Title: Obtain and Manage Grants and Funding for Orphan Drug Development
1Obtain and Manage Grants and Funding for Orphan
Drug Development
Debra Lewis, OD, MBA Associate Director FDA
Office of Orphan Products Development FDA
Seminar 2009 - Copenhagen November 3-4, 2009
2Overview
- Orphan Background
- Grants Programs (Orphan and Pediatric Device
Consortia Grants) - FDA OOPD Grant Program Application and Review
Additional Resources - Warning No Fear these very dense slides are for
reference purposes only
3Objectives
- FDAs Office of Orphan Products Development
(OOPD) focusing on Grants Processes - Understand regulatory requirements for grants
before applying, including grants.gov electronic
application system - Ensure a successful program and continued funding
through study conduct and grants management
4A Common Perspective of Grant Review
5The 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.
6How does OOPD serve its Mission?
- Conducts review of orphan product and
humanitarian use device designation requests - Serves as liaison for medical product companies,
FDA review divisions, patient advocacy groups,
and other government agencies. - Awards and administers grants to defray orphan
product clinical study costs and to advance
Pediatric Device Development
7Orphan Diseases
- Rare defined as prevalence of lt200,000 in the
U.S. - Includes over 6,000 rare diseases
- Collectively affects approximately 25 million
Americans - Frequently serious/life threatening
8Orphan Products Grants Programs
9Grants Programs in OOPD
- Pediatric Device Consortia Grant Program (New as
of FY 2009) - OPD Clinical Research Grants (R01) for Orphan
Diseases
10The Pediatric Device Consortia Grant Program
- .charting a course for the development of
medical devices for children
11Pediatric Device Consortia Grant Program
- Established from FDAAA 2007
- Does not have to be Orphan Administered by
OOPD, but encompasses devices used in all
pediatric diseases, not just rare diseases. - Receipt date this year was June 15, 2009 Paper
submission - See RFA at www.fda.gov/orphan
12The Challenges
- The development of pediatric devices currently
lags five to ten years behind those for adults. - Many pediatricians are forced to adapt adult
devices to suit their pediatric patients - Children differ from adults in terms of their
size, growth, development, and body chemistry.
13The Law
- The Pediatric Medical Device Safety and
Improvement Act of 2007 - Calls for Non-Profit Consortia Grants to
Stimulate Device Development -
142009 Omnibus Appropriations Bill
- Provided 2 million for demonstration grants for
improving pediatric device availability, as
authorized in FDAAA of 2007. - The program will provide grants to nonprofit
pediatric medical device consortia, which will
assist scientists and innovators with technical
and financial resources to improve the number of
devices available to children. - The Office of Orphan Products Development is
responsible for carrying out this program.
15Pediatric Medical Device Safety and Improvement
Act of 2007
- Establishes Non-Profit Consortia to Stimulate
Pediatric Device Development - What is a consortium?
www
www.images.inmagine.com
16A nonprofit consortium that receives a grant or
contract under this section shall 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.
17A nonprofit consortium that receives a grant or
contract under this section shall facilitate the
development, production, and distribution of
medical devices by--
- Assessing the scientific and medical merit
- Providing assistance as needed on business
development, personnel training, prototype
development, post-market needs and other
activities consistent with the purpose of this
section
18H.R. 3580, Title 3, Section 305
- Demonstration Grants for Improving Pediatric
Device Availability - Typically when we at FDA think of grants, we
think of grants to directly fund research. - This is a grant program that will fund consortia
that in turn support pediatric device developers - A RESULTS Driven Provision, aimed at moving
products forward along the development continuum.
19H.R. 3580, Title 3, Section 305
- Coordination,
- NIH
- Each consortium . shall coordinate with the
NIHs pediatric device contact point or office
(Dr. Steven Hirschfeld) - Provide to NIH
- any identified pediatric device needs that the
consortium lacks sufficient capacity to address
or - those needs the in which the consortium has been
unable to stimulate manufacturer interest.
20H.R. 3580, Title 3, Section 305
- Coordination, continued.
- FDA
- Each consortium .shall coordinate with the
Commissioner of Food and Drugs and device
companies to facilitate the application for
approval or clearance of devices labeled for
pediatric use.
21H.R. 3580, Title 3, Section 305
- Coordination, continued.
