Dear Experts,
I am currently facing a challenge from a regulator for a class III (CE) medical device. Issue is in italics font and my response is in bold. Can someone please advise if justification is acceptable?
With respect to the sterility test applied to product X:
The submission includes a 2010 report of the validation of the sterility test, using the direct inoculation method. Each filled syringe contains 3.6 mL Solution A. The validated method is ‘the contents of one syringe [is] divided equally into two 100 mL volumes of media’, Soybean Casein Digest Medium and Fluid Thioglycollate Medium. The validation was deemed successful in that the growth of each test organism was assessed as comparable in test and control.
Please:
a) justify the continued use of the sterility test method described in the 2010 validation report
The sterility test method as per USP 33R Sterility Tests <71> Method Suitability did not change.
b) explain the inconsistent results observed in the validation studies for bioburden test method and sterility test method. The results of the bioburden validation study suggest that the results of the sterility test validation study may not be valid in that:
There is still no obvious reason why a greater level of antimicrobial activity was observed in the Total Aerobic Microbial Count and Total Yeast and Mold Count as compared to in the Sterility test. Again, the procedures/ diluents/ media/ etc. are quite different between the tests, so it’s possibly just a difference in these parameters that is affecting the microbial response.
Thank you.
Medwise
I am currently facing a challenge from a regulator for a class III (CE) medical device. Issue is in italics font and my response is in bold. Can someone please advise if justification is acceptable?
With respect to the sterility test applied to product X:
The submission includes a 2010 report of the validation of the sterility test, using the direct inoculation method. Each filled syringe contains 3.6 mL Solution A. The validated method is ‘the contents of one syringe [is] divided equally into two 100 mL volumes of media’, Soybean Casein Digest Medium and Fluid Thioglycollate Medium. The validation was deemed successful in that the growth of each test organism was assessed as comparable in test and control.
Please:
a) justify the continued use of the sterility test method described in the 2010 validation report
The sterility test method as per USP 33R Sterility Tests <71> Method Suitability did not change.
b) explain the inconsistent results observed in the validation studies for bioburden test method and sterility test method. The results of the bioburden validation study suggest that the results of the sterility test validation study may not be valid in that:
-for the bioburden test method validation: B. subtilis and C. albicans could not be recovered from a 1 in 100 dilution of Solution A prepared in ‘phosphate buffer with 5g/L lecithin and 40 mL/L Tween 80’
-for the sterility test method validation: satisfactory evidence of growth of challenge organisms was stated to be observed after 1.8 mL of Solution A was added (initially) to 100 mL SCDB and 1.8 mL of Solution A was added (initially) to 100 mL FTM. Challenge organisms included B. subtilis and C. albicans.
There is no obvious reason why we observed a greater level of antimicrobial activity in the Total Aerobic Microbial Count and Total Yeast and Mold Count as compared to in the Sterility test, but because the procedures/ diluents/ media/ etc. are quite different between the tests, it’s not entirely unusual that there are be differences in microbial response.
In a first project it was included the 1:10 product dilution, which was found to inhibit growth of B. subtilis and C. albicans. The decision to test at 1:100 and 1:1000, and to incorporate neutralizers into the diluent, was made and the 1:1000 dilution was found to be successful. There is still no obvious reason why a greater level of antimicrobial activity was observed in the Total Aerobic Microbial Count and Total Yeast and Mold Count as compared to in the Sterility test. Again, the procedures/ diluents/ media/ etc. are quite different between the tests, so it’s possibly just a difference in these parameters that is affecting the microbial response.
Thank you.
Medwise