Chemistry Reference
In-Depth Information
procedures, reference standard qualification and characterization, format of ana-
lytical procedures submitted in NDAs and ANDAs, validation of noncompendial
analytical procedures, compendial analytical procedures, content and processing of
validation packages, and revalidation. As of the year 2010, this draft guidance is the
most recent guideline available from the FDA, and is briefly outlined here; subse-
quent chapters of this volume address the guidance in more detail.
1.5.1 t
yPeS
of
A
nAlytIcAl
P
rocedureS
The guidelines break methods or procedures into three different types:
1. Regulatory analytical procedures
2. Alternative analytical procedures
3. Stability indicating assays
A regulatory analytical procedure
is the analytical procedure used to evaluate a
defined characteristic of the drug substance or drug product. Regulatory analytical
procedures are found, for example, in the USP.
An alternative analytical procedure
is an analytical procedure proposed by the
applicant for use instead of the regulatory analytical procedure. A validated alterna-
tive analytical procedure should be submitted only if it is shown to perform equal to
or better than the regulatory analytical procedure. If an alternative analytical pro-
cedure is submitted, the applicant should provide a rationale for its inclusion and
identify its use (e.g., release, stability testing), validation data, and comparative data
to the regulatory analytical procedure.
A stability indicating assay
is a validated quantitative analytical procedure that can
detect the changes with time in the pertinent properties of the drug substance and drug
product. It accurately measures the active ingredients, without interference from degra-
dation products, process impurities, excipients, or other potential impurities. Additional
information on validating stability indicating assays can be found in Chapter 7.
1.5.2 r
eference
S
tAndArdS
A reference or primary standard
may be obtained from the USP or other source, and
when necessary, FDA review staff can be consulted regarding alternative sources
for standards. When there is no official source, a reference standard should be of the
highest possible purity and be fully characterized. Working, in-house, or secondary
standards are also commonly used; however, they should be qualified against the
primary reference standard.
1.5.3 c
ertIfIcAte
of
A
nAlySIS
A certificate of analysis (CoA) for reference standards from nonofficial sources should
be submitted in the section of the application on analytical procedures and controls.
CoAs should include a list of each test performed on the standard, and the methods
used to perform the test. The acceptance limits and the results for each test should
