# Presentation: 241318

## The Office of Orphan Products Development Grant ProgramJanet Whitley, Ph.D.Office of Orphan Products DevelopmentFood and Drug Administration

## Office of Orphan Products Development

- Orphan Drug Designation
- 	Drugs/biologics
- Orphan Products Grants
- 	Drugs, Biologics, Devices, Foods
- Humanitarian Use Device Designation
- 	Humanitarian Device Exemption

## Grant Program Objective

**Grant Program Objective**

- To fund **clinical** research that will accelerate or assist in the approval of products which demonstrate promise for rare diseases/disorders.

-    Basic   Research Funding

## Grant Program Objective

- To fund studies leading to publications in peer-reviewed journals.
- Supports mainly Phase 1 and 2 trials
- Funding may be used to cover portion of larger trial
- Importance of funding

## Grant Support for Investigation of Rare Disease Treatment

- Awarded to both academic and industry-sponsored research
- FDA funds approximately 20-30 new grants per year
- Provides $150,000 to $300,000 in direct costs per year -- up to 3 years

**Notes:**
Through the Orphan Drug Act, FDA provides grants to fund clinical trials of products for rare diseases or conditions -- studies that produce data acceptable to the agency that result in or substantially contribute to approval of these products.
	This incentive of the Act provides financial support for clinical studies to determine the safety and efficacy of products to treat rare disorders, and achieve marketing approval from the FDA under the Federal Food, Drug, and Cosmetic Act.  
	Most orphan drugs are originally studied by academic researchers.  The early-- Phase I and Phase II -- studies by these investigators provide the initial data necessary to interest commercial sponsorship for further development, and for preparation of a new drug approval application leading to market approval.  
	FDA awards between 20 and 30 grants each year, funded through the orphan products grants program.  Early clinical trials are eligible to receive $100,000 in direct costs for up to 3 years; later stage trials may receive up to $200,000 per year, also for 3 years.  
	The products to be tested must be intended to treat conditions affecting fewer than 200,000 people in the United States.

## OPD Grant

- >50/400 grants awarded to industry sponsors
- Grantees are US and abroad
- Orphan Designation not required
- New drug/product or new use of approved product

**Notes:**
Orphan Medical
Inhibitex
Ucyclyd
Sigma Tau
Therapeutic Antibodies, Inc
Chen, Inc; Discovery Labs; Phoenix Pharma

## Funding

- FY 2003:
- 	101 responsive applications
- 	15 received funding
- Currently: 65 Active grants

## Slide 8

## Orphan Grant Application Process

- Issue *Federal Register* notice (RFA).
- Meets program review criteria.
- Review panels:
- Ad hoc panels of outside experts review scientific merit
- Regulatory review
- Prepare summary statements.
- Present to Advisory Council.
- Advise - Fund - Monitor.

## Grant review: Responsive to Program Review Criteria?

- Study is a clinical trial.
- Prevalence is fewer than 200,000 U.S. patients.
- Study must be performed under an active IND/IDE (except medical foods).
- Budget is within limits.
- Availability of sufficient product.

## Grant review: Scientific and Technical Merit?

- Soundness of the rationale
- Appropriateness of study design
- Statistical justification for proposed enrollment - POWER
- Potential for patient accrual
- Qualifications of investigator & support staff

## Grant review: Scientific and Technical Merit?

- Adequacy of resources and environment
- Budget Justification
- Informed consent documents and IRB approval
- Potential for completion of study within stated time and budget

## Not funded because:

- Non-responsive application
- Overall quality of application – clarity and detail
- Scientific merit
- Preliminary data, poor study design, weak rationale, sketchy analysis plan
- Compelling nature of study
- Resubmissions that don’t follow/address panel’s suggestions/concerns
- Feasibility
- Number of patients, drug supply, too much to do in too little time

## Management of Funded Grants

- Assignment to Project Officer
- Liaison between grantee and FDA review division.
- Enrollment goals/achievement.
- Quarterly progress updates.
- Site visits to assure grant compliance.
- Sponsor acquisition.
- Continuation funding dependent on progress.

## Grant Program Accomplishments

- 36 product approvals supported by OPD grants
- Hundreds of publications, abstracts, and presentations have been produced as a result of orphan product grant studies.

## FY2005 Request for Applications (RFA)

*Federal Register* Announcement
- August
- OPD website
- Application Due Dates:
**October 2004 **
**April 2005**

## Responsibilities of the Office of Orphan Products Development in Evaluating Humanitarian Use Devices (HUD)	

**Notes:**
In addition to Drug Designations and the Grants Program, 

The third major activity of our office is our HUD program.

What is a HUD? (NEXT SLIDE)

## Makers of new medical devices ordinarily must show that products are safe and effective.
For humanitarian purposes, FDA will approve devices limited to use only in rare diseases/conditions if  manufacturers demonstrate the safety and probable benefit to patients.

- For humanitarian purposes, FDA will approve devices limited to use only in rare diseases/conditions if  manufacturers demonstrate the safety and probable benefit to patients.

**Background**

**Notes:**
To encourage development of medical devices for rare diseases,
CONGRESS decided, via the SAFE MEDICAL DEVICES ACT in 1990 that FDA...

In other words, sponsors are exempt from the requirement to demonstrate EFFECTIVENESS.

That EXEMPTION is called an HDE or HUMANITARIAN DEVICE EXEMPTION

## HUDs vs HDEs

**Two-step process**:
- 1 – HUD: FDA will consider the use and size of the proposed patient population
- 2-  HDE: Device is evaluated for safety and probable benefit in the CDRH Office of Device Evaluation.

## What is a HUD?	

- A Humanitarian Use Device (HUD) is a medical device intended to benefit patients in the diagnosis and/or treatment of a disease or condition that affects or is manifested in fewer than 4,000 patients per year in the United States.

## What is an HDE?

- A Humanitarian Device Exemption (HDE) is a provision that exempts sponsors of devices for orphan diseases from the effectiveness requirements of the medical device law, provided the device meets safety conditions and will not expose patients to significant or unreasonable risk.

**Notes:**

Here is a definition of an HDE
Sponsors must demonstrate safety
Do not have to show effectiveness
Show that probable benefits outweigh risks
Show that no comparable treatment is available
Show that without HDE status, would not otherwise be able to bring device to market

## Diagnostic/prevention devices

- Sponsor must demonstrate that the less than 4,000 patients/year would be subjected to diagnosis by the device in the U.S.
- PKU screening in newborns
- Rare disease
- 4,000,000 newborns screened yearly

## How is a HUD Review Performed?

- Evaluate rationale and population.
- Approve, disapprove, or request additional information.
- Review clock:  45 days from receipt of request/supplemtent.

## Refusal to approve HUD request

- Population >4,000
- OPD consults with review division re: use
- Sponsor points to approved HUD population
- Medically plausible basis to *limit* the use of a product to a particular population
- Usually risk-to-benefit
- Feasibility of assay/rationale
- Cost not a factor (not in regs)

## Statistics

**Since October 1996**
- 138 requests received.
- 96 devices designated as HUDs by OPD.
- 36 devices approved as HDEs by CDRH.

**Notes:**
Next, I would like to introduce Bob Steeves.
Bob is a pharmacist, a lawyer and a wine-maker. 
His topic is “HOT BUTTON ISSUES”
Bob...

## Contact Information

- Website:  	_[www.fda.gov/orphan](http://www.fda.gov/orphan)_
- Information on HUDs, Orphan Designation, and grants (RFA)
- Phone: 	301-827-3666
- Snail:	5600 Fishers Lane
- HF-35, Room 6A55
- Rockville, MD 20857