Best practices for development of pediatric medicines in the EU
What became evident with the introduction of the Paediatric Investigation Plan (PIP) procedure in Europe is that Regulatory Experts need to keep a careful eye on all product development activities ongoing and understand how they might interact with the (potential) PIP.
Here are some best practice tips for you to consider when thinking or working on your next PIP:
One of the most common tasks we worked on is a detailed strategic planning related to development and update of PIPs. These are our high-level lessons learned:
Start early: No matter if it is an initial PIP discussion (that should occur around adult Phase 1 study completion) or submission of Request for modification of agreed PIP or compliance check preparation, you should incorporate PIP discussions into any parallel discussions on adult indications;
It will take longer than you initially thought: Calculate the most “pessimistic” timeline scenario, if possible. It is simply because one part of the PIP procedure is dependent on you and the other is not and it is completely out of your control. The mandate of the EMA’s Pediatric Committee (PDCO) is to explore any possible ways to gather more information on use of medicines in children. This often means that they will ask you to go one step further in thinking about your development plans and this might result in multiple PIP modification procedures which all require time to be done, submitted and agreed by the PDCO.
SPC extension is a long and diverse process: Supplementary Protectoin Certificate (SPC) extension doesn’t occur automatically and not so fast. Our calculations and experience showed us that it takes around 18 months from Last Subject Out (LSO) of the last study listed in your PIP to prepare everything (write Clinical Study Report, submit for indication extension and SmPC update and prepare packages for patent extension) for submission to the National Patent Offices (NPOs) that grant the SPC extension per every EU country. Then, each NPO evaluates SPC extension for their country and issues the SPC extension. Time for this evaluation can take from 1 month to 24 months. So, if you were to calculate the overall process for SPC extension you may end up with approximately 3.5 years. This time must be calculated backwards from your patent expiration since the SPC can only be “attached” to the currently valid patent, i.e. not to the expired patent. The figure below outlines schematically this calculation with figurative deadlines.
*LSO= Last Subject Out; NPO= National Patent Office; MAA= Marketing Authorisation Application; CT= Clinical Trial; SPC= Supplementary Protection Certificate; PIP= Paediatric Investigation Plan
In order to appropriately manage all PIP procedures, especially if there are more than one PIP (i.e. for different conditions and indications) and/or more than one product under development within the company, companies needed to assign especially dedicated pediatric teams. Among them are also Regulatory Experts called e.g. Regulatory Pediatric Experts or similar. It quickly became clear that this special allocation of expertise is possible only in big companies while Small and Medium Enterprises (SMEs) required usually external support in these matters.
In any case, there is a definitive need for experts who are taking care of the PIPs within a company. Of paramount benefit is that these experts have previous experience working with the PDCO and PIPs.
One of the tasks we were invited to perform was to re-submit PIP after it has been rejected by the PDCO. Reason for rejection was inadequate company presentation of information and inadequate adjustments after the PDCO’s comments. The company had no previous experience in preparing PIPs and it resulted in approximately 8-10 months of lost time to adequately prepare and agree on this PIP by the PDCO.
While the “not so new” Paediatric Regulation opened a new horizon for development of innovative medicines for children it also was matched with increased requirements in time and resources to perform all required activities. Having an overview of all opportunities the Regulation brought, together with the best practices explained above should help you navigate this filed more easily.
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