- Effectiveness and Outcomes
- Each consortium. shall annually report to the
Secretary of Health and Human Services on the
status of pediatric device development,
production, and distribution that has been
facilitated by the consortium
22H.R. 3580, Title 3, Section 305
- There are authorized to be appropriated to carry
out this section 6M for each of fiscal years
2008 through 2012. - 2008 - no appropriation no program
- 2009 2 M appropriation March
23PDCGP Timeline
- March 2009--
- Draft Request For Applications Federal Register
Notice - Schedule initial meetings with key stakeholders
both within and outside of FDA - April 2009--
- Clear RFA and FR Notice through the agency and
with NIH Guide get them circulated publicly by
May 1st. - June 15, 2009
- Receipt of Applications Deadline
- July 2009
- Hold Review Panel of Proposed Grants
- September 2009
- Council Review by National Cancer Advisory Board
- Distribute Funds to Consortia
24The Pediatric Device Consortia Grants Program
- 2 Million Dollars were distributed between 3
Consortia - Using the P50, Center Grant Mechanism
- Grant proposals were critiqued on the Consortias
Organization/ Capability AND Portfolio of
Proposed Projects
25WHO?
- 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.
26Points of Contact
- Linda C. Ulrich, M.D., F.A.A.P
- Pediatric Consortia Grants Program
- (301) 827-7252 Linda.Ulrich_at_fda.hhs.gov
- Debra Y. Lewis, O.D., M.B.A, Associate Director,
OOPD and Director of the HUD Program 301 827-0059 - OOPD Main line (301) 827-3666
-
27Points of Contact
- Grants Management
- Camille Peake,
- Grants Management Specialist
- (301) 827-7175
- Camille.Peake_at_fda.hhs.gov
28QUESTIONS?
www.elderoptionsof texas.com
29Rare Disease Grant Opportunities
- FDA OPD Grant Program (R01)
- Other Federally funded grants
- Grants.gov- search under find grant
opportunities - Small business funding opportunities
- Small Business Innovation Research (SBIR) program
- Small Business Technology Transfer (STTR) Program
- NIH grants http//grants.nih.gov/grants/guide/in
dex.html - NORDs Research Grant Program
- Small grants to academic scientists studying new
treatments or diagnostics for rare diseases.
(www.rarediseases.org)
30Orphan Products Grants Program
- Goal to advance clinical development of drugs,
biologics, medical devices, or medical foods, for
use in rare diseases. - Academic and industry sponsored research.
- Domestic or foreign, public or private,
for-profit or nonprofit entities - The disease must affect lt200K persons in the
U.S.), but orphan designation is not a grant
requirement
31Orphan Products Grants Program
- A practical program advancing marketing
approvals and relevant publications that impact
care - lt 100 applications/year
- Competitive grant program 30 success
- Fund about 15-20 new grants per year
- Request for Application (RFA) available at
www.fda.gov/orphan - Application, review, and scoring much like NIH
grant application - Electronic submissions Grants.gov
32FDA OPD Grant Program Overview
- Eligibility/Requirements
- Any entity except DHHS Federal agencies
- Clinical study of an orphan disease or condition
- A study must advance info towards a market
approval - Must have active IND (not on clinical hold)
- Evidence that drug product is sufficiently
available - Funding dependent on quality of application and
availability of Federal funds - For more information visit the OPD Grant Program
website http//www.fda.gov/ForIndustry/Developing
ProductsforRareDiseasesConditions/WhomtoContactabo
utOrphanProductDevelopment/ucm134580.htm
33OPD Grants Program Budget
- The current annual budget for grant funding is
approximately 14 million. - Clinical trials cycle award limits
- 200K/yr (Phase 1) for up to 3years
- or
- 400K/yr (Phase 2 and 3) up to 4 years.
34Annual Number of OPD Grant Applications
35Overview Timeline FY 2011 Grant Program
- Next receipt date - February 3, 2010 (October
15, 2010 will be a receipt date only for
resubmissions) - IND/IDE needs to be in effect at time of the
grant application submission and must include the
protocol for which funding is requested) - Protocol should be submitted to IND by January 4,
2010 (earlier if submitted with original IND) - Application summary statement - August 2010
- Earliest start date for award - November 2010
- All FY 2011 funding completed by September 2011
36Types of Products Supported by Active OPD Grants
Excluding no-cost extension and supplemental
grants
37Composition of Orphan Grants
- 25 have a Phase 1 component
- 55 have a Phase 2 component
- 20 have a Phase 3 component
- About 25 of awards are to companies
- About 50 are company/academic institution
collaboration
38Grants Statistics
- To date, since 1983, FDA has provided more than
246 million for more than 500 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.
