Federal Register / Vol. 83, No. 145 / Friday, July 27, 2018 / Notices 35649 

not withdrawn from sale for reasons of 

safety or effectiveness. 

Accordingly, the Agency will 

continue to list metaxalone tablets, 640 

mg, in the ‘‘Discontinued Drug Product 

List’’ section of the Orange Book. The 

‘‘Discontinued Drug Product List’’ 

delineates, among other items, drug 

products that have been discontinued 

from marketing for reasons other than 

safety or effectiveness. ANDAs that refer 

to metaxalone tablets, 640 mg, may be 

approved by the Agency as long as they 

meet all other legal and regulatory 

requirements for the approval of 

ANDAs. If FDA determines that labeling 

for this drug product should be revised 

to meet current standards, the Agency 

will advise ANDA applicants to submit 

such labeling. 

Dated: July 20, 2018. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2018–16031 Filed 7–26–18; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2016–N–0007] 

Generic Drug User Fee Rates for Fiscal 

Year 2019 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Federal Food, Drug, and 

Cosmetic Act (FD&C Act), as amended 

by the Generic Drug User Fee 

Amendments of 2017 (GDUFA II), 

authorizes the Food and Drug 

Administration (FDA, Agency, or we) to 

assess and collect fees for abbreviated 

new drug applications (ANDAs), drug 

master files (DMFs), generic drug active 

pharmaceutical ingredient (API) 

facilities, finished dosage form (FDF) 

facilities, contract manufacturing 

organization (CMO) facilities, and 

generic drug applicant program user 

fees. In this document, FDA is 

announcing fiscal year (FY) 2019 rates 

for GDUFA II fees. 

FOR FURTHER INFORMATION CONTACT: 

Melissa Hurley, Office of Financial 

Management, Food and Drug 

Administration, 8455 Colesville Rd., 

COLE–14202J, Silver Spring, MD 

20993–0002, 240–402–4585. 

SUPPLEMENTARY INFORMATION: 

I. Background 

Sections 744A and 744B of the FD&C 

Act (21 U.S.C. 379j–41 and 379j–42) 

establish fees associated with human 

generic drug products. Fees are assessed 

on: (1) Certain types of applications for 

human generic drug products; (2) 

certain facilities where APIs and FDFs 

are produced; (3) certain DMFs 

associated with human generic drug 

products; and (4) generic drug 

applicants who have approved ANDAs 

(the program fee) (see section 

744B(a)(2)–(5) of the FD&C Act). 

GDUFA II stipulates that user fees 

should total $493,600,000 annually 

adjusted each year for inflation. For FY 

2019, the generic drug fee rates are: 

ANDA ($178,799), DMF ($55,013), 

domestic API facility ($44,226), foreign 

API facility ($59,226), domestic FDF 

facility ($211,305), foreign FDF facility 

($226,305), domestic CMO facility 

($70,435), foreign CMO facility 

($85,435), large size operation generic 

drug applicant program ($1,862,167), 

medium size operation generic drug 

applicant program ($744,867), and small 

business generic drug applicant program 

($186,217). These fees are effective on 

October 1, 2018, and will remain in 

effect through September 30, 2019. 

II. Fee Revenue Amount for FY 2019 

The base revenue amount for FY 2019 

is $493,600,000, as set in the statute (see 

section 744B(b)(1) of the FD&C Act). 

GDUFA II directs FDA to use the yearly 

revenue amount as a starting point to set 

the fee rates for each fee type. For more 

information about GDUFA II, please 

refer to the FDA website (https://

www.fda.gov/gdufa). The ANDA, DMF, 

API facility, FDF facility, CMO facility, 

and generic drug applicant program fee 

(GDUFA program fee) calculations for 

FY 2019 are described in this document. 

GDUFA II specifies that the 

$493,600,000 is to be adjusted for 

inflation increases for FY 2019 using 

two separate adjustments—one for 

personnel compensation and benefits 

(PC&B) and one for non-PC&B costs (see 

sections 744B(c)(1)(B) and (C) of the 

FD&C Act). 

