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Orphan Drug Designation


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Overview of FDA’s Orphan Drug Designation Program and qualification criteria for drug and disease.

Published in: Health & Medicine
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Orphan Drug Designation

  1. 1. Devanand Jillapalli, MD Office of Orphan Products Development (OOPD) U.S. Food and Drug Administration
  2. 2. 2 OOPD Mission To promote the development of products, including drugs, devices, biologics, and medical foods, for the treatment, diagnosis and prevention of rare diseases and conditions.
  3. 3. 3 Rare Diseases • More than 6,800 rare diseases • Affect an estimated 25-30 million Americans Accessed August 3, 2016
  4. 4. 4 Orphan Drug Act Created by the Congress in 1983 to motivate industry to develop drugs and biologics for rare diseases by providing financial incentives.
  5. 5. 5 OOPD Designation Programs • Orphan Drug Designation • Rare Pediatric Disease Designation • Humanitarian Use Device Designation* *Not discussed in this presentation
  6. 6. 6 OOPD Grant Programs • Orphan Products Clinical Trials Grants Program • Orphan Products Natural History Grants Program • Pediatric Device Consortia Grant Program* *Not discussed in this presentation
  7. 7. 7 Orphan Drug Designation Program
  8. 8. 8 Orphan Drug Designation Program Provides orphan status to drugs and biologics* which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders. *“Drugs” in this presentation includes both drugs and biological products.
  9. 9. 9 Incentives Associated With Orphan Drug Designation • Tax Credits for 50% of Clinical Trial Costs • Waiver of Marketing Application User Fee (PDUFA): >$2M • Eligibility for 7-Year Marketing Exclusivity • Now associated with additional financial “incentives” under the Affordable Care Act (e.g., pharmaceutical fee, 340B pricing)
  10. 10. 10
  11. 11. 11 Orphan Drug Designation Process Sponsor CDER Center for Drug Evaluation and Research CBER Center for Biologics Evaluation and Research Step 2 : Submit Marketing Application (NDA or BLA) Disapproval or Complete Response Letter Approval to Market Product Office of Orphan Products Development Step 1 : Submit Orphan Drug Designation Issue Deficiency or Denial Letter Grant Designation Receive financial incentives OOPD Step 3 : Orphan Exclusivity Determination
  12. 12. 12 Review of a Designation Request Orphan drug designation based on disease or condition, not on indication. • Five critical questions: – What is the disease or condition the drug is treating, diagnosing or preventing? – Is this disease or condition rare? – If this disease or condition is not rare, is there orphan subset demonstration? – Is there a description of the drug and scientific rationale? – Is it “same drug” as a previously approved drug for same use?
  13. 13. 13 What is the Disease? What is the disease or condition the drug is treating, diagnosing or preventing? • Challenging and can evolve • Depends on a number of factors, assessed cumulatively, including: • pathogenesis of the disease or condition; • course of the disease or condition; • prognosis of the disease or condition; • and resistance to treatment.
  14. 14. 14 Is the Disease Rare? Is the disease or condition rare? • “Rare disease” for drugs is generally* defined by the Orphan Drug Act as: – Disease or condition that affects <200,000 people in the US • Therapeutic drugs: prevalence < 200,000 • Vaccines, diagnostic and preventative drugs: number of persons drug will be administered to < 200,000 per year *Prevalence can be >200,000 (or if applicable incidence >200,000 per year) if no reasonable expectation that the cost of drug development and marketing will be recovered in future sales of the drug in the US.
  15. 15. 15 Orphan Subset If disease or condition occurs in > 200,000 persons (non- rare): • A demonstration of an “orphan subset”: use of the drug appropriate in orphan subset due to one or more properties of the drug, but inappropriate in the remaining persons with such disease or condition. • “Orphan subset” meets the regulatory threshold of 200,000 in the US. Note: orphan subset cannot be considered without reference to the drug, specifically to the property(ies) of the drug (next slide).
  16. 16. 16 Orphan Subset Property(ies) of the drug that limit its use to the orphan subset but preclude its use in the remaining persons with the non-rare disease or condition: • Mechanism of action: For example, use of targeted therapy (e.g., antibody-specific or biomarker-based drug) • Toxicity of a drug limits its use to patients refractory to, or intolerant of, other less toxic treatments • Previous clinical experience may be used to identify an appropriate orphan subset
