Frequently Asked Questions on 
Prescription Drug User Fees (PDUFA)

• Introduction
• What is PDUFA?
• Application Fees
  • What is a human drug application?
  • What is a 505(b)(1) application?
  • What is a 505(b)(2) application?
• Establishment Fees
• Product Fees
• Exceptions to Fee Requirements
• Waivers, Reductions, and Refunds
• Payment Information and Procedures
• Procedures for Waiver, Reduction, or Refund Requests
• Additional Information

INTRODUCTION

1. What is PDUFA?

The Prescription Drug User Fee Act (PDUFA), enacted in 1992 and renewed in 1997 (PDUFA II) and 2002 (PDUFA III) authorizes FDA to collect fees from companies that produce certain human drug and biological products. PDUFA established three types of user fees - application fees, establishment fees, and product fees. Since the passage of PDUFA, user fees have played an important role in expediting the drug approval process.

APPLICATION FEES

2. What is a human drug application?

PDUFA levies a user fee on certain human drug applications. Under PDUFA, the term human drug application means an application for

• approval of a new drug submitted under section 505(b)(1) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) after September 1, 1992
• approval of a new drug submitted under section 505(b)(2) of the FD&C Act after September 30, 1992, which requests approval of
  • a molecular entity which is an active ingredient (including any salt or ester of an active ingredient), or
  • an indication for a use that had not been approved under an application submitted under section 505(b), or
• licensure of certain biological products under section 351 of the Public Health Service Act (PHS Act) submitted after September 1, 1992

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3. What is a 505(b)(1) application?

A 505(b)(1) application is an application that contains full reports of investigations of safety and effectiveness.

The investigations the applicant relied on for approval were conducted by or for the applicant or the applicant has obtained a right of reference or use for the investigations.

4. What is a 505(b)(2) application?

A 505(b)(2) application is an application submitted under section 505(b)(1) for which

• the investigations the applicant relied on for approval were not conducted by or for the applicant and
• the applicant has not obtained a right of reference or use for the investigations (21 U.S.C. 355(b)(2)).

Section 505(b)(2) expressly permits FDA to rely, for approval of an NDA, on data not developed by the applicant - such as published literature or the agency's finding of safety and/or effectiveness of a previously approved drug product.

5. What is a supplement?

The Federal Food, Drug, and Cosmetic Act (FD&C Act) says, "The term supplement means a request to the Secretary to approve a change in a human drug application which has been approved." Each indication or claim is considered a separate change for which a separate supplement should be submitted. This policy allows FDA to approve each indication or claim as it is ready for approval rather than delaying approval until the last of a group of indications or claims is ready to be approved.

6. What are application fees?

Each person that submits a human drug application or supplement after September 1, 1992, is assessed an application fee as follows.

• A human drug application for which clinical data (other than bioavailability or bioequivalence studies) with respect to safety or effectiveness are required for approval is assessed a full application fee.
• A human drug application for which clinical data with respect to safety or effectiveness are not required for approval is assessed one-half of a full fee.
• A supplement to a human drug application for which clinical data (other than bioavailability or bioequivalence studies) with respect to safety or effectiveness are required for approval is assessed one-half of a full fee.

Human drug application fees are due when the application or supplement is submitted.

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ESTABLISHMENT FEES

7. What are establishment fees?

Establishment fees are assessed annually of each person who

• is named as the applicant in a human drug application and
• had a human drug application or supplement pending after September 1, 1992.

An establishment fee is assessed for each prescription drug establishment listed in the approved human drug application as an establishment that manufactures the prescription drug product.

• The establishment fee is assessed for each prescription drug product that is assessed a product fee - unless the establishment listed in the application does not manufacture the product during the fiscal year.
• Each establishment is assessed only one establishment fee for a fiscal year.
• If more than one applicant lists an establishment in a human drug application, the establishment fee for the fiscal year is divided equally among the applicants whose prescription drug products are manufactured at the establishment.

8. What is a prescription drug establishment?

The term prescription drug establishment means a foreign or domestic place of business

• which is at one general physical location consisting of one or more buildings, all of which are within 5 miles of each other, and
• at which one or more prescription drug products are manufactured in final dosage form.

For purposes of user fees, the term manufactured does not include packaging.

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9. What does final dosage form mean?

Final dosage form means a finished dosage form which is approved for administration to a patient without substantial further manufacturing.

PRODUCT FEES

10. What are product fees?

For Fiscal Year 2002 and before:

Prescription drug product fees are assessed annually for eligible products. The product fees are assessed on products for each person who

• is named as the applicant in a human drug application for a prescription drug product that has been submitted for listing under section 510 of the FD&C Act, and
• had a human drug application or supplement pending after September 1, 1992.

