December 30, 2003

Re: Current USP Sterility Test <71>

Dear Colleague,

We are keeping an eye out for you. For example, a harmonization process has been under way for the last several years for the USP sterility test which has been relatively unchanged for 20 years. As an update, we would like to summarize the portions of the sterility test that

(a) have not been harmonized, (USP, only until further notice) and (b) have been harmonized, (USP, European, British, and Japanese Pharmacopeias).

We will attempt to keep our clients informed as to the approval or non-approval of these various tests by our review of upcoming editions of the Pharmacopeia Forum in the year 2004.

Table 1. Non Harmonized

1. Anything related to devices.
2. Growth promotion allowed as “periodic” testing of different batches prepared from the same lot of dehydrated medium.
3. Use of alternative strains for Staphylococcus aureus, Pseudomonas aeruginosa, and Clostridium sporogenes.
4. Storage of media for one month in unsealed containers, performing growth promotion within 2 weeks of use. Storage for 1 year is acceptable if using tight containers and growth promotion is performed within 3 months of use.
5. Rinsing fluids A, D and K.
6. Alternative thioglycollate medium.

Table 2. Harmonized

The following portions of the sterility testing chapter have been harmonized.

1. Growth promotion for bacteria is 3 days and 5 days for fungi.
2. Bacteriostasis & Fungistasis test is now called the “validation test”.
3. Different minimal amounts (weight or volume) have been promulgated per container of sterile liquids, insoluble topicals, solids and devices.
4. For membrane filtration, do not exceed a washing cycle of
   
   5 x 200mL.
   
   
5. All incubation periods are for 14 days.
6. It is recommended that the following incubation temperatures for soybean casein digest broth be changed from 20 - 25⁰C to 25 – 30⁰C.

Table 3. USP <61> and a Variety of Informational Chapters

As we are doing for the Sterility chapter, we will also attempt to keep our clients aware of the approval or changes in the current Chapter on Microbial Limits <61> and on the changes and/or acceptance of General Information chapters as follows:

Title

1. <1072>Disinfectants and Antiseptics
1. <1111>Microbiological Quality of Non-Sterile Products
2. <1112>Applications of Water Activity
3. <1116>Microbiological Evaluation of Clean Rooms and other Controlled Environment
4. <1117>Microbiological Good Laboratory Practices
5. <1209>Chemical and Physicochemical Indicators and Integrators
6. <1222>Terminology Sterilized Products-Parametric Release
7. <1223>Validation of Alternative Microbiological Methods
8. <1225>Validation of Compendial Methods
9. <1227>Validation of Microbial Recovery
10. <1231>Water for Pharmaceutical Purposes

Please feel free to contact us on these or other matters dealing with the Microbial Attributes of sterile or non-sterile articles as used worldwide.

Respectfully,

Daniel L. Prince, Ph.D.
President