CONFIDENTIAL Assessment of Micro-Biological Stability of common Vehicles Bev Halliday May 2012

CONFIDENTIAL 3 Objectives To determine the acceptable shelf-life of Vehicles –Background Previous Practice Previous stability work Changed Facility and water type Assumptions –How the Stability trial was set up How many vehicles ? What storage temperatures ? What Vessel type to use ? What tests to run ?, Media to use, incubation time etc ?

CONFIDENTIAL 4 What we did Water type – Purified water from in-house system Vehicles –1.0% w/v aq MethylCellulose (400 cp) –1.0% w/v aq HPMC (1500 cp) –0.5% MethyCellulose, 0.5% Tween 80 –1.0% w/v aq CMC, medium viscosity Storage Temperature –Cool (2 to 8 degrees C) –RT ( 15 TO 25 degrees C)

CONFIDENTIAL 5 What we did (cont) Vessel type – 10 litre Polypropylene (considered worse case) Plates –Nutrient Agar plates –Looked at colony counts at time zero and after storage at upto 14 days. All plates were incubated at 37 degrees for 14 days (and read daily).

CONFIDENTIAL 6 –With all the vehicles investigated at both storage conditions, the majority of all samples taken showed no colonies found. –For all vehicles there were the odd sample plate that showed colonies (usually >50 counts), but were clear the following day, they were discounted as suspected to be isolated contamination in sampling. Results

CONFIDENTIAL 7 For the standard vehicles investigated, prepared with purified water from our in-house system prepared following out SOP methods, are stable for upto 14 days storage. The change in Facility and water purification system has enabled longer term storage of our vehicles. Conclusions

CONFIDENTIAL 8 Discussion points