Bioavailability studies assess the performance of drug products by examining the effects of drug properties, formulations, and manufacturing processes on drug absorption and availability in systemic circulation. These studies are crucial for establishing dosage regimens, understanding pharmacokinetics, and play a significant role in regulatory approvals of new and generic drugs. They also investigate food effects and drug-drug interactions, providing essential data for clinical safety and efficacy.

1. IMPORTANCE OF
BIOAVAILABILITY STUDIES
Presenter:
Muhammad Abdul Islam
(02332011025)
MPhil 1st semester

2. Bioavailability
Bioavailability studies are drug product performance studies used to
define the effect of changes in the physicochemical properties of the
drug substance, the formulation of the drug and the manufacture
process of the drug product (dosage form).

3. Drug Product Performance
• Drug product performance,in vivo, may be defined as the release of
the drug substance from the drug product leading to bioavailability of
the drug substance.
• The assessment of drug product performance is important since
bioavailability is related both to the pharmacodynamic response and
to adverse events.
• Thus, performance tests relate the quality of a drug product to clinical
safety and efficacy.

4. Continued
• Drug product performance studies are used in the development of
new and generic drug products.
• Bioavailability is one aspect of drug product quality that links the in
vivo performance of a new drug product to the original formulation
that was used in clinical safety and efficacy studies.

5. Significance
• Bioavailability data provide an estimate of the fraction of
administered dose that is absorbed into the systemic circulation from
the formulation, and provide information about the pharmacokinetics
of the drug.
• Bioavailability studies provide useful information that is important to
establish dosage regimens and to support drug labelling, such as
distribution and elimination characteristics of the drug.

6. Continued
• Bioavailability studies provide an indirect information regarding the
presystemic and systemic metabolim of the drug and the the role of
transporters such as p-glycoproteins.
• such studies when designed appropriately provide information on the
linearity or non-linearity in the pharmacokinectics of the drug and
dose proportionally.

7. Continued
• Bioavailability data play vital roles in regulatory submissions for
marketing approval of new and generic drugs throughout the world.
• Relative bioavailability studies are frequently included in regulatory
submissions. For example, the FDA recommends that new drug
developers routinely use an oral solution as the reference for a new
oral formulation, for the purpose of assessing how formulation
impacts bioavailability.

8. Continued
• Relative bioavailability studies used in drug development include studies to
characterize
food effects and
drug–drug interactions.
• In a food-effect bioavailability study, oral bioavailability of the drug product
given with food (usually a high-fat, high-calorie meal) is compared to oral
bioavailability of the drug product given under fasting conditions. The drug
product given under fasting conditions is treated as the reference
treatment.
• Drug–drug interaction study determines whether there is an increase or
decrease in bioavailability in the presence of the interacting drug. As such,
the general drug–drug interaction study design compares drug relative
bioavailability with and without (reference treatment) the interacting drug.

9. Continued
• Relative bioavailability studies are used in developing new
formulations of existing immediate-release drug products, such as
new modified-release versions or new fixed dose combination
formulations.
• In the case of a new modified-release version, the reference product
is the approved immediate-release product.
• In the case of a new fixed-dose combination, the reference product
can be the single-entity drug products administered either separately
(ie, three treatments for a fixed-dose combination doublet) or
concurrently according to an approved combination regimen (ie, two
treatments).

10. Continued
• Relative bioavailability study designs are also used for bridging
formulations during drug development.
• For example, to evaluate how drug systemic availability from a new
premarket formulation compares with that from an existing
premarket formulation.

11. Elements of a Bioavailability Study Protocol
I. Title
A. Principal investigator (study director)
B. Project/protocol number and date
II. Study objective
III. Study design
A. Design
B. Drug products
1. Test product(s)
2. Reference product
C. Dosage regimen

12. Continued
D. Sample collection schedule
E. Housing/confinement F. Fasting/meals schedule
G. Analytical methods
IV. Study population
A. Subjects
B. Subject selection
1. Medical history
2. Physical examination
3. Laboratory tests

13. Continued
C. Inclusion/exclusion criteria
1. Inclusion criteria
2. Exclusion criteria
D. Restrictions/prohibitions
V. Clinical procedures
A. Dosage and drug administration
B. Biological sampling schedule and handling procedures
C. Activity of subjects

14. Continued
VI. Ethical considerations
A. Basic principles
B. Institutional review board
C. Informed consent
D. Indications for subject withdrawal
E. Adverse reactions and emergency procedures
VII. Facilities
VIII. Data analysis
A. Analytical validation procedure
B. Statistical treatment of data
IX. Drug accountability
X. Appendix