106510 Federal Register / Vol. 89, No. 249 / Monday, December 30, 2024 / Notices 

thickness thermal burns. Subsequent to 

this approval, the USPTO received a 

patent term restoration application for 

NEXOBRID (U.S. Patent No. 8,540,983) 

from MediWound, Ltd., and the USPTO 

requested FDA’s assistance in 

determining this patent’s eligibility for 

patent term restoration. In a letter dated 

January 30, 2024, FDA advised the 

USPTO that this human biological 

product had undergone a regulatory 

review period and that the approval of 

NEXOBRID represented the first 

permitted commercial marketing or use 

of the product. Thereafter, the USPTO 

requested that FDA determine the 

product’s regulatory review period. 

II. Determination of Regulatory Review 

Period 

FDA has determined that the 

applicable regulatory review period for 

NEXOBRID is 7,427 days. Of this time, 

6,514 days occurred during the testing 

phase of the regulatory review period, 

while 913 days occurred during the 

approval phase. These periods of time 

were derived from the following dates: 

1. The date an exemption under 

section 505(i) of the Federal Food, Drug, 

and Cosmetic Act (21 U.S.C. 355(i)) 

became effective: August 30, 2002. The 

applicant claims August 29, 2002, as the 

date the investigational new drug 

application (IND) became effective. 

However, FDA records indicate that the 

IND effective date was August 30, 2002, 

which was 30 days after FDA receipt of 

the IND. 

2. The date the application was 

initially submitted with respect to the 

human biological product under section 

351 of the Public Health Service Act (42 

U.S.C. 262): June 29, 2020. FDA has 

verified the applicant’s claim that the 

biologics license application (BLA) for 

NEXOBRID (BLA 761192) was initially 

submitted on June 29, 2020. 

3. The date the application was 

approved: December 28, 2022. FDA has 

verified the applicant’s claim that BLA 

761192 was approved on December 28, 

2022. 

This determination of the regulatory 

review period establishes the maximum 

potential length of a patent extension. 

However, the USPTO applies several 

statutory limitations in its calculations 

of the actual period for patent extension. 

In its application for patent extension, 

this applicant seeks 5 years of patent 

term extension. 

III. Petitions 

Anyone with knowledge that any of 

the dates as published are incorrect may 

submit either electronic or written 

comments and, under 21 CFR 60.24, ask 

for a redetermination (see DATES). 

Furthermore, as specified in § 60.30 (21 

CFR 60.30), any interested person may 

petition FDA for a determination 

regarding whether the applicant for 

extension acted with due diligence 

during the regulatory review period. To 

meet its burden, the petition must 

comply with all the requirements of 

§ 60.30, including but not limited to: 

must be timely (see DATES), must be 

filed in accordance with § 10.20, must 

contain sufficient facts to merit an FDA 

investigation, and must certify that a 

true and complete copy of the petition 

has been served upon the patent 

applicant. (See H. Rept. 857, part 1, 98th 

Cong., 2d sess., pp. 41–42, 1984.) 

Petitions should be in the format 

specified in 21 CFR 10.30. 

Submit petitions electronically to 

https://www.regulations.gov at Docket 

No. FDA–2013–S–0610. Submit written 

petitions (two copies are required) to the 

Dockets Management Staff (HFA–305), 

Food and Drug Administration, 5630 

Fishers Lane, Rm. 1061, Rockville, MD 

20852. 

Dated: December 13, 2024. 

P. Ritu Nalubola, 

Associate Commissioner for Policy. 

[FR Doc. 2024–31022 Filed 12–27–24; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2023–D–5016] 

Protocol Deviations for Clinical 

Investigations of Drugs, Biological 

Products, and Devices; 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 ‘‘Protocol 

Deviations for Clinical Investigations of 

Drugs, Biological Products, and 

Devices.’’ This draft guidance provides 

recommendations to assist sponsors, 

clinical investigators, and institutional 

review boards (IRBs) in defining, 

identifying, and reporting protocol 

deviations. The guidance provides 

definitions for protocol deviations and 

important protocol deviations. In 

addition, the guidance provides a 

recommended classification system for 

sponsors to report protocol deviations to 

FDA in clinical study reports for drugs, 

biological products, and devices; for 

investigators to report protocol 

deviations to sponsors and to IRBs; and 

for IRBs to evaluate protocol deviations. 

DATES: Submit either electronic or 

written comments on the draft guidance 

by February 28, 2025 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–5016 for ‘‘Protocol Deviations 

for Clinical Investigations of Drugs, 

Biological Products, and Devices.’’ 

