IGMPI India

On 27 March 2015, Eurpoean Medicine Agency (EMA) has published guideline “Elemental impurities in marketed products. Recommendations for implementation” in order to have a common approach among National Competent Authorities and to avoid an unnecessary workload due to a lot of variations, the following proposals below are made. The guideline covers elemental impurities from all possible sources (including equipment), since toxicity is independent of the source of an impurity. To ensure control for elements likely to be present at a safe level the guideline describes the principles of a risk-based approach to be followed.

The main points of the "recommendations" are as follows:

1. Each national authority should notify to the Marketing Authorisation Holder (MAH) in its own country about this new guideline according to its national information procedure.


2. During the transition period the MAH should perform a risk assessment of the manufacture of the medicinal product covering all potential sources such as active substance starting materials, reagents, catalysts, process water, excipients, equipment, container closure materials etc. It is envisaged that parts of this risk analysis may be common for several products while others may be product specific. The risk assessment should form the basis for a control strategy that is able to ensure compliance with the Permitted Daily Exposures (PDE) given in the guideline for each element. In the guideline it is indicated by the classification which elements should be included in the risk assessment based on the circumstances.


3. In cases a variation is needed, it should be categorised according the Variation Guidelines (Official Journal 2013/C 223/01) and accompanied with the documentation required there. In addition, the variation should contain a short summary of the risk assessment and the conclusions drawn.

 Products should comply with the Guideline for Elemental Impurities under the following timeframe:

New Marketing authorisation for new product (containing new active substance): June 2006.

New Marketing authorisation for product containing an established active substance: June 2006

Marketed products including new mutual recognition applications of already approved products: December 2017.