Federal Register / Vol. 87, No. 79 / Monday, April 25, 2022 / Notices 24311 

1The guidance ‘‘Medical Device User Fee Small 

Business Qualification and Certification Guidance 

for Industry, Food and Drug Administration Staff 

and Foreign Governments’’ is available at https://

www.fda.gov/regulatory-information/search-fdaguidance-documents/medical-device-user-feesmall-business-qualification-and-certification. 

$30 million (including all affiliates, 

partners, and parent firms), they will 

also qualify for a waiver of the fee for 

their first (ever) premarket application, 

product development protocol, 

biological licensing application, or 

premarket report. A ‘‘small business’’ is 

eligible for reduced or waived fees. If an 

applicant does not provide information 

to FDA demonstrating to FDA’s 

satisfaction that the applicant is a small 

business, the applicant must pay the 

standard (full) fee for any application it 

submits. 

Forms FDA 3602 (‘‘MDUFA Small 

Business Certification Request for a 

Business Headquartered in the United 

States’’) and 3602A (‘‘MDUFA Foreign 

Small Business Certification Request for 

a Business Headquartered Outside the 

United States’’) are submitted to FDA to 

demonstrate that an applicant qualifies 

as a MDUFA small business. The 

guidance ‘‘Medical Device User Fee 

Small Business Qualification and 

Certification; Guidance for Industry, 

Food and Drug Administration Staff and 

Foreign Governments’’ 1 describes the 

process by which a business may 

request certification as a small business 

and the criteria FDA will use to decide 

whether an entity qualifies as a MDUFA 

small business and is eligible for a 

reduction in user fees. 

In the Federal Register of December 

23, 2021 (86 FR 72983), we published a 

60-day notice requesting public 

comment on the proposed collection of 

information. One comment was 

received, however it did not respond to 

the functional elements solicited in our 

60-day notice or suggest a revision to 

our burden estimate. 

We estimate the burden of this 

collection of information as follows: 

TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1

FDA form No. Number of 

respondents 

Number of 

responses per 

respondent 

Total annual 

responses 

Average 

burden per 

response 

Total hours 

FDA 3602—MDUFA Small Business Certification Request 

For a Business Headquartered in the United States ....... 2,500 1 2,500 1 2,500 

FDA 3602A—MDUFA Foreign Small Business Certification 

Request For a Business Headquartered Outside the 

United States .................................................................... 2,000 1 2,000 1 2,000 

Total .............................................................................. ........................ ........................ ........................ ........................ 4,500 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

Our estimated burden is based on the 

number of applications received in the 

last few years and includes the time we 

assume necessary to prepare and submit 

required information. Based on our 

experience with Forms FDA 3602 and 

3602A, we assume it will take 

respondents 1 hour to complete either 

form. We have adjusted our estimated 

‘‘No. of Respondents’’ to better reflect 

recent submission volume. This 

adjustment results in a 2,500-hour 

decrease to the information collection. 

Dated: April 19, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–08726 Filed 4–22–22; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–1975–N–0336 (formerly 

1975N–0184)] 

Drugs for Human Use; Drug Efficacy 

Study Implementation; Oral 

Prescription Drugs Containing an 

Anticholinergic or Antispasmodic in 

Combination With a Sedative, and 

Single-Entity Antispasmodic Drug 

Products, in Oral Dosage Form; 

Withdrawal of Hearing Requests; Final 

Resolution of Drug Efficacy Study 

Implementation 

AGENCY: Food and Drug Administration, 

Health and Human Services (HHS). 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) is 

announcing that all outstanding hearing 

requests regarding drug products 

containing an anticholinergic or 

antispasmodic in combination with a 

sedative, and single-entity 

antispasmodic drug products, in oral 

dosage form, under Docket FDA–1975– 

N–0336 (formerly 75N–0184) (DESI 

10837) have been withdrawn. Therefore, 

shipment in interstate commerce of any 

such product identified in Docket FDA– 

1975–N–0336 covered by DESI 10837, 

or any identical, related, or similar (IRS) 

product, that is not the subject of an 

approved new drug application (NDA) 

or abbreviated new drug application 

(ANDA) is unlawful as of the date of 

this notice. This notice does not affect 

products covered by DESI 597 under the 

same docket. 

DATES: This notice is applicable April 

25, 2022. 

