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PharmD clinical pharmacy program Level 3, Semester 2 Biopharmaceutics & Pharmacokinetics (PT608(

The establishment of a predictive IVIVC provides with:

 A better understanding of the release properties of the drug product

 Enables to decrease the number of in vivo studies needed to approve and maintain a

drug product on the market resulting in an economic benefit and a decreased

regulatory burden.

 Enables to set clinically meaningful dissolution specifications based on the predicted

plasma concentration-time profile.

 A meaningful and predictive IVIVC is a correlation that can predict the C max and
AUC.

Categories of In Vitro–In Vivo Correlations

Level A Correlation

• It is the highest level of correlation and represents a point-to-point (1:1) relationship
between an in vitro dissolution and the in vivo input rate of the drug from the dosage

form. Level A correlation compares the percent (%) drug released versus percent (%)
drug absorbed.

• The major advantage of a Level A correlation is that a point-to-point correlation is

developed. All in vitro dissolution data and all in vivo plasma drug concentration–time

profile data are used. Once a Level A correlation is established, an in vitro dissolution

profile can serve as a surrogate for in vivo performance. A change in manufacturing

site, method of manufacture, raw material supplies, minor formulation modification,

and even product strength using the same formulation can be justified without the need

for additional human studies.

• Level A correlation enables the in vitro dissolution test to become meaningful and

clinically relevant quality control test that can predict in vivo drug product

performance.

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