Careful evaluation of paediatric medicines is necessary to ensure they meet the unique needs of child patients. In the EU, pharmaceutical firms must adhere to strict Paediatric Investigation Plan (PIP) guidelines from the European Medicines Agency. A PIP outlines the tests needed at each stage of development. It facilitates collaboration with regulators to address pediatric patient needs. By navigating this systematic approach, companies have the opportunity to develop safe and effective medicines that can improve children's health for years to come.

Ensuring the safety and efficacy of medicines tailored for paediatric use demands a precise and systematic approach. At the heart of this process lies the Paediatric Investigation Plan (PIP), a tool designed to guide the collection of necessary data through paediatric studies, and if necessary, quality, and nonclinical studies. By adhering to the European Medicines Agency's (EMA) rigorous guidelines, pharmaceutical companies can navigate the path to obtaining market authorisation for their developed drugs in the paediatric population within the European Union (EU).

A PIP is a development plan sponsors must implement to collect necessary data through quality, nonclinical and paediatric studies, supporting the authorisation of paediatric medicines. The scientific part of the application, structured per EMA's well-defined PIP guidelines, serves as the core deliverable.

For most marketing authorisation applications (MAA) for new medicines, a PIP is mandatory. This requirement also applies for some line extensions when adding new indications, forms, or routes of administration to authorised medicines with intellectual property rights. The PIP must be regularly updated via a modification procedure once agreed upon.

Waiver and Deferrals

Sponsors can request waivers from the Paediatric Committee (PDCO) when paediatric medicine development is unnecessary or inappropriate, especially if it might be unsafe or ineffective for children, or when diseases solely affect adults. Waiver requests are categorised as:

  • Class waiver: For conditions affecting only adults.
  • Full waiver: Applicable to all paediatric age groups and indications.
  • Partial waiver: Pertaining to specific paediatric age groups and indications.

During PIP deferrals, sponsors may delay some or all measures until sufficient evidence demonstrates the medicine's safety and efficacy in adults, preventing unnecessary approval delays for adult patients. However, sponsors must still provide details of the planned paediatric studies and their associated timelines.

Scientific Advice for PIP

Although scientific advice is not mandatory, it can greatly contribute to the development of a comprehensive PIP, particularly in relation to clinical study designs; paediatric scientific guidance from EMA is free.

EMA advises against submitting scientific advice requests and PIP applications simultaneously to avoid any potential conflicts or complications.

The submission

A PIP must be submitted "not later than upon completion of human pharmacokinetic studies in adults." Early dialogue with the Paediatric Committee is encouraged especially for medicines being developed in paediatric-only conditions. The PIP should specify timing and measures for assessing quality, safety, and efficacy in all paediatric age groups from birth to less than 18 years of age, addressing age-specific needs and potential formulation adaptations.

Additionally, it should provide an overview of the disease, its diagnosis, treatment, and differences between children and adults. It should also include a summary of the existing quality, non-clinical and clinical data. The PIP assessment process typically takes 9 to 12 months from submission to decision.

Compliance Check

A compliance check (CC) verifies that some or all studies/measures agreed in a PIP have been completed in accordance with the PIP decision, including compliance with the agreed timelines. If required, it is possible for sponsors to request that a PIP compliance check be conducted before submitting their MAA.

Alternatively, the CC may be conducted as part of the MAA validation process. Sponsors are strongly recommended to apply for the CC before submission of the MAA to avoid delays during the validation phase. This check verifies that all the measures mentioned in the PIP decision, including the timelines for the conduct of the studies or collection of the data, have been completed in accordance with the key elements specified in the PIP decision.

Conclusion

The PIP is a pivotal element in EU paediatric medicine development and authorisation. Complying with the EMA guidelines and PIP requirements ensures the safety and efficacy of paediatric treatments. The PIP streamlines data collection and fosters early dialogue with regulatory authorities, ultimately benefiting the paediatric population.

Fulfilling the PIP obligations for your MAA submission can be a challenge. For over 15 years NDA have successfully supported sponsors in navigating global paediatric regulations. Contact us to explore how our specialised expertise can help ensure that your application addresses all the paediatric investigation requirements.

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