[Federal Register Volume 86, Number 187 (Thursday, September 30, 2021)]
[Notices]
[Pages 54217-54219]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-21329]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2021-N-0982]


Fee Rate for Using a Rare Pediatric Disease Priority Review 
Voucher in Fiscal Year 2022

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is 
announcing the fee rate for using a rare pediatric disease priority 
review voucher for fiscal year (FY) 2022. The Federal Food, Drug, and 
Cosmetic Act (FD&C Act), as amended by the Food and Drug Administration 
Safety and Innovation Act (FDASIA), authorizes FDA to determine and 
collect rare pediatric disease priority review user fees for certain 
applications for review of human drug or biological products when those 
applications use a rare pediatric disease priority review voucher. 
These vouchers are awarded to sponsors of rare pediatric disease 
product applications that meet all the requirements of this program and 
are submitted 90 days or more after July 9, 2012, upon FDA approval of 
such applications. The amount of the fee for using a rare pediatric 
disease priority review voucher is determined each FY, based on the 
difference between the average cost incurred by FDA to review a human 
drug application designated as priority review in the previous FY, and 
the average cost incurred in the review of an application that is not 
subject to priority review in the previous FY. This notice establishes 
the rare pediatric disease priority review fee rate for FY 2022 and 
outlines the payment procedures for such fees.

FOR FURTHER INFORMATION CONTACT: Tim Davidson, Office of Financial 
Management, Food and Drug Administration, 4041 Powder Mill Rd., Rm. 
61077A, Beltsville, MD 20705-4304, 301-796-3254.

SUPPLEMENTARY INFORMATION:

I. Background

    Section 908 of FDASIA (Pub. L. 112-144) added section 529 to the 
FD&C Act (21 U.S.C. 360ff). In section 529 of the FD&C Act, Congress 
encouraged development of new human drugs and biological products for 
prevention and treatment of certain rare pediatric diseases by offering 
additional incentives for obtaining FDA approval of such products. 
Under section 529 of the FD&C Act, the sponsor of an eligible human 
drug application submitted 90 days or more after July 9, 2012, for a 
rare pediatric disease (as defined in section 529(a)(3)) shall receive 
a priority review voucher upon approval of the rare pediatric disease 
product application. The recipient of a rare pediatric disease priority 
review voucher may either use the voucher for a future human drug 
application submitted to FDA under section 505(b)(1) of the FD&C Act 
(21 U.S.C. 355(b)(1)) or section 351(a) of the Public Health Service 
Act (42 U.S.C. 262(a)), or transfer (including by sale) the voucher to 
another party. The voucher may be transferred repeatedly until it 
ultimately is used for a human drug application submitted to FDA under 
section 505(b)(1) of the FD&C Act or section 351(a) of the Public 
Health Service Act. A priority review is a review conducted with a 
Prescription Drug User Fee Act (PDUFA) goal date of 6 months after the 
receipt or filing date, depending on the type of application. 
Information regarding current PDUFA goals is available at: https://www.fda.gov/media/99140/download.
    The sponsor that uses a rare pediatric disease priority review 
voucher is entitled to a priority review of its eligible human drug 
application, but must pay FDA a rare pediatric disease priority review 
user fee in addition to any user fee required by PDUFA for the 
application. Information regarding the rare pediatric disease priority 
review voucher program is available at: https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm375479.htm.
    This notice establishes the rare pediatric disease priority review 
fee rate for FY 2022 at $1,266,651 and outlines FDA's payment 
procedures for rare

[[Page 54218]]

pediatric disease priority review user fees. This rate is effective on 
October 1, 2021, and will remain in effect through September 30, 2022.

