Federal Register / Vol. 88, No. 242 / Tuesday, December 19, 2023 / Notices 87781 

establish any rights for any person and 

is not binding on FDA or the public. 

You can use an alternative approach if 

it satisfies the requirements of the 

applicable statutes and regulations. 

On December 29, 2022, the President 

signed the Consolidated Appropriations 

Act, 2023 (Pub. L. 117–328) into law, 

which included MoCRA. Among other 

provisions, MoCRA added section 607 

to the Federal Food, Drug, and Cosmetic 

Act (FD&C Act), establishing 

requirements for cosmetic product 

facility registration and cosmetic 

product listing. Section 607(a) of the 

FD&C Act (21 U.S.C. 364c(a)) requires 

every person that owns or operates a 

facility that engages in the 

manufacturing or processing of a 

cosmetic product for distribution in the 

United States to register each facility 

with FDA no later than 1 year after the 

date of enactment. In addition to the 

registration requirements, section 607(c) 

of the FD&C Act requires that for each 

cosmetic product, the responsible 

person submit to FDA ‘‘a cosmetic 

product listing.’’ Certain small 

businesses, as defined in section 612 of 

the FD&C Act (21 U.S.C. 364h), are 

exempt from the registration and listing 

requirements. 

In the Federal Register of August 8, 

2023 (88 FR 53490), we made available 

a draft guidance for industry entitled 

‘‘Registration and Listing of Cosmetic 

Product Facilities and Products’’ and 

gave interested parties an opportunity to 

submit comments by September 7, 2023, 

for us to consider before beginning work 

on the final version of the guidance. We 

received numerous comments on the 

draft guidance and have modified the 

final guidance where appropriate. 

Changes to the guidance include 

additional information on the facility 

registration number, United States 

agent, electronic and paper submission, 

as well as incorporating FDA’s 

compliance policy we made available in 

a guidance for industry as described in 

the Federal Register of November 8, 

2023 (88 FR 77323). In addition, we 

made editorial changes to improve 

clarity. New appendix B of this 

guidance is highlighted in grey, 

describes frequently asked questions 

and answers, and is marked ‘‘for 

comment purposes only’’ to provide an 

opportunity for comment before it is 

finalized. Aside from appendix B, this 

guidance finalizes the draft guidance 

that was published on August 8, 2023. 

II. Paperwork Reduction Act of 1995 

While this guidance contains no 

collection of information, it does refer to 

previously approved FDA collections of 

information. The previously approved 

collections of information are subject to 

review by the Office of Management and 

Budget (OMB) under the Paperwork 

Reduction Act of 1995 (PRA) (44 U.S.C. 

3501–3521). The collections of 

information in section 607 of the FD&C 

Act have been approved under 0910– 

0599. 

III. Electronic Access 

Persons with access to the internet 

may obtain the guidance at https://

www.fda.gov/CosmeticGuidances, 

https://www.fda.gov/regulatoryinformation/search-fda-guidancedocuments, or https:// 

www.regulations.gov. Use the FDA 

websites listed in the previous sentence 

to find the most current version of the 

guidance. 

Dated: December 12, 2023. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2023–27649 Filed 12–18–23; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2023–P–4596] 

Determination That MEPHYTON 

(Phytonadione) Tablets, 5 Milligrams, 

Were Not Withdrawn From Sale for 

Reasons of Safety or Effectiveness 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) has 

determined that MEPHYTON 

(phytonadione) tablets, 5 milligrams 

(mg), were not withdrawn from sale for 

reasons of safety or effectiveness. This 

determination means that FDA will not 

begin procedures to withdraw approval 

of abbreviated new drug applications 

(ANDAs) that refer to this drug product, 

and it will allow FDA to continue to 

approve ANDAs that refer to the 

product as long as they meet relevant 

legal and regulatory requirements. 

FOR FURTHER INFORMATION CONTACT: 

Stacy Kane, Center for Drug Evaluation 

and Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 51, Rm. 5236, Silver Spring, 

MD 20993–0002, 301–796–8363, 

Stacy.Kane@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: Section 

505(j) of the Federal Food, Drug, and 

Cosmetic Act (FD&C Act) (21 U.S.C. 

355(j)) allows the submission of an 

ANDA to market a generic version of a 

previously approved drug product. To 

obtain approval, the ANDA applicant 

must show, among other things, that the 

generic drug product: (1) has the same 

active ingredient(s), dosage form, route 

of administration, strength, conditions 

of use, and (with certain exceptions) 

labeling as the listed drug, which is a 

version of the drug that was previously 

approved, and (2) is bioequivalent to the 

listed drug. ANDA applicants do not 

have to repeat the extensive clinical 

testing otherwise necessary to gain 

approval of a new drug application 

(NDA). 

