orphan drug designation
TRANSCRIPT
Devanand Jillapalli, MD
Office of Orphan Products Development (OOPD)
U.S. Food and Drug Administration
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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.
www.fda.gov
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Rare Diseases
• More than 6,800 rare diseases
• Affect an estimated 25-30 million Americans
https://www.genome.gov/27531963/ Accessed August 3, 2016
www.fda.gov
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Orphan Drug Act
Created by the Congress
in 1983 to motivate
industry to develop
drugs and biologics for
rare diseases by
providing financial
incentives.
4www.fda.gov
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OOPD Designation Programs
• Orphan Drug Designation
• Rare Pediatric Disease Designation
• Humanitarian Use Device Designation*
*Not discussed in this presentation
www.fda.gov
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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
www.fda.gov
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Orphan Drug Designation Program
www.fda.gov
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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.
www.fda.gov
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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)
www.fda.gov
10www.fda.gov
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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
www.fda.gov
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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?
www.fda.gov
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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.
www.fda.gov
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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.
www.fda.gov
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Orphan SubsetIf 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).
www.fda.gov
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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
www.fda.gov
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Orphan SubsetExamples 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
www.fda.gov
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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)
www.fda.gov
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Same Drug & Clinical SuperiorityIs 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
www.fda.gov
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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
www.fda.gov
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Rare Pediatric DiseaseDesignation Program
www.fda.gov
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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.
www.fda.gov
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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.
www.fda.gov
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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:
http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/ucm2005525.htm
– Draft guidance, Rare Pediatric Disease Priority Review Vouchers Draft Guidance for Industry
www.fda.gov
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Orphan Products Clinical Trial Grants Program
www.fda.gov
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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
www.fda.gov
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Orphan Products Natural History Grants Program
www.fda.gov
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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
www.fda.gov
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OOPD Resources and Contact Information
www.fda.gov
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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:http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/HowtoapplyforOrphanProductDesignation/default.htm
www.fda.gov
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OOPD Contact InformationOOPD Website: www.fda.gov/orphan
Program Contact
Orphan Drug Designations Jeff Fritsch (301-796-8682)[email protected]
Jim Bona (301-796-8673)[email protected]
RPD Designations Jim Bona (301-796-8673)[email protected]
HUD Designations Jim Bona (301-796-8673)[email protected]
OPD Grants Mary Limon (301-796-8689)[email protected]
PDC Grants Eric Chen (301-796-6327)[email protected]
NHS Grants Mary Limon (301-796-8689)[email protected]
Still have questions?Email us at [email protected] | Call us at 301-796-8660
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