Detaljerad miljöinformation

Detailed background information

According to the European Medicines Agency (EMA) guideline for Environmental Risk Assessment of pharmaceuticals (EMEA/CHMP/SWP/4447/00 corr 2), an ERA consisting of a justification for not submitting ERA studies is sufficient for certain active pharmaceutical ingredients:

"In the case of products containing vitamins, electrolytes, amino acids, peptides, proteins, carbohydrates and lipids as active pharmaceutical ingredient(s), an ERA should be provided. This ERA may consist of a justification for not submitting ERA studies, e.g. due to their nature they are unlikely to result in a significant risk to the environment. The same applies to vaccines and herbal medicinal products."

Ofatumumab is a human monoclonal antibody (IgG1) that binds specifically to a distinct epitope encompassing both the small and large extracellular loops of the CD20 molecule. The CD20 molecule is a transmembrane phosphoprotein expressed on B lymphocytes from the pre-B to mature B lymphocyte stage and on B cell tumours. The CD20 molecule is not shed from the cell surface and is not internalised following antibody binding. The binding of ofatumumab to the membrane-proximal epitope of the CD20 molecule induces recruitment and activation of the complement pathway at the cell surface, leading to complement-dependent cytotoxicity. Ofatumumab has been shown to induce appreciable lysis of cells with high expression levels of complement defence molecules. Ofatumumab has also been shown to induce cell lysis in both high and low CD20 expressing cells and in rituximab-resistant cells. In addition, the binding of ofatumumab allows the recruitment of natural killer cells allowing the induction of cell death through antibody-dependent cell-mediated cytotoxicity.

Being natural proteins, therapeutic antibodies such as ofatumumab are not excreted unchanged and do not give rise to metabolites with potential biological activity. Furthermore, even if such naturally occurring molecules such as amino acids, peptides or proteins were excreted unchanged in environmentally relevant quantities, the chemical characteristics of such molecules are such that they are highly unlikely to be environmentally persistent. Based on these observations it has been concluded that there is no need for a detailed environmental assessment of ofatumumab, and therefore, no further assessment of this drug substance has been undertaken.

Novartis therefore believes there is no appreciable risk for the environment emerging from the introduction of the additional use of ofatumumab on the EU market. It is therefore deemed unnecessary to perform a detailed environmental risk assessment.

References

EMEA/CHMP/SWP/4447/00 corr 2. Guideline on the environmental risk assessment of medicinal products for human use. London, 01 June 2006.