  17. 17. 17 Orphan Subset Examples of subsets of non-rare conditions arbitrarily chosen without reference to the drug: • Clinical trial eligibility: subset defined only on basis of inclusion/exclusion criteria in a clinical trial to support a specific indication for use of a drug • Sponsor’s plan to study the drug for a select indication within the non-rare disease • Particular disease grade or stage • Any clinically distinguishable subset of persons with a particular disease or condition • Price: high price of drug may render it unlikely to be used in broader population with the disease
  18. 18. 18 Drug Description & Scientific Rationale • Description of the drug – Active moiety • Scientific rationale: to establish a medically plausible basis for the use of the drug for the rare disease or condition • What is Scientific Rationale based on? • Clinical data, case study reports • Acceptable animal model(s) of human disease • In vitro data (with proposed mechanism of action and pathogenesis of disease when no adequate animal model of human disease exists)
  19. 19. 19 Same Drug & Clinical Superiority Is it “same drug” as a previously approved drug for same use? • “Same drug” defined in 21 CFR 316.3(b)(14); does not mean identical. • If composed of a small molecule, it contains same active moiety as previously approved drug. • If composed of macromolecules, it contains the same principal molecular structural features of previously approved drug. E.g.,: two protein drugs are same if the only differences were due to post-translational events, minor differences in amino acid sequences, different glycosylation patterns, etc. • When seeking designation of a drug that is the “same” as an already approved drug for the same use, must provide a plausible hypothesis of clinical superiority
  20. 20. 20 Same Drug & Clinical Superiority “Clinical superiority” demonstrated in one or more of following ways: • Greater effectiveness • Greater safety • Major contribution to patient care To get 7-years of market exclusivity, regulations require sponsors to demonstrate product is actually clinically superior
  21. 21. 21 Rare Pediatric Disease Designation Program
  22. 22. 22 Rare Pediatric Disease (RPD) Designation Program • Under Section 529 to the Federal Food, Drug, and Cosmetic Act, and amended by the Advancing Hope Act of 2016, FDA awards priority review vouchers to sponsors of rare pediatric disease product applications that meet certain criteria. • OOPD implements the “rare pediatric disease” designation component of this authority.
  23. 23. 23 What is a Rare Pediatric Disease? A rare pediatric disease is a disease that meets each of the following criteria: • The disease is a serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years, including age groups often called neonates, infants, children, and adolescents. • The disease is a rare disease or condition, within the meaning of Section 526.
  24. 24. 24 Eligibility Criteria for a Voucher • RPD designation is not required, nor sufficient, to receive a voucher. • To receive a voucher, application for the drug must meet all eligibility criteria. For additional information: – FDA OOPD website: RareDiseasesConditions/ucm2005525.htm – Draft guidance, Rare Pediatric Disease Priority Review Vouchers Draft Guidance for Industry
  25. 25. 25 Orphan Products Clinical Trial Grants Program
  26. 26. 26 Orphan Products Clinical Trial Grants Program Awards and administers grants for clinical studies of drugs, biologics, devices, and medical foods • Current fiscal year alone: 68 grant applications received; awarded 21 research grants totaling more than $23 million over the next four years • Current funding levels: • Phase 1 studies: up to $250, 000 per year for 3 years • Phase 2 and 3 studies: up to $500,000 per year for 4 years • For additional information, see OOPD’s website
  27. 27. 27 Orphan Products Natural History Grants Program
  28. 28. 28 Orphan Products Natural History Grants Program NEW grant program to fund targeted natural history studies for rare diseases • Approximately $2M in FY 2017 to award 2-5 grants • Funding levels: • Prospective Natural History Studies: up to $400,000 per year for up to 5 years • Retrospective or Survey Natural History Studies: up to $150,000 per year for up to 2 years • For additional information, see OOPD’s website
  29. 29. 29 OOPD Resources and Contact Information
  30. 30. 30 Orphan Drug Regulations and Resources • 21 Code of Federal Regulations (CFR) Part 316 – Subpart C – Designation of an Orphan Drug – Subpart D – Orphan Drug Exclusive Approval • Proposed and Final Rules – 2013 Final Rule – 78 Fed. Reg. 35117 (Jun. 12, 2013) – 2011 Proposed Rule - 76 Fed. Reg. 64868 (Oct. 19, 2011) – 1992 Final Rule - 57 Fed. Reg. 62076 (Dec. 29, 1992) – 1991 Proposed Rule - 56 Fed. Reg. 3338 (Jan.29, 1991) • Additional information available at: DiseasesConditions/HowtoapplyforOrphanProductDesignatio n/default.htm
  31. 31. 31 OOPD Contact Information OOPD Website: Program Contact Orphan Drug Designations Jeff Fritsch (301-796-8682) Jim Bona (301-796-8673) RPD Designations Jim Bona (301-796-8673) HUD Designations Jim Bona (301-796-8673) OPD Grants Mary Limon (301-796-8689) PDC Grants Eric Chen (301-796-6327) NHS Grants Mary Limon (301-796-8689) Still have questions? Email us at | Call us at 301-796-8660