The FDA received inquiries regarding dissolution testing
from some FDA Investigators as well as from members of the pharmaceutical
industry. What kinds of USP dissolution test failures are significant
enough to be noted on Forms 483? Is a failure in dissolution testing at
stage 1 level, for instance, significant enough to be cited on an FD-483?
the Human Drug CGMP Notes of March 1995 and March 1996, the FDA clarified
this question to the satisfaction of the pharmaceutical industry:
"Routine failure of manufactured batches of a
product to pass USP Dissolution tests at Stage 1 is not significant enough
to be noted on Forms FD-483; neither is occasional failure of individual
dosage units at Stage 2. A batch does not fail the USP Dissolution Test
until it fails at Stage 3. However, frequent failures
at Stage 2 are significant when other batches of the same product
have Stage 3 failures, and therefore should be noted on Forms
The above paragraph is meant to summarise the most important statements
on dissolution testing in the Human Drug CGMP Notes.
A very topical publication on dissolution testing dating from 2003,
which has been created with FDA's co-operation, are the "FIP/AAPS Guidelines to
Dissolution/in Vitro Release Testing of Novel /Special Dosage Forms."
You can download them by clicking here.