Studies Of TOC Method Used In Cleaning For Sterile APIs Manufacturing Equipments

In order to improve the utilization rate of manufacturing equipments,there are usually more than one products manufactured on the same production line,which may increase the risk of cross contamination.By using an effective cleaning method,residue attached on the equipments can be removed,and the possibility of cross contamination can be reduced.This is also one of the basic GMP requirements in pharmaceutical industry.This article is based on a production line that manufactures two sterile APIs(Cefotaxime Sodium and Ceftriaxone Sodium),by calculating the residue max permitted limit with two different methods,together with risk assessment,Ceftriaxone Sodium was determined as the high risk target compound.In this study,typical sterile APIs manufacturing equipments were used,by comparing the results obtained by TOC and HPLC method,a TOC standard curve was established,the linearly dependent coefficient for the regression equation of which can reach up to 0.9998.Sampling method was also studied.By comparing the TOC recovery rates of two different swabbing methods,method 2(turn around method)was selected,the recovery rate of which can reach up to 83.5%.Furthermore,the hardest cleaning position of the equipment was determined with Vitamin B2 experiment(fluorescent test),on this basis,equipment CIP procedure was optimized.With this current CIP procedure,60 min can be saved per batch,and 5 more batches can be produced per month.By this advantage,1.1 million RMB profit is expected each year.There are obvious advantages by using TOC method,e.g.rapid,especially suitable for consecutively sterile API production.This study can be referred by other companies in pharmaceutical industry.