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FDA Initiatives for Orphan Products New Lessons and Future Work FDA Seminar 2009 November 34 Copenha

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Title: FDA Initiatives for Orphan Products New Lessons and Future Work FDA Seminar 2009 November 34 Copenha


1
FDA Initiatives for Orphan Products New Lessons
and Future WorkFDA Seminar 2009November
3-4Copenhagen, Denmark
Debra Lewis, OD MBA Associate Director Orphan
Products Development Food and Drug Administration
2
PRESENTATION OUTLINE
  • Overview of the Office of Orphan Products
    Development (OOPD) and its Programs
  • Key Initiatives/Incentives - Updates/Lessons
  • Designations including Humanitarian Use Devices
  • Grants (Orphan and Pediatric Device Consortia)
  • Science of Small Trials Course Results
  • Partnerships and Future Analysis

3
A Common Perspective of The FDA
4
U.S. Orphan Drug Act Signed in 1983
  • Established the public policy that the Federal
    Government could/would assist in the development
    of products for the diagnosis, prevention or
    treatment of rare diseases or conditions.

5
What is an Orphan Product?
  • A product intended to treat a rare disease or
    condition affecting lt 200,000 persons in the U.S,
    or
  • A product which will not be profitable within 7
    years following approval by the U.S. FDA.

6
Orphan Diseases
  • Includes gt 6,000 rare diseases
  • Collectively affects approximately 25 million
    Americans
  • Frequently serious/life threatening diseases

7
The Mission of The Office of Orphan Products
Development
To assist and encourage the identification,
development, and availability of safe and
effective products for people with rare
diseases/disorders.
8
How does OOPD serve its Mission?
  • Conducts scientific and regulatory review of
    orphan product and humanitarian use device
    designation requests
  • Awards and administers grants to defray orphan
    product clinical study costs and advance
    pediatric device development

9
How does OOPD serve its Mission?
  • Serve as a liaison for the public, including
    medical product companies, patient advocacy
    groups, and other government agencies.
  • Provides patients, health care providers and drug
    sponsors with information regarding the orphan
    products and about the FDA processes
  • http//www.fda.gov/orphan

10
What the OOPD Does NOT do
  • Pricing
  • Access/Insurance
  • Intramural research
  • Pre-Clinical research

11
INCENTIVES THROUGH OOPD
  • DESIGNATION
  • of ORPHAN STATUS

12
What Products are Designated?
  • Eligibility
  • A previously unapproved drug
  • A new orphan indication for an approved drug
  • The same drug as one already approved but with
    a potential to be clinically superior
  • Designation request submitted prior to filing a
    New Drug Application (NDA) for marketing

13
Primary IncentivesOrphan-Drug Designation
  • 7-yr marketing exclusivity for first FDA
    approval of a designated drug
  • Tax credit 50 of clinical investigation
    expenses
  • Waiver of application (filing) fees PDUFA)
    1,405,500 drug

14
To Obtain Designation
  • Sponsor submits designation request to FDA/OOPD
  • OOPD Staff reviews requests
  • Criteria
  • Is population lt200,000 in the U.S. (prevalence)
  • Is there a valid scientific rationale for the use
    of the drug in the proposed indication/ disease/
    condition

15
New Joint Template Form for US and EMEA
  • Established 11/2007
  • Can be submitted for designation to US and EMEA
  • Streamlines the approach
  • Form FDA 3671 (http//intranet.fda.gov/omp/forms/i
    nternal/FDA-3671_508.pdf)

16
Successes Since 1983
  • 2932 Designation requests submitted
  • Approximately 2037 products have received
    orphan-drug designation.
  • 341 orphan-designated products have received FDA
    approval for marketing.
  • Approved orphan-designated products are available
    to treat patient populations over 15 million in
    the U.S.

17
Incentives Through OOPD
  • DEVICE Designation.
  • Humanitarian Use Device Program

18
Why HUDs and Humanitarian Device Exemptions?
  • Premarket approval applications for new medical
    devices ordinarily must show that products are
    safe and effective.
  • For very rare diseases, FDA will approve such
    devices if manufacturers demonstrate the safety
    and probable benefit to patients.

19
What is a HUD? An HDE?
  • HUD Device treating a disease affecting lt4,000
    in the US per year (incidence). If a diagnostic,
    it is the number subjected to the test per year
  • HDE refers to the exemption for a device to
    receive marketing approval based on its probable
    benefit outweighing its risk

20
How are HUDs Regulated?
  • Part 1 OOPD HUD Review Is this a device for a
    disease or condition that affects lt4,000
    individuals in the U.S./year 45 Days
  • Part 2 A HUD then may undergoes a CDRH review
    for a Humanitarian Device Exemption (HDE) - 75
    days
  • FDA approval of a HDE authorizes marketing of the
    HUD with conditions

21
A few points about HUDs.
  • Incidence lt4,000 in the United States
  • Not for profit (unless pediatric device see
    FDAAA 2007)
  • Device to be used with facility IRB approval
  • No comparable device marketed