II. Rare Pediatric Priority Review User Fee Rate for FY 2022

    Under section 529(c)(2) of the FD&C Act, the amount of the rare 
pediatric disease priority review user fee is determined each fiscal 
year based on the difference between the average cost incurred by FDA 
in the review of a human drug application subject to priority review in 
the previous fiscal year, and the average cost incurred by FDA in the 
review of a human drug application that is not subject to priority 
review in the previous fiscal year.
    A priority review is a review conducted with a PDUFA goal date of 6 
months after the receipt or filing date, depending on the type of 
application. As described in the PDUFA goals letter, FDA has committed 
to reviewing and acting on 90 percent of the applications granted 
priority review status within this expedited timeframe. Normally, an 
application for a human drug or biological product will qualify for 
priority review if the product is intended to treat a serious condition 
and, if approved, would provide a significant improvement in safety or 
effectiveness. An application that does not receive a priority 
designation receives a standard review. As described in the PDUFA goals 
letter, FDA has committed to reviewing and acting on 90 percent of 
standard applications within 10 months of the receipt or filing date, 
depending on the type of application. A priority review involves a more 
intensive level of effort and a higher level of resources than a 
standard review.
    FDA is setting a fee for FY 2022, which is to be based on standard 
cost data from the previous fiscal year, FY 2021. However, the FY 2021 
submission cohort has not been closed out yet, thus the cost data for 
FY 2021 are not complete. The latest year for which FDA has complete 
cost data is FY 2020. Furthermore, because FDA has never tracked the 
cost of reviewing applications that get priority review as a separate 
cost subset, FDA estimated this cost based on other data that the 
Agency has tracked. The Agency expects all applications that received 
priority review would contain clinical data. The application categories 
with clinical data for which FDA tracks the cost of review are: (1) New 
drug applications (NDAs) for a new molecular entity (NME) with clinical 
data and (2) biologics license applications (BLAs).
    The total cost for FDA to review NME NDAs with clinical data and 
BLAs in FY 2020 was $227,248,467. There was a total of 86 applications 
in these two categories (53 NME NDAs with clinical data and 33 BLAs). 
(Note: These numbers exclude the President's Emergency Plan for AIDS 
Relief NDAs; no investigational new drug review costs are included in 
this amount.) Of these applications 55 (35 NDAs and 20 BLAs) received 
priority review and the remaining 31 (18 NDAs and 13 BLAs) received 
standard reviews. Because a priority review compresses a review 
schedule that ordinarily takes 10 months into 6 months, FDA estimates 
that a multiplier of 1.67 (10 months / 6 months) should be applied to 
non-priority review costs in estimating the effort and cost of a 
priority review as compared to a standard review. This multiplier is 
consistent with published research on this subject, which supports a 
priority review multiplier in the range of 1.48 to 2.35 (Ref. 1). Using 
FY 2020 figures, the costs of a priority and standard review are 
estimated using the following formula:

(55 [alpha] x 1.67) + (31 [alpha]) = $227,248,467

where ``[alpha]'' is the cost of a standard review and ``[alpha] times 
1.67'' is the cost of a priority review. Using this formula, the cost 
of a standard review for NME NDAs and BLAs is calculated to be 
$1,849,804 (rounded to the nearest dollar) and the cost of a priority 
review for NME NDAs and BLAs is 1.67 times that amount, or $3,089,173 
(rounded to the nearest dollar). The difference between these two cost 
estimates, or $1,239,369, represents the incremental cost of conducting 
a priority review rather than a standard review.
    For the FY 2022 fee, FDA will need to adjust the FY 2020 
incremental cost by the average amount by which FDA's average costs 
increased in the 3 years prior to FY 2021, to adjust the FY 2020 amount 
for cost increases in FY 2021. That adjustment, published in the 
Federal Register on August 16, 2021 (86 FR 45732), setting the FY 2022 
PDUFA fees, is 2.2013 percent for the most recent year, not compounded. 
Increasing the FY 2020 incremental priority review cost of $1,239,369 
by 2.2013 percent (or 0.022013) results in an estimated cost of 
$1,266,651 (rounded to the nearest dollar). This is the rare pediatric 
disease priority review user fee amount for FY 2022 that must be 
submitted with a priority review voucher for a human drug application 
in FY 2022, in addition to any PDUFA fee that is required for such an 
application.

III. Fee Rate Schedule for FY 2022

    The fee rate for FY 2022 is set in table 1:

  Table 1--Rare Pediatric Disease Priority Review Schedule for FY 2022
------------------------------------------------------------------------
                                                         Priority review
                      Fee category                         fee rate for
                                                             FY 2022
------------------------------------------------------------------------
Application submitted with a rare pediatric disease          $1,266,651
 priority review voucher in addition to the normal
 PDUFA fee.............................................
------------------------------------------------------------------------