The component of the inflation 

adjustment for PC&B costs shall be one 

plus the average annual percent change 

in the cost of all PC&B paid per full-time 

equivalent position (FTE) at FDA for the 

first 3 of the 4 preceding fiscal years, 

multiplied by the proportion of PC&B 

costs to total FDA costs of human 

generic drug activities for the first 3 of 

the preceding 4 fiscal years (see section 

744B(c)(1)(B) of the FD&C Act). 

Table 1 summarizes the actual cost 

and total FTE for the specified fiscal 

years, and provides the percent change 

from the previous fiscal year and the 

average percent change over the first 3 

of the 4 fiscal years preceding FY 2019. 

The 3-year average is 2.4152 percent. 

TABLE 1—FDA PERSONNEL COMPENSATION AND BENEFITS (PC&B) EACH YEAR AND PERCENT CHANGE

Fiscal year 2015 2016 2017 3-Year average 

Total PC&B .............................................................................. $2,232,304,000 $2,414,728,159 $2,581,551,000 ..............................

Total FTE ................................................................................. 15,484 16,381 17,022 ..............................

PC&B per FTE ......................................................................... $144,168 $147,408 $151,660 ..............................

Percent Change from Previous Year ...................................... 2.1136 2.2474 2.8845 2.4152 

The statute specifies that this 2.4152 

percent should be multiplied by the 

proportion of PC&B expended for 

human generic drug activities for the 

first 3 of the preceding 4 fiscal years. 

Table 2 shows the amount of PC&B and 

the total amount obligated for human 

generic drug activities from FY 2015 

through FY 2017. 

TABLE 2—PC&B AS A PERCENT OF FEE REVENUES SPENT ON THE PROCESS OF HUMAN GENERIC DRUG APPLICATIONS

OVER THE LAST 3 YEARS

Fiscal year 2015 2016 2017 3-Year average 

PC&B ....................................................................................... $201,116,305 $242,963,571 $271,748,229 ..............................

Non-PC&B ............................................................................... $251,589,013 $250,987,599 $262,058,852 ..............................

Total Costs ............................................................................... $452,705,318 $493,951,170 $533,807,081 ..............................


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TABLE 2—PC&B AS A PERCENT OF FEE REVENUES SPENT ON THE PROCESS OF HUMAN GENERIC DRUG APPLICATIONS

OVER THE LAST 3 YEARS—Continued 

Fiscal year 2015 2016 2017 3-Year average 

PC&B Percent .......................................................................... 44.4254 49.1878 50.9076 48.1736 

Non-PC&B Percent .................................................................. 55.5746 50.8122 49.0924 51.8264 

The payroll adjustment is 2.4152 

percent multiplied by 48.1736 percent 

(or 1.1635 percent). 

The statute specifies that the portion 

of the inflation adjustment for nonPC&B costs for FY 2019 is the average 

annual percent change that occurred in 

the Consumer Price Index (CPI) for 

urban consumers (WashingtonBaltimore, DC-MD-VA-WV; not 

seasonally adjusted; all items; annual 

index) for the first 3 of the preceding 4 

years of available data multiplied by the 

proportion of all costs other than PC&B 

costs to total costs of human generic 

drug activities (see section 744B(c)(1)(C) 

of the FD&C Act). Table 3 provides the 

summary data for the percent change in 

the specified CPI. The data are 

published by the Bureau of Labor 

Statistics and can be found on its 

website at: https://data.bls.gov/pdq/ 

SurveyOutputServlet?data_

tool=dropmap&series_

id=CUURA311SA0,CUUSA311SA0. 

TABLE 3—ANNUAL AND 3-YEAR AVERAGE PERCENT CHANGE IN CPI FOR BALTIMORE-WASHINGTON AREA

Year 2015 2016 2017 3-Year average 

Annual CPI ............................................................................... 155.353 157.180 159.202 ..............................

Annual Percent Change .......................................................... 0.3268 1.1760 1.2864 0.9297 

To calculate the inflation adjustment 

for non-pay costs, we multiply the 3- 

year average percent change in the CPI 

(0.9297 percent) by the proportion of all 

costs other than PC&B to total costs of 

human generic drug activities obligated. 