Section 505(j)(7) of the FD&C Act 

requires FDA to publish a list of all 

approved drugs. FDA publishes this list 

as part of the ‘‘Approved Drug Products 

With Therapeutic Equivalence 

Evaluations,’’ which is known generally 

as the ‘‘Orange Book.’’ Under FDA 

regulations, drugs are removed from the 

list if the Agency withdraws or 

suspends approval of the drug’s NDA or 

ANDA for reasons of safety or 

effectiveness or if FDA determines that 

the listed drug was withdrawn from sale 

for reasons of safety or effectiveness (21 

CFR 314.162). 

A person may petition the Agency to 

determine, or the Agency may 

determine on its own initiative, whether 

a listed drug was withdrawn from sale 

for reasons of safety or effectiveness. 

This determination may be made at any 

time after the drug has been withdrawn 

from sale, but must be made prior to 

approving an ANDA that refers to the 

listed drug (§ 314.161 (21 CFR 314.161)). 

FDA may not approve an ANDA that 

does not refer to a listed drug. 

MEPHYTON (phytonadione) tablets, 5 

mg, are the subject of NDA 010104, held 

by Bausch Health Americas, Inc., and 

initially approved in 1955. MEPHYTON 

is a vitamin K replacement indicated for 

the treatment of adults with the 

following coagulation disorders, which 

are due to faulty formation of factors II, 

VII, IX and X when caused by vitamin 

K deficiency or interference with 

vitamin K activity: 

• Anticoagulant-induced prothrombin 

deficiency caused by coumarin or 

indanedione derivatives 

• Hypoprothrombinemia secondary to 

antibacterial therapy 

• Hypoprothrombinemia secondary to 

factors limiting absorption or 

synthesis of vitamin K, e.g., 

obstructive jaundice, biliary fistula, 

sprue, ulcerative colitis, celiac 

disease, intestinal resection, cystic 

fibrosis of the pancreas, and regional 

enteritis 

• Other drug-induced 

hypoprothrombinemia where it is 


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87782 Federal Register / Vol. 88, No. 242 / Tuesday, December 19, 2023 / Notices 

definitively shown that the result is 

due to interference with vitamin K 

metabolism, e.g., salicylates 

MEPHYTON (phytonadione) tablets, 5 

mg, are currently listed in the 

‘‘Discontinued Drug Product List’’ 

section of the Orange Book. 

Lachman Consults submitted a citizen 

petition dated October 17, 2023 (Docket 

No. FDA–2023–P–4596), under 21 CFR 

10.30, requesting that the Agency 

determine whether MEPHYTON 

(phytonadione) tablets, 5 mg, were 

withdrawn from sale for reasons of 

safety or effectiveness. 

After considering the citizen petition 

and reviewing Agency records and 

based on the information we have at this 

time, FDA has determined under 

§ 314.161 that MEPHYTON 

(phytonadione) tablets, 5 mg, were not 

withdrawn for reasons of safety or 

effectiveness. The petitioner has 

identified no data or other information 

suggesting that MEPHYTON 

(phytonadione) tablets, 5 mg, were 

withdrawn for reasons of safety or 

effectiveness. We have carefully 

reviewed our files for records 

concerning the withdrawal of 

MEPHYTON (phytonadione) tablets, 5 

mg, from sale. We have also 

independently evaluated relevant 

literature and data for possible 

postmarketing adverse events. We have 

found no information that would 

indicate that this drug product was 

withdrawn from sale for reasons of 

safety or effectiveness. 

Accordingly, the Agency will 

continue to list MEPHYTON 

(phytonadione) tablets, 5 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. FDA will not 

begin procedures to withdraw approval 

of approved ANDAs that refer to this 

drug product. Additional ANDAs for 

this drug product may also 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: December 14, 2023. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2023–27858 Filed 12–18–23; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2023–D–4395] 

Use of Real-World Evidence To 

Support Regulatory Decision-Making 

for Medical Devices, Draft Guidance for 

Industry and Food and Drug 

Administration Staff; 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 the draft 

guidance entitled ‘‘Use of Real-World 

Evidence to Support Regulatory 

Decision-Making for Medical Devices.’’ 

FDA is issuing this draft guidance to 

clarify how FDA evaluates real-world 

data (RWD) to determine whether they 

are of sufficient quality for generating 

real-world evidence (RWE) that can be 

used in FDA regulatory decision-making 

for medical devices. This draft guidance 

proposes expanded recommendations to 

the 2017 guidance entitled ‘‘Use of RealWorld Evidence to Support Regulatory 

Decision-Making for Medical Devices.’’ 

This draft guidance is not final nor is it 

for implementation at this time. 

DATES: Submit either electronic or 

written comments on the draft guidance 

by February 20, 2024 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– 

2023–D–4395 for ‘‘Use of Real-World 

Evidence to Support Regulatory 

Decision-Making for Medical Devices.’’ 

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, 240–402–7500. 

• 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 


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