Fact Sheet: Stability Storage and Testing

Description:
•    Stability testing provides evidence on how the quality of a drug substance or drug product varies with time under the influence of numerous environmental factors e.g. temperature, humidity, and light. This is to establish a retest period for the drug substance or a shelf life for the drug product and its recommended storage conditions.
•    Storage conditions for a study will depend upon the product type, its recommended storage temperature (e.g. refrigerated) and the markets into which the product is to be sold.

Stability Testing Overview:
•    Every product registration must contain proof of product stability under a range of storage conditions, guidance on which is given in the ICH Harmonised Tripartite Guidelines “Stability Testing of New Drug Substances and Products Q1A (R2)”.
•    ICH guidelines recommend the testing frequency and study lengths, however the ICH guidelines also offer suggestions in reducing testing. These guidelines are intended to recommend the application of matrixing and bracketing to stability studies conducted in accordance with all principles outlined in ICH Q1A® Harmonised Tripartite guideline on Stability Testing of New Drug Substances and Products.
•    When testing at the intermediate storage condition is called for as a result of significant change at the accelerated storage condition, a minimum of four time points, including the initial and final time points (e.g. 0, 6, 9, 12 months), from a 12-month study is recommended.
•    In general all drug substances should be evaluated under storage conditions that test thermal stability and if applicable, their sensitivity to moisture. The storage conditions and the length of study chosen should be sufficient to cover supplier warehouse shipment, local storage and subsequent use.

In the Lab / at Wickham Micro Ltd:
•    At Wickham Laboratories we have 5 large stability cabinets (1 set as spare). These cabinets have undergone full qualification and are continually monitored for temperature and humidity; this is done via a hard-wired system which is alarmed and monitored 24 / 7 with any temperature or humidity changes triggering an alert to our dedicated staff.
•    For an ambient product, the general approach is three-fold: samples are tested using stability indicating assays at the initial time point and then at 3, 6, 9 and 12 months. Shelf life assessment would also potentially require 18, 24 and 36 months testing.
•    We offer three main types of study – long term (at 25°C ± 2°C / 60% RH ± 5% RH), intermediate (at 30°C ± 2°C / 65% RH ± 5% RH) and accelerated (at 40°C ± 2°C / 75% RH ± 5% RH).
•    The stability indicating assays will measure the level of active ingredient with a <5% drop considered a significant loss of activity.  Physical attributes such as colour, phase separation, caking, hardness and pH are also assessed.
•    The results of the temperature and humidity storage conditions will usually be reported within 10 working days from pull of samples after the stability time point.
•    From a microbiological view, we would also consider the preservative activity in multi-dose formulations. Sterility and bacterial endotoxin levels in parenteral products as well as microbial limits testing including Total Aerobic Microbial (TAMC) counts, Total Yeast and Mould (TYMC) counts, and absence of specified microorganisms testing may also be required depending on the product