ADDRESSES: For access to the docket to 

read background documents or the 

electronic and written/paper comments 

received, go to https://

www.regulations.gov and insert the 

docket number, found in brackets in the 

heading of this document, into the 

‘‘Search’’ box and follow the prompts 

and/or go to the Dockets Management 

Staff (HFA–305), 5630 Fishers Lane, 

Rm. 1061, Rockville, MD 20852. The 

most relevant background documents 

regarding this matter are available in the 

docket. However, additional background 

documents are available upon request 

(see FOR FURTHER INFORMATION CONTACT). 

FOR FURTHER INFORMATION CONTACT: 

Jeffrey Trunzo, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, Rm. 5111, 


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24312 Federal Register / Vol. 87, No. 79 / Monday, April 25, 2022 / Notices 

Silver Spring, MD 20993–0002, 301– 

796–2029, email: Jeffrey.Trunzo@

fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

When enacted in 1938, the Federal 

Food, Drug, and Cosmetic Act (FD&C 

Act) required that ‘‘new drugs’’ (21 

U.S.C. 321(p)) be approved for safety by 

FDA before they could legally be sold in 

interstate commerce. Between 1938 and 

1962, if a drug obtained approval, FDA 

considered drugs that were IRS (see 21 

CFR 310.6(b)(1)) to the approved drug to 

be covered by that approval and allowed 

those IRS drugs to be marketed without 

independent approval. 

In 1962, Congress amended the FD&C 

Act to require that new drugs be proven 

effective for their labeled indications, as 

well as safe, in order to obtain FDA 

approval. This amendment also required 

FDA to conduct a retrospective 

evaluation of the effectiveness of the 

drug products that FDA had approved 

as safe between 1938 and 1962. FDA 

contracted with the National Academy 

of Sciences/National Research Council 

(NAS/NRC) to make an initial 

evaluation of the effectiveness of over 

3,400 products that had been approved 

only for safety between 1938 and 1962. 

The NAS/NRC reports for these drug 

products were submitted to FDA in the 

late 1960s and early 1970s. The Agency 

reviewed and reevaluated the reports 

and published its findings in Federal 

Register notices. FDA’s administrative 

implementation of the NAS/NRC reports 

was called the Drug Efficacy Study 

Implementation (DESI). DESI covered 

the approximately 3,400 products 

specifically reviewed by the NAS/NRC, 

as well as the even larger number of IRS 

products that entered the market 

without FDA approval. 

All drugs covered by the DESI review 

are ‘‘new drugs’’ under the FD&C Act. 

If FDA’s final DESI determination 

classifies a drug product as lacking 

substantial evidence of effectiveness for 

one or more indications, that drug 

product and those IRS to it may no 

longer be marketed for such indications 

and are subject to enforcement action as 

unapproved new drugs. If FDA’s final 

DESI determination classifies the drug 

product as effective for one or more of 

its labeled indications, the drug can be 

marketed for such indications, provided 

it is the subject of an application 

approved for safety and effectiveness. 

Sponsors of drug products that have 

been found to be effective for one or 

more indications through the DESI 

process may rely on FDA’s effectiveness 

determinations, but typically must 

update their labeling to conform to the 

indication(s) found to be effective by 

FDA and include any additional safety 

information required by FDA. Those 

drug products with NDAs approved 

before 1962 for safety therefore require 

approved supplements to their original 

applications if one or more indications 

are found to be effective under DESI; 

IRS drug products require an approved 

NDA or ANDA, as appropriate. 

Furthermore, labeling for drug products 

classified as effective may contain only 

those indications for which the review 

found the product effective unless the 

firm marketing the product has received 

an approval for the additional 

indication(s). 

II. Final Resolution of Hearing Requests 

Regarding Oral Prescription Drugs 

Containing an Anticholinergic or 

Antispasmodic in Combination With a 

Sedative, and Single-Entity 

Antispasmodic Drug Products, in Oral 

Dosage Form Under Docket No. FDA– 

1975–N–0336 (Formerly 75N–0184); 

