Federal Register / Vol. 89, No. 191 / Wednesday, October 2, 2024 / Notices 80257 

Signatures—Scope and Application’’ 

(August 2003); (3) provide 

recommendations on using information 

technology service providers to provide 

services during a clinical investigation; 

(4) provide recommendations regarding 

the collection of data through digital 

health technologies; (5) facilitate the use 

of electronic signatures; and (6) 

facilitate the use of electronic systems, 

electronic records, and electronic 

signatures to improve the quality and 

efficiency of clinical investigations. 

This guidance finalizes the draft 

guidance of the same title issued on 

March 16, 2023 (88 FR 16268). FDA 

considered comments received on the 

draft guidance as the guidance was 

finalized. Changes from the draft to the 

final guidance include: (1) clarifying the 

applicability of part 11 (21 CFR part 11) 

to real-world data sources submitted to 

FDA; (2) clarifying the applicability of 

part 11 to clinical investigations 

conducted outside of the United States; 

(3) describing electronic systems 

deployed by regulated entities in 

clinical investigations and using a riskbased approach for validation; (4) 

clarifying the focus of FDA inspections 

of regulated entities; (5) providing 

recommendations for agreements 

between information technology service 

providers and regulated entities; (6) 

providing recommendations regarding 

data collection from digital health 

technologies used in clinical 

investigations; and (7) clarifying 

recommendations for the use of 

electronic signatures in clinical 

investigations, including information on 

submission of letters of non-repudiation 

to certify that an electronic signature is 

the legally binding equivalent of a 

traditional handwritten signature. In 

addition, editorial changes were made 

to improve clarity. 

This guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The guidance represents the current 

thinking of FDA on ‘‘Electronic 

Systems, Electronic Records, and 

Electronic Signatures in Clinical 

Investigations: Questions and Answers.’’ 

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 part 11 have been 

approved under OMB control number 

0910–0303; the collections of 

information in 21 CFR parts 50 and 56 

have been approved under OMB control 

number 0910–0130; the collections of 

information in 21 CFR part 211 have 

been approved under OMB control 

number 0910–0139; 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 parts 314 and 

601 have been approved under OMB 

control numbers 0910–0001 and 0910– 

0338, respectively; the collections of 

information in 21 CFR part 511 have 

been approved under OMB control 

number 0910–0117; and the collections 

of information in 21 CFR part 812 have 

been approved under OMB control 

number 0910–0078. 

III. Electronic Access 

Persons with access to the internet 

may obtain the guidance at https://

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

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

vaccines-blood-biologics/guidancecompliance-regulatory-informationbiologics/biologics-guidances, https://

www.fda.gov/TobaccoProducts/ 

Labeling/RulesRegulationsGuidance/ 

default.htm, https://www.fda.gov/ 

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

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

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

www.regulations.gov. 

Dated: September 26, 2024. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2024–22562 Filed 10–1–24; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2024–N–4310] 

Center for Drug Evaluation and 

Research Quantitative Medicine Center 

of Excellence; Program Announcement 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) is 

publishing this notice to announce the 

establishment of the Center for Drug 

Evaluation and Research (CDER) 

Quantitative Medicine Center of 

Excellence (QM CoE). Quantitative 

medicine (QM) is used to inform 

premarket product review, post-market 

product assessment, policy 

development, and policy 

implementation within several CDER 

offices. The QM CoE will act as a 

coordinating body that drives 

innovation and facilitates integration of 

QM methodologies and principles 

across CDER. To realize this purpose, 

the QM CoE will introduce new 

activities and coordinate existing 

activities in key areas, including 

multidisciplinary education and 

exchange, development and 

implementation of applied science 

policy, knowledge management, and 

community engagement. 

DATES: The formation of the QM CoE 

was announced on March 25, 2024. For 

more details, please visit https://

www.fda.gov/about-fda/center-drugevaluation-and-research-cder/cderquantitative-medicine-centerexcellence-qm-coe. 

FOR FURTHER INFORMATION CONTACT: 

Daphne Guinn, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Silver Spring, MD 

20993, 301–837–7122, Daphne.Guinn@

fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

QM involves the development and 

application of exposure-based, 

biological, and quantitative modeling 

and simulation approaches derived from 

nonclinical, clinical, and real-world 

sources to inform: (1) drug 

development, (2) regulatory decisionmaking, and (3) patient care. The 

technical scope includes pharmacostatistical modeling, mechanistic 

modeling, biomarker-endpoint 

development, artificial intelligence and 

machine learning, and clinical trial 

simulations and in silico predictions. 

Within CDER, QM approaches have 

been used to inform premarket product 

review, post-market product assessment, 

policy development, and policy 

implementation. 

