The EU’s long-awaited reform of its pharmaceutical legislation (the ‘Pharma Package’) has now been formally adopted by the Council and is in the final stages of the legislative process. Once published in the Official Journal, most provisions will apply after a transition period (expected around 2028). The reform consolidates and replaces the current frameworks, including the Paediatric Regulation (EC) No 1901/2006 and the Orphan Regulation (EC) No 141/2000.
For companies developing medicines for children or rare diseases, two areas which we focused on are Paediatric Investigation Plans (PIPs) and Orphan Designations (ODs). The impact brought by these changes is significant and will require earlier and more strategic planning by Sponsors.
Impact on Paediatric Investigation Plans (PIPs)
Several important changes are expected:
- Earlier submission timing: PIPs (or waiver requests) will generally need to be submitted before the start of clinical safety and efficacy studies in adults, rather than after adult pharmacokinetic studies as is often the case today. This shifts paediatric strategy much earlier in development.
- Introduction of Initial / Stepwise PIPs: The reform formalises more flexible, evolutionary PIPs. Sponsors can submit an initial PIP covering what is known at an early stage and update it later as data emerge. This is particularly useful for novel mechanisms of action or indications.
- Mechanism-of-action (MoA) based waivers: Waivers will become harder to obtain where a product’s mechanism of action is considered relevant to a paediatric disease or condition in the same therapeutic area, even if the adult indication does not occur in children. This aligns the EU more closely with approaches such as the US RACE Act and is expected to increase the number of paediatric studies, especially in oncology and other areas with shared pathways.
- Extended obligations: The PIP requirement will also apply to new strengths of authorised products (in addition to new indications, forms or routes of administration).
- Committee structure: The Paediatric Committee (PDCO) is expected to be abolished, with paediatric expertise integrated into working groups under the CHMP.
- Rewards: The current +2 years of orphan market exclusivity linked to completion of an agreed PIP will be removed. The 6-month Supplementary Protection Certificate (SPC) extension for completing a PIP remains available for both orphan and non-orphan products. There will also be a new obligation to place a product with a paediatric indication on the market in relevant Member States within two years of approval of that indication.
Impact on Orphan Designations (ODs)
The orphan framework is being substantially restructured:
- Reduced baseline exclusivity: Standard orphan market exclusivity will fall from 10 years to 9 years.
- Breakthrough orphan products: A new category of ‘breakthrough’ orphan medicines (those for conditions with no authorised treatment and that deliver a clinically relevant reduction in morbidity or mortality) will receive 11 years of market exclusivity.
- Product-based rather than indication-based exclusivity: Separate exclusivity periods for each new orphan indication of the same active substance will no longer be available. Instead, exclusivity is anchored to the first orphan marketing authorisation. Additional orphan indications can extend the exclusivity by 1 year (up to a maximum of 2 years total), provided the application is submitted at least 2 years before the end of the existing period.
- Removal of the paediatric reward: The current +2 years of orphan exclusivity for completing a PIP will disappear.
- Limited duration of the designation itself: Orphan designations will be valid for only 7 years (extendable in certain cases of ongoing promising studies), rather than remaining in force indefinitely.
- Committee structure: The Committee for Orphan Medicinal Products (COMP) is expected to be abolished, with orphan expertise moved into CHMP working groups.
- Well-established use products: Orphan products authorised on the basis of bibliographic data will receive only 4 years of exclusivity.
Practical implications for sponsors
- Earlier integration of paediatric and orphan strategy is essential. Decisions on PIP timing, waiver strategy and orphan designation now need to be made well before the start of pivotal adult studies.
- Exclusivity planning becomes more complex. Companies will need to model the new 9- or 11-year baseline carefully and decide whether and when to pursue additional orphan indications to secure the limited extensions.
- Transitional rules matter. Many existing designations and marketing authorisations will continue under the old rules for a period, but new applications submitted after the new legislation applies will fall under the revised framework.
- Scientific advice remains critical. Early dialogue with the EMA on both PIP design and orphan criteria (especially “breakthrough” status) will help de-risk programmes.
Conclusion
The Pharma Package retains the core principles of the PIP and orphan systems but introduces earlier obligations, reduced or restructured rewards, and greater flexibility in some areas (notably stepwise PIPs). For rare-disease and paediatric programmes, the changes reward breakthrough innovation while tightening the overall exclusivity landscape. Sponsors who adapt their development and regulatory strategies early will be best placed to navigate the new rules.