Federal Register / Vol. 88, No. 197 / Friday, October 13, 2023 / Notices 70997 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2023–D–4177] 

Quality Considerations for Topical 

Ophthalmic Drug Products; 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 ‘‘Quality 

Considerations for Topical Ophthalmic 

Drug Products.’’ This draft guidance 

discusses certain quality considerations 

for ophthalmic drug products (i.e., 

solutions, suspensions, emulsions, gels, 

ointments, and creams) intended for 

topical delivery in and around the eye. 

Specifically, this draft guidance 

discusses approaches to evaluating 

visible particulate matter, extractables 

and leachables, and impurities and 

degradation products; use of in vitro 

drug release/dissolution testing as an 

optional quality control strategy for 

certain ophthalmic dosage forms; 

recommendations for design and 

delivery and dispensing features of 

container closure systems; and 

recommendations for stability studies. 

The draft guidance applies to 

ophthalmic drug products approved 

under new drug applications (NDAs), 

abbreviated new drug applications 

(ANDAs), and biologics license 

applications (BLAs), as well as to overthe-counter (OTC) monograph drugs. 

DATES: Submit either electronic or 

written comments on the draft guidance 

by December 12, 2023 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draft guidance before it begins work on 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–4177 for ‘‘Quality 

Considerations for Topical Ophthalmic 

Drug Products.’’ 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: 

Ranjani Prabhakara, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 75, Rm. 6648, 

Silver Spring, MD 20993–0002, 240– 

402–4652. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘Quality Considerations for Topical 

Ophthalmic Drug Products.’’ This draft 

guidance provides information 

regarding quality considerations for 

ophthalmic drug products consistent 

with the requirements outlined in 

section 501(a)(2)(B) of the Federal Food, 

Drug, and Cosmetic Act (21 U.S.C. 

351(a)(2)(B)) and 21 CFR parts 210 and 

211 for all drug products, 21 CFR part 

601 for biological products, 21 CFR part 

4 for combination products, and, for 

ophthalmic drug products with a United 

States Pharmacopeia (USP) monograph, 

the applicable criteria from the USP. 

The draft guidance also provides 

recommendations to industry on the 

documentation that should be submitted 

in the chemistry, manufacturing, and 

controls (CMC) section of NDAs, 


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70998 Federal Register / Vol. 88, No. 197 / Friday, October 13, 2023 / Notices 

1https://www.selectagents.gov/sat/list.htm. 

2https://www.bis.doc.gov/index.php/regulations/ 

commerce-control-list-ccl. 

ANDAs, and BLAs for certain CMC 

attributes for ophthalmic drug products. 

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 ‘‘Quality Considerations for Topical 

Ophthalmic Drug Products.’’ 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 (PRA) (44 U.S.C. 

3501–3521). The collections of 

information in 21 CFR parts 314 and 

601 have been approved under OMB 

control numbers 0910–0001 and 0910– 

0338, respectively. The collections of 

information in 21 CFR parts 210 and 

211 have been approved under OMB 

control number 0910–0139. 

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: October 10, 2023. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2023–22650 Filed 10–12–23; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Screening Framework Guidance for 

Providers and Users of Synthetic 

Nucleic Acids 

AGENCY: Administration for Strategic 

Preparedness and Response (ASPR), 

Department of Health and Human 

Services (HHS). 

ACTION: Notice. 

SUMMARY: The Administration for 

Strategic Preparedness and Response is 

issuing this screening framework 

guidance, which sets forth baseline 

standards for the gene and genome 

synthesis industry, as well as best 

practices for all entities involved in the 

provision, use, and transfer of synthetic 

nucleic acids, regarding screening 

orders and recipients and maintaining 

records. In addition, this guidance seeks 

to encourage best practices to address 

biosecurity concerns associated with the 

potential misuse of synthetic nucleic 

acids in order to bypass existing 

regulatory controls and commit 

unlawful acts. 

FOR FURTHER INFORMATION CONTACT: C. 