Because 48.1736 percent was obligated 

for PC&B as shown in table 2, 51.8264 

percent is the portion of costs other than 

PC&B. The non-pay adjustment is 

0.9297 percent times 51.8264 percent, or 

0.4818 percent. 

To complete the inflation adjustment 

for FY 2019, we add the PC&B 

component (1.1635 percent) to the nonPC&B component (0.4818 percent) for a 

total inflation adjustment of 1.6453 

percent (rounded), making 1.016453. 

We then multiply the base revenue 

amount for FY 2019 ($493,600,000) by 

1.016453, yielding an inflation-adjusted 

amount of $501,721,000 (rounded to the 

nearest thousand dollars). 

III. ANDA Filing Fee 

Under GDUFA II, the FY 2019 ANDA 

filing fee is owed by each applicant that 

submits an ANDA on or after October 1, 

2018. This fee is due on the submission 

date of the ANDA. Section 744B(b)(2)(B) 

of the FD&C Act specifies that the 

ANDA fee will make up 33 percent of 

the $501,721,000, which is 

$165,567,930. 

To calculate the ANDA fee, FDA 

estimated the number of full application 

equivalents (FAEs) that will be 

submitted in FY 2019. The submissions 

are broken down into three categories: 

New originals (submissions that have 

not been received by FDA previously); 

submissions that have been refused to 

receive (RTR) for reasons other than 

failure to pay fees; and applications that 

are resubmitted after having been RTR 

for reasons other than failure to pay 

fees. An ANDA counts as one FAE; 

however, 75 percent of the fee paid for 

an ANDA that has been RTR shall be 

refunded according to GDUFA II if (1) 

the ANDA is refused for a cause other 

than failure to pay fees, or (2) the ANDA 

has been withdrawn prior to receipt 

(section 744B(a)(2)(D)(i) of the FD&C 

Act). Therefore, an ANDA that is 

considered not to have been received by 

FDA due to reasons other than failure to 

pay fees or withdrawn prior to receipt 

counts as one-fourth of an FAE. After an 

ANDA has been RTR, the applicant has 

the option of resubmitting. For user fee 

purposes, these resubmissions are 

equivalent to new original 

submissions—ANDA resubmissions are 

charged the full amount for an 

application (one FAE). 

FDA utilized data from ANDAs 

submitted from October 1, 2013, to 

April 30, 2018, to estimate the number 

of new original ANDAs that will incur 

filing fees in FY 2019. For FY 2019, the 

Agency estimates that approximately 

918 new original ANDAs will be 

submitted and incur filing fees. Not all 

of the new original ANDAs will be 

received by the Agency and some of 

those not received will be resubmitted 

in the same fiscal year. Therefore, the 

Agency expects that the FAE count for 

ANDAs will be 926 for FY 2019. 

The FY 2019 application fee is 

estimated by dividing the number of 

FAEs that will pay the fee in FY 2019 

(926) into the fee revenue amount to be 

derived from ANDA application fees in 

FY 2019 ($165,567,930). The result, 

rounded to the nearest dollar, is a fee of 

$178,799 per ANDA. 

The statute provides that those 

ANDAs that include information about 

the production of active pharmaceutical 

ingredients other than by reference to a 

DMF will pay an additional fee that is 

based on the number of such active 

pharmaceutical ingredients and the 

number of facilities proposed to 

produce those ingredients (see section 

744B(a)(3)(F) of the FD&C Act). FDA 

considers that this additional fee is 

unlikely to be assessed often; therefore, 

FDA has not included projections 

concerning the amount of this fee in 

calculating the fees for ANDAs. 

