1. Condition vs. indication Chairs & Introduction: Nathalie Rampal, European Medicines Agency (EMA); Genevieve Michaux, Covington & Burling, Belgium Rapporteur: Gesine Bejeuhr, Pediatric Special Interest Area Community (Ped SIAC), DIA & vfa Research-Based Pharmaceutical Companies, Germany

2. Condition vs. indication Ralf Bax/Paolo Tomasi explained briefly the Policy on the determination of the condition(s) for a PIP/Waiver PUBLISHED TODAY!!!!! Scope of Framework with classification how to find the condition and where the limits are and what is PDCO is looking at Policy does not define but serves as a backbone

3. Condition vs. indication 1.Usually the adult indication is the starting point (because data will be collect in this indication, MEDDRA classification), PDCO will check the consistency of the proposal compared with mechanism of action 2. PDCO looks at properties of the drug and check the condition level (other MEDDRA level) 3. what is the paediatric need – if there is a need for a specific indication within the condition then no broad waiver would be issued, in most cases companies agree to conduct studies 4. Scientific background for PDCO opinion Request takes into account which data can be collected in the adult indication and the paediatric development need to related in a way that an extrapolation of safety data is still possible Pilot phase of one year

4. Condition vs. indication Nathalie Rampal, European Medicines Agency (EMA); gave an overview of the complex scientific discussion that ended in a decision that can be viewed as a case to be used in future Company: Product = Diagnostic to detect CAD; only in adults PDCO: Product intended to detect myocardial perfusion anormalities Quote of the court goes beyond the PDCO’s practice EMA: The decision is not limited to diagnostics but is seen as a generally applicable decision. The applied science might be different but the mechanism how to approach the matter should be the same.

5. Condition vs. indication Genevieve Michaux, Covington & Burling, Belgium Gives a caveat: The European Court of Justice rules on specific facts and does not automatically issue „case law“. Another court case on a therapeutic indication is needed to confirm that this decision also applies to therapeutic medicinal products. Companies choose an adult indication based on the commercial potential of a medicinal product. This does not imply any circumvention of any law but is simply a business decision. In article 8 “indication” is mentioned and the court decision should be limited to article 7 (EMA clarified that they put it to the court but it was not taken into the decision. They performed exercises with examples of therapeutical products.)

6. Condition vs. indication Discussion There is no way to pose a general question to the court. Another court decision seems very difficult because it costs lots of money and time. Court neglected urgent decision: Companies should ask for a PIP with deferral to be able to file the adult indication. But the PIP could not contain a provision that it will fall after the court decision. It needs to be based on science and needs to be modified after the court decision in the usual procedure. Agreed PIP – in the past several indications in one PIP, now the policy allows to split PIPs. Would it be possible to get a compliance statement for one of the indication. The idea was to allow companies to get the chance for a reward earlier. Decision on a case by case basis. In theory: the new PIPs are purely administrative and no new scientific decisions

7. Condition vs. indication Discussion Policy recommends to come for pre-submission meetings. Engage early in discussions with EMA and to find the best way for your development. Oncology – same product might be employed in totally different indications; ICH E11 guideline allows for trials in the paediatric oncology if no other treatment option is available; CHMP has authorised medicinal products based on biological data (biomarkers?) Therapeutical area could be a wide area: what are the limits for PDCO? Nausea – difficult example, depends on mechanism of action, e.g. nausea caused by anticancer treatment than no PIP for general nausea Klaus Rose example: Post menopausal osteoporosis – osteoporosis class waiver revoked, osteoporosis PIP Diabetes: insuline condition = for both Type 1 and Type 2 but an oral antidiabetic condition = Type 2

8. Condition vs. indication Discussion New EMA Policy on determination of conditions states: PIPs and waivers are agreed for conditions. EMA is waiting for comments from European Commission and from industry How will the pilot phase work? The new policy will be applied to all future procedures and it will be reassessed after one year (together with comments) EMA Policy on Scope of PIP decisions: Once a PIP is agreed on one indication within a certain condition then all other indications within this condition are considered to be covered by the PIP. In case of uncertainties ask for pre-submission or ask your Paediatric coordinator at EMA.