EMA Policy on Changes in Scope of Paediatric Investigation Plan Decisions

The European Medicines Agency (EMA) has published guidance explaining how changes to the scope of Paediatric Investigation Plan (PIP) Decisions should be managed when a medicine’s development plans or regulatory submission strategy changes. The policy addresses situations where existing PIP Decisions no longer match the scope of a planned regulatory application and explains when PIP Decisions may need to be linked, modified or reduced in scope.

The policy aims to ensure that the PIP Decision submitted with a regulatory application is consistent with the conditions, indications, pharmaceutical forms and routes of administration covered by the application.

What is a Paediatric Investigation Plan (PIP)?

A Paediatric Investigation Plan (PIP) is a plan relating to the development of a medicine for use in children. Under the Paediatric Regulation, a PIP Decision must be included in certain regulatory applications for marketing authorisation and for new indications, routes of administration or pharmaceutical forms.

A PIP Decision sets out the agreed paediatric measures that need to be completed during medicine development.

Why Can a PIP Decision Need to Change?

During medicine development, an applicant may change its regulatory strategy. For example, several conditions may initially be planned separately but later be submitted simultaneously. Alternatively, a PIP Decision may cover several conditions while the first regulatory submission concerns only one.

This can result in an existing PIP Decision no longer matching the scope of the planned regulatory application. The EMA policy explains how such situations can be addressed.

PIP Decisions and Regulatory Applications

For applications under Article 7 of the Paediatric Regulation, when several indications are developed simultaneously and included in the same regulatory submission, a single comprehensive PIP Decision should cover the relevant conditions.

For authorised medicines under Article 8, the PIP Decision should cover existing and new indications, as well as relevant pharmaceutical forms and routes of administration.

However, a Decision does not need to include conditions, routes or pharmaceutical forms that will only be the subject of a later, separate regulatory submission.

Linking PIP Decisions

Linking may be required when separate PIP Decisions together correspond to a single regulatory submission.

In this situation, one Decision must be modified to include a cross-reference to the other Decision. The measures in both Decisions must be completed for the PIP to be considered completed.

The EMA will not accept independent PIP Decisions without the required cross-reference when they correspond to a single regulatory application or applications submitted at the same time.

Splitting the Scope of a PIP Decision

Splitting may be relevant when a PIP Decision covers several conditions but the applicant intends to submit only some of those conditions.

For example, if a Decision covers conditions A and B but the first regulatory submission concerns condition A only, the applicant may request modification of the Decision to remove condition B. This can help avoid delaying PIP completion because of measures relating to a condition that is not part of the intended submission.

The excluded part becomes void. A PIP Decision cannot simply be divided into two or more Decisions. Instead, the existing Decision may be modified by excluding measures that are not relevant to the intended regulatory submission.

A separate PIP application may subsequently be submitted for the excluded condition if it is intended to support a later regulatory application.

Indication Versus Condition

Applicants may need to determine whether a new indication is already covered by a condition in an existing PIP or waiver Decision.

If EMA confirms that the new indication belongs to the same condition, the existing PIP or waiver Decision may be sufficient for validation of the new indication application.

If the indication relates to a condition not covered by the existing Decision, the applicant needs to apply for a new PIP or waiver covering that condition.

Applicants should submit the PIP or waiver request early enough to obtain the Decision before validation of the marketing authorisation application.

New Pharmaceutical Forms or Routes of Administration

A new indication may be covered by an existing PIP Decision when it falls within the same condition.

However, a new PIP Decision is required when a subsequent regulatory submission concerns a new pharmaceutical form or new route of administration. The new Decision will include the relevant new and existing forms and routes and cross-reference the previous Decision.

Changes in Conditions

If an existing Decision covers conditions A and B but the applicant later plans a first regulatory submission for conditions A and C, a modified Decision covering A and C is required.

Measures relating to condition C may be added, while condition B may be removed from the modified Decision.

Practical Examples

If separate PIP Decisions exist for conditions A and B and the applicant later decides to submit both conditions simultaneously, a consolidated Decision covering both conditions is required. One of the Decisions must be modified to include a cross-reference to the other before the regulatory application is submitted.

The EMA encourages applicants to submit a PIP covering both conditions upfront when simultaneous development is planned.

Where a PIP Decision covers conditions A and B but the first submission concerns condition A only, the applicant may request modification to remove condition B. If condition B is subsequently developed, a separate PIP application may support a later regulatory submission. If development of condition B is discontinued, a new PIP Decision is not necessary.

Deferral of PIP Measures

The policy also covers situations where some or all PIP measures have been deferred.

Where a later regulatory submission involves another condition and a different PIP Decision, subsequent submissions may need to include both relevant Decisions where the conditions have been authorised.

Confirmation Through IRIS

Applicants can request confirmation through IRIS on whether an indication is included within a condition covered by an agreed PIP or waiver Decision. Following review, EMA communicates the outcome to the applicant.

Reference

European Medicines Agency – European Medicines Agency policy on changes in scope of paediatric investigation plan (PIP) decisions