IV. DMF Fee 

Under GDUFA II, the DMF fee is 

owed by each person that owns a type 

II active pharmaceutical ingredient DMF 

that is referenced, on or after October 1, 

2012, in a generic drug submission by 

an initial letter of authorization. This is 

a one-time fee for each DMF. This fee is 

due on the earlier of the date on which 

the first generic drug submission is 

submitted that references the associated 

DMF or the date on which the drug 

master file holder requests the initial 

completeness assessment. Under section 

744B(a)(2)(D)(iii) of the FD&C Act, if a 

DMF has successfully undergone an 

initial completeness assessment and the 

fee is paid, the DMF will be placed on 

a publicly available list documenting 

DMFs available for reference. 

To calculate the DMF fee, FDA 

assessed the volume of DMF 


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submissions over time. The Agency 

assessed DMFs from October 1, 2016, to 

April 30, 2018, and concluded that 

averaging the number of fee-paying 

DMFs provided the most accurate model 

for predicting fee-paying DMFs for FY 

2019. The monthly average of paid DMF 

submissions the Agency received in FY 

2017 and FY 2018 is 38. To determine 

the FY 2019 projected number of feepaying DMFs, the average of 38 DMF 

submissions is multiplied by 12 months, 

which results in 456 estimated FY 2019 

fee-paying DMFs. FDA is estimating 456 

fee-paying DMFs for FY 2019. 

The FY 2019 DMF fee is determined 

by dividing the DMF target revenue by 

the estimated number of fee-paying 

DMFs in FY 2019. Section 744B(b)(2)(A) 

of the FD&C Act specifies that the DMF 

fees will make up 5 percent of the 

$501,721,000, which is $25,086,050. 

Dividing the DMF revenue amount 

($25,086,050) by the estimated feepaying DMFs (456), and rounding to the 

nearest dollar, yields a DMF fee of 

$55,013 for FY 2019. 

V. Foreign Facility Fee Differential 

Under GDUFA II, the fee for a facility 

located outside the United States and its 

territories and possessions shall be 

$15,000 higher than the amount of the 

fee for a facility located in the United 

States and its territories and 

possessions. The basis for this 

differential is the extra cost incurred by 

conducting an inspection outside the 

United States and its territories and 

possessions. 

VI. FDF and CMO Facility Fees 

Under GDUFA II, the annual FDF 

facility fee is owed by each person who 

owns an FDF facility that is identified 

in at least one approved generic drug 

submission owned by that person or his 

affiliates. The CMO facility fee is owed 

by each person who owns an FDF 

facility that is identified in at least one 

approved ANDA but is not identified in 

an approved ANDA held by the owner 

of that facility or its affiliates. These fees 

are due no later than the first business 

day on or after October 1 of each such 

year. Section 744B(b)(2)(C) of the FD&C 

Act specifies that the FDF and CMO 

facility fee revenue will make up 20 

percent of the $501,721,000, which is 

$100,344,200. 

To calculate the fees, data from FDA’s 

Integrity Services (IS) were utilized as 

the primary source of facility 

information for determining the 

denominators of each facility fee type. 

IS is the master data steward for all 

facility information provided in generic 

drug submissions received by FDA. A 

facility’s reference status in an approved 

generic drug submission is extracted 

directly from submission data rather 

than relying on data from selfidentification. This information 

provided the number of facilities 

referenced as FDF manufacturers in at 

least one approved generic drug 

submission. Based on FDA’s IS data, the 

FDF and CMO facility denominators are 

180 FDF domestic, 216 FDF foreign, 73 

CMO domestic, and 97 CMO foreign 

facilities for FY 2019. 

GDUFA II specifies that the CMO 

facility fee is to be equal to one-third the 

amount of the FDF facility fee. 

Therefore, to generate the target 

collection revenue amount from FDF 

and CMO facility fees ($100,344,200), 

FDA must weight a CMO facility as onethird of an FDF facility. FDA set fees 

based on the estimate of 180 FDF 

domestic, 216 FDF foreign, 24.33 CMO 

domestic (73 multiplied by one-third), 

and 32.33 CMO foreign facilities (97 

multiplied by one-third), which equals 

452.66 total weighted FDF and CMO 

facilities for FY 2019. 

