• 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

• 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

• 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

• 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