Interactive Session: Presentation of Scenarios and Q&A Linda Bowen Meredith Brown-Tuttle Amy Grant And YOU the audience

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We welcome your participation! Interactive Session Scenarios representing real-life development and life-cycle management challenges Demonstration of thought process, information gathering, and analysis of the situation Participation from the audience Demonstration of use of Regulatory Strategy Plan throughout life-cycle of the product We welcome your participation!

Special Attention to Specific Regulatory Procedures EU US Fast Track; Rolling Submissions; Frequent Agency Meetings Conditional Approval Accelerated Approval (Subpart H) Accelerated Development (Subpart E) Approval under Exceptional Circumstances Accelerated Assessment Priority Review Scientific Advice EOP1/EOP2 Meetings/ Special Protocol Assessment (SPA) Named Patient Use Single Patient IND/Physician IND Orphan designation

Data Protection Type US EU Orphan 7 years 10 years NCE 5 years 10 (CP) 8+2+1 (National/ MRP/DCP/CP) New indication 3 years +1 year marketing protection for new indication with significant therapeutic benefit Pediatric/Paediatric 6 months added to current protection 6 months SPC extension For orphan products: 2-year extension of the 10-year market exclusivity PUMA 8 + 2 years (pediatric use marketing authorization) Generic 180 days to first ANDA filer No protection

Details from the Original Applications Indication: post-surgical pain Dosage form: two separate traditional NDAs/ 505(b)(1) applications for IV and tablet dosage forms; both dosage forms approved 1986 (US) and tablet approved in 1990 via the national procedure and marketed in the UK, France and Italy (EU) No remaining patent protection/data exclusivity Underwent standard review Indicated for adults only 6

Our Goal To develop a strategy for a new dosage form, to accommodate either a new indication and/or target population, or both. The following scenarios are indicative of the types of issues you would encounter when developing a strategy. 7

The Scenarios Pediatric Indication & exclusivity Least burdensome pathway to approval Orphan Designation Priority/Accelerated Assessment/ Fast Track Risk Minimization 8

Scenario 1: Pediatric Indication Is there a possibility of a pediatric indication for post-surgical pain with the new dosage form? Other indications? Could we get 6 months of pediatric exclusivity for this product in the US and EU? How would we account for this in the regulatory plan? 9

Scenario 2: Pathway to Approval What would be the least burdensome U.S. regulatory pathway for approval of: New dosage form, but no new indication? New dosage form and a new indication? How would you support your application? 10

Scenario 3: Orphan designation Would the new indication, adult and/or pediatric neuropathic pain, support an application for orphan designation in the US and EU? What would be the benefits of orphan designation? What would be the regulatory pathway? 11

Scenario 4: Priority/Fast Track Would the new indication, adult and/or pediatric neuropathic pain, be eligible for: Priority review (US) Accelerated Assessment (EU) Fast Track Designation (US) 12

Scenario 5: Risk Management Although the earlier dosage forms were approved without a risk management plan, would the company have to provide a REMS to FDA for a new NDA or supplement? What about in Europe? 13