To calculate the fee for domestic 

facilities, FDA first determines the total 

fee revenue that will result from the 

foreign facility differential by 

subtracting the fee revenue resulting 

from the foreign facility fee differential 

from the target collection revenue 

amount ($100,344,200) as follows. The 

foreign facility fee differential revenue 

equals the foreign facility fee differential 

($15,000) multiplied by the number of 

FDF foreign facilities (216) plus the 

foreign facility fee differential ($15,000) 

multiplied by the number of CMO 

foreign facilities (97), totaling 

$4,695,000. This results in foreign fee 

differential revenue of $4,695,000 from 

the total FDF and CMO facility fee target 

collection revenue. Subtracting the 

foreign facility differential fee revenue 

($4,695,000) from the total FDF and 

CMO facility target collection revenue 

($100,344,200) results in a remaining 

facility fee revenue balance of 

$95,649,200. To determine the domestic 

FDF facility fee, FDA divides the 

$95,649,200 by the total weighted 

number of FDF and CMO facilities 

(452.66), which results in a domestic 

FDF facility fee of $211,305. The foreign 

FDF facility fee is $15,000 more than the 

domestic FDF facility fee, or $226,305. 

According to GDUFA II, the domestic 

CMO fee is calculated as one-third the 

amount of the domestic FDF facility fee. 

Therefore, the domestic CMO fee is 

$70,435, rounded to the nearest dollar. 

The foreign CMO fee is calculated as the 

domestic CMO fee plus the foreign fee 

differential of $15,000. Therefore, the 

foreign CMO fee is $85,435. 

VII. API Facility Fee 

Under GDUFA II, the annual API 

facility fee is owed by each person who 

owns a facility that is identified in (1) 

at least one approved generic drug 

submission or (2) in a Type II API DMF 

referenced in at least one approved 

generic drug submission. These fees are 

due no later than the first business day 

on or after October 1 of each such year. 

Section 744B(b)(2)(D) of the FD&C Act 

specifies the API facility fee will make 

up 7 percent of $501,721,000 in fee 

revenue, which is $35,120,470. 

To calculate the API facility fee, data 

from FDA’s IS were utilized as the 

primary source of facility information 

for determining the denominator. As 

stated above, IS is the master data 

steward for all facility information 

provided in generic drug submissions 

received by FDA. A facility’s reference 

status in an approved generic drug 

submission is extracted directly from 

submission data rather than relying on 

data from self-identification. This 

information provided the number of 

facilities referenced as API 

manufacturers in at least one approved 

generic drug submission. 

The total number of API facilities 

identified was 613; of that number, 79 

were domestic and 534 were foreign 

facilities. The foreign facility differential 

is $15,000. To calculate the fee for 

domestic facilities, FDA must first 

subtract the fee revenue that will result 

from the foreign facility fee differential. 

FDA takes the foreign facility 

differential ($15,000) and multiplies it 

by the number of foreign facilities (534) 

to determine the total fee revenue that 

will result from the foreign facility 

differential. As a result of that 

calculation, the foreign fee differential 

revenue will make up $8,010,000 of the 

total API fee revenue. Subtracting the 

foreign facility differential fee revenue 

($8,010,000) from the total API facility 

target revenue ($35,120,470) results in a 

remaining balance of $27,110,470. To 

determine the domestic API facility fee, 

we divide the $27,110,470 by the total 

number of facilities (613), which gives 

us a domestic API facility fee of 

$44,226. The foreign API facility fee is 

$15,000 more than the domestic API 

facility fee, or $59,226. 

VIII. Generic Drug Applicant Program 

Fee 

Under GDUFA II, if a person and its 

affiliates own at least one but not more 

than five approved ANDAs on October 

1, 2018, the person and its affiliates 

shall owe a small business GDUFA 

program fee. If a person and its affiliates 

own at least 6 but not more than 19 


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approved ANDAs, the person and its 

affiliates shall owe a medium size 

operation GDUFA program fee. If a 

person and its affiliates own at least 20 

approved ANDAs, the person and its 

affiliates shall owe a large size operation 

GDUFA program fee. These fees are due 

no later than the first business day on 

or after October 1 of each such year. 

