Federal Register / Vol. 88, No. 248 / Thursday, December 28, 2023 / Notices 89703 

Grantee respondent type Form/report name Number of 

respondents 

Number of 

responses per 

respondent 

Average 

burden per 

response 

(in minutes) 

Total burden 

hours 

SMP .................................................. Individual Interaction ........................ 6,935 41 5 23,694.58 

SMP .................................................. Team Member .................................. 216 31 5 558 

SMP .................................................. SIRS Team Member Activity ............ 216 31 5 558 

*SMP ................................................. OIG Report ....................................... * 0 0 0 0 

*SMP ................................................. Time Spent Report ........................... * 0 0 0 0 

SHIP/MIPPA ...................................... Media Outreach & Education ........... 3,750 15 4 3,750 

SHIP/MIPPA ...................................... Group Outreach & Education ........... 3,750 15 4 3,750 

SHIP/MIPPA ...................................... STARS Team Member ..................... 216 75 5 1,350 

SHIP/MIPPA ...................................... Beneficiary Contact .......................... 15,000 233 5 291,250 

*SHIP/MIPPA .................................... SHIP Performance Report ............... * 0 0 0 0 

*SHIP/MIPPA .................................... Resource Report .............................. * 0 0 0 0 

*SHIP/MIPPA .................................... MIPPA Performance Report ............ * 0 0 0 0 

SHIP/MIPPA ...................................... SHIP Team Member Activity ............ 216 40 7 1,008 

SHIP/MIPPA ...................................... Team Member Training .................... 216 40 6 864 

*SHIP/SMP/MIPPA ........................... Summary Reports ............................ * 0 0 0 0 

*SHIP/MIPPA .................................... Part D Enrollment Outcomes Report * 0 0 0 0 

Totals ......................................... ........................................................... 37,666 571 ........................ 329,294.31 

* This data collection activity is an automated task in the system and does not compute to an estimate of time for burden. 

Dated: December 21, 2023. 

Alison Barkoff, 

Principal Deputy Administrator for the 

Administration for Community Living, 

performing the delegable duties of the 

Administrator and the Assistant Secretary for 

Aging. 

[FR Doc. 2023–28623 Filed 12–27–23; 8:45 am] 

BILLING CODE 4154–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2023–D–5408] 

Reformulating Drug Products That 

Contain Carbomers Manufactured With 

Benzene; 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 final 

guidance for industry entitled 

‘‘Reformulating Drug Products That 

Contain Carbomers Manufactured With 

Benzene.’’ The purpose of this guidance 

is to provide recommendations to 

applicants and manufacturers on what 

tests should be performed and what 

documentation should be submitted or 

available to support the reformulation of 

drug products that use carbomers 

manufactured with benzene. Certain 

United States Pharmacopeia (USP) 

carbomer monographs currently allow 

for unacceptable levels of benzene, 

which raises safety concerns. FDA has 

requested that the USP omit (or remove) 

these monographs, and applicants and 

manufacturers may need to reformulate 

their drug products to avoid use of these 

carbomers. This guidance provides 

recommendations for tests and 

documentation related to reformulation 

based on various routes of 

administration and dosage forms of 

affected drug products, and provides 

recommendations for application 

holders on the appropriate submission 

types to notify the Agency of 

reformulation changes. The intended 

effect of this guidance is to, as 

appropriate, provide a less burdensome 

risk-based approach to reformulation 

submissions relative to existing 

guidances on scale-up and postapproval changes (SUPAC), and address 

the immediate public health need to 

expedite the discontinuation of the use 

of carbomers manufactured with high 

levels of benzene in drug products. 

DATES: The announcement of the 

guidance is published in the Federal 

Register on December 28, 2023. 

ADDRESSES: You may submit either 

electronic or written comments on 

Agency guidances 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–5408 for ‘‘Reformulating Drug 

Products That Contain Carbomers 

Manufactured With Benzene; Guidance 

for Industry.’’ 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. 


khammond on DSKJM1Z7X2PROD with NOTICES
89704 Federal Register / Vol. 88, No. 248 / Thursday, December 28, 2023 / Notices 

• 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.govinfo.gov/content/pkg/FR-2015- 

09-18/pdf/2015-23389.pdf.

