The release of the drug substance from the drug product leading to the bioavailability of the drug substance. The assessment of drug product performance is imp. Since bioavailability is related both to the pharmacodynamic responses and the adverse events. The performance tests relate the quality of a drug product to clinical safety and efficacy. 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 manufacturing process of the drug product.

1. DRUG PRODUCT PERFORMANCE,
IN VIVO
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2. 2

3. 3

4.  The release of the drug substance from the drug product leading to bioavailability
of the drug substance. The assessment of drug product performance is imp. Since
bioavailability is related both to the pharmacodynamic responses and the
adverse events. The performance tests relate the quality of a drug product to
clinical safety and efficacy.
 Bioavailabilty 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.
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5. BIOEUIVALENCE STUDIES IN NEW DRUG DEVELOPMENT (NDA)
 Used to compare :
 Early and late clinical trial formulations
 Formulations used in clinical trials and stability studies, if different
 Clinical trial formulations and to be marketed drug products , if different
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7.  Bioavailability studies are performed for both approved active drug ingredients
and therapeutic moieties not yet approved for marketing by the FDA.
 New formulations of active drug ingredients must be approved by the FDA before
marketing.
 FDA ensures that the drug product is safe and effective for its labeled indications
are use.
 The drug product must meet all applicable standards of identity , strength ,
quality , and purity. 7

8. Absolute availability
(Fabs) =
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9.  In vivo measurement of active moiety or moieties in biological fluids
 Plasma drug concentration
 tmax
 Cmax
 AUC
 Urinary Drug excretion
 In vivo pharmacodynamic comparison
 Clinical endpoint study
 In vitro studies
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11.  Differences in the predicted clinical response or an adverse event may be due to
differences in the pharmacokinetic or pharmacodynamic behaviour of the drug.
 Bioequivalent drug products that have the same systemic drug
bioavailability will have the same predictable drug response.
However, variable clinical responses among individuals that are unrelated to
bioavailability may be due to differences in the pharmacodynamics of the drug.
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12.  Bioequivalence studies are performed to compare the Bioavailability of the
generic drug product to the brand name product.
 Statistical techniques should be of sufficient sensitivity to detect differences in
rate and extent of absorption that are not attributable to subject variability.
 Once bioequivalence is established, it is likely that both the generic and
brand name dosage forms will produce the same therapeutic effect.
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13.  For many drug products, the FDA, Division of Bioequivalence, Office of Generic
Drugs, provides guidance for the performance of in-vitro dissolution and in-vivo
bioequivalence studies. Similar guidelines appear in the United States
Pharmacopoeia NF.
 Currently, three different studies may be required for solid oral dosage
forms, including
1. Fasting study
2. Food intervention study
3. Multiple-dose study 13

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Group Formulation Formulation
Group 1 A A
Group 2 B B

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17.  The contents of NDAs and ANDAs are similar in terms
of the quality of manufacture .
 The submission for an NDA must contain safety and
efficacy studies as provided by animal toxicology
studies, clinical efficacy studies, and
pharmacokinetic/bioavailability studies.
 For the generic drug manufacturer, the bioequivalence
study is the pivotal study in the ANDA that replaces the
animal, clinical, and pharmacokinetic studies.
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