DESI 10837 

In a Federal Register notice published 

on June 22, 1971 (36 FR 11875) (1971 

Federal Register notice), FDA 

announced its evaluation of reports 

received from NAS/NRC under DESI 

10837, regarding anticholinergic drug 

products containing the following active 

ingredients: Prochlorperazine maleate 

and isopropamide iodide; 

oxyphencyclimine hydrochloride and 

meprobamate; oxyphencyclimine 

hydrochloride and hydroxyzine 

hydrochloride; tridihexethyl chloride 

and meprobamate; and propantheline 

bromide and thiopropazate 

hydrochloride. The drugs were found to 

be possibly effective as adjunctive 

therapy in peptic ulcer and in the 

irritable bowel syndrome (irritable 

colon, spastic colon, mucous colitis, 

functional gastrointestinal disorders); 

functional diarrhea; drug induced 

diarrhea; ulcerative colitis, and urinary 

bladder spasm, and urethral spasm (i.e., 

smooth muscle spasm). In addition, 

oxyphencyclimine and meprobamate 

preparations were found to be possibly 

effective for dysmenorrhea. These drugs 

were found to lack substantial evidence 

of effectiveness for their other labeled 

indications. 

In a Federal Register notice published 

November 11, 1975 (40 FR 52644) (1975 

Federal Register notice), the Agency 

explained that several of the products 

listed in the 1971 Federal Register 

notice may remain on the market while 

clinical studies were being conducted to 

determine their efficacy for the 

indications rated as ‘‘possibly effective,’’ 

because they were widely used in the 

treatment of peptic ulcer disease and 

functional bowel syndrome and were 

perceived as important and useful tools 

of therapy by many gastroenterologists 

and general practitioners (40 FR 52644 

at 52648). In addition to the products 

from the 1971 Federal Register notice, 

the 1975 Federal Register notice 

included several products, among them 

Librax Capsules, NDA 12–750, 

containing clidinium bromide and 

chlordiazepoxide, now manufactured by 

Bausch Health Companies, Inc. 

(Bausch), that had been the subject of 

safety-only applications approved 

before 1962 and that had not been 

reviewed by NAS/NRC. Librax Capsules 

was included in the 1975 Federal 

Register notice notwithstanding the 

Stipulation for Dismissal in Hoffman-La 

Roche, Inc. v. Richardson, et. al., Civil 

Action 11–73 (D.N.J. August 2, 1973), 

discussed below. The 1975 Federal 

Register notice set forth a timetable for 

conducting clinical efficacy studies for 

drug products subject to the notice. In 

a Federal Register notice published 

June 20, 1978 (43 FR 26490) (1978 

Federal Register notice), FDA 

announced a change in its previous 

policy for testing and marketing of the 

drugs that were subject of the November 

11, 1975, notice (e.g., Librax), including 

an extension of deadline for completion 

of the studies for 1 year. 

In a Federal Register notice published 

January 16, 1981(46 FR 3977) (1981 

Federal Register notice), FDA 

announced its evaluation of study 

reports received in response to the 1975 

Federal Register notice. FDA concluded 

that there was a lack of substantial 

evidence demonstrating the 

effectiveness of the drugs listed in the 

1975 notice, proposed to withdraw 

approval of the new drug applications, 

and offered an opportunity for hearing 

to manufacturers of the drugs listed in 

the notice, as well as to the 

manufacturers of IRS products. 

As set forth in a Federal Register 

notice published July 24, 2012 (77 FR 

43337) (2012 Federal Register notice), 

several companies submitted timely 

hearing requests in response to the 1981 

Federal Register notice, but the only 

such request that had not been 

withdrawn as of July 2012, was the 

request regarding Librax Capsules, filed 

by Roche Laboratories, manufacturer of 

Librax Capsules in 1981 (77 FR 43337 

at 43341). In response to the 2012 

Federal Register notice, Valeant 

Pharmaceuticals North America LLC 

(now Bausch) affirmed the hearing 

request regarding Librax Capsules by 

letter dated August 22, 2012. 

On May 23, 2016, FDA posted a 

Notice to Docket 1975–N–0336, 


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Federal Register / Vol. 87, No. 79 / Monday, April 25, 2022 / Notices 24313 

explaining that Librax is not subject to 

review under DESI because a new drug 

application for Librax was approved by 

the Agency on September 1, 1966, and 

at that time the Agency determined that 

Librax was safe and effective for the 

indications set forth in its labeling, 

(consistent with the Stipulation for 

Dismissal in Hoffman-La Roche, Inc. v. 

Richardson, et al., Civil Action 11–73 

(D.N.J. August 2, 1973)). On June 2, 

2016, Valeant responded by 

withdrawing its hearing request. 