Section 744B(b)(2)(E) of the FD&C Act 

specifies the GDUFA program fee will 

make up 35 percent of $501,721,000 in 

fee revenue, which is $175,602,350. 

To determine the appropriate number 

of applicants for each tier, the Agency 

has posted lists of approved ANDAs on 

the FDA website (https://www.fda.gov/ 

gdufa) and asked applicants on the list 

to claim which ANDAs and affiliates 

belong to the parent company. The 

original list of approved ANDAs came 

from the Agency’s Document Archiving, 

Reporting, and Regulatory Tracking 

System (DARRTS), which included all 

ANDAs with the status of ‘‘approved’’ as 

of April 30, 2018. 

In determining the appropriate 

number of approved ANDAs, the 

Agency has factored in a number of 

variables that could affect the collection 

of the target revenue: (1) Inactive 

ANDAs—applicants who have not 

submitted an annual report for one or 

more of their approved applications 

within the past 2 years; (2) FY 2018 

Program Fee Arrears List—applicants 

who failed to satisfy the FY 2018 

program fee and were unresponsive to 

attempts to collect; and (3) Prediction of 

Approvals Due to Goal Dates and Office 

of Generic Drugs Approval Rate—Due to 

the low percentage of additional 

approved ANDAs for a specified time 

period and the difficulties in 

determining how this population would 

affect the program fee tier of each 

company, this variable was not included 

in the determination of the FY 2019 

GDUFA program fee. The list of original 

approved ANDAs from the DARRTS 

database as of April 30, 2018, shows 259 

applicants in the small business tier, 62 

applicants in the medium size tier, and 

58 applicants in the large size tier. This 

list also takes into account all the 

withdrawals, consolidations, and 

transfer of ownerships from industry as 

of April 30, 2018. Factoring in all the 

variables for the second year of GDUFA 

II, the Agency estimates there will be 

177 applicants in the small business 

tier, 49 applicants in the medium size 

tier, and 57 applicants in the large size 

tier for FY 2019. 

To calculate the GDUFA program fee, 

GDUFA II provides that large size 

operation generic drug applicants pay 

the full fee, medium size operation 

applicants pay two-fifths of the full fee, 

and small business applicants pay onetenth of the full fee. To generate the 

target collection revenue amount from 

GDUFA program fees ($175,602,350), 

we must weigh medium and small 

tiered applicants as a subset of a large 

size operation generic drug applicant. 

FDA will set fees based on the weighted 

estimate of 17.70 applicants in the small 

business tier (177 multiplied by 10 

percent), 19.60 applicants in the 

medium size tier (49 multiplied by 40 

percent), and 57 applicants in the large 

size tier, arriving at 94.30 total weighted 

applicants for FY 2019. 

To generate the large size operation 

GDUFA program fee, FDA divides the 

target revenue amount of $175,602,350 

by 94.30, which equals $1,862,167. The 

medium size operation GDUFA program 

fee is 40 percent of the full fee 

($744,867), and the small business 

operation GDUFA program fee is 10 

percent of the full fee ($186,217). 

IX. Fee Schedule for FY 2019 

The fee rates for FY 2019 are set out 

in table 4. 

TABLE 4—FEE SCHEDULE FOR FY 2019 

Fee category Fees rates for 

FY 2019 

Applications: ........................

Abbreviated New Drug Application (ANDA) ................................................................................................................................. $178,799 

Drug Master File (DMF) ............................................................................................................................................................... 55,013 

Facilities: ........................

Active Pharmaceutical Ingredient (API) Domestic .............................................................................................................................. 44,226 

API—Foreign ................................................................................................................................................................................ 59,226 

Finished Dosage Form (FDF)—Domestic .................................................................................................................................... 211,305 

FDF—Foreign ............................................................................................................................................................................... 226,305 

Contract Manufacturing Organization (CMO)—Domestic ............................................................................................................ 70,435 

CMO—Foreign .............................................................................................................................................................................. 85,435 

GDUFA Program: ........................

