*ASSIGNMENT ON*

“BIOEQUIVALENCE”

Subject: “Biopharmaceutics & Pharmacokinetics”

SUBBMITTED TO
DR. RISHI PALIWAL SIR,
“PHARMACEUTICAL SCIENCE”
ASSISTANT PROFESSOR
DEPT.OF PHARMACY, I.G.N.T.U.
AMARKANTAK (M.P.)
SUBBMITTED BY
MD. HAROON ANSARI
B.PHARMA VI th sem.
en.no. - 17251031
dept. of pharmacy,
i.g.n.t.u. amarkantak

Generic Drug product: Definition

• Same active ingredient.
• Same strength.
• Same dosage form.
• Same route of administration.
• Same indications.

*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 : IR PRODUCT

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
90% CI within 80-125%
Batch size …. of Ref. (Cmax & AUC)
Documented Bioequivalence

“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:-
 Key Measurements
Study Compound • AUC
Reference Compound – Area under the concentration- time curve
m ax
• Cm a x
– Maximum concentration
– A difference of greater than 20% in Cm a x or
the AUC represents a significant difference
between the study and reference
compounds
Concentration

• Tm a x
– Time to maximum concentration
AUC

Tm a x 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.
COMPARATIVE CLINICAL
STUDIES:-

• Pharmacokinetic profile not possible.

• Lack of suitable pharmacodynamic endpoint.
• eg : (Nasal suspensions)

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.
 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.

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).

“THANKYO
U”