For FY 2003 and after:

Prescription drug product fees are assessed annually for eligible products. The product fees are assessed on products for each person who

• is named as the applicant in a human drug application, and
• had a human drug application or supplement pending after September 1, 1992.

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11. What is the definition of a prescription drug product?

Prescription drug product means a specific strength or potency of a drug in final dosage form for which a human drug application has been approved and which may be dispensed only by prescription under section 503(b) of the FD&C Act, and, after October 1, 2002, is also on the list of products described in section 505(j)(7)(A) or is on a list created and maintained by the Secretary of products approved under human drug applications under section 351 of the Public Health Service Act. (Section 351 of the PHS Act provides the authority for regulating biological products. Biological products are regulated by the Center for Biologics Evaluation and Research.)

12. What does "listing under section 510 of the FD&C Act" mean?

For user fee assessments, this applies only to FY 2002 and before:

Section 510 of the FD&C Act requires manufacturers, repackers, and relabelers that engage in the manufacture, preparation, propagation, compounding or processing of human or veterinary products to register their establishments and submit a list of every product in commercial distribution with the FDA. Additional information on drug registration and listing can be found at http://www.fda.gov/cder/drls/registration_listing.htm

13. Are there drugs that are not included in the term prescription drug product?

Yes. The term prescription drug product does not include the following drugs.

• Whole blood or a blood component for transfusion
• A bovine blood product for topical application licensed before September 1, 1992, an allergenic extract product, or an in vitro diagnostic biologic product licensed under section 351 of the PHS Act (Section 351 of the PHS Act provides the authority for regulating biological products. Biological products are regulated by the Center for Biologics Evaluation and Research.)
• A biological product that is licensed for further manufacturing use only
• A drug that is not distributed commercially AND is the subject of an application or supplement submitted by a State or Federal Government entity
• A large volume parenteral drug product approved before September 1, 1992
• After October 1, 2002, any large volume parenteral drug product regardless of when it was submitted (unless it is a large volume biological product intended for single dose injection for intravenous use or infusion)

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EXCEPTIONS TO FEE REQUIREMENTS

14. Are there any exceptions to the fee requirements?

Yes, there are exceptions.

For Application Fees

• Previously Filed Applications or Supplements.  If an application or supplement
  • was submitted by a person that paid the fee for the application or supplement,
  • was accepted for filing, and
  • was not approved or was withdrawn (without a waiver),

The resubmission of the application or supplement for the same product (by the same person) does not require an application fee.

• Designated Orphan Drug or Indication
  • An application for a prescription drug product that has been designated as a drug for a rare disease or condition under section 526 of the Act is not subject to an application fee unless the application includes an indication for other than a rare disease or condition.
  • A supplement proposing to include a new indication for a rare disease or condition is not subject to an application fee if the drug has been designated a drug for a rare disease or condition with regard to the indication proposed in the supplement.

For Establishment Fees

• If the establishment listed in the human drug application does not engage in the manufacture of the prescription drug product during the fiscal year, the applicant is not assessed an establishment fee.
• When the manufacture of a prescription drug is started during the year and after the establishment fee has already been assessed, the applicant is not assessed an establishment fee for that year. The product must not have been manufactured at the establishment in the previous fiscal year to be exempt.

For Product Fees

Applies only to FY 2002 and before:

An annual product fee is not assessed:

• if the product is not listed under section 510, or
• if the product listed is the same product as a product approved under
  • an application filed under sections 505(b)(2) or 505(j) of the FD&C Act,
  • an abbreviated application filed under section 507 of the Act (as in effect on the day before the date of enactment of the Food and Drug Administration Modernization Act of 1997), or
  • an abbreviated new drug application prior to the implementation of the Drug Price Competition and Patent Term Restoration Act of 1984.

After FY 2002

An annual product fee is not assessed:

• if the product is not on the list compiled under section 505(j)(7)(A) (Prescription Drug Product List (the active portion) in the Approved Drug Products with Therapeutic Equivalence Evaluations (the Orange Book)), or
• if the product is listed in the Orange book with a potency described in terms of per 100 mL, or,
• if the product listed is the same product as another product approved under
  • an application filed under sections 505(b) or 505(j) of the FD&C Act,
  • an abbreviated application filed under section 507 of the Act (as in effect on the day before the date of enactment of the Food and Drug Administration Modernization Act of 1997), or,
  • an abbreviated new drug application prior to the implementation of the Drug Price Competition and Patent Term Restoration Act of 1984.