Large size operation generic drug applicant ................................................................................................................................ 1,862,167 

Medium size operation generic drug applicant ............................................................................................................................ 744,867 

Small business operation generic drug applicant ........................................................................................................................ 186,217 

X. Fee Payment Options and 

Procedures 

The new fee rates are effective 

October 1, 2018. To pay the ANDA, 

DMF, API facility, FDF facility, CMO 

facility, and GDUFA program fees, a 

Generic Drug User Fee Cover Sheet must 

be completed, available at https://

www.fda.gov/gdufa and https://

userfees.fda.gov/OA_HTML/ 

gdufaCAcdLogin.jsp, and a user fee 

identification (ID) number must be 

generated. Payment must be made in 

U.S. currency drawn on a U.S. bank by 

electronic check, check, bank draft, U.S. 

postal money order, credit card, or wire 

transfer. The preferred payment method 

is online using electronic check 

(Automated Clearing House (ACH), also 

known as eCheck) or credit card 

(Discover, VISA, MasterCard, American 

Express). Secure electronic payments 

can be submitted using the User Fees 

Payment Portal at https://

userfees.fda.gov/pay. (Note: IOnly full 

payments are accepted; no partial 

payments can be made online.) Once an 

invoice is located, ‘‘Pay Now’’ should be 

selected to be redirected to https://

www.pay.gov/public/home (Pay.gov). 

Electronic payment options are based on 

the balance due. Payment by credit card 

is available for balances 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. 

FDA has partnered with the U.S. 

Department of the Treasury to utilize 

Pay.gov, a web-based payment 

application, for online electronic 

payment. The Pay.gov feature is 

available on the FDA website after 

completing the Generic Drug User Fee 


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Cover Sheet and generating the user fee 

ID number. 

The user fee ID number must be 

included on the check, bank draft, or 

postal money order and must be made 

payable to the order of the Food and 

Drug Administration. Payments can be 

mailed to: Food and Drug 

Administration, P.O. Box 979108, St. 

Louis, MO 63197–9000. If checks are to 

be sent by a courier that requests a street 

address, the courier can deliver checks 

to: U.S. Bank, Attention: Government 

Lockbox 979108, 1005 Convention 

Plaza, St. Louis, MO 63101. (Note: This 

U.S. Bank address is for courier delivery 

only. For questions concerning courier 

delivery, U.S. Bank can be contacted at 

314–418–4013. This telephone number 

is only for questions about courier 

delivery.) The FDA post office box 

number (P.O. Box 979108) must be 

written on the check, bank draft, or 

postal money order. 

For payments made by wire transfer, 

the unique user fee ID number must be 

referenced. Without the unique user fee 

ID number, the payment may not be 

applied. If the payment amount is not 

applied, the invoice amount will be 

referred to collections. The originating 

financial institution may charge a wire 

transfer fee. Applicable wire transfer 

fees must be included with payment to 

ensure fees are fully paid. Questions 

about wire transfer fees should be 

addressed to the financial institution. 

The following account information 

should be used to send payments by 

wire transfer: U.S. Department of 

Treasury, TREAS NYC, 33 Liberty St., 

New York, NY 10045, account number: 

75060099, routing number: 021030004, 

SWIFT: FRNYUS33. FDA’s tax 

identification number is 53–0196965. 

Dated: July 24, 2018. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2018–16067 Filed 7–26–18; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2018–D–2456] 

Slowly Progressive, Low-Prevalence 

Rare Diseases With Substrate 

Deposition That Results From Single 

Enzyme Defects: Providing Evidence 

of Effectiveness for Replacement or 

Corrective Therapies; Draft Guidance 

for Industry; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice of availability. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) is 

announcing the availability of a draft 

guidance for industry entitled ‘‘Slowly 

Progressive, Low-Prevalence Rare 

Diseases with Substrate Deposition That 

Results from Single Enzyme Defects: 

Providing Evidence of Effectiveness for 

Replacement or Corrective Therapies.’’ 