Docket: 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, 5630 Fishers Lane, Rm. 1061, 

Rockville, MD 20852, 240–402–7500. 

You may submit comments on any 

guidance at any time (see 21 CFR 

10.115(g)(5)). 

Submit written requests for single 

copies of this guidance to the Division 

of Drug Information, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10001 New 

Hampshire Ave., Hillandale Building, 

4th Floor, Silver Spring, MD 20993– 

0002. Send one self-addressed adhesive 

label to assist that office in processing 

your requests. See the SUPPLEMENTARY

INFORMATION section for electronic 

access to the guidance document. 

FOR FURTHER INFORMATION CONTACT: 

Pallavi Nithyanandan, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, Rm. 4156, 

Silver Spring, MD 20993–0002, 301– 

796–7546, Pallavi.Nithyanandan@

fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background

FDA is announcing the availability of

a guidance for industry entitled 

‘‘Reformulating Drug Products That 

Contain Carbomers Manufactured With 

Benzene.’’ FDA is issuing this guidance 

consistent with its good guidance 

practices (GGP) regulation (§ 10.115 (21 

CFR 10.115)). The Agency is 

implementing this guidance without 

prior public comment because it has 

determined that prior public 

participation is not feasible or 

appropriate (§ 10.115(g)(2) and (3)). FDA 

made this determination because 

benzene is a known human carcinogen, 

and the Agency seeks to facilitate the 

transition away from using carbomers 

manufactured with high levels of 

benzene. Publishing this guidance 

without prior public comment addresses 

the immediate public health need to 

expedite the discontinuation of the use 

of these carbomers and provides a less 

burdensome risk-based approach to 

applicant submissions, relative to 

existing guidances on SUPAC. Although 

this guidance document is immediately 

in effect, it remains subject to comment 

in accordance with FDA’s GGP 

regulation. 

The purpose of this guidance is to 

provide recommendations to applicants 

and manufacturers on what tests should 

be performed and what documentation 

should be submitted or available to 

support the reformulation of drug 

products that use carbomers 

manufactured with benzene. Certain 

USP carbomer monographs currently 

allow for unacceptable levels of 

benzene, which raises safety concerns. 

FDA has requested that the USP omit (or 

remove) these monographs, and 

applicants and manufacturers may need 

to reformulate their drug products to 

avoid use of these carbomers. 

Carbomers are a group of polymers 

composed of acrylic acid. They are 

widely used as inactive ingredients in 

drug products as fillers, emulsifiers, 

gelling agents, and binding agents. 

There are carbomers currently used as 

inactive ingredients that are 

manufactured using benzene as a 

polymerization solvent. Benzene is a 

known human carcinogen. As such, 

both the International Conference for 

Harmonisation (ICH) guidance for 

industry entitled ‘‘Q3C—Tables and 

List’’ (available at https://www.fda.gov/ 

media/133650/download) and USP 

General Chapter <467> ‘‘Residual 

Solvents’’ designate benzene as a Class 

1 solvent (i.e., solvents that should be 

avoided) and recommend that benzene 

should not be employed in the 

manufacture of drug substances, 

excipients, and drug products. However, 

there are still several grades of 

carbomers that are manufactured using 

benzene as a solvent being used in 

pharmaceutical products even though 

alternative grades of carbomers are 

available that are manufactured without 

the use of benzene. 

At the time of publication, carbomers 

manufactured with benzene may fall 

under the United States PharmacopeiaNational Formulary (USP–NF) 

monographs Carbomer 934, Carbomer 

934P, Carbomer 940, Carbomer 941, or 

Carbomer 1342. These monographs 

permit benzene levels as high as 5,000 

parts per million (ppm), which is 

significantly higher than the limit of 2 

ppm on benzene as an impurity in the 

USP–NF Carbomer Homopolymer, 

Carbomer Copolymer, and Carbomer 

Interpolymer monographs. To avoid 

confusion, and because of the safety 

concerns associated with these 

unacceptable levels of benzene 

permitted by these monographs, FDA 

has asked the USP to remove (or ‘‘omit’’) 

the Carbomer 934P, Carbomer 940, 

Carbomer 934, Carbomer 1342, and 

Carbomer 941 monographs from the 

USP–NF compendium. 