Matthew Sharkey, Administration for 

Strategic Preparedness and Response, 

Department of Health and Human 

Services, 400 7th St. SW, Washington, 

DC 20024; 202–868–9224, 

syndnaguidance@hhs.gov. 

SUPPLEMENTARY INFORMATION: A request 

for public comments on the issues 

covered in this Notice was published in 

the Federal Register (85 FR 52611 [Aug. 

26, 2020]; 85 FR 69630 [Nov. 3, 2020], 

Review and Revision of the Screening 

Framework Guidance for Providers of 

Synthetic Double-Stranded DNA) with a 

comment period of more than 120 days. 

Following consideration of the 

comments received in response to this 

Notice, HHS issued proposed draft 

revised guidance as a Federal Register 

Notice (87 FR 25495 [Apr. 29, 2022], 

Screening Framework Guidance for 

Providers and Users of Synthetic 

Oligonucleotides) and solicited 

additional comments for a period of 60 

days. This Guidance was drafted 

through a deliberative interagency 

process to address the topics raised in 

public comments received in response 

to these prior Notices as well as other 

considerations. Responses received from 

these prior Notices and summaries of 

updates contained in this Guidance are 

available for public review at the 

following website https://aspr.hhs.gov/ 

legal/synna. 

Screening Framework Guidance for 

Providers and Users of Synthetic 

Nucleic Acids 

I. Introduction 

Synthetic biology is an 

interdisciplinary field that focuses on 

the design and fabrication of novel 

biological components and systems as 

well as the redesign and fabrication of 

existing biological systems. Modern 

biotechnologies have made the 

conversion of different types of nucleic 

acids possible (e.g., RNA to DNA), and 

longer genomic sequences can now be 

constructed from very short nucleic 

acids with higher fidelity. Additionally, 

synthetic biology is not limited to 

naturally derived genetic material. 

Thus, this scientific field has the 

potential to generate existing or novel 

components, systems, or organisms 

directly, using only genetic sequence 

data. 

Advances in nucleic acid synthesis 

technology and the open-source 

availability of genetic sequence data 

have significantly contributed to 

discovery and innovation in areas such 

as health and agriculture research and 

development. However, there are 

concerns among the scientific 

community, the nucleic acid synthesis 

industry, the U.S. government, and the 

public that individuals with ill intent 

could exploit biotechnology for harmful 

purposes. The U.S. government has 

acted to minimize risks to public health, 

agriculture, plants, animals, animal or 

plant products, and the environment 

due to biological pathogens and toxins. 

For instance, it has issued the Federal 

Select Agent Regulations, which 

regulate a subset of microbial organisms 

and toxins determined to have the 

potential to pose a severe threat to 

public health and safety, animal health, 

plant health, animal or plant products, 

or the environment. These regulations 

are administered jointly by the CDC, 

Division of Select Agents and Toxins 

and the Animal and Plant Health 

Inspection Service, Division of 

Agricultural Select Agents and Toxins, 

through the Federal Select Agent 

Program (FSAP),1 which sets forth 

requirements for the possession, use, 

and transfer of biological select agents 

and toxins. A second layer of regulation 

is provided by the Bureau of Industry 

and Security (BIS) Export 

Administration Regulations’ Commerce 

Control List (CCL),2 which identifies 

agents and genetic sequences that 

require licenses before export from the 

United States. However, these regulated 

pathogens and toxins do not represent 

the entirety of the potential risks to 

public health, agriculture, plants, 

animals, animal or plant products, or 

the environment that could arise from 

the misuse of synthetic nucleic acids. 

Non-regulated pathogens and toxins, as 

well as other novel types of nucleic acid 

sequences, may also pose significant 

risks if they are misused. To minimize 

these risks, a shift is needed from 

relying solely on lists of regulated 

pathogens and toxins to also assessing 

the risks associated with other nucleic 

acid sequences that may contribute to 

pathogenicity or harm if introduced into 

new genetic frameworks (i.e., Sequences 

of Concern [SOCs]). Also, modern 

molecular biological techniques allow 

the conversion between different types 

of nucleic acids (e.g., RNA to DNA, and 


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