22
HUDs and HDEs
  • 226 HUD requests received 142 granted (63)
  • 49 HDE Humanitarian Device Exemption Marketing
    Approval via CDRH with probable benefit
    outweighing the risks
  • Examples Deep Brain Stimulation for OCD
    Titanium Rib, Implantable Replacement Heart,,
    Fetal Bladder Stent

23
HDE Approvals
  • Enterra Therapy System for the Treatment of
    chronic, drug refractory symptoms, secondary to
    gastroparesis of diabetic, post surgical, and
    idiopathic etiology.
  • Medtronic Activa Dystonia Therapy Kit for Deep
    brain stimulation (DBS) therapy for chronic,
    intractable (drug refractory) dystonia, including
    generalized and segmental dystonia, hemidystonia,
    and cervical dystonia (torticollis).
  • NeuRx DPS RA/4 Respiratory Stimulation System
    electrically stimulates the muscles and nerves
    that run through the diaphragm which allows some
    spinal cord injury patients to breathe for at
    least four hours a day without a mechanical
    ventilator.

24
Contacts
  • 1. Request for HUD Designation
  • Office of Orphan Products Development
    http//www.fda.gov/orphan/HUDS
  • Contact Debra.Lewis_at_fda.hhs.gov 301-827-0059
  • 2. HDE application
  • CDRH/ODE http//www.fda.gov/cdrh/ode/guidance/138
    1.pdf
  • Contact Stephen.Rhodes_at_fdahhs.gov
  • 240-276-4036

25
INCENTIVES THROUGH OOPD
  • GRANTS PROGRAMS
  • Orphan Products AND Pediatric Device Consortia

26
Orphan Products Grants Goal
  • To advance clinical development of drugs,
    biologics, medical devices, or medical foods, for
    rare diseases or conditions (lt200K individuals in
    U.S.)

27
Orphan Products Grants Program
  • Also, a practical program for advancing marketing
    approvals and relevant publications that impact
    on rare diseases

28
Orphan Products Grants Program
  • Request for Application (RFA) available at
    http//www.fda.gov/orphan (deadline Feb. 3)
  • Application, review, and scoring much like NIH
    grant application
  • Electronic submissions http//grants.gov

29
Orphan Products Grants Program
  • lt 100 applications per year
  • Competitive 30 success
  • Fund about 18-20 new grants per year
  • Supports academic and industry sponsored
    research
  • Domestic or foreign, public or private,
    for-profit or nonprofit entities

30
OPD Grants Program Requirements
  • Clinical studies to be conducted under
  • ACTIVE IND or IDE
  • Good Clinical Practices (GCP)
  • Human Subjects Assurance from OHRP Federal-Wide
    Assurance or FWA (www.hhs.gov/ohrp)
  • IRB approval

31
OPD Grants Program Budget
  • The current annual budget for grant funding is
    approximately 14 million
  • Clinical trials may be awarded
  • Up to 200,000 (Phase 1) per year for up to 3
    years
  • Or
  • Up to 400,000 (Phase 2 and 3) per year for up to
    4 years

32
OPD Grants Program Review Process
  • Primary Review Grants scored by independent ad
    hoc expert panels for technical merit.
  • Second Level Review by a National Council
    (Process Approval)

33
Overview Timeline FY 2011 Grant Program
  • Next Application receipt date - February 3, 2010
  • IND/IDE must be in effect at time of the grant
    application submission (IND must be active and
    include the protocol for which funding is
    requested)

34
Grants Statistics
  • To date, since 1983, FDA has provided more than
    232 million for more than 460 grants for studies
    on rare diseases.
  • Current annual budget 14 million
  • 44 FDA approved products were at least partially
    funded through the OOPD Grants Program.

35
RARE Disease Grant Opportunities
  • FDA OPD Grant Program
  • Other Federally funded grants
  • Grants.govsearch find grant opportunities
  • Small Business Innovation Research (SBIR) Small
    Business Technology Transfer (STTR)
  • http//grants.nih.gov/grants/guide/index.html
  • NORDs Research Grant Program
  • Small grants to academic scientists studying new
    treatments or diagnostics for rare diseases
    (www.rarediseases.org)

36
Objective
Accelerate development of therapies for rare
diseases

36
37
2009 Strategies

37
38
Strategy 1 Dont fix whats not broken.
  • Core activities are working well
  • Orphan designations
  • Advocacy/facilitation
  • Grants-making.
  • Protect the spirit of the ODA
  • Non-orphans

38
39
Orphan Designations Orphan Marketing Approvals
40
Trends in Orphan Designations
  • 165 designations last year---Most in 26 yr of ODA
  • Continued increase
  • Jan 1-Oct 28, 2008 147 designations requests
    received
  • Jan 1-May15, 2009 203 designations requests
    received
  • 2000th designation granted this year
  • 40 of new molecular entities were orphans in
    2008

41
Strategy 2 Nurture and expand relationships
  • Why work in orphan-space?
  • 343 approvals cant be wrong, viable model.
  • Blockbusters happen.
  • Right medicine for trust deficit.
  • Orphans are stepping-stones to personalized
    medicine
  • Compounds are on the shelf Right thing to do.
  • Do even more through partnerships

41
42
Strategy 3 Push for Orphan Grants Program
42
43
Strategy 4 Know thyself
  • gt2000 orphans, 343 approvals.
  • How many INDs? How many NDA/BLAs?
  • What is the timeline for progression?
  • What are the predictors of approval?
  • Analytic Group FDA Commissioners Fellow, ORISE
    Fellow UMinn and Keck Grad Students

43
44
Orphan Analytic Activities
  • Initial inquires of
  • Descriptive statistics
  • Populations of rare diseases served by designated
    product.
  • Maturation from designation to product approval.