There are no longer outstanding 

hearing requests pertaining to drug 

products containing an anticholinergic 

or antispasmodic in combination with a 

sedative, and single-entity 

antispasmodic drug products, in oral 

dosage form under Docket No. FDA– 

1975–N–0336, DESI 10837. Shipment in 

interstate commerce of any drug product 

identified in this docket under DESI 

10837, or any IRS product, that is not 

the subject of an approved NDA or 

ANDA is unlawful as of the applicable 

date of this notice (see DATES). Any 

person who wishes to determine 

whether a specific product is covered by 

this notice should write to Jeffrey 

Trunzo (see FOR FURTHER INFORMATION

CONTACT). Firms should be aware that, 

after the applicable date of this notice 

(see DATES), FDA intends to take 

enforcement action without further 

notice against any firm that 

manufactures or ships in interstate 

commerce any unapproved product 

covered by this notice. 

III. Discontinued Products 

Firms must notify the Agency of 

certain product discontinuations in 

writing under section 506C(a) of the 

FD&C Act (21 U.S.C. 356c) (see https:// 

www.fda.gov/Drugs/DrugSafety/ 

DrugShortages/ucm142398.htm). Some 

firms may have previously discontinued 

manufacturing or distributing products 

covered by this notice without 

discontinuing the listing as required 

under section 510(j) of the FD&C Act (21 

U.S.C. 360(j)). Other firms may 

discontinue manufacturing or 

distributing listed products in response 

to this notice. All firms are required to 

electronically update the listing of their 

products under 510(j) of the FD&C Act 

to reflect discontinuation of unapproved 

products covered by this notice (21 CFR 

207.57(b)). Questions on electronic drug 

listing updates should be sent to 

eDRLS@fda.hhs.gov. In addition to the 

required update, firms can also notify 

the Agency of product discontinuation 

by sending a letter, signed by the firm’s 

chief executive officer and fully 

identifying the discontinued product(s), 

including the product National Drug 

Code (NDC) number(s), and stating that 

the manufacturing and/or distribution of 

the product(s) have been discontinued. 

The letter should be sent electronically 

to Jeffrey Trunzo (see FOR FURTHER

INFORMATION CONTACT). FDA plans to 

rely on its existing records, including its 

drug listing records, the results of any 

future inspections, or other available 

information, when it identifies violative 

products for enforcement action. 

IV. Reformulated Products 

FDA cautions firms against 

reformulating products and marketing 

under the same name or substantially 

the same name (including a new name 

that contains the old name). 

Reformulated products marketed under 

a name previously identified with a 

different active ingredient or 

combinations of active ingredients have 

the potential to confuse healthcare 

practitioners and harm patients. 

Dated: April 20, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–08740 Filed 4–22–22; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2022–N–0081] 

Agency Information Collection 

Activities; Proposed Collection; 

Comment Request; Tradeoff Analysis 

of Prescription Drug Product Claims in 

Direct-to-Consumer and Healthcare 

Provider Promotion 

AGENCY: Food and Drug Administration, 

Health and Human Services (HHS). 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA, Agency, or we) is 

announcing an opportunity for public 

comment on the proposed collection of 

certain information by the Agency. 

Under the Paperwork Reduction Act of 

1995 (PRA), Federal Agencies are 

required to publish notice in the 

Federal Register concerning each 

proposed collection of information and 

to allow 60 days for public comment in 

response to the notice. This notice 

solicits comments on research entitled 

‘‘Tradeoff Analysis of Prescription Drug 

Product Claims in Direct-to-Consumer 

and Healthcare Provider Promotion.’’ 

DATES: Submit either electronic or 

written comments on the collection of 

information by June 24, 2022. 

ADDRESSES: You may submit comments 

as follows. Please note that late, 

untimely filed comments will not be 

considered. Electronic comments must 

be submitted on or before June 24, 2022. 

The https://www.regulations.gov 

electronic filing system will accept 

comments until 11:59 p.m. Eastern Time 

at the end of June 24, 2022. Comments 

received by mail/hand delivery/courier 

(for written/paper submissions) will be 

considered timely if they are 

postmarked or the delivery service 

acceptance receipt is on or before that 

date. 

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– 

2022–N–0081 for ‘‘Agency Information 

Collection Activities; Proposed 

Collection; Comment Request; Tradeoff 

Analysis of Prescription Drug Product 


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