IGMPI India

European Medical Agency (EMA) has published a new Guideline entitled as “Guideline on stability testing for applications for variations to a marketing authorisation”. This guideline will be applicable as of July 2014. It replaced the current "Guideline on stability testing for applications for variations to a marketing authorisation" from 2005 and is intended as extension of the "Guideline on stability testing of existing active substances and related finished products.

The new Guideline contains detailed variations scenarios for Type II variations and the stability data to be respectively submitted. For Type I variations, the text refers to the provisions laid down in the "Guidelines on the details of the various categories of variations..." which sufficiently specify the requirements with regard to stability studies. The following Type II variations are described:

•  Change in the manufacturer of a starting material / reagent / intermediate used in the manufacturing process of the    API or change in the manufacturer of the active substance
•  Changes in the manufacturing process of the API; other geographical source of the herbal active substance
•  Changes in immediate packaging of the active substance
•  Changes in the composition of the excipients in the finished product
•  Changes in coating weight of oral dosage forms or change in weight of capsule shells
•  Change in concentration of a single-dose, total use parenteral product, where the amount of the active substance    per unit dose remains the same
•  Replacement or addition of a manufacturing site for part or all of the manufacturing process of the finished product
•  Change in the manufacturing process of the finished product (..) that may have a significant impact on the quality,    safety and efficacy of the medicinal product
•  Introduction of a non-standard terminal sterilisation method in the manufacturing process of the finished product
•  Introduction or increase in the overage that is used for the active substance
•  Change in the batch size of the finished product
•  Change in immediate packaging of the finished product
•  Change in shape or dimensions of the container or closure (immediate packaging) of the finished product
•  Change in pack size of the finished product

In most of the situations, the following stability data must be submitted: long term and accelerated conditions of 6 months; at least two batches of the finished product should be of pilot scale. Three pilot batches are partly necessary - i.e. for active substances known to be unstable. The Annex I of the Guideline defines the term stability: an active substance is considered as stable if it is within the initial specifications when stored at 25°C/ 60 % RH or 30°C/65% RH, respectively, (2 years) and 40°C/75 % RH (6 months). Annex II sets the rules to the postponement of the expiry date of the medicinal product and the extension of the retest period of the active substance in those cases where favorable real time data are available.