Regulatory Focus™ > News Articles > Following FDA's Lead, EMA Moves to Restrict use of Phthalates in Human Medicines

Following FDA's Lead, EMA Moves to Restrict use of Phthalates in Human Medicines

Posted 08 May 2013 | By Alexander Gaffney, RAC

The European Medicines Agency (EMA) has announced the release of a new recommendation restricting the use of phthalates or parabens as excipients in human medicines, bringing the EU closer to a similar finding issued in December 2012 by the US Food and Drug Administration (FDA).


Phthalates are essentially plasticizers. When added to other materials, such as polyvinyl chloride (PVC), phthalates cause the harder material to become more soft and pliable, allowing it to be molded into more useful shapes. Though phthalates are relatively ubiquitous in industrial applications, they have also long been used in cosmetic products, as coatings on pills, in the manufacturing process, and as drug-release modifiers in delayed-release formulations.

In December 2012, FDA moved to heavily restrict two such phthalates, Di-n-butyl phthalate (DBP) and di(2ethylhexyl)phthalate (DEHP), from pharmaceutical medicines, saying they were concerned about the numerous health risks now associated with the products. The compounds have been shown to be developmentally and reproductively toxic-at least in laboratory animals-and FDA said it will recommend against their use and require any company using either phthalate to justify its use.

Extended Scope

But as EMA's 8 May 2013 statement explains, there are more variants of phthalates than those restricted by FDA. In addition to DBP and DEHP, EU-recognized medicines commonly contain polyvinyl acetate phthalate (PVAP), cellulose acetate phthalate (CAP) and hydroxypropyl methylcellulose acetate phthalate (HPMCP).

Those phthalates have been associated with similar adverse health findings, according to EMA.

"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," it wrote. "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, DEHP and PVAP in animal studies." A review of human data did not find any indications that similar effects are present in humans, however.

As a result, CHMP has recommended-and EMA will implement-new limits on the use of phthalates in human medicines, stopping short of FDA's recommendation to abandon their use if at all possible. Under the new EMA rules, a permitted daily exposure of 0.01, 4 and 2 mg/kg/day will be established for DBP, DEHP and PVAP, respectively.

EMA added that a transition period will be put into place for those requirements, though the terms of that transition were not explained in either the agency's press statement or its phthalates guideline.

EMA: Draft guideline on the use of phthalates as excipients in human medicinal products

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

Tags: EU

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