IV. Implementation of Rare Pediatric Disease Priority Review User Fee

    Under section 529(c)(4)(A) of the FD&C Act, the priority review 
user fee is due (i.e., the obligation to pay the fee is incurred) when 
a sponsor notifies FDA of its intent to use the voucher. Section 
529(c)(4)(B) of the FD&C Act specifies that the application will be 
considered incomplete if the priority review user fee and all other 
applicable user fees are not paid in accordance with FDA payment 
procedures. In addition, section 529(c)(4)(C) specifies that FDA may 
not grant a waiver, exemption, reduction, or refund of any fees due and 
payable under this section of the FD&C Act.
    The rare pediatric disease priority review fee established in the 
new fee schedule must be paid for applications submitted with a 
priority review voucher received on or after October 1, 2021. To comply 
with this requirement, the sponsor must notify FDA 90 days prior to 
submission of the human drug application that is the subject of a 
priority review voucher of an intent to submit the human drug 
application, including the estimated submission date.
    Upon receipt of this notification, FDA will issue an invoice to the 
sponsor for the rare pediatric disease priority review voucher fee. The 
invoice will include instructions on how to pay the fee via

[[Page 54219]]

wire transfer, check, or online payments.
    As noted in section II, if a sponsor uses a rare pediatric disease 
priority review voucher for a human drug application, the sponsor would 
incur the rare pediatric disease priority review voucher fee in 
addition to any PDUFA fee that is required for the application. The 
sponsor would need to follow FDA's normal procedures for timely payment 
of the PDUFA fee for the human drug application.
    Payment must be made in U.S. currency by electronic check, check, 
bank draft, wire transfer, credit card, or U.S. postal money order 
payable to the order of the Food and Drug Administration. The preferred 
payment method is online using electronic check (Automated Clearing 
House (ACH) also known as eCheck). Secure electronic payments can be 
submitted using the User Fees Payment Portal at https://userfees.fda.gov/pay (Note: Only full payments are accepted. No partial 
payments can be made online). Once you search for your invoice, select 
``Pay Now'' to be redirected to Pay.gov. Note that electronic payment 
options are based on the balance due. Payment by credit card is 
available for balances that are less than $25,000. If the balance 
exceeds this amount, only the ACH option is available. Payments must be 
made using U.S bank accounts as well as U.S. credit cards.
    If paying by paper check the invoice number should be included on 
the check, followed by the words ``Rare Pediatric Disease Priority 
Review.'' All paper checks must be in U.S. currency from a U.S. bank 
made payable and mailed to: Food and Drug Administration, P.O. Box 
979107, St. Louis, MO 63197-9000.
    If checks are sent by a courier that requests a street address, the 
courier can deliver the checks to: U.S. Bank, Attention: Government 
Lockbox 979107, 1005 Convention Plaza, St. Louis, MO 63101. (Note: This 
U.S. Bank address is for courier delivery only. If you have any 
questions concerning courier delivery, contact the U.S. Bank at 314-
418-4013. This telephone number is only for questions about courier 
delivery). The FDA post office box number (P.O. Box 979107) must be 
written on the check. If needed, FDA's tax identification number is 53-
0196965.
    If paying by wire transfer, please reference your invoice number 
when completing your transfer. The originating financial institution 
may charge a wire transfer fee. If the financial institution charges a 
wire transfer fee, it is required to add that amount to the payment to 
ensure that the invoice is paid in full. The account information is as 
follows: U.S. Dept. of the Treasury, TREAS NYC, 33 Liberty St., New 
York, NY 10045, Account Number: 75060099, Routing Number: 021030004, 
SWIFT: FRNYUS33.

V. Reference

    The following reference is on display at the Dockets Management 
Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 
1061, Rockville, MD 20852, 240-402-7500, and is available for viewing 
by interested persons between 9 a.m. and 4 p.m., Monday through Friday; 
it is not available electronically at https://www.regulations.gov as 
this reference is copyright protected. FDA has verified the website 
address, as of the date this document publishes in the Federal 
Register, but websites are subject to change over time.

1. Ridley, D.B., H.G. Grabowski, and J.L. Moe, ``Developing Drugs 
for Developing Countries,'' Health Affairs, vol. 25, no. 2, pp. 313-
324, 2006, available at: https://www.healthaffairs.org/doi/full/10.1377/hlthaff.25.2.313.

    Dated: September 27, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-21329 Filed 9-29-21; 8:45 am]
BILLING CODE 4164-01-P