Biopharmaceutical companies and regulators across Europe have said that in the 10 years since the Pediatric Regulation took effect, some pediatric therapeutic areas have seen progress, though the pediatric-use marketing authorization (PUMA) has not lived up to expectations.
Overall, according to a summary of the comments received from 75 stakeholders on the consultation from last November, the European Commission noted that the reward system built into the regulation from 2007 "functions well, but some pointed to inefficiencies or questioned whether it is sufficient across all therapeutic areas, including for products that are developed exclusively for a pediatric disease and not as an add-on to an adult development."
According to the European Medicines Agency (EMA), the PUMA is a dedicated marketing authorization covering the indication(s) and appropriate formulation(s) for medicines that have already been authorized, are no longer covered by patents and are developed exclusively for use in pediatric populations.
One of the main goals of the PUMA is to stimulate research into existing products and to help transform known off-label use into authorized use that is safer and better circumscribed. Incentives to encourage applying for a PUMA were also established, including additional data and marketing protection and partial fee exemptions.
In 2014, the Commission and EMA clarified that a pediatric investigation plan for a PUMA "does not have to necessarily address all age groups," though the measure does not seem to have stimulated further industry interest.
To date, only three PUMAs have been authorized.
Many respondents agreed that the PUMA "is a disappointment," according to the Commission summary.
German regulator BfArM said it "certainly did not meet the expectations," while the Dutch government said, "the effect of the PUMA-concept is rather falling short" and the UK government described the PUMA concept as "a failure."
One of the main reasons for this conclusion, the Commission said, is "the lack of sufficient incentives to promote the research in off patent pediatric indications, especially pricing pressure for established compounds."
Or, as Novartis explained: "The fundamental issue with the PUMA concept is that even after a PUMA is granted, off-label use continues as medicinal products with the same active ingredient are available at a cheaper price and used off label in children. Critical to this issue is that there has been no effort at national level in term of pricing/reimbursement for on-label pediatric medicinal products."
Keep the PUMA?
On whether the PUMA concept should be maintained or abolished, the Commission noted that respondents did not come to an agreement.
"Some argued that despite the small number of authorized products, it may still prove beneficial to have such a specific marketing authorization. Others took the view that the concept could be shelved, especially in case alternative methods would be developed to financially support pediatric research into off-patent medicines," the summary said.
Industry group EFPIA, for instance, argued on behalf of keeping the PUMA, noting that it "would not advocate abolishing it, because if the PUMA encourages even a few new pediatric developments, it is worthwhile having it."
And Novartis explained further: "No reward will be of any value if the product is not prescribed and used. Therefore, future activities should explore other avenues that could not only add efficiency by enhancing the access of new therapies to pediatric patients, but also could be attractive for industry, such as guaranteed access to the market (e.g. new therapeutic uses in children being granted automatic inclusion in pediatric formularies, automatic guarantee of reimbursement)."
COMMISSION REPORT ON THE PAEDIATRIC REGULATION: Replies to the public consultation