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15. What is a 505(j) application?

A 505(j) application is an abbreviated new drug application (ANDA) that contains information to show that the proposed product is identical in active ingredient, dosage form, strength, route of administration, labeling, quality, performance characteristics and intended use, among other things, to a previously approved product - the reference listed drug (RLD).

ANDAs do not contain clinical studies as required in NDAs but are required to contain information establishing bioequivalence to the RLD.

In general, the bioequivalence determination allows the ANDA to rely on the Agency's finding of safety and efficacy for the RLD.

A drug product that is the subject of an ANDA is referred to as a generic drug.

WAIVERS, REDUCTIONS, AND REFUNDS

16. Are there any waivers of user fees?

Under section 736(d) of the FD&C Act, a waiver may be granted for one or more fees where:

• a waiver or reduction is necessary to protect the public health;
• assessment of the user fees would present a significant barrier to innovation due to limited resources or other circumstances;
• the fees will exceed the anticipated present and future costs incurred by FDA for conducting the process for the review of the new drug applications for the person;
• before October 1, 2002 only, assessment of the fee for an application or a supplement filed under section 505(b)(1) pertaining to a drug product would be inequitable because an application for a product containing the same active ingredient filed by another person under section 505(b)(2) could not be assessed user fees.

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17. Are there any waivers of fees specifically for small businesses?

Yes. The Agency will waive the application fee for the first human drug application that a small business or its affiliate submits for review (section 736(d)(1)(E) of the FD&C Act).

• the term small business is defined as a business that has fewer than 500 employees, including employees of affiliates.
• an affiliate is a business entity that has a relationship with a second business entity if one business entity controls, or has the power to control, the other business entity, or a third party controls, or has the power to control, both entities. (Section 735(9) of the FD&C Act).

To be granted a waiver, the small business must submit a written request for the waiver.

After a waiver for a first human drug application is granted, the small business is assessed appropriate user fees for all subsequent human drug applications and supplements submitted for review.

There are no small business waivers for product or establishment fees.

For additional information on user fee waivers, go to http://www.fda.gov/cder/pdufa/default.htm under Guidance.

18. Is there a reduction of fees for human drug applications and supplements that are refused for filing? Also is there a reduction or refund of fees for human drug applications and supplements that are withdrawn before or after filing?

Yes. The following reductions or refunds are available:

• 75 percent of the application fee is refunded for any application or supplement that is refused for filing or is withdrawn before filing.
• if an application or supplement is withdrawn after it is filed, FDA may refund the fee or a portion of the fee if no substantial work was performed on the application or supplement. FDA has the sole discretion to refund a fee or a portion of the fee. The FDA's determination concerning a refund is not reviewable.

To be granted a waiver, the human drug applicant must submit a written request for the waiver.

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19. What is the timeframe for submitting requests for waivers, reductions, and refunds?

To qualify for consideration for a waiver, reduction or refund of any fee, a written request must be submitted not later than 180 days after the fee is due. See the Procedures for Waiver, Reduction, or Refund Requests section for more information.

PAYMENT INFORMATION AND PROCEDURES

20. How does FDA determine fees?

For FY 1998 through 2002, under the PDUFA II, the human drug application fee rates are set in the statute, but are to be adjusted annually for cumulative inflation since FY 1997. Total application fees revenues are structured to increase or decrease each year as the number of applications submitted to FDA increases or decreases.

For additional information, see the Federal Register notice of January 6, 2002, "Establishment of Prescription Drug User Fee Rates for Fiscal Year 2002" at http://www.fda.gov/OHRMS/DOCKETS/98fr/011602a.htm

For FY 2003 through 2007, under PDUFA III, the fee revenue amounts are set in the statute and are adjusted annually for cumulative inflation after FY 2003. After adjustment for inflation, the revenues are also adjusted annually to reflect changes in the workload for the process for the review of human drug applications. For additional information, see the Federal Register notice establishing Prescription Drug User Fee Rates for Fiscal Year 2003 at http://www.fda.gov/cder/pdufa/default.htm under Federal Register Documents.

21. When are user fees due?

For FY 1998 through FY 2002

• Application and supplement fees are due when the application or supplement is submitted.
• ·Establishment and product fees are payable on or before January 31 of each year.
• FDA issues invoices for establishment and product fees for the fiscal year on or before December 31 of each year using the fee schedule for that year.

For FY 2003 through FY 2007

• Application and supplement fees are due when the application or supplement is submitted.
• Establishment and product fees are payable on or before October 1 of each fiscal year.
• FDA issues invoices for establishment and product fees for the coming fiscal year in August of each year using the fee schedule for the coming fiscal year.

