Erfahrungen mit
Endotoxin-Kontrollstandards
Originale
Key WordsKontrollstandard-Endotoxin | Validierung | Standzeit | Stabilität | Vergleichsstudie
Abstract
Experience with Endotoxin Control Standards
The present validation of the hold time and stability of a control standard endotoxin (CSE) shows how such a validation can be performed in a pharmaceutical company. It was investigated whether the hold time/stability of the dissolved CSE was affected during handling in the laboratory for 120 minutes at room temperature and then storage in the refrigerator at 2–8 °C for a total of 28 days. For all parameters it could be shown that the storage conditions used did not have a negative influence on the quality of the CSE. It could therefore be concluded that after reconstitution, the CSE can be used for 28 days after storage in the refrigerator at 2–8 °C and subsequent use at room temperature for a maximum of 120 minutes per working day. However, the validation revealed a problem. The reaction time of the blank (Limulus amebocyte lysate (LAL) water) in the turbidimetric method was five times smaller than that of the smallest standard (0.005 EU/ml) when distributed over all three batches, making the corresponding run invalid. Due to this deviation an intensive root cause investigation was started. For this purpose, a comparative study with materials from two manufacturers was carried out using 10 runs each. Based on the comparative study it could be shown that the test kit from manufacturer B for endotoxin determination is a more suitable quality for the site.
Korrespondenz:
Patrick Koch, CSL Behring Lengnau AG, Industriestrasse 11, 2543 Lengnau BE (Switzerland), E-Mail: patrick.koch@cslbehring.com
Zusammenfassung
In der vorliegenden Validierung der Standzeit und Stabilität eines Kontrollstandard-Endotoxins (KSE) wird gezeigt, wie eine solche Validierung in einem Pharmaunternehmen durchgeführt werden kann. Es wurde untersucht, ob die Haltbarkeit/Stabilität des gelösten KSE bei der Handhabung im Labor während jeweils 120 Minuten bei Raumtemperatur und anschließender Lagerung im Kühlschrank bei 2–8 °C während insgesamt 28 Tagen beeinträchtigt wurde. Für alle
