Detaljerad miljöinformation

Follitropin alfa is a recombinant human protein expressed by stable transfected Chinese Hamster Ovary (CHO) cell lines by recombinant DNA technology under controlled culture conditions. It is harvested from the cell culture medium and is purified using several chromatographic steps.

Follitropin alfa is a recombinant glycoprotein essentially similar to the naturally occurring human hormone FSH, and is therefore likely to follow the same pathways in patients: proteolysis followed by degradation to simple sugars and aminoacids. A minor portion undergoes internalization followed by lysosomal degradation as a consequence of binding to specific cell surface receptors. As for the endogenous human hormone, follitropin alfa is absorbed in a biologically active form only when it is administrered by a parenteral route and a minor bioactive quantity is excreted into the urine.

Follitropin alfa is one of two active drugs in Pergoveris, the other being lutropin alfa.

Based on the Pergoveris prescribed dosage, each patient receives daily 150 IU (11 µg) follitropin alfa + 75 IU (3 µg) lutropin alfa for a maximum of 5 weeks. The Phase 1 calculation of the Predicted Environmental Concentration (PEC_SW) is based on this exposure and on the formula contained in the "Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use" (CHMP/SWP/4447/00).

PEC_SW (mg/L) = (DOSE_AS × F_PEN)/(WASTEW_INHAB × DILUTION)

Where: PEC_SW = Predicted environmental concentration for surface water calculated in Phase I; DOSE_AS = Maximum daily dose of the active substance consumed per inhabitant; F_PEN = Fraction of a population receiving the active substance; WASTEW_INHAB = Amount of wastewater per inhabitant per day; DILUTION = Dilution factor.

The cumulative dose of the active ingredients (0.014 mg) and the default values from the guideline, i.e., F_PEN (0.01), WASTEW_INHAB (200 L inh^-1d^-1) and DILUTION (10) were inserted in the above equation. As a consequence, a PEC_SW of 0.00007 µg/L is obtained. Such a value is notably lower than the action limit (0.01 µg/L) set in the guideline and no other environmental concerns are apparent. Moreover, the drug product is intended for treatment of a relatively small patient population (i.e. stimulation of follicular development in adult women with severe FSH and LH deficiency) and the amount of the active components that could eventually reach the environment is expected to be very small.

If any of the active aubstances should reach the environment during therapeutic use, dilution and rapid catabolism by common environmental microflora would rapidly lead to its utilisation by normal metabolic pathways and its elimination.

According to the European Medicines Agency guideline on environmental risk assessments for pharmaceuticals (EMA/CHMP/SWP/4447/00), vitamins, electrolytes, amino acids, peptides, proteins, carbohydrates, lipids, vaccines and herbal medicinal products are exempted because they are unlikely to result in significant risk to the environment.

Even though biomolecules are exempted, they should still be regarded as biologically active.