The guidance represents the current 

thinking of FDA on ‘‘Reformulating 

Drug Products That Contain Carbomers 

Manufactured With Benzene.’’ It does 

not 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. 

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 (44 U.S.C. 3501– 

3521). The collections of information in 

21 CFR part 314 pertaining to the 

submission of new drug applications 

have been approved under OMB control 

number 0910–0001. The collections of 

information in 21 CFR parts 210 and 

211 pertaining to current good 

manufacturing practice requirements 

have been approved under OMB control 

number 0910–0139. 

III. Electronic Access

Persons with access to the internet

may obtain the guidance at https://

www.fda.gov/drugs/guidanceVerDate Sep<11>2014 20:14 Dec 27, 2023 Jkt 262001 PO 00000 Frm 00051 Fmt 4703 Sfmt 4703 E:\FR\FM\28DEN1.SGM 28DEN1

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Federal Register / Vol. 88, No. 248 / Thursday, December 28, 2023 / Notices 89705 

compliance-regulatory-information/ 

guidances-drugs, https://www.fda.gov/ 

regulatory-information/search-fdaguidance-documents, or https://

www.regulations.gov. 

Dated: December 21, 2023. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2023–28675 Filed 12–27–23; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2021–N–0039] 

Electronic Submissions; Update to the 

Specifications for Preparing and 

Submitting Postmarket Individual Case 

Safety Reports for Vaccines; Technical 

Specification 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) Center 

for Biologics Evaluation and Research 

(CBER) is announcing the availability of 

version 2.3 of the Specifications for 

Preparing and Submitting Postmarket 

Individual Case Safety Reports (ICSRS) 

for Vaccines (Specifications). The 

version update is not applicable to 

CBER-regulated drug products marketed 

for human use with approved New Drug 

Applications (NDAs) and Abbreviated 

New Drug Applications (ANDAs); 

CBER-regulated therapeutic biological 

products marketed for human use with 

approved Biologic License Applications 

(BLAs); Whole Blood or blood 

components; and human cells, tissues, 

and cellular and tissue-based products 

(HCT/Ps) regulated solely under the 

Public Health Service Act. 

ADDRESSES: You may submit either 

electronic or written comments 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– 

2021–N–0039 for ‘‘Electronic 

Submissions; Update to the 

Specifications for Preparing and 

Submitting Postmarket Individual Case 

Safety Reports for Vaccines; Technical 

Specification’’. 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 laws. 

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.govinfo.gov/content/pkg/FR-2015- 

09-18/pdf/2015-23389.pdf.

Docket: 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, 5630 Fishers Lane, Rm. 1061, 

Rockville, MD 20852, 240–402–7500. 

FOR FURTHER INFORMATION CONTACT: 

Victoria Wagman, Center for Biologics 

Evaluation and Research, Food and 

Drug Administration, Bldg. 71, Rm. 

7301, Silver Spring, MD 20993–0002, 

240–402–7911. 

SUPPLEMENTARY INFORMATION: 

Background 

CBER is announcing the availability 

of version 2.3 of the Specifications for 

Preparing and Submitting Postmarket 

ICSRs for Vaccines (available at https:// 

www.fda.gov/industry/about-esg/cbervaccine-icsr-implementation). The 

version update has been prepared to 

provide updated specifications on 

submitting re-challenge information, to 

correct values for the ‘Vaccination 

Facility Type’ (FDA.G.k.4.r.14.8), and to 

record modifications to the ‘Attachment 

File Name’ (FDA.C.1.6.1.r.3) as well as 

various document formatting 

refinements. In addition, version 2.3 

includes updated business rules 

(Appendix I of the Specifications) 

which provide details on data field 

specifications. The version update is not 

applicable to CBER-regulated drug 

products marketed for human use with 

approved NDAs and ANDAs; CBERregulated therapeutic biological 

products marketed for human use with 

approved BLAs; Whole Blood or blood 

components; and HCT/Ps regulated 

solely under section 361 of the Public 

Health Service Act (42 U.S.C. 264). 

At this time, all existing eVAERS 

submitters (vaccine manufacturers and 

others responsible for reporting ICSRs 

for vaccines) have successfully 

transitioned to reporting in version 2.2. 


khammond on DSKJM1Z7X2PROD with NOTICES