In July 2006, the FDA published a warning letter in which one of the main
points of criticism was non-GMP compliance of HPLC analysis.
The most important contents of the warning letter regarding HPLC were:
The reference standard injection following assay and content
uniformity testing of ... failed to show any peaks due to a leaking
column. There was no documented investigation of this deviation, there
was no assessment of the impact of the leaking column on the
or any other analysis conducted with the same column, and the
were not reinjected.
There was no documented investigation regarding HPLC malfunctions
requiring external repair. Both HPLC
required repair in June
2005; however there is no documentation regarding whether the
malfunctions impacted any analysis, and if so, what the corrective
actions were regarding those analyses.
Laboratory records fail to include the initials or signature of the
person who performs each laboratory test. Specifically, laboratory
analysis records for analyses performed by HPLC
do not indicate
which analyst performed the injections.
Failure to maintain complete records of any modification of an
established method employed in testing. Specifically, the records of
laboratory methods stored in the computer system do not include the
identity of the person initiating method changes.
Appropriate controls are not exercised over computers or related
systems to assure that changes in analytical methods or other control
records are instituted only by authorized personnel. Specifically: Due
to the common password and lack of varying security levels, any analyst
or manager has access to, and can modify any HPLC analytical method or
record. Furthermore, review of audit trails is not required.
This recent warning letter shows that HPLC analysis is one of the focal
points in FDA inspections and that the inspectors sometimes have a very
close look at it.