INDA and NDA 135

Fig. 9.7: Bioequivalence study is the process of estimation of closeness of the effects innovator drug

and its generic version.

Important pharmacokinetic parameters are:

AUC: Area under the concentration–time curve. It is a measure of the extent of

absorption.

Cmax: It is the observed maximum concentration of a drug. It is a measure of rate and

extent of absorption.

t

max: It is the time at which Cmax is observed. It is a measure of the rate of absorption.

Types of bioequivalence studies (Figs 9.8 and 9.9)

Fig. 9.8: Types of bioequivalence studies

Fig. 9.9: Types of in vivo bioequivalence studies

136 Industrial Pharmacy II

Biowavers

Biowavers are the exemptions that are granted by USFDA from conducting human

bioequivalence studies. Biowavers reduce the need for bioequivalence studies. They

are given when in vitro studies data provides sufficient estimate of a relative in vivo

performance of two products. These are given when API meets certain solubility and

permeability criteria. Biowavers are given in case if:

i. Drugs are highly soluble and highly permeable.

ii. Highest dose strength of the drug is soluble in 250 ml aqueous solution over a

pH 1–7.5 at 37°C.

iii. 90% of the drug is absorbed if administered orally.

iv. 80% of the drug is absorbed within 15 min of administration at 37°C.

v. Clinical research protocols

Bioequivalence studies are not required in case of:

i. Drugs are parenterally administered

ii. Drugs in solution form

iii. Drugs in gaseous form

iv. The new drug has a high therapeutic window.

v. Drugs with rapid and similar dissolution.

9.5 BIOSTATISTICS IN PHARMACEUTICAL PRODUCT DEVELOPMENT

Statistics is the science which deals with collection, tabulation and classification of

numerical facts as the basis for explanation, description and comparison of the

phenomenon.

Biostatistics is the branch of statistics concerned with mathematical facts and data

related to biological events. Sir Francis Galton is the Father of biostatistics.

There are two types of biostatistics

1. Inferential biostatistics: It is the methods of generalising a larger group. The

generalization is based on information about a sample. The sample is considered to

be similar to the population.

2. Descriptive biostatistics: These are used to explain the basic features of the data.

They also provide simple summary of the data (Fig. 9.10)