SUPAC

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. 

There are a number of FDA regulatory guidances that are associated with IVIVC development and validation, as well as the application of IVIVC to SUPAC. The specific IVIVC guidance for oral modified-release formulations was first published in September 1997 (1). There are several guidances on SUPAC, including those for both modified release (2) and immediate-release solid oral dosage forms (3). The recent... 

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

For IR forms, the SUPAC-IR guidance (15) distinguishes between the following classes of change ... 

Analogously, the SUPAC-MR guidance (1,2) defines level of changes for ... 

Figure 4 Postapproval changes of IR forms supported by in vitro dissolution data according to SUPAC-IR guidance.

However, most transfer exercises do involve scale-up of some sort, often to a one-tenth, or indeed full production scale (SUPAC, 1995) and the scalability of the unit processes must be assessed. 

I The composition of the new product is similar to an existing product i.e. slight changes in the product covered by SUP AC IR level 1 change (SUPAC, 1995) and is analysed by analytical procedures with which the receiving laboratory already has experience. 

FDA. Guidance for industry SUPAC-SS In-vitro release testing and in-vivo bioequivalence documentation, Center for Drug Evaluation and Research (CDER), 1997. 

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. 

Guidance for Industry, SUPAC-IR/MR-Manufacturing Equipment Addendum, PDA, CDER, January 1999. http //www.fda.gov/cder/guidance/1721fnl.pdf. 

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