Received comments will be placed in 

the docket and, except for those 

submitted as ‘‘Confidential 

Submissions,’’ publicly viewable at 


ddrumheller on DSK120RN23PROD with NOTICES1
Federal Register / Vol. 89, No. 249 / Monday, December 30, 2024 / Notices 106511 

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; the Office of Communication, 

Outreach and Development, Center for 

Biologics Evaluation and Research, 

Food and Drug Administration, 10903 

New Hampshire Ave., Bldg. 71, Rm. 

3128, Silver Spring, MD 20993–0002; or 

the Office of Policy, Guidance and 

Policy Development, Center for Devices 

and Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 5431, Silver Spring, 

MD 20993–0002. Send one selfaddressed 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: Dat 

Doan, Center for Drug Evaluation and 

Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 51, Rm. 3334, Silver Spring, 

MD 20993, 240–402–8926; or James 

Myers, Center for Biologics Evaluation 

and Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 71, Rm. 7301, Silver Spring, 

MD 20993–0002, 240–402–7911; or 

Soma Kalb, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. G318, Silver Spring, 

MD 20993–0002, 301–796–6359. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘Protocol Deviations for Clinical 

Investigations of Drugs, Biological 

Products, and Devices.’’ Protocols 

document the study design, objectives, 

population, planned procedures, 

investigational product management, 

method(s) of data capture, monitoring 

and oversight plans, and statistical 

analysis plans either directly or by 

reference to associated investigational 

plans. In the conduct of a clinical 

investigation, some deviations from the 

specifics outlined in the protocol may 

occur. 

This guidance provides 

recommendations to assist sponsors, 

clinical investigators, and IRBs in 

defining, identifying, and reporting 

protocol deviations. FDA regulations do 

not include a definition of the term 

protocol deviation or provide a system 

for classifying the various types of 

deviations that may occur during the 

conduct of a clinical investigation. A 

system that applies consistent 

classification, reporting, and 

documentation standards is important 

to assure the most interpretable and 

useful information emerges from the 

reporting of protocol deviations. To 

address these considerations, this 

guidance includes (1) definitions for 

protocol deviations and important 

protocol deviations, (2) 

recommendations on the types of 

protocol deviations that sponsors 

should report to FDA in clinical study 

reports, (3) recommendations on the 

types of protocol deviations that 

investigators should report to sponsors 

and to IRBs, and (4) recommendations 

for IRBs in their evaluation of protocol 

deviations. 

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 ‘‘Protocol Deviations for Clinical 

Investigations of Drugs, Biological 

Products, and Devices.’’ 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 part 56 have been 

approved under OMB control number 

0910–0130; the collections of 

information in 21 CFR part 312 have 

been approved under OMB control 

number 0910–0014; 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 have 

been approved under OMB control 

number 0910–0291; the collections of 

information in 21 CFR part 601 have 

been approved under OMB control 

number 0910–0338; the collections of 

information in 21 CFR part 812 have 

been approved under OMB control 

number 0910–0078; and the collections 

of information in 21 CFR part 814 have 

been approved under OMB control 

number 0910–0231. 

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, https://

www.fda.gov/vaccines-blood-biologics/ 

guidance-compliance-regulatoryinformation-biologics/biologicsguidances, https://www.fda.gov/ 

medical-devices/device-advicecomprehensive-regulatory-assistance/ 

guidance-documents-medical-devicesand-radiation-emitting-products, or 

https://www.regulations.gov. 


ddrumheller on DSK120RN23PROD with NOTICES1
106512 Federal Register / Vol. 89, No. 249 / Monday, December 30, 2024 / Notices 

Dated: December 17, 2024. 

P. Ritu Nalubola, 

Associate Commissioner for Policy. 

[FR Doc. 2024–31261 Filed 12–27–24; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2024–N–2149] 

Agency Information Collection 

Activities; Submission for Office of 

Management and Budget Review; 

Comment Request; De Novo 

Classification Process (Evaluation of 

Automatic Class III Designation) 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing 

that a proposed collection of 

information has been submitted to the 

Office of Management and Budget 

(OMB) for review and clearance under 

the Paperwork Reduction Act of 1995. 

DATES: Submit written comments 

(including recommendations) on the 

collection of information by January 29, 

2025. 

ADDRESSES: To ensure that comments on 

the information collection are received, 

OMB recommends that written 

comments be submitted to https://

www.reginfo.gov/public/do/PRAMain. 