22. What is the Federal government's fiscal year?

The Federal government's fiscal year begins on October 1 and ends on September 30.

For example, fiscal year 2002 begins October 1, 2001, and ends September 30, 2002. Fiscal year 2003 begins October 1, 2002 and ends September 30, 2003.

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23. What are the instructions for the payment of fees? (updated 3/20/2008)

Payment must be made in U.S. currency by check, bank draft, or U.S. postal money order payable to the order of the U.S. Food and Drug Administration. Mail the payment to:

Food and Drug Administration
P.O. Box 70963

Charlotte, NC 28272-0963

If checks are sent by a courier that requests a street address, the courier can deliver the checks to the address below. Note: This address is for courier delivery only.

Wachovia Bank

Attn: Food and Drug Administration Lockbox 70963

1525 West WT Harris Blvd., Room NC0810
Charlotte, NC 28262

If a phone number is also required for the courier delivery, note 800-590-7868, team 622. ext 85749 on the courier form.

Include the user fee I.D. number (for application and supplement submissions only), the BLA/NDA number, or the invoice number and the FDA P.O. Box number 70963 on the enclosed check or in the documentation that comes with the payment.

It would be helpful to include either 1) the user fee cover sheet (Form FDA 3397) for application or supplement fee payments, or 2) the invoice cover sheet for annual product or establishment fees.

UFID Numbers for application and supplement submissions are obtained by completing the online user fee coversheet at www.fda.gov/oc/pdufa/coversheet.html.

PROCEDURES FOR WAIVER, REDUCTION, OR REFUND REQUESTS

24. What is the timeframe for requesting a waiver, reduction, or refund of fees?

To qualify for consideration, a written request for waiver, reduction or refund must be submitted not later than 180 days after such fee is due.

25. Where should I send my request?

If you wish to send us mail (e.g. waiver request, refund request) you can send it to:

Michael Jones
Food and Drug Administration
10903 New Hampshire Ave, Building 51, Room 6216
Silver Spring, MD 20993-0002

Phone: 301-796-3602
Email: michael.jones@fda.hhs.gov
Fax: 301 847-8711

or

Beverly Friedman
Food and Drug Administration
10903 New Hampshire Ave, Building 51, Room 6222
Silver Spring, MD 20993-0002

Phone: 301-796-3602
Email: beverly.friedman@fda.hhs.gov
Fax: 301 847-8711

Note: Only FedEx and UPS delivers directly to the 6th floor

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26. What information should I include in my request?

The written request should include the following information:

• the name and address of the entity, including the company name, and the name and telephone number of the contact person for the fee waiver or reduction request
• identification of the specific fee for which a waiver, refund, or reduction is requested
• for an application or supplement fee - the application or supplement number for which the waiver, refund, or reduction is requested, the date the application was submitted, and whether the application requires clinical data for approval
• for product fees - the name of the product (generic and brand names), the application number, the name of the applicant, the specific strength or potency of the product, the dosage form, the invoice number, and the invoice date
• for establishment fees - the name and address of the establishment for which the waiver or reduction is requested, the establishment number as listed on the invoice, the invoice number, and the invoice date
• the statutory provision under which the waiver or reduction is requested
• information and analyses demonstrating that the criteria for the waiver, refund, or reduction of fees are met
• date on which payment was or will be made to FDA of the fee for which a waiver or reduction is requested
• for establishment and/or product fees - a copy of the fee invoice sent by FDA

ADDITIONAL INFORMATION

27. Where can I find additional information about user fees?

There are several guidances that may be helpful.

• Classifying Resubmissions in Response to Action Letters http://www.fda.gov/cder/guidance/2360fnl.pdf
• Fees-Exceed-the-Costs Waivers Under the Prescription Drug User Fee Act http://www.fda.gov/cder/guidance/3250fnl.pdf
• Submitting and Reviewing Complete Responses to Clinical Holds
  http://www.fda.gov/cder/guidance/3082fnl.pdf
• Submitting Separate Marketing Applications and Clinical Data for Purposes of Assessing Fees
  http://www.fda.gov/cder/guidance/4052dft.pdf

There are also several websites available.

• http://www.fda.gov/cder/pdufa/default.htm
• http://www.fda.gov/cber/pdufa.htm
• http://www.fda.gov/oc/pdufa/default.htm

28. Who should I contact if I still have questions about user fees?

For Drug products, contact Mike Jones or Beverly Friedman in the Office of Regulatory Policy, CDER, 301-796-3602.

For Licensed Biologic products, contact the Regulatory Information Staff, CBER, 301-827-3503.