Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Make off-patent drugs available to children: Regulatory approaches in Europe and the US ***

Dr. Stephanie Schwarz (Abschlußjahr: 2010)

Summary
Language: English
For many medicinal products, safety and efficacy for paediatric use have never been properly established. In the past, pharmaceutical companies often refrained from testing their products in the paediatric population because of ethical concerns, high complexity of clinical trials and financial considerations.
Because of a significant lack of both paediatric labeling information and age-appropriate formulations, off-label or unlicensed use is common in paediatric drug therapy. Paediatric doses are often extrapolated from adult data, and this approach may involve an increased risk for inefficacy and/or unpredictable adverse reactions; the paediatric organism is still developing and thus a childs drug response may differ from that of an adult. The lack of paediatric information in drug labels has been a rising concern and consensus has developed that children also should have access to safe and effective medicines. This includes off-patent medicines, where paediatric development is even less attractive than within the on-patent sector, mainly due to expected low return on investment because of a combination of high costs for clinical development, small markets, and generic competition.
To remedy this situation in respect of off-patent medicines, regulatory instruments have been established in both the EU and US that aim at improving paediatric labelling of medicines and increasing number and availability of off-patent medicines, preferably in age-appropriate formulations, appropriately tested in children. In the US, a Written Request mechanism to initiate study programmes for studies into off-patent drugs was introduced with the Best Pharmaceuticals for Children Act (BPCA) in 2002. Europe followed in 2006, when the Paediatric Regulation established the Paediatric Use Marketing Authorisation (PUMA) intended for medicinal products for exclusive use in children, and EU Paediatric Worksharing, a tool that is not limited to off-patent medicines, but nevertheless offers chances for an improvement of paediatric labelling of off-patents, based on e.g. previously unpublished study results.
All these regulatory instruments have been in place for several years now but what has actually been achieved so far? An analysis based on data made publicly available by EU and US authorities, respectively, shows that as of August 2010, despite a number of ongoing projects, overall progress is slow in both regions. While EU Paediatric Worksharing, despite not being the primary tool for increasing the availability of off-patent drugs for children, has led to improved paediatric labelling for a number of off-patent medicines and even to new paediatric indications for some of them, the more specific instruments have not yet led to more medicinal products authorised for children. So far, no PUMA has been granted, and to date only three percent of all PIP applications submitted to EMA were for clinical studies that may eventually lead to a PUMA. At present, there is a total of nine projects funded under FP7; as these projects typically take several years to be completed, paediatric marketing authorisations based on results from the respective studies are not to be expected in the near future. The situation is similar in the US, where at present, there are several NIH/NICHD funded clinical studies into off-patent drugs ongoing; however, these efforts have not led to a paediatric labelling change so far.
The analyses led to the overall conclusion that the instruments in place have not proven too effective so far; the final breakthrough has yet to happen. The projects that have been started do not cover too many off-patent drug substances and indications where there is paediatric need, thus being only a drop in the ocean of medicines that had to be studied in order to meet all paediatric therapeutic needs, and even these projects will take significantly more time until they may actually show results. Maybe combined EU and US efforts, in terms of cooperation or even combined instruments, might eventually lead to more success in finally meeting childrens needs and significantly improving paediatric drug therapy by expanding the therapeutic armamentarium with medicines adequately developed and tested for paediatric use.
Pages: 55,
Annexes: 8 pages