Paediatric Investigation Plan (PIP)
The development of medicinal products for the paediatric population is an important consideration to be undertaken at an early stage in drug development, as there are some challenges such as recruitment of paediatric patients, ethical considerations, effective dosage as well as suitable pharmaceutical form development and complex regulatory requirements.
A Paediatric Investigation Plan (PIP) is an integral part of the Marketing Authorisation Application (MAA) in Europe: The results of the paediatric studies agreed upon in the PIP have to be included in the MAA. A PIP is also required when applying for a new indication, pharmaceutical form or route of administration for an already authorised medicinal product. Compliance with the agreed PIP will be checked either during the assessment of the MAA or after the authorisation of the medicinal product, depending on the agreed timelines.
The Paediatric Regulation (EC) No 1901/2006, Article 16 (1.), requires sponsors to submit a PIP not later than upon completion of the human pharmaco-kinetic studies. However, there is an option to apply for a deferral, which allows the applicant to delay development of the medicinal product in children until for example, safety and effectiveness of the medicinal product have been demonstrated in adults.
Even when studies are deferred, the PIP should include details of the planned paediatric studies and the timelines for their completion.
A PIP waiver is submitted to exempt an applicant from the obligation to conduct clinical trials in paediatric patients when developing a medicinal product in cases where the medicinal product is not needed or is not appropriate for children. This situation may arise when the indication only affects the adult population, the medicinal product is likely to be ineffective or unsafe for children, or the medicinal product does not provide a significant therapeutic benefit over existing treatments for paediatric patients.
The evaluation and approval of a PIP follows a multi-step procedure:
Following submission, the application is assessed by the Paediatric Committee (PDCO) which provides its opinion to the applicant. If necessary, the applicant may request re-assessment of the opinion. Once the PDCO issues its final opinion, the final decision on the application is made by the European Medicines Agency.
In February 2023 EMA launched a pilot programme to test a 'stepwise PIP'. This applies to exceptional cases where crucial information needed to define relevant parts of the plan is not yet available at the time of the initial PIP application (e.g., whether a clinical study for a specific age group is necessary, and if so, the details of the study). This type of PIP consists of a partial development programme only. However, the development of a full PIP (once the crucial information becomes available) is still required.