Paediatric Investigation Plans.
An early strategy pays dividends.
What is a Paediatric Investigation Plan?
In January 2007 the Paediatric Regulation came into force in the EU. Its objective is to improve the health of children in Europe by facilitating the development and availability of medicines for children aged 0 to 17 years. It is applicable to all new medicines and any new indications, pharmaceutical forms, or routes of administration.
It is an important regulatory milestone to overcome as any application for a Marketing Authorisation Application (MAA) for a new product will not be validated unless the Marketing Authorisation Holder (MAH) can evidence an approved PIP or PIP waiver.
The Paediatric Committee (PDCO) is the EMA’s scientific committee responsible for review of all PIP waiver applications.
The Regulation stipulates that PIP/waiver applications should be submitted unless duly justified “not later than upon completion of the human pharmaco-kinetic (PK) studies”.
What incentives does the EMA offer?
The EMA offers the following incentives for the development of medicines in children:
- If the results of studies included in a PIP are included in the product information, then a medicine is eligible for extension of the supplementary protection certificate by six months.
- For products with an orphan designation the incentive is an additional two-year market exclusivity.
- Scientific Advice and Protocol Assistance related to paediatric development is free of charge. Please see our page on Scientific Advice for more information on how Arriello may support you with this service.
- Medicines developed specifically for children that are already authorized but are not protected by a patent or supplementary protection certificate are eligible for a Paediatric-Use Marketing Authorisation (PUMA). If a PUMA is granted, the product will benefit from 10 years of market protection as an incentive.
How can we help you with your PIP Strategy?
As referenced above, it is incredibly important to think about your PIP strategy sooner rather than later.
Not overcoming this regulatory hurdle in good time can ultimately lead to a delay in MAA filing and therefore a potential delay to commercialization in the EU.
Arriello’s PIP consultants can assist sponsors with reviewing their development plan and proposing an optimal PIP strategy that satisfies regulators whilst attempting to not be over-burdensome on the company. Our experts will review the proposed adult indication(s) and product to advise on the possibility of a class waiver or product specific waiver covering all or subsets of the paediatric population.
If waivers are not feasible, they can prepare and propose a PIP strategy covering all relevant paediatric subsets considering the following possible measures as applicable:
- Paediatric formulation requirements.
- Nonclinical studies.
- Modelling and simulation studies
- Extrapolation studies
- Clinical studies
The strategy will also cover the timing of any proposed measures, including the possibility of requesting deferrals.
What is required for the Preparation and Submission of a PIP or PIP Waiver Application?
PIP and PIP waiver applications are submitted electronically and typically consist of the following documents:
- Covering Letter.
- Letter of authorization (if applicable).
- Application Form (Part A).
- Scientific Document (Parts B-F) – This is the main scientific document that gives all the necessary background information and proposals along with any scientific justifications.
- Annexes (any literature referenced, Investigator Brochure, scientific advice, etc).
- Key Elements Form – a summary form used to summarise key elements for each proposed measure/study in the scientific document. This acts like an informal “contract” between the MAH and EMA on the agreed measures.
Your Arriello Regulatory Lead will work with you and our PIP experts to ensure the submission is completed to a mutually agreed timeline.
Upon finalization of these documents Arriello can submit the PIP application to EMA through the EMA gateway and can act as EMA and PDCO liaison on behalf of sponsors.
For sponsors that find it difficult to implement any element of a PIP (e.g they may struggle to recruit in a study) or if something changes that means it’s no longer feasible, then there is a possibility to apply for PIP modification.
As with initial PIP applications, Arriello can support sponsors with both the strategic and operational submission aspects of a modification application
PIP Compliance Check.
The EMA perform compliance checks on PIPs to check that the some or all of the measures agreed in the PIP have been undertaken as agreed and on time. It is best practice to have a compliance check prior to submitting a MAA to avoid issues at validation.
Furthermore, upon completion of all PIP measures a compliance check is needed for the EMA to confirm all the measures have been adhered to as agreed, and to be eligible for any potential incentives as described above.
Arriello’s regulatory team can support with both full and partial compliance check submissions as required.
The UK PIP requirements following Brexit.
Since Brexit the UK MHRA has essentially adopted the EU requirements for PIP and PIP waiver submissions. For sponsors lucky enough to have an EMA PIP decision agreed before 1st January 2021, these will have automatically been adopted as UK-PIPs and no re-submission is required.
PIP submissions after 1 January 2021 will need to be submitted and assessed independently by the MHRA.
If the UK is an important market for your company, it’s important to not forget the UK PIP requirements as again this could delay any UK commercialization plans.
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