1. Obtaining Orphan Product Designation Challenges and pitfalls Marlene E. Haffner, MD, MPH President and CEO Haffner Associates, LLC mhaffner3@verizon.net

2. Requirements for Designation Population less than 200,000 in the US Reasonable consideration that the product will have utility for the stated indication Need some data – preferably clinical or animal IND helpful but not a requirement 2

3. Obtaining your designation Orphan Products “tip sheet” http://www.fda.gov/ForIndustry/DevelopingPr oductsforRareDiseasesConditions/Howtoapp lyforOrphanProductDesignation/ucm135122. htmhttp://www.fda.gov/ForIndustry/DevelopingPr oductsforRareDiseasesConditions/Howtoapp lyforOrphanProductDesignation/ucm135122. htm Aka – www.fda.gov/orphan - how to apply for orphan products designationwww.fda.gov/orphan 3

4. What is the Disease – what is a subset Define the disease Is that what you are treating or are you treating a symptom of the disease? What is a subset of a disease? A part of a disease that can be treated by the drug. However, the disease as a whole cannot be treated by the drug. WHY?? 4

5. When is a subset valid NOT because that is what you wish to study Because the drug is not useful for the “larger” disease –It is too toxic –Genetic markers make it ineffective – HER2 +, KRAS mutant – except in the subset More effective treatments for other segments of the disease – surgery for stage 1 Pediatric manifestations of a disease are valid 5

6. Not always straightforward Erythropoietin for anemia of: –ESRD –Anemia of prematurity –Blackfan Diamond syndrome Product for obesity in –Obese adults –Prader Willi syndrome 6

7. How is subsetting determined Review the disease What is the mechanism of action in the disease Are you treating the disease or a symptom of the disease – if a symptom, then is the symptom prevalence attributed only to “that” disease – post-op pain vs pain 7

8. Defining Prevalence If an oncology drug – NIH SEER Data – http://Seer.cancer.gov If a metabolic disease – published literature; Mendelian inheritance (McKusick) – www.OMIM.org If infectious disease – start with CDC Sometimes hospital discharge summaries All other – published literature – texts and current articles in peer reviewed literature Not always easy 8

9. Establishing Prevalence Use of experts – only in VERY rare diseases Discuss issues of defining prevalence in your designation request Be straightforward. The OOPD (Office of Orphan Products Development) reads the literature If a range – OOPD will assume upper end Importance in higher numbers - >100,000 9

10. Non Profitability in 7 years Has occurred only 3 times since 1983 Twice for products to treat narcotic addiction Once for a product already marketed for another indication and about to go off patent Difficult hurdle; must open books for review Developing an unprofitable product is “not the usual.” 10

11. THANK YOU ? 11

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