45
Number of Designations sorted by Rare Disease
Prevalence
46
Diseases with 100 or fewer US patients
47
Life table analysis of Progression from
Designation to Market
Proportion of Designations Approved
0 5
10 15
20 25
YEARS
48
Strategy 5 Explore small population study
issues.
  • FDA policy People with rare diseases are
    entitled to the same evidentiary standards as
    people with common diseases.
  • Sense, sensibility, sensitivity, all exist at
    FDA, but distribution is not homogeneous.
  • Course in Small Trials for FDA reviewer and NIH
    January 2009

48
49
Explore small population study issues
  • Appeal to hearts and minds, especially minds.
  • Body of methodology, emphasis strengths and
    weaknesses.
  • Create a cadre of go-to reviewers.

49
50
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51
Explore small population study issues
  • 221 Attendees, 70 were FDA Reviewers
  • Alternative study design methods
  • Adaptive Designs
  • Bayesian approaches
  • Enrichment theories
  • Other
  • Objective Education, sensitization

51
52
Strategy 6 Advance Medical Devices for Rare
Diseases and Pediatric Devices
  • Humanitarian Device Exemptions
  • HDE Guidance Profit for pediatric devices
  • Pediatric Reporting Requirements
  • Institute of Medicine Study
  • New Pediatric Device Consortium Grants
  • 2M for 1-4 Consortia to advance pediatric
    devices
  • Non-traditional Grants

52
53
Pediatric Medical Device Safety and Improvement
Act of 2007
  • Establishes Non-Profit Consortia to Stimulate
    Pediatric Device Development

www
www.images.inmagine.com
54
A nonprofit consortiumshall facilitate the
development, production, and distribution of
medical devices by--
  • Encouraging innovation and connecting qualified
    individuals with pediatric device ideas with
    potential manufacturers
  • Mentoring and managing pediatric device projects
    through the development process, including
    product identification, prototype design, device
    development, and marketing.
  • Connecting innovators and physicians to existing
    Federal Sources and non-Federal Resources.

55
A nonprofit consortiumshall facilitate the
development, production, and distribution of
medical devices by--
  • Assessing the scientific and medical merit of
    proposed pediatric device projects.
  • Providing assistance as needed on business
    development, personnel training, prototype
    development, post-market needs and other
    activities consistent with the purpose of this
    section

56
The Process
  • Request for Applications was issued in May 2009.
    With a 6 week turn-around time for applicants
  • 18 applicants replied, 16 of which were deemed
    responsive to the RFA
  • Those 16 applications underwent peer review and
    then a secondary process review

57
WHO?
  • James Geiger, MD and the Michigan Pediatric
    Device Consortium, 1,000,000.
  • Michael Harrison, MD and the UCSF Pediatric
    Device Consortium, 500,000.
  • Pedro del Nido, MD and the Pediatric
    Cardiovascular Device Consortium, 500,000.

58
Strategy 7 Act Globally
  • Shared science, shared patients, shared spirit.
  • Joint application
  • Joint Annual report plan
  • Spring Exchange students
  • Outside EMEA opportunities

58
59
Global Work Neglected Diseases
  • Especially glacial class of orphan development.
  • Priority Review Voucher (FDAAA 2007).
  • Uses current market forces for a new development
    incentive.
  • Create facilitative Orphanage WHO

59
60
  • Priority Review Voucher Mechanics

(Orphan) Tropical Disease Drug
Marketing Approval for Tropical Disease Drug
Successful NDA/BLA
Voucher generation
Priority Review Voucher
Voucher Redemption
Voucher Transfer
(Possible Blockbuster) Other Drug NDA/BLA
Big PhRMA Company
?
FASTER
60
61
Strategy 8, 9 and 10 Act effectively for our
customer- the patients
  • Understanding
  • Partnerships
  • Action
  • Transparency
  • Results

61
62
Update on Orphan Successes
  • More than 340 orphan products have been brought
    to the U.S. market since the Act in 1983
  • In contrast, lt10 such products for rare diseases
    approved in the decade prior to 1983
  • 44 products approved through Grants Program
  • 49 Humanitarian Use Devices approved.
  • gt15M patients treated
  • Much more to do

63
OOPD Website
  • http//www.fda.gov/orphan
  • Your Link to
  • Overview of Office of Orphan Products Development
    Programs
  • Guidelines for designation application
  • List of designated and approved orphan products
  • Grant application information
  • Contact information for OOPD staff
  • Main Telephone is (301) 827-3666

64
A Better Perspective of The FDA
65
Questions
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