Post-approval changes

Multidrug resistant-related protein family Polar molecular surface area Solubilization ratio Scale-up and post-approval changes... 

CDER Guidance for Industry. SUPAC-IR Immediate-Release Solid Oral Dosage Forms Scale-Up and Post-Approval Changes Chemistry, Manufacturing and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation US Food and Drug Administration, 1995. 

Dissolution is also used to identify bioavailability (BA) problems and to assess the need for further BE studies relative to scale-up and post-approval Changes (SUPAC), where it functions as a signal of bioinequivalence. In vitro dissolution studies for all product formulations investigated (including prototype formulations) are encouraged, particularly if in vivo absorption characteristics can be defined for the different product formulations. With such efforts, it may be possible to achieve an in vitro/in vivo correlation. When an in vitro correlation or association is available, the in vitro test can serve not only as a quality control (QC) specification for the manufacturing process, but also as an indicator of in vivo product performance. 

Scale-up/ s Post-Approval / Changes / What is a significant change / in the i n vitro profile Target Specification N. What in vitro characteristics will achieve i n vi vo ta rget ... 

Figure 14 Schematic showing the decision-making process for pre- and post-approval changes with and without an IVIVC.

SUPAC Dissolution Profile Comparison Supporting Post-approval Changes... 

Notably, new methods may be required if there are post-approval changes in either the DS synthesis or in the DP formulation. 

Product marketing Quality control Post-approval change + + + + + + + + + + +... 

In 1995, the FDA issued Scale-up and Post-Approval Changes (SUPAC) guidance for the industry (128) for immediate release dosage forms and in 1997, SUP AC MR guidance was released for modified release dosage forms (129). 

FDA, September 1997, Guidance for Industry SUPAC-MR modified release solid oral dosage forms scale-up and post-approval changes chemistry, manufacturing and controls, in vitro dissolution testing, and in vitro bioequivalence documentation. 

Establishing in vitro in vivo correlation (IVIVC) for modified release dosage form provides a justification for waiving in vivo bioequivalence evaluation only for certain specified post approval changes. Since a correlation is dependent on the mechanism of drug release, it is not used in situations that could potentially alter its mechanism (16). 

ACPS recommendations on regulatory flexibility for post approval changes (e.g., reduce the need for prior review) will be considered for improving the draft Comparability Protocol Guidance (for small molecules only). 

The regulatory aspects of scale-up and post-approval changes are addressed in detail throughout the book and in a separate chapter. A diligent attempt was made to keep all references to the Food and Drug Administration (FDA) regulations as complete and current as possible. 

SUPAC-SS Nonsterile semisolid dosage forms scale-up and post-approval changes Chemistry, manufacturing and controls in vitro release testing and in vivo bioequivalence documentation http //www.fda.gov/cder/guidance/1447fnl. pdf... 

Augsburger, L. L., Shangraw, R., Lesko, L. J., and Williams, R. W. An approach toward establishing a scientific foundation for interpreting regulations and workshop reports on scale-up and post approval changes. Pharm. Res. ll(10) S-143,1994. 

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