Study On The Particle Test Method Of Medical Device For GMP Application

Purpose:Referring to the fact that insoluble particle was found in medical transfusion,this paper holds the point that there are risks for sterile medical devices carrying contaminated particles.By analyzing current regulations and standards on medical device management,looking into the current status of lacking unified standards on the particle test methodologies for sterile medical devices and studying the practice of risk management,this paper studied on test methodologies for contaminated particles on sterile medical devices and acceptance criteria.This paper started from the contaminated particles on sterile medical devices and primary packaging materials as the beginning and specifically looked into medical devices for artificial heart valves,pressure valves,the implant and auxiliary sutures,cloth tube,tube,and other typical high risk sterile medical materials such as filling materials used for medical beauty industries which includes silicone implants and allogeneic costal cartilage etc..Test Method:Referring to the test methodology of insoluble particle under item 0903 section four of Chinese pharmacopoeia and GB8368-2005 standard for disposable infusion gravity infusion style,category Ⅰ(25-50μm),Ⅱ(51-100μm),and Ⅲ(100μm)was selected for experiments.Before executing the experiment,according to the standard material certificate request latex particle granularity material standard solution 500 ml was compounded for the repeated testing of particle concentration of the solution and calculation of interference recovery.Based upon the characteristic and the surface coverage of the selected sample,carried contaminated particles were extracted through mechanical vibration and surface immersion.And then applying light particles resistance tester to test the three types of particle quantity and calculating its pollution index N.That is,the number of particles in the eluent Na(na1×0.1+na2×0.2+×na3×5)and the number of particles in the blank control Nb((nb1×0.1+nb2×0.2+×nb3×5).In parallel with the particle extraction experiment,the blank control experiment should be conducted with the same method as well for result comparison.Results:According to the standard,the substance density varies by different particle categories.class Ⅰ(25-50 m):5091 particles/ml,class Ⅱ(51-100 m):736 particles/ml,and class Ⅲ(100 m):219 particles/ml.The RSD for 6 repeated experiences is controlled within 5%,which indicates that these solutions could be used for recovery experiments as well.For the interference experiment after adding 10 different types of particles,the recovery rate of was turned out to be all within the preset standard range 80-120%.The particle pollution index N of all samples selected for particle extraction experiment are all less than 90 while the pollution index N for blank control experiment are all less than 9,which meets the preset criteria as well.According to the experiment results,it is preliminarily suggested that the level receiving standard of particle pollution index of raw materials,intermediate products,finished products and packaging materials should not be higher than 90.Conclusion:Based on the GMP regulations and medical equipment management standard,following the international pharmacopoeia regulations and in consistent with drug quality risk management and procedures for official audit,the paper verifies that the proposed test methodology of contaminated particles for sterile medical devices can be applied for the enterprise.For enterprises,which manufactures sterile medical devices and packaging materials,the pollution index below 90 is recommended in consistent with GMP regulations.This criteria can be used as a reference for raw material receiving,in-process control and finished product release.Considering the fact that the sterile medical device manufacturers need to apply quality control for different manufacturing stages,such as raw materials,WIP and finished goods,which involves different risk levels,it is suggested that manufacturers can refer to the different type of samples indicated in the paper and establish their own acceptance criteria.