EMA has published a draft guideline on the use of phthalates as excipients in human medicinal products. The guideline establishes new Permitted Daily Exposure (“PDE”) values for the following phthalates that are among the most commonly used as excipients in medicinal products:

  • dibutyl phthalate: 0.01 mg/kg/day
  • diethyl phthalate: 4 mg/kg/day
  • polyvinyl acetate phthalate: 2 mg/kg/day

The guideline also concludes that data currently available for cellulose acetate phthalate and hydroxypropyl methylcellulose acetate phthalate do not indicate that their presence in human medicinal products constitutes a potential risk for human safety.

As from the final adoption of the guideline, applications for the marketing authorization of new medicinal products will be expected to comply with the PDE values of the guideline.  Already authorized medicinal products will have a maximum of three years to comply with the new PDE values.

Importantly, the guideline states that its recommendations should be considered precautionary measures and that daily exposure values above the PDE values “could be accepted as exceptions, on a case-by-case basis, taking into consideration the intended patient population, the disease seriousness and the presence or not of alternative treatment options.”

It is noteworthy that the use of dibutyl phthalate and other phthalates in non-medicinal products is already subject to restrictions under the REACH Regulation on chemicals and other EU product specific legislation.

Interested parties may submit comments on the draft guideline until October 31, 2013.  Comments should follow the template document provided in the draft guideline and should be sent by email to SWP-H@ema.europa.eu.