INDIRA GANDHI NATIONAL TRIBAL

UNIVERSITY AMARKANTAK

ASSIGNMENT ON – BIOEQUIVALENCE

- SUBMITTED TO SUBMITTED BY •
DR>. RISHI PALIWAL MD. HAROON ANSARI •
DEPT. OF PHARMACY B.PHARM (6TH SEM)
ENROLLMENT-17251031
 Generic Drug product: Definition
• Same active ingredient (s)
• Same strength
• Same dosage form
• Same route of administration
• Same indications
FDA Definitions Used in Bioequivalence
Determinations
 FDA Determinations of Bioequivalence
Main Terms

• Pharmaceutical equivalents
• Pharmaceutical alternatives
• Therapeutic equivalents
• Bioavailability
• Bioequivalence
 Pharmaceutical Equivalents
• Drug products are considered pharmaceutical
equivalents if they contain the same active
ingredient(s), have the same dosage form and route
of administration, and are identical in strength or
concentration
• Equivalent products contain the same amount of
ingredient in the same dosage form but may differ in
characteristics, such as shape, release mechanisms,
and packaging
 Pharmaceutical Alternatives
• Drug products are considered pharmaceutical alternatives if
they contain the same therapeutic moiety, are different
salts, esters, or complexes of the same moiety, are different
dosage forms, or are different strengths
• Other pharmaceutical alternatives
– Different dosage forms and strengths within a single product line by a
single manufacturer
– Extended-release formulations when compared with immediate- or
standard-release formulations
 Therapeutic Equivalents
• Drug products are considered therapeutic equivalents if
they are all of the following
– Pharmaceutical equivalents
– Bioequivalent
– Approved as safe and effective
– Adequately labeled
– Manufactured in compliance with current Good Manufacturing Practice
regulations
• Therapeutic equivalents are expected to have the same
clinical effect and safety profile
 Bioequivalence
• A comparison of the bioavailability of two or more
• drug products.
• Two products or formulations containing the same
• active ingredient are bioequivalent if their rates
• and extents of absorption are the same
• Bioequivalence may be demonstrated through in vivo or
in vitro test methods, comparative clinical trials, or
pharmacodynamic studies
 Bioequivalence
90
Concentration (ng/m L)

80
70
60
Test/Generic
50
Reference/Brand
40
30
20
10
0
0 5 10 15 20 25 30
Time (hours)
 Bioequivalence: IR Products
Pharmaceutical Equivalent
Products
Reference Test
Possible Differences
.. ,Drug particle size
Excipients
Normal healthy subjects
Manufacturing process Crossover design
Equipment Overnight fast
Glass of water
Site of manufacture
CI within 80-125% 90%
.… Batch size of Ref. (Cmax & AUC)
Documented Bioequivalence
Therapeutic Equivalence =
).Note: Generally,Ajaz Hussain,
same FDA spec(
dissolution
 FDA Methods to Determine
Bioequivalence
• Generic drug manufacturers must demonstrate
that a drug is bioequivalent to a reference drug
product
• In order of FDA preference, methods used to
define bioequivalence
– Pharmacokinetic studies
– Pharmacodynamic studies
– Comparative clinical trials
– In vitro studies
 Pharmacokinetic Studies
Key Measurements
Study Compound • AUC
Reference Compound – Area under the concentration- time curve
Cmax • Cmax
– Maximum concentration
– A difference of greater than 20% in Cmax or
Concentration

the AUC represents a significant difference

between the study and reference
compounds
• Tmax
– Time to maximum concentration
AUC

Tmax Time
 Comparative Pharmacodynamic Studies
• Not recommended when:
– active ingredient is absorbed into the systemic
circulation
– pharmacokinetic study can be conducted
• Local action / no systemic absorption
• eg. : Topical Corticosteroid

15 Hanoi, 2006-19-01
 Comparative Clinical Studies
• Pharmacokinetic profile not possible
• Lack of suitable pharmacodynamic endpoint

• eg . : (Nasal suspensions)

16 Hanoi, 2006-19-01
 Study Designs

-Single-dose, two-way crossover design

- Single-dose, parallel design

-Multiple-dose studies( in case of :

-Drugs too potent/toxic
Extended/modified release products
 Crossover vs. Parallel Designs
• Crossover design preferred
– Intra-subject comparison
– Lower variability
– Generally fewer subjects required
• Parallel design may be useful
– Drug with very long half-life
– Crossover design not practical

19 Hanoi, 2006-19-01
 Fasted vs. Fed Designs
– Minimize variability not attributable to formulation
– Better able to detect formulation differences

Fed Study Designs may be employed when:

- Significant gastrointestinal (GI) disturbance caused by fasted
administration
-Product labeling restricts administration to fed state
20 Hanoi, 2006-19-01
 When equivalence studies are NOT
necessary (Biowaivers)
•
• Aqueous parenteral solutions
• Solutions for oral use ( syrups, elixirs, tinctures & other
soluble forms but not suspensions)
• Pdrs for reconstitution as a solution
• Otic or ophthalmic aqueous solutions
• Topical aqueous solutions
• Aqueous nebulizing inhalations or nasal sprays
• B. For some products bioequivalence may be
demonstrated by evidence obtained in vitro instead
of in vivo data:
– The drug product is in the same dosage form, but in a
different strength, and is proportionally similar in its
active and inactive ingredients to another product by
the same manufacturer that was found to be
bioequivalent.
• For high potency drug substances, the same
inactive ingredients are used for all strengths, and
the change in any strength is obtained by altering
the amount of the active ingredients and one or
more of the inactive ingerdients are within the
limits defined by the SUPAC guidances (up to level
II).