Federal Register / Vol. 87, No. 72 / Thursday, April 14, 2022 / Notices 22217 

FDA welcomes the attendance of the 

public at its advisory committee 

meetings and will make every effort to 

accommodate persons with disabilities. 

If you require accommodations due to a 

disability, please contact Christina Vert 

at ctgtac@fda.hhs.gov (see FOR FURTHER

INFORMATION CONTACT) at least 7 days in 

advance of the meeting. 

FDA is committed to the orderly 

conduct of its advisory committee 

meetings. Please visit our website at 

https://www.fda.gov/ 

AdvisoryCommittees/AboutAdvisory

Committees/ucm111462.htm for 

procedures on public conduct during 

advisory committee meetings. 

Notice of this meeting is given under 

the Federal Advisory Committee Act (5 

U.S.C. app. 2). 

Dated: April 11, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–08022 Filed 4–13–22; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2022–D–0108] 

Considerations for Waiver Requests 

for pH Adjusters in Generic Drug 

Products Intended for Parenteral, 

Ophthalmic, or Otic Use; 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 

‘‘Considerations for Waiver Requests for 

pH Adjusters in Generic Drug Products 

Intended for Parenteral, Ophthalmic, or 

Otic Use.’’ This guidance is intended to 

assist abbreviated new drug application 

(ANDA) applicants that reference a drug 

product intended for parenteral, 

ophthalmic, or otic use in seeking 

approval of a drug that is qualitatively 

(Q1) different or quantitatively (Q2) 

different from the reference listed drug 

(RLD) with respect to the pH adjuster(s). 

This draft guidance describes how FDA 

intends to evaluate a request for a 

waiver of Agency requirements for a Q1 

or Q2 difference in pH adjuster, 

including recommendations on the type 

of information to provide in support of 

such a waiver request. This draft 

guidance also includes 

recommendations on the timing and 

process for submitting such waiver 

requests. 

DATES: Submit either electronic or 

written comments on the draft guidance 

by June 13, 2022 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draft guidance before it begins work on 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– 

2022–D–0108 for ‘‘Considerations for 

Waiver Requests for pH Adjusters in 

Generic Drug Products Intended for 

Parenteral, Ophthalmic, or Otic Use.’’ 

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 

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 the draft 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 draft guidance document. 

FOR FURTHER INFORMATION CONTACT: 

Melissa Mannion, Center for Drug 


lotter on DSK11XQN23PROD with NOTICES1
22218 Federal Register / Vol. 87, No. 72 / Thursday, April 14, 2022 / Notices 

1See section 505(j)(2)(A) of the FD&C Act (setting 

forth the required contents of an ANDA). 

2Section 505(j)(4)(H) of the FD&C Act. 

3 21 CFR 314.127(a)(8)(ii); 54 FR 28871 at 28903 

(July 10, 1989). 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 75, Rm. 1611, 

Silver Spring, MD 20993–0002, 301– 

796–2747. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘Considerations for Waiver Requests for 

pH Adjusters in Generic Drug Products 

Intended for Parenteral, Ophthalmic, or 

Otic Use.’’ This draft guidance is being 

issued consistent with FDA’s good 

guidance practices regulation (21 CFR 

10.115). The draft guidance, when 

finalized, will represent the current 

thinking of FDA on ‘‘Considerations for 

Waiver Requests for pH Adjusters in 

Generic Drug Products Intended for 

Parenteral, Ophthalmic, or Otic Use.’’ 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. 

The Federal Food, Drug, and Cosmetic 

Act (FD&C Act) does not require an 

ANDA to have the same inactive 

ingredients as the RLD.1 Section 

505(j)(4)(H) of the FD&C Act (21 U.S.C. 

355(j)(4)(H)) does, however, state that an 

ANDA shall not be approved if 

information submitted in the 

application (or other information 

available) shows (1) the inactive 

ingredients of the drug are unsafe for 

use under the conditions prescribed, 

recommended, or suggested in the 

labeling proposed for the drug, or (2) the 

type or quantity of inactive ingredients 

included or the manner in which the 

inactive ingredients are included is 

unsafe under such conditions.2

The Agency has interpreted section 

505(j)(4)(H) of the FD&C Act as 

permitting the Agency to deny approval 

of an ANDA ‘‘if there is a reasonable 

basis to conclude that its inactive 

ingredients or composition raise serious 

questions about the drug’s safety.’’ 3

The regulations at § 314.94(a)(9)(iii) 

