Provide the results of stability testing of the formulation in each of the proposed marketing packs.
Describe the methodology used during stability studies; if this is identical to methodology described elsewhere in the data set, a cross-reference will suffice. If different methodology was used, the test procedures applied to the stability tests on the finished product should be validated or verified, and the accuracy as well as the precision (standard deviations) should be recorded.
The tests for related compounds or products of decomposition should be validated to demonstrate that they are specific to the product being examined and are of adequate sensitivity
The data submitted must result from both accelerated and real time studies.
The real time studies should be carried out under a range of controlled test conditions and should cover the whole shelf-life. For each study the mean temperature, the ranges of temperature and the mean relative humidity (RH) should be stated.
Test conditions for accelerated studies (stable API) should include the following:
• For Zone IV 40±2C° and 75±5% RH for six months
• For Zone II 40±2C° and 75±5% RH for three months (extended to six months for less stable API).
Real time studies should also include Zone IV climatic conditions (30C° and 70% RH)
For products containing new active pharmaceutical ingredients the ICH method mentioned on page 2 should be used.
Characteristics studied should be those in the finished product specification that are likely to be affected by storage and/or not monitored routinely at the time of manufacture, but which may be indicative of the stability/instability of the particular dosage form. These include:
• Physical characteristics (organoleptic properties, physical properties characteristic to the dosage form, important quality parameters-in vitro dissolution, moisture content).
• Efficacy of additives, such as antimicrobial agents, to determine whether such additives remain effective and unchanged throughout the projected shelf-life.
• Chemical characteristics (assay of the active ingredient, content of decomposition products, content of other ingredients).
• Chromatographic characteristics.
• Container/closure interaction with the product-study of the container and closure interaction with the contents in any case where necessary.
• Where the product is to be diluted or reconstituted before being administered to the patient (e.g. a powder for injection or a concentrate for oral suspension) “in use” stability data must be submitted to support the recommended storage time and conditions for those storage forms.