New Regulations on Paediatric Development
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What is a PIP?
PIP stands for Paediatric Investigation Plan. It is a dossier describing the research and development programme for a product in order to generate data to support authorisation for the treatment of children. It forms part of your European Marketing Authorisation Application (MAA).
What is it for?
The PIP is submitted to the Paediatric Committee (PDCO) at the EMEA to gain approval of the proposed paediatric development plan. It is one of the measures contained in the European "Paediatric Regulation" (Regulation 1901/2006 on medicinal products for paediatric use) which has the objective of improving the quality and range of clinical data in paediatric populations without exposing children to studies which are not deemed necessary or valid by the regulatory authorities.
Do I need a PIP?
If you are developing a new chemical entity or a new indication/formulation for an authorised product still under patent, and you plan to submit your MAA in Europe after 26th July 2008, this MAA must contain the results of the studies described in a PIP and agreed by the PDCO, unless a deferral or a waiver has been granted. This means you must think about paediatric development at an early stage of your clinical development - you can't just tag it on to the end - so that completion of the paediatric studies can be incorporated into your regulatory strategy. Guidelines suggest that an appropriate time would be no later than the completion of the pharmacokinetic studies in adults.
Some products may qualify for a waiver. This might be because it is indicated in a condition that does not occur in children, such as Alzheimer's or Parkinnson's, or because of limited efficacy, safety or therapeutic advantage in paediatric patients. Some may also qualify for a deferral of the need to provide paediatric data, for example if recruitment to the planned studies is likely to be slow.
An application for a PUMA (see below) will also need to comply with a PIP.
When the MAA is submitted it will be checked against the PIP and if it is deemed to be non-compliant it will not qualify for the market exclusivity incentives provided in the Regulation.
Can I use the same PIP in my NDA?
No, but there is a similar system in the US under the Pediatric Research Equity Act. An NDA for a new API, indication, dosage form or regimen or route of administration must include paediatric data and the nature of these data are agreed in advance with the FDA.
What is a PUMA?
PUMA stands for Paediatric Use Marketing Authorisation. It is a marketing authorisation covering only therapeutic indications in the paediatric population (or some age groups), including the appropriate strength, pharmaceutical form or route of administration for a given product.
What is it for?
If a currently approved product does not have an indication specifically for paediatric use, a PUMA can be submitted for paediatric indications, formulations and dosage recommendations. It is one of the measures contained in the "Paediatric Regulation" (Regulation 1901/2006 on medicinal products for paediatric use) which has the objective of improving the quality and range of clinical data in paediatric patients. The PUMA is intended to stimulate the development of off-patent products for use in the paediatric population.
How is it different from an ordinary MA?
It isn't really. You still need to demonstrate quality, safety and efficacy. Rather more thought should be applied to formulations, as different subsets of the paediatric population (which ranges from pre-term to 18 years) will have different needs.
A PUMA is eligible for the Centralised Procedure as well as the more customary Decentralised (DP) or Mutual Recognition Procedures (MRP). Normally, the application would be submitted as a hybrid, biosimilar or combination (Article 10(3); 10(4); and 10b of Directive 2001/83/EC respectively). The generic, well-established use or informed consent articles would not be appropriate.
You will also need a PIP (see above) as part of your PUMA, although if you choose the DP or MRP the PIP must be agreed by the Reference Member State, and not PDCO.
Do I need a PUMA?
It is entirely up to you. There is no obligation to apply for a PUMA, but there are incentives.
Does the FDA operate a similar programme?
Yes. The Pediatric Research Equity Act includes the provisions of what was previously the Best Pharmaceuticals for Children Act. The FDA has a list of approved APIs for which it would like to see an approved paediatric indication. The FDA sends a 'Written Request' to the licence holder asking them to submit data. A company can prompt a Written Request by submitting a Proposed Pediatric Study Request.
Need help?
Don't worry! Contact Akos. An experienced regulatory professional will be able to advise on the best strategy for your product. If you like, we can also co-ordinate a protocol assistance meeting with the Scientific Advice Working Group, write the PIP, submit it to the PDCO and negotiate approval, all in accordance with agreed project timelines.
To discuss your regulatory questions with Akos please contact us:
Tel: +44 (0)1582 766 339
Email: regulatory@akos.co.uk