
medicine (the 'reference medicine').
Biosimilars are approved according to the
same standards of pharmaceutical quality,
safety and efficacy that apply to all biological
medicines.

24. SCOPE FOR BA-BE
Clinical research-CRO centre
CDSCO vacancies
sugam portal
Clinical trials,BA-Be trails- co-ordinator
Medical Writer- Protocol, EC ,Informed consent
writing,Clinical study report..etc.
Ethical committee member