39OPD Grants Program KEY 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
40Grant Application Process
- Grants.gov
- Submit electronically through www.grants.gov
- Follow instructions under Apply for Grants
- Search using RFA information (FD09-001)
- Download copy of application package (SF-424RR)
and instructions - Applicant Help section provides Users Guide,
FAQs and other support - Complete offline
- Upload and submit via grants.gov web site
- Track status of application via grants.gov
- FOA link in NIH Guide at http//grants.nih.gov/gr
ants/guide/rfa-files/RFA-FD-09-001.html
41Application Process
- Grants.gov
- Documents completed in Adobe are added as
attachments - Text attachments must be PDF files
- Format specifications for attachments
- Registration
- Request a DUNS number
- Register with CCR (Central Contractor
Registration) - Register with Credential Provider
- Register with Grants.gov
- Register eRA
42Specifics on Application Process
- See website for requirements such as page limits,
appendices, character restrictions, and face page
requirements - http//www.fda.gov/ForIndustry/DevelopingProducts
forRareDiseasesConditions/ucm124552.htm
43Sections of Application
- Key Application Sections
- SF 424 RR Form
- Applicant info, Type of application, Title,
Project Period, Contact - Senior / Key Person Profiles
- Biographical sketches limited to 4 pages per
person- use CV to complete - Other Project Information
- Human Subjects, IRB, Project Summary/Abstract,
Narrative - Project/Performance Site Locations
- Budget
- OPD requires non-modular budget
44Sections of Application
- PHS 398 Cover Page Supplement
- PI info, New Investigator, Organization Contact
- PHS 398 Checklist
- Application Type, Program Income if applicable,
Change Investigator if applicable - PHS 398 Research Plan
- Use study protocol and IND documents to create
- Proprietary Information
- Only include what is necessary for application
evaluation - Mark confidential information with ()
45Sections of Application
- PHS 398 Research Plan
- Sections
- Introduction
- Specific Aims
- Background and Significance
- Rationale for study contributing to product
approval - Orphan prevalence data
- Preliminary Studies / Progress Report (if
applicable) - Research Design and Methods
- Inclusion Enrollment report
- Progress Report Publication List
46Sections of Application
- PHS 398 Research Plan - Sections Contd
- Human Subjects Sections
- Protection of Human Subjects (e.g., DSMB)
- IRB approval required following peer review
- Inclusion of Women, Minorities, Children
- Targeted/Planned Enrollment
- Other Research Plan Sections
- Consortium/Contractual Arrangements
- Letters of Support
- Contracts with CRO, consultants, service
providers (e.g., labs) - Appendix
- Protocol, informed consent, DSMB charter,
Investigators Brochure, FDA meeting minutes,
product availability
47Grantee Hints on the Process
- FDA grant submission process for grants.gov is
similar to the NIH process. - 1. Do your homework.
- 2. Develop a submission plan.
- Who will be responsible for completing the
different forms within the application? - When must the forms be completed in order to
allow time for the actual submission? - 3. Prepare to submit.
- Register with Grants.gov and NIH eRA Commons
- Registration can take 2-4 weeks start early!
48Grantee Hints on Process
- 4. Verify successful submission.
- Login to eRA Commons to see if any errors or
warning were identified for your submission. An
application must be error-free to complete the
electronic submission process. - 5. See Check Submission Status for details.
- You are responsible for checking eRA Commons to
ensure successful submission of your
application. - 6. View your assembled application.
- Once an error-free application is received, FDA
holds that application for two days
(Monday-Friday, excluding Federal holidays) to
allow submitters and PIs a chance to view the
final assembled application in eRA Commons.
49OPD Grant Program Review
- Primary Review Grants scored by independent ad
hoc expert panels for technical merit - Criteria are in the RFA
- Funding based on scores (100-500 lower scores
are better) - The recent fundable range was 100-190
- Summary Statements contain review specifics
- Second Level review by a National Council
(process approval) - OPD Project Officer checks prefunding
certifications prior to funding (check IRB,
foreign sites, etc.)
