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Eine aktuelle Durchsicht von FDA Warning Letters ergab, dass in 48 Warning
Letters Beanstandungen zu HPLC zu finden waren. Darunter finden sich
sowohl recht allgemeine Findings, als auch sehr spezifische Punkte, wie
die unten aufgeführten Beispiele zu einigen Themen zeigen:
HPLC in der Stabilitätsprüfung:
- Unidentified HPLC peaks found during stability testing were not
identified or evaluated
- No attempt is made to identify or evaluate degradation products
during routine stability testing. The HPLC recorder is turned off as
soon as the analytical peak elutes
- The stability indicating HPLC method used for related substances
testing of a product has not been fully validated in that the linear
range and Limit of Detection/Limit of Quantitation for all known
impurities has not been determined
HPLC - Kalibrierung/Qualifizierung:
- There is no documentation regarding calibration and preventive
maintenance for HPLC's used by QC Chemistry Laboratory
- Procedure for HPLC Calibration Method 013 has no predetermined
acceptance criteria for the autosampler calibration. The autosampler
calibration does not demonstrate that the instrument is capable of
accurately accessing linearity
- The calibration procedure for HPLC systems is inadequate in that it
did not include integrator and detector's linearity, injector's
reproducibility, and accuracy of temperature settings for column
heater and detector
Computervalidierung/Part 11 Compliance bei HPLC:
- The HPLC computer software, which is used for data acquisition,
calculations, and change control, is not validated in that areas such
as system operations, system maintenance, change control, data back-up
and archival, system security and disaster recovery have not been
evaluated
- Lack of validation data to support the adequacy of the computer
software used to run the HPLC systems
- It was noted during the inspection that there is an option on the
HPLC that allows analysts to delete results after they were processed
Sonstige Findings:
- Assay peaks with shoulders and unresolved peaks were observed on
release and stability for…
- Your firm did not perform the required standard injection bracketing
required for the HPLC method for both assay and content uniformity
- There is no assurance that the laboratory HPLC columns can produce
valide, reliable and reproducible results
- There is no data to demonstrate that the in-house HPLC method used
to release…is equivalent to compendial methods
- The method for integrating HPLC peaks of the same product was
inconsistent
Wenn schon in den Warning Letters so häufig HPLC Verfahren beanstandet
werden, kann man davon ausgehen, dass in den eigentlichen
Inspektionsberichten (483er) HPLC –Beanstandungen bei FDA-Inspektionen
noch viel häufiger ein Thema sind.
Hierzu findet am 12./13. Februar 2003 in Heidelberg die ECA Conference
"HPLC
in a GMP-/FDA-Regulated Environment" statt, die viele der bei
FDA-Inspektionen aufkommenden Fragestellungen, wie Methodenvalidierung,
Gerätequalifizierung, Part 11 Compliance oder Methodentransfer aufgreift.
Im anschließenden Post Conference Workshop geht es einen ganzen Tag um
die Validierung von Chromatographie Daten Systemen (CDS) gemäß den
Anforderungen des 21 CFR Part 11.
Autor:
Dr. Günter Brendelberger
CONCEPT HEIDELBERG
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