New recommendations on the use of phthalates and parabens as excipients in human medicines released for public consultation

8 May 2013

The European Medicines Agency has published today a Draft guideline on the use of phthalates as excipients in human medicinal products and a Draft reflection paper on the use of methyl- and propylparaben as excipients in human medicinal products for oral use, which include precautionary recommendations.

Phthalates are synthetic chemicals widely used in consumer products, including oral medicines as excipients. The most commonly used phthalates in medicinal products authorised in the European Union (EU) are dibutyl phthalate (DBP), diethyl phthalate (DEP), polyvinyl acetate phthalate (PVAP), cellulose acetate phthalate (CAP) and hydroxypropyl methylcellulose acetate phthalate (HPMCP).

Data from animal studies in the literature have shown that certain phthalates are associated with effects on reproduction and development in relation to their endocrine-disrupting properties.

A review of data by the Agency's Committee for Medicinal Products for Human Use (CHMP) has concluded that adverse reproductive or developmental effects have been observed with the phthalates DBP, DEP and PVAP in animal studies. In the absence of clinical evidence, as a precaution, the CHMP has recommended limits to the amounts of these phthalates used in human medicines. Permitted-daily-exposure (PDE) values of 0.01, 4 and 2 mg/kg/day for DBP, DEP and PVAP, respectively, are proposed. A transitional period for implementing the PDE requirements is being proposed for existing medicines.

In addition, the CHMP noted that there are presently no data indicating that the presence of CAP or HPMCP in human medicines constitutes a potential risk for human safety.

In the draft reflection paper on the use of parabens as excipients in medicinal products, which focuses on the most commonly used parabens methyl- and propylparaben, the CHMP has concluded that available data from animal studies do not point to a risk in humans. However, further data are needed to evaluate the potential risk of propylparabens in children below two years of age. The use of propylparaben-containing medicines in this age group will therefore need to be justified on a case-by-case basis, by weighing the need for treatment against the potential risk.

The guideline on phthalates and the reflection paper on parabens are open for public consultation until October 2013.