While CDER has been at the forefront 

of advancing QM over the decades, the 

efforts in outreach and education, 

scientific and regulatory initiatives, and 

operations have largely been 

decentralized. Recognizing the 

opportunity for synergy, CDER has 

begun a coordinated QM effort that 

maximally leverages its subject matter 


lotter on DSK11XQN23PROD with NOTICES1
80258 Federal Register / Vol. 89, No. 191 / Wednesday, October 2, 2024 / Notices 

experts, functional areas, and collective 

regulatory experience across different 

offices. 

II. Objectives of QM CoE 

The QM CoE will facilitate and 

coordinate the continuous evolution 

and consistent application of QM for 

drug development and regulatory 

decision-making to advance therapeutic 

medical product development, inform 

regulatory decision-making, and 

promote public health, by: 

• spearheading QM-related policy 

development and best practices to 

facilitate the consistent use of QM 

approaches during the drug 

development and regulatory assessment; 

• providing strategic direction for 

CDER’s QM activities; and 

• coordinating CDER’s efforts around 

QM education, training, and community 

engagement. 

III. Anticipated Outcomes of QM CoE 

The QM CoE will harmonize existing 

activities and identify and initiate new 

activities in the areas of 

multidisciplinary education and 

exchange, science policy development 

and implementation, knowledge 

management, and community 

engagement. The centralization of QM 

efforts across CDER within the CoE will 

allow for operational optimization and 

consistent application of QM 

approaches to advance therapeutic 

medical product development, inform 

regulatory decision-making, and 

promote public health. 

Dated: September 26, 2024. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2024–22580 Filed 10–1–24; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2024–P–2314] 

Determination That AUGMENTIN XR 

(Amoxicillin; Clavulanate Potassium) 

Extended-Release Tablets, 1 Gram; 

Equivalent to 62.5 Milligram Base, Was 

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, Agency, or we) 

has determined that AUGMENTIN XR 

(amoxicillin; clavulanate potassium) 

Extended-Release Tablets, 1 gram (gm); 

equivalent to (EQ) 62.5 milligram (mg) 

base, was not withdrawn from sale for 

reasons of safety or effectiveness. This 

determination will allow FDA to 

approve abbreviated new drug 

applications (ANDAs) for AUGMENTIN 

XR (amoxicillin; clavulanate potassium) 

Extended-Release Tablets, 1 gm; EQ 62.5 

mg base, if all other legal and regulatory 

requirements are met. 

FOR FURTHER INFORMATION CONTACT: Awo 

Archampong-Gray, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, Rm. 6243, 

Silver Spring, MD 20993–0002, 301– 

796–0110, Awo.Archampong-Gray@

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. 

AUGMENTIN (amoxicillin; 

clavulanate potassium) ExtendedRelease Tablets, 1 gm; EQ 62.5 mg base, 

is the subject of NDA 050785, held by 

US Antibiotics, LLC, and initially 

approved on September 25, 2002. 

AUGMENTIN XR is indicated for 

treatment of adults and pediatric 

patients with community-acquired 

pneumonia or acute bacterial sinusitis 

due to confirmed, or suspected betalactamase-producing pathogens (i.e., H. 

influenzae, M. catarrhalis, H. 

parainfluenzae, K. pneumoniae, or 

methicillin-susceptible S. aureus) and S. 

pneumoniae with reduced susceptibility 

to penicillin (i.e., penicillin minimum 

inhibitory concentrations EQ 2 

microgram/milliliter). 

AUGMENTIN XR (amoxicillin; 

clavulanate potassium) ExtendedRelease Tablets, 1 gm; EQ 62.5 mg base, 

is currently listed in the ‘‘Discontinued 

Drug Product List’’ section of the Orange 

Book. 

Aurobindo Pharma, USA, Inc. 

submitted a citizen petition dated May 

9, 2024 (Docket No. FDA–2024–P– 

2314), under 21 CFR 10.30, requesting 

that the Agency determine whether 

AUGMENTIN XR (amoxicillin; 

clavulanate potassium) ExtendedRelease Tablets, 1 gm; EQ 62.5 mg base, 

was 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 AUGMENTIN XR 

(amoxicillin; clavulanate potassium) 

Extended-Release Tablets, 1 gm; EQ 62.5 

mg base, was not withdrawn for reasons 

of safety or effectiveness. The petitioner 

has identified no data or other 

information suggesting that 

AUGMENTIN XR (amoxicillin; 

clavulanate potassium) ExtendedRelease Tablets, 1 gm; EQ 62.5 mg base, 

was withdrawn for reasons of safety or 

effectiveness. We have carefully 

reviewed our files for records 

concerning the withdrawal of 

AUGMENTIN XR (amoxicillin; 

clavulanate potassium) ExtendedRelease Tablets, 1 gm; EQ 62.5 mg base, 

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 AUGMENTIN XR 

(amoxicillin; clavulanate potassium) 

Extended-Release Tablets, 1 gm; EQ 62.5 

mg base, 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 


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