Regulations introduced four years ago in Europe to encourage research into medicines for children have lead to important therapeutic breakthroughs for pediatric patients.  Yet concerns also have been raised about how well the system works.

The European law, similar to one passed in the United States, provides drug sponsors an additional six months of marketing exclusivity for a drug in return for studies into the safety and effectiveness of the medicine in pediatric populations. The regulations have resulted in an increase in the number of applications to develop pediatric treatments, new pediatric formulations and important labeling changes, including pediatric dosing recommendations for high blood pressure and fungal infection medicines.

Yet according to a recent report in the Financial Times, critics believe the pediatric program could prevent drug developers from investing in important treatments for adults. Medical researchers, including pediatric cancer specialists, also maintain the system fails to focus research on areas of unmet medical need, and instead has resulted in drug sponsors adding pediatric information to drugs developed for adults in lower priority areas.

Concerns also have been raised about the financial incentives provided under the law. Pfizer, which plans to introduce a chewable, grape-flavored form of its blockbuster anti-cholesterol drug Lipitor in Europe in November, has asked for an additional six months of marketing exclusivity in European Union countries in return for developing the child-friendly version of the drug. That additional time, which would postpone generic competition until May 2012, could be worth about $800 million to Pfizer, according to figures prepared for the Financial Times by healthcare data consultancy IMS.

According to the Financial Times report, the Pfizer case will spark new debate about whether there should be upper limits placed on the incentives available in Europe under pediatric trial regulations, which will be reviewed by the European Commission in 2017, since few expected the system would provide drug companies with the level of revenue that could be earned by Pfizer. The report noted that the additional tests Pfizer has conducted have not led to significant changes in the drug’s authorized use in children.

“The regulations have been a big advance in developing medicines for children, but throw up some issues which it may be time to revisit,” Alasdair Breckenridge, chairman of the U.K.’s Medicines and Healthcare Products Regulatory Agency, told the newspaper.

The biopharmaceutical industry also has raised concerns. Companies now incorporate pediatric testing as a routine part of drug development, yet drug sponsors report they feel constrained by the European system. In a survey conducted earlier this year by the European Federation of Pharmaceutical Industries and Associations, drug sponsors indicated the pediatric regulations are overly bureaucratic and have lead to marketing delays. The survey found that pediatric development and trials are more expensive per subject than adult development and that they risk diverting money from global development of drugs for adults.

Members of the European Medicines Agency, however, have supported the regulations, saying they have led to an increase in clinical research for drugs used in children. A 2010 EMA report found the pediatric regulation has stimulated high-quality research and has produced valuable clinical trial data for the industry.

“It is already clear that the regulation has created real awareness of the need for conducting appropriate pediatric clinical trials and for developing suitable formulations for use in children,” the report concluded. “It has become the norm to include the development of a medicinal product in children within the development in adults, where relevant.”

Karyn Korieth