Chemistry Reference
In-Depth Information
7.5.4 b
IoAnAlytIcAl
m
ethod
d
ocumentAtIon
Good record keeping and documented SOPs are an essential part of any validated
method. Once the validity of a bioanalytical method is established and verified by
laboratory studies, pertinent information is provided in an assay validation report.
Data generated during method development and QC should be available for audit
and inspection. Documentation for submission to the FDA should include (1) sum-
mary information, (2) method development and validation reports, (3) reports of the
application of the method to routine sample analysis, and (4) other miscellaneous
information (e.g., SOPs, abbreviations, and references).
The
summary information
should include a tabular listing of all reports, proto-
cols, and codes. The documentation for
method development and validation
should
include a detailed operational description of the experimental procedures and stud-
ies, purity and identity evidence, method validation specifics (results of studies to
determine accuracy, precision, recovery, etc.), and any protocol deviations with jus-
tifications. Documentation of the
application of the method to routine sample analy-
sis
is usually quite extensive. It should include
• Summary tables describing sample processing and storage
• Detailed summary tables of analytical runs of preclinical or clinical samples
• Calibration curve data
• QC sample summary data including raw data, trend analysis, and summary
statistics
• Example chromatograms (unknowns, standards, QC samples) for up to
20% of the subjects
• Reasons and justiication for any missing samples or any deviations from
written protocols or SOPs
• Documentation for any repeat analyses, or reintegrated data
7.6 vAlIdAtIng peptIde mAppIng metHods
Peptide mapping is one of the preferred techniques for the comprehensive character-
ization of biopharmaceutical products and is often the analytical method of choice
for studying a protein's primary structure. It is a very common application in the bio-
pharmaceutical laboratory and has become a true workhorse technique [37]. Similar
to any other analytical technique used in a regulated environment, methods for pep-
tide analysis must also be validated. Although most of the underlying principles still
apply, the validation of a peptide map includes some additional considerations when
it comes to LOD, robustness, and precision, and depends on the stage of the regula-
tory process. While mostly involving comparative testing, when properly validated,
a peptide map can be used to accomplish its intended purposes: to confirm the pri-
mary structure of a protein, to detect whether or not alterations have occurred, and to
demonstrate process consistency. Typically used as an identity test for proteins, espe-
cially those obtained by r-DNA technology, a peptide map is generated by a chemi-
cal or enzymatic treatment of a protein followed by a reproducible high-resolution
