The UK's Medicines and Health care products Regulatory Agency has unveiled a new initiative to encourage the development of medicines designed specifically for use in children, ahead of the European Union Regulation which is unlikely to be finalized before 2006. The UK initiative will produce concrete short- to medium- term gains and raise pharmaceutical industry awareness of the need to take action now to ensure products are appropriately labeled and formulated for pediatric use, said the MHRA (part of the Department of Health).
The plan includes: strongly encouraging companies to provide much better pediatric clinical trial data for new and current medicines; providing better information on the use of medicines in children in Patient Information Leaflets; publishing, for the first time, a separate British National Formulary for Children; and investing part of the extra L100 million ($183.4 million) announced in the budget to promote research into medicines for children through new research networks coordinated by the UK Clinical Research Collaboration.
'A strong message to pharma'
Health Minister Lord Warner said the strategy sought to 'give a strong message to pharmaceutical companies to focus on the needs of children when developing new medicines. Health professionals need the latest information so that they can make the right choices about the medicines and treatment for their younger patients, and that is why the new British National Formulary for Children is so important,' he added.
Until relatively recently, there has been 'widespread reluctance' to conduct pediatric drug studies, due to a number of factors including ethical concerns, practical difficulties and commercial considerations. As a result, prescribers have had no option but to prescribe unlicensed and off-label medications, often in unsuitable formulations, and this may result in reluctance to use newly-introduced drugs, medication errors, inappropriate dosing (both too high and too low), inadequate efficacy and unforeseen adverse events, says the MHRA.
There is now no legislative requirement for firms to develop medicines for use in a particular patient population, but this will change with the new EU Regulation, says the MHRA.
Meantime, the UK strategy has been organized according to what is considered achievable in the short, medium and long term. The short-term strategy includes:
- access to data from studies already completed: the MHRA asks Marketing Authorization Holders which already possess data which may impact on the safe and effective use of their products in the pediatric population to submit it for evaluation and variation of the MA, as appropriate. The Association of the British Pharmaceutical Industry has encouraged its members to comply with these requests, it adds;
- regulatory incentives: the MHRA is offering pediatric scientific advice for free and fee waivers for applications to include pediatric safety information in the Summary of Product Characteristics. It will also be consulting on extending fee waivers to all pediatric-specific applications, where this is judged to be in the public interest; and
- pediatric development plans: the MHRA will systematically raise the subject of pediatric development plans at appropriate stages in product development, where there is therapeutic need; eg, when advising on product development, assessing MA applications or variations to an MA and renewing the MA.
- discontinued medicines: the MHRA will contact a company which has signaled its intention to discontinue producing a drug for which there is pediatric therapeutic need, alerting it to this use and asking what steps are being taken to ensure this need continues to be met. It will also explore the scope for securing an alternative source of supply;
- imports: the agency will identify needed pediatric medicines licensed outside the UK and invite their MA applications, focusing on medicines authorized elsewhere in the EU;
- extemporaneous formulations: work is in progress to include best-practice guidances in the new BNF for Children. The MHRA will also explore direct actions to standardize throughout the UK the quality of such formulations for pediatric use;
- off-patent medicines; the MHRA will continue to contact firms to encourage the development of appropriate pediatric formulations, focusing on a short priority list:
- on-patent medicines: a new system will monitor information on pediatric trials conducted in the EU. The summary reports produced after trial completion will be used to request further information from the companies, as appropriate;
- priorities: a list of 10-20 products will be published where efforts will be focused in the UK, stressing what is achievable in licensing terms;
- regulatory guidance: the UK is rapporteur for a guideline on pediatric pharmacovigilence and will contribute to a guideline which includes information on pediatric dose response;
- pediatric R&D: extra funds under the UKCRC will be used to bring together existing pediatric research centers for faster progress in drug development. The Department of Health is also, with stakeholders, developing plans for a managed clinical research network for medicines for children; and
- PILs: an exercise is underway at the MHRA to improve PILs' readability; it will also address the improvement of pediatric-specific information.
The government is very supportive of the EU Regulation's aims and it will be a priority for the UK's EU presidency in second-half 2005, but the legislation must strike the right balance of costs and benefits for the National Health Service and the pharmaceutical industry, says the MHRA, adding that it must also be practical and workable.