This document summarizes a seminar presentation on IVIV correlation and biowaiver considerations. It defines IVIV as establishing a relationship between an in vitro property (e.g. drug dissolution rate) and an in vivo response (e.g. plasma drug concentration). It discusses the different levels of IVIV correlation from A to C and their meaning. It also covers parameters used for correlation, purposes of IVIV including reducing regulatory burden and justification for product quality, and biowaiver considerations when in vivo studies can be substituted with in vitro data.

1. A
SEMINAR ON
Topic: IVIV Correlation & Biowaiver Considerations
Presented By:
Hariom Jaiswal (2101200566005)
M. Pharm (Pharmaceutics)
1st Year / 2st Sem
(2021-22)
INSTTITUTE OF TECHNOLOGY OF MANAGEMENT
GIDA, GORAKHAPUR, U.P

2. CONTENTS:
 Introduction of IVIV
 Definition of IVIV
 Purpose of IVIV
 Parameters used for Correlating in IVIV
 Level of IVIV
 Biowaiver Considerations
 References

3. Introduction of IVIV:
 IVIV plays an critical role in drug development and in
optimization of formulation which is certainly a time
consuming and expensive process.
 IVIV allow dosage form optimization with the fewest
possible trail in man, fixes dissolution acceptance for
further bioequivalence studies.

4. Definition of IVIV:
 As per USP:- The establishment of rational relationship
between a biological property, or parameter derived for
biological property produced by dosage form, and a
physiochemical property or characteristic of dosage form.
 As per FDA:- A predictive mathematical model
describing relationship between an IN- VITRO property
of dosage form and IN-VIVO response.
• Generally, In-Vitro property is rate and extend of drug
dissolution or release while the In-Vivo response in
plasma drug concentration or amount of drug absorbed.

5. Purpose of IVIV:
 Reduction of regulatory burden.
 Optimization of formulation.
 Justification for therapeutic product quality.
 SUPAC (Scale Up and Post Approval Changes.
 To minimize the unnecessary human testing.
 Minimizing the cost and time required in the additional
bioavailability studies.

6. Parameters used for Correlating in IVIV:
In Vitro Parameters
 Time for a specific
amount dissolved
 Amount dissolved a
specific a time point
 Mean dissolution
In Vivo Parameters
 Area under the conc. Vs
time curve
 Fraction absorbed,
absorption rate constant
 Mean residence time

7. Correlation Level of IVIV:
 There are 5 types of levels described in FDA guideline
which include.
• Level A
• Level B
• Level C
• Multiple level C

8. Level- A:
 Highest Category of correlation.
 Linear correlation.
 Superimposable In Vitro and In Vivo input curve or
can be superimposable by use of a constant offset
value.
 Most informative and useful form a regulatory
perspective.

9. Level-B:
 Uses the principles of statistical moment analysis.
 The mean In Vitro dissolution time is compared either
to the mean residence time (MRT) or to the mean In
Vivo dissolution time.
 Is not a point to point correlation.
 Level B correlations are rarely seen in NDAs.

10. Level-C:
 Level C correlation represent a single point correlation.
 One dissolution time point (t50%, t90%, etc.) is
compared to one mean pharmacokinetics parameter
such as AUC , Tmax & Cmax.
 Weakest level of correlation as partial relationship
between absorption and dissolution is established.

11. Multiple Level –C Correlation:
 It is relates one or several pharmacokinetic parameter
of interest to the amount of drug dissolved at several
time points of the dissolution profile.
 Its correlation is more meaningful than that of Level-
C as several time points are considered.

12. Biowaiver Consideration:
 Its refers to the situations in which In Vivo BE studies
can be substituted with the relevant In Vitro data.
 Most common type of biowaiver adopted by the
regulatory authorities includes the application of the
BCS- based scheme or the application of IVIV.
 According to the FDA, biowaivers for IR drug
products may be requested in solely in the cases of
highly soluble and highly permeable substances when
the drug product is very rapidly dissolving and
exhibits similar dissolution profile to the reference
product, while the IVIV- based approach has been
narrowed down to application for XR products.

13. References:
 Computer Application in Pharmaceutical Research and
Development, Sean Ekins, 2006 John Wiley & Sons.
 https://www.slideshare.net/MOHDIMRAN139/ivivc-
87394566
 https://www.slideshare.net/Zahid1392/iv-dissolution-
iviv-corelation
 https://www.slideshare.net/ANUSHANADIKATLA/in
-vitro-in-vivo-correlation-122984972