Opportunities to improve the PIP outcome during the PIP submission process

by Linsey Reavie

The process of preparing a PIP can be lengthy and challenging, with numerous potential pitfalls along the way. In this article, we present you an overview of all critical steps for the successful preparation and submission of your PIP – outlining for you when to act to save precious time and effort.

An evaluation of the paediatric investigation plan (PIP) by the European Medicines Agency (EMA) Paediatric Committee (PDCO) takes place over 120 days (Figure 1). Briefly, after submission, the application is reviewed by the PDCO for completeness (validation period). The PIP then undergoes two rounds of discussion by the PDCO at Day 30 and Day 60, at which point a summary report, list of outstanding issues/request for modifications or an opinion is issued. The Applicant has roughly 3 months to respond to the Day 60 request. Once the updated application is submitted, a similar review procedure takes place with Day 90 and Day 120 PDCO discussions. If an agreement is not reached between the Applicant and the PDCO, the applicant can be invited for an oral explanation to further discuss the application before the final PDCO opinion is issued (Day 120). If a positive opinion is not achieved, the Applicant has the opportunity to request a re-examination, lasting roughly 30 days, at the end of which the final opinion is issued by the PDCO.

During this process, there are several key opportunities to interface with the EMA, which will help to optimise the application and increase the likelihood for a positive outcome from the PDCO.

Below are some of the important interactions between the applicant and the PDCO office:

• Pre-submission interaction

• Validation

• Day 30 summary report

• Day 60 list of outstanding issues/request for modification

• Day 90 summary report

1) Pre-submission interaction

During this process, the Applicant has the opportunity to submit a list of questions for discussion with the PDCO. This interaction can be conducted by a scheduled teleconference or through written correspondence. In either case, the PDCO team will review the questions, and in some cases a draft PIP application, to provide adequate feedback. This type of interaction provides feedback on the Applicant’s paediatric plans, the presentation of the PIP application and often how the PDCO will likely view the global paediatric program for a given product (e.g. if the same product is planned to be used in more than one indication). The latter view‑point can be very important to inform the Applicant’s overall strategy for PIP submission, which is particularly relevant if multiple PIP applications for the same product will be submitted.

2) Validation

Validation occurs within 30 days of the PIP submission. While this is usually only performed to verify that all required documents have been submitted with the application, this can be a time where the PDCO communicates that certain key information is missing from the documents. Thus, it is another opportunity to clarify unclear or outstanding issues with the PDCO.

 
3) Day 30 summary report

The Day 30 summary report is the first communication from the PDCO which consists of review and feedback from the paediatric co-ordinator, rapporteur and peer-reviewer. This document also contains a summary of the PDCO discussion about the application (although there are no formal requests yet). This report supplies the Applicant with a good idea on the position of the PDCO and what the likely requests will be in the Day 60 report. Many times, this document offers key suggestions on how the Applicant can modify the application to address the requests that will come in the Day 60 report.

 
4) Day 60 list of outstanding issues/request for modifications

The Day 60 list of outstanding issues/request for modifications is the outcome of two rounds of PIP application review. This document details the official list of outstanding issues/request for modifications that the PDCO is requesting from the Applicant in order to consider a positive outcome for the application. At this stage, the Applicant should be prepared to address all requests in the application. If the Applicant has previously interacted with the PDCO, either during the pre-submission stage or after the Day 30 summary report, often the Applicant has a good idea how to respond to these requests. This could also be a good time to touch base with the paediatric co-ordinator for further clarification of the PDCO requests, if anything may be unclear.

 
5) Day 90 summary report

Similar to the Day 30 summary report, the Day 90 summary report contains review and feedback from the paediatric co-ordinator, rapporteur, peer-reviewer, and a summary of the PDCO discussion about the updated application (although there are no formal requests). Again, this summary will give the Applicant a good idea on what the likely position of the PDCO will be on the PIP application. If there are issues that remain, this is the time to discuss with the PDCO on how to modify the application to ensure a successful outcome before the Day 120 opinion. This could occur through written communication with the paediatric co-ordinator as well as during an oral explanation.

While the PIP evaluation process can be lengthy, it is a very dynamic process that enables many important interactions with the PDCO that, when followed-up closely, will surely increase the likelihood of a positive PIP opinion at Day 120.

 
Biopharma Excellence has been involved in assisting clients throughout all stages of the PIP process and would be pleased to assist you in any aspect that would be of interest. Do not hesitate to contact us for more information.