50OPD Grant Program Review
- Ad hoc expert panel reviews application based
on the following scientific and technical merit
criteria - Soundness of study rationale and design
- Appropriateness of statistical powering and plans
for results analysis - Evidence that the proposed number of subjects can
be recruited in the requested timeframe - Qualifications of the investigator and support
staff and availability of resources - Justification for financial support request
- Adequacy of plans for protection of human
subjects and study monitoring - Ability of applicant to complete study within its
budget and within the time limits of the grant
51OPD Grant Program Review
- Numbers Overview
- lt 100 applications per year
- Ave. 30 of new applications awarded per year
- 82 active grants about 15-20 new grants each
year - Future years of noncompetitive continuation of
support depends on - Performance during the preceding year
- Compliance with regulatory requirements of IND
- Availability of Federal funds
52Approved Products Supported by Orphan Grants
- 44 products funded by OPD grants approved for
marketing - Examples
- Elaprase (idursulfase) Enzyme replacement
therapy for patients with MPS II (Hunter
Syndrome). - BabyBIG (botulism immune globulin) infant
botulism - ORFADIN (nitisinone) tyrosinemia type 1
- VEPTR (vertical expandable prosthetic titanium
rib) thoracic insufficiency syndrome
5310 FDA Hints Useful Homework
- Start early, plan carefully, write clearly, and
objectively - Establish good relations w/FDA review divisions
via IND/IDE process. OPD invites FDA review
divisions to the review as a resource (FDA does
not score the application). - Read the RFA and instructions carefully not just
for deadlines - Use the Grant Writing Tips from NIH Extramural
Programs http//grants.nih.gov/grants/grant_tips.
htm - Call OPD for program clarifications
301-827-3666
5410 FDA Hints Useful Homework
- Call Grants Management for budget help contact
Vieda Hubbard (301-827-7177) and electronic
submissions help contact Marc Pitts
(301-827-7162) - If you do not have expertise for issues, provide
letters of collaboration for the needed expertise - Panel Reviewers are busy, so say it in fewer
words if possible - Use outside readers improve the quality of the
proposal - Dont be discouraged read summary statements
and address all critiques
55Responsibilities after Review
- Complete OPD Pre-Certification Form sent by OPD
to those applications with scores in fundable
range - Send response to Summary Statement Critiques
- Submit IRB approval letter
- Submit FWA information
- IND must be active (not on hold) and protocol
must match protocol going to be used for funded
study - Verify an adequate supply of study product is
available
56Responsibilities after Funding
- Set enrollment goals
- Clinicaltrials.gov registration and maintenance
- IND maintenance
- Must comply with all regulations to keep IND in
effect (not on clinical hold), Annual Report
submissions - Keep OPD Project officer aware of key IND
submissions (e.g., IND Annual Report, Protocol
Amendments) - Project officer periodic monitoring including
Phone calls, correspondences and Site visit from
OPD - Comply with GCP
57Responsibilities after Funding
- Quarterly progress reports
- Purpose is to ensure there is acceptable progress
in enrollment and study conduct is kept within
the scope of the grant - Summary of study progress, enrollment, problems
or challenges, adverse events, changes in
protocol, study monitoring activities that ensure
integrity of the data collected in study, and how
you are ensuring compliance with the protocol. - Publication of study results encouraged
- Submit IRB approval renewal yearly to OPD
- Submit Type V Applications for following years
with Progress report
58Summary
- FDA OPD Grant Program
- Practical program to facilitate marketing
approval of products for rare diseases - Up to 400,000 x 4 years
- Competitive program (30 success)
- Key recommendations include
- Plan resources and timing
- Regulatory compliance and adequate study progress
critical to continued grant funding
59Useful Links
- OPD Website
- www.fda.gov/orphan or (301) 827-3666
- FOA
- http//edocket.access.gpo.gov/2008/E8-30061.h
tm or at NIH guide - SF424 (RR) Application Guide
- http//grants.nih.gov/grants/funding/424/SF424_RR
_Guide_General_Ver2.doc
60A Better Perspective of FDA Grants
61Questions