This document is intended to provide 

guidance to sponsors on the evidence 

necessary to demonstrate the 

effectiveness of new drugs, including 

biological drugs, or new drug uses 

intended for slowly progressive, lowprevalence rare diseases that are 

associated with substrate deposition and 

are caused by single enzyme defects. 

This guidance applies only to those lowprevalence rare diseases with a wellcharacterized pathophysiology and in 

which changes in substrate deposition 

can be readily measured in relevant 

tissue(s). 

DATES: Submit either electronic or 

written comments on the draft guidance 

by September 25, 2018 to ensure that 

the Agency considers your comment on 

this draft guidance before it begins work 

on the final version of the guidance. 

ADDRESSES: You may submit comments 

on any guidance at any time as follows: 

Electronic Submissions 

Submit electronic comments in the 

following way: 

• Federal eRulemaking Portal: 

https://www.regulations.gov. Follow the 

instructions for submitting comments. 

Comments submitted electronically, 

including attachments, to https://

www.regulations.gov will be posted to 

the docket unchanged. Because your 

comment will be made public, you are 

solely responsible for ensuring that your 

comment does not include any 

confidential information that you or a 

third party may not wish to be posted, 

such as medical information, your or 

anyone else’s Social Security number, or 

confidential business information, such 

as a manufacturing process. Please note 

that if you include your name, contact 

information, or other information that 

identifies you in the body of your 

comments, that information will be 

posted on https://www.regulations.gov. 

• If you want to submit a comment 

with confidential information that you 

do not wish to be made available to the 

public, submit the comment as a 

written/paper submission and in the 

manner detailed (see ‘‘Written/Paper 

Submissions’’ and ‘‘Instructions’’). 

Written/Paper Submissions 

Submit written/paper submissions as 

follows: 

• Mail/Hand delivery/Courier (for 

written/paper submissions): Dockets 

Management Staff (HFA–305), Food and 

Drug Administration, 5630 Fishers 

Lane, Rm. 1061, Rockville, MD 20852. 

• For written/paper comments 

submitted to the Dockets Management 

Staff, FDA will post your comment, as 

well as any attachments, except for 

information submitted, marked and 

identified, as confidential, if submitted 

as detailed in ‘‘Instructions.’’ 

Instructions: All submissions received 

must include the Docket No. FDA– 

2018–D–2456 for ‘‘Slowly Progressive, 

Low-Prevalence Rare Diseases with 

Substrate Deposition That Results from 

Single Enzyme Defects: Providing 

Evidence of Effectiveness for 

Replacement or Corrective Therapies; 

Draft Guidance for Industry; 

Availability.’’ Received comments will 

be placed in the docket and, except for 

those submitted as ‘‘Confidential 

Submissions,’’ publicly viewable at 

https://www.regulations.gov or at the 

Dockets Management Staff between 9 

a.m. and 4 p.m., Monday through 

Friday. 

• Confidential Submissions—To 

submit a comment with confidential 

information that you do not wish to be 

made publicly available, submit your 

comments only as a written/paper 

submission. You should submit two 

copies total. One copy will include the 

information you claim to be confidential 

with a heading or cover note that states 

‘‘THIS DOCUMENT CONTAINS 

CONFIDENTIAL INFORMATION.’’ The 

Agency will review this copy, including 

the claimed confidential information, in 

its consideration of comments. The 

second copy, which will have the 

claimed confidential information 

redacted/blacked out, will be available 

for public viewing and posted on 

https://www.regulations.gov. Submit 

both copies to the Dockets Management 

Staff. If you do not wish your name and 

contact information to be made publicly 

available, you can provide this 

information on the cover sheet and not 

in the body of your comments and you 

must identify this information as 

‘‘confidential.’’ Any information marked 

as ‘‘confidential’’ will not be disclosed 

except in accordance with 21 CFR 10.20 

and other applicable disclosure law. For 

more information about FDA’s posting 

of comments to public dockets, see 80 

FR 56469, September 18, 2015, or access 

the information at: https://www.gpo.gov/ 

fdsys/pkg/FR-2015-09-18/pdf/2015- 

23389.pdf. 


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