and (iv) (21 CFR 314.94(a)(9)(iii) and 

(iv)), with parallel provisions in the 

approval regulations at 

§ 314.127(a)(8)(ii)(B) and (C) (21 CFR 

314.127(a)(8)(ii)(B) and (C)), specify that 

FDA will consider an inactive 

ingredient in, or the composition of, a 

generic drug product intended for 

parenteral, ophthalmic, or otic use to be 

unsafe and will refuse to approve the 

ANDA unless the generic drug product 

contains the same inactive ingredients 

(with certain listed exceptions) in the 

same concentration as the RLD. These 

regulations also identify permissible 

differences in certain inactive 

ingredients for drug products intended 

for parenteral, ophthalmic, or otic use, 

commonly referred to as ‘‘exception 

excipients,’’ if the ANDA contains 

sufficient information to demonstrate 

that any such differences do not affect 

the safety or efficacy of the drug. The 

regulations do not, however, expressly 

identify pH adjusters as one of these 

‘‘exception excipients,’’ and, as such, 

the inactive ingredient requirements in 

§ 314.94(a)(9)(iii) and (iv) apply to pH 

adjusters. 

Under § 314.99(b) (21 CFR 314.99(b)), 

however, an applicant may ask FDA to 

waive any requirement that applies to 

the applicant under §§ 314.92 through 

314.99 (21 CFR 314.92 through 314.99). 

Such a request under § 314.99(b) must 

comply with the requirements at 21 CFR 

314.90. FDA may grant a § 314.99(b) 

waiver if the Agency finds one of the 

following: (1) The applicant’s 

compliance with the requirement is 

unnecessary for the Agency to evaluate 

the ANDA or compliance cannot be 

achieved; (2) the applicant’s alternative 

submission satisfies the requirement; or 

(3) the applicant’s submission otherwise 

justifies a waiver. Even if FDA grants a 

waiver of a requirement in §§ 314.92 

through 314.99 in a particular 

application, the application still must 

meet all applicable statutory 

requirements for approval. If FDA grants 

the applicant’s waiver request with 

respect to a requirement under 

§§ 314.92 through 314.99, the waived 

requirement will not constitute a basis 

for refusal to approve an ANDA under 

§ 314.127. Thus, an ANDA applicant for 

a drug product intended for parenteral, 

ophthalmic, or otic use who seeks to use 

a pH adjuster(s) that is Q1 or Q2 

different from the RLD may ask the 

Agency to waive the inactive ingredient 

requirements at § 314.94(a)(9)(iii) or (iv) 

for the pH adjuster(s). This draft 

guidance document provides 

recommendations on (1) the type of 

information that applicants should 

consider submitting with a § 314.99(b) 

waiver request when an ANDA 

applicant asks the Agency to waive the 

inactive ingredient requirements for pH 

adjusters and (2) the format and process 

for submitting such waiver requests. 

II. Paperwork Reduction Act of 1995 

While this guidance contains no 

collection of information, it does refer to 

previously approved FDA collections of 

information. Therefore, clearance by the 

Office of Management and Budget 

(OMB) under the Paperwork Reduction 

Act of 1995 (PRA) (44 U.S.C. 3501– 

3521) is not required for this guidance. 

The previously approved collections of 

information are subject to review by 

OMB under the PRA. The collections of 

information in 21 CFR part 314 have 

been approved under OMB control 

number 0910–0001; the collections of 

information in 21 CFR part 320 been 

approved under OMB control numbers 

0910–0014 and 0910–0291; and the 

collections of information for the 

submission of controlled 

correspondence related to generic drug 

development and FDA approval have 

been approved under OMB control 

number 0910–0797. 

III. Electronic Access 

Persons with access to the internet 

may obtain the draft guidance at https:// 

www.fda.gov/drugs/guidancecompliance-regulatory-information/ 

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

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

www.regulations.gov. 

Dated: April 11, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–08012 Filed 4–13–22; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2021–N–0313] 

Lisett Raventos: Final Debarment 

Order 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) is 

issuing an order under the Federal 

Food, Drug, and Cosmetic Act (FD&C 

Act) permanently debarring Lisett 

Raventos from providing services in any 

capacity to a person that has an 

approved or pending drug product 

application. FDA bases this order on a 

finding that Lisett Raventos was 

convicted of a felony under Federal law 

for conduct that relates to the 

development or approval, including the 

process of development or approval, of 

a drug product under the FD&C Act. Ms. 

Raventos was given notice of the 

proposed permanent debarment and 

was given an opportunity to request a 

hearing to show why she should not be 


lotter on DSK11XQN23PROD with NOTICES1