Find this particular information 

collection by selecting ‘‘Currently under 

Review—Open for Public Comments’’ or 

by using the search function. The OMB 

control number for this information 

collection is 0910–0844. Also include 

the FDA docket number found in 

brackets in the heading of this 

document. 

FOR FURTHER INFORMATION CONTACT: 

Amber Sanford, Office of Operations, 

Food and Drug Administration, Three 

White Flint North, 10A–12M, 11601 

Landsdown St., North Bethesda, MD 

20852, 301–796–8867, PRAStaff@

fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: In 

compliance with 44 U.S.C. 3507, FDA 

has submitted the following proposed 

collection of information to OMB for 

review and clearance. 

De Novo Classification Process 

(Evaluation of Automatic Class III 

Designation)—21 CFR Part 860, Subpart 

D 

OMB Control Number 0910–0844— 

Revision 

This information collection supports 

FDA regulations and information 

collection discussed in associated 

guidance. Sections 201(h), 513(a) and 

(f), 701(a), and 704 of the Federal Food, 

Drug, and Cosmetic Act (FD&C Act) (21 

U.S.C. 321(h), 360c(a) and (f), 371(a), 

and 374) establish a comprehensive 

system for the regulation of medical 

devices intended for human use. 

Section 513(f)(2) of the FD&C Act 

provides for a ‘‘De Novo’’ classification 

process, most recently amended by 

section 3101 of the 21st Century Cures 

Act (Pub. L. 114–255). The final rule 

‘‘Medical Device De Novo Classification 

Process’’ (86 FR 54826), established part 

860, subpart D (21 CFR part 860, subpart 

D) (§§ 860.200 through 860.260) to 

implement provisions in section 

513(f)(2) of the FD&C Act. These 

regulations govern format and content 

elements for De Novo device 

classification requests, as well as 

withdrawal of the requests, and explain 

FDA procedures for acceptance, review, 

and granting or denying a request. 

FDA’s guidance for industry and FDA 

staff, ‘‘De Novo Classification Process 

(Evaluation of Automatic Class III 

Designation)’’, provides guidance on the 

process for the submission and review 

of a De Novo classification request 

under section 513(f)(2) of the FD&C Act, 

also known as the De Novo 

classification process. This process 

provides a pathway to class I or class II 

classification for medical devices for 

which general controls or general and 

special controls provide a reasonable 

assurance of safety and effectiveness, 

but for which there is no legally 

marketed predicate device. 

In addition to regulatory requirements 

set forth in part 860, subpart D, the 

guidance document entitled 

‘‘Acceptance Review for De Novo 

Classification Requests’’ communicates 

our thinking on criteria set out in 

§ 860.230, in assessing whether a De 

Novo request should be accepted for 

substantive review. The guidance 

document includes an ‘‘Acceptance 

Checklist’’ to assist respondents in this 

regard. 

The guidance document ‘‘Electronic 

Submission Template for Medical 

Device De Novo Requests,’’ provides the 

standards for the submission of De Novo 

requests by electronic format, a 

timetable for establishment of these 

standards, and criteria for waivers of 

and exemptions from the requirements 

to meet a statutory requirement. This 

guidance is also intended to represent 

one of several steps in meeting FDA’s 

commitment to the development of 

electronic submission templates to serve 

as guided submission preparation tools 

for industry to improve submission 

consistency and enhance efficiency in 

the review process. 

The collections of information 

described by this notice are necessary to 

satisfy the previously mentioned 

statutory requirements for 

administration of this voluntary 

submission program. FDA uses the 

information to evaluate whether a 

medical device may be reclassified from 

class III into class I or II and, if 

applicable, to determine the general 

and/or special controls necessary to 

sufficiently regulate the medical device. 

Respondents to this information 

collection are private sector or other forprofit businesses. 

In the Federal Register of May 29, 

2024 (89 FR 46402), FDA published a 

60-day notice requesting public 

comment on the proposed collection of 

information. No comments were 

received. 

FDA estimates the burden of this 

collection of information as follows: 

TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN

21 CFR part 860, subpart D; 

information collection activity 

Number of 

respondents 

Number of 

responses per 

respondent 

Total annual 

responses Average burden per response Total hours 

§§ 860.210, 860.220, 860.230; De 

Novo requests—format, content, 

and acceptance elements.

79 1 79 182 ................................................... 14,378 

§ 860.230; FDA acceptance of request (GFI Acceptance Checklist; 

Appendix A) 1.

79 1 79 ........................................................... ........................


ddrumheller on DSK120RN23PROD with NOTICES1