83802 Federal Register / Vol. 88, No. 229 / Thursday, November 30, 2023 / Proposed Rules 

area which may result in impaired 

wound healing. 

(vii) Any statements in the labeling 

must be clear such that they may be 

understood by the end user, supported 

by appropriate evidence, and consistent 

with the intended use of mechanically 

irrigating a wound or maintaining 

appropriate moisture balance within a 

solid wound dressing. 

Dated: November 21, 2023. 

Robert M. Califf, 

Commissioner of Food and Drugs. 

[FR Doc. 2023–26209 Filed 11–29–23; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 878 

[Docket No. FDA–2023–N–3275] 

Effective Date of Requirement for 

Premarket Approval Applications for 

Certain Solid Wound Dressings; 

Wound Dressings Formulated as a Gel, 

Cream, or Ointment; and Liquid Wound 

Washes Containing Medically 

Important Antimicrobials 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Proposed amendment; proposed 

order. 

SUMMARY: The Food and Drug 

Administration (FDA, Agency, or we) is 

proposing to require the filing of a 

premarket approval application (PMA) 

for certain solid wound dressings; 

wound dressings formulated as a gel, 

cream, or ointment; and liquid wound 

washes containing antimicrobials with a 

high level of antimicrobial resistance 

(AMR) concern (i.e., medically 

important antimicrobials) acting as 

either protectants or preservatives, 

which are unclassified, preamendments 

devices. FDA is summarizing its 

proposed findings regarding the degree 

or risk of illness or injury designed to 

be eliminated or reduced by requiring 

the devices to meet the PMA 

requirements of the Federal Food, Drug, 

and Cosmetic Act (FD&C Act) and the 

benefits to the public from the use of the 

devices. 

DATES: Either electronic or written 

comments on the proposed order must 

be submitted by February 28, 2024. FDA 

intends that, if a final order based on 

this proposed order is issued, anyone 

who wishes to market solid wound 

dressings, wound dressings formulated 

as a gel, cream, or ointment, and liquid 

wound washes containing medically 

important antimicrobials acting as either 

protectants or preservatives must submit 

a PMA prior to the last day of the 30th 

calendar month beginning after the 

month in which the classification of the 

device in class III became effective. See 

section III for the effective date of any 

final order that may publish based on 

this proposed order. See section VI of 

this document for more information 

about submitting a PMA. 

ADDRESSES: You may submit comments 

as follows. Please note that late, 

untimely filed comments will not be 

considered. The https://

www.regulations.gov electronic filing 

system will accept comments until 

11:59 p.m. Eastern Time at the end of 

February 28, 2024. Comments received 

by mail/hand delivery/courier (for 

written/paper submissions) will be 

considered timely if they are received 

on or before that date. 

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–N–3275 for ‘‘Effective Date of 

Requirement for Premarket Approval 

Applications for Certain Solid Wound 

Dressings, Wound Dressings Formulated 

as a Gel, Cream, or Ointment, and 

Liquid Wound Washes Containing 

Medically Important Antimicrobials.’’ 

Received comments, those filed in a 

timely manner (see ADDRESSES), 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. 


khammond on DSKJM1Z7X2PROD with PROPOSALS4
Federal Register / Vol. 88, No. 229 / Thursday, November 30, 2023 / Proposed Rules 83803 

1 In December 2019, FDA began adding the term 

‘‘Proposed amendment’’ to the ‘‘ACTION’’ caption 

for these documents to indicate that they ‘‘propose 

to amend’’ the Code of Federal Regulations. This 

editorial change was made in accordance with the 

Office of the Federal Register’s interpretations of the 

Federal Register Act (44 U.S.C. chapter 15), its 

implementing regulations (1 CFR 5.9 and parts 21 

and 22), and the Document Drafting Handbook. 

FOR FURTHER INFORMATION CONTACT: 

Brandon Kitchel, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 4626, Silver Spring, 

MD 20993–0002, 301–796–6055, 

brandon.kitchel@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background—Regulatory Authorities 

The FD&C Act, as amended, 

establishes a comprehensive system for 

the regulation of medical devices 

intended for human use. Section 513 of 

the FD&C Act (21 U.S.C. 360c) 

established three classes of devices, 

reflecting the regulatory controls needed 

to provide reasonable assurance of their 

safety and effectiveness. The three 

classes of devices are class I (general 

controls), class II (special controls and 

general controls), and class III 

(premarket approval and general 

controls). Under section 513(d)(1) of the 

FD&C Act, devices that were in 

commercial distribution before the 

enactment on May 28, 1976 of the 1976 

amendments (Medical Device 

Amendments of 1976, Pub. L. 94–295) 

(generally referred to as 

‘‘preamendments devices’’) are 

classified after FDA has (1) received a 

recommendation from a device 

classification panel (an FDA advisory 

committee); (2) published the panel’s 

recommendation for comment, along 

with a proposed regulation classifying 

the device; and (3) published a final 

regulation classifying the device. FDA 

has classified most preamendments 

devices under these procedures. 

A person may market a 

preamendments device that has been 

classified into class III through 

premarket notification procedures, 

without submission of a PMA until FDA 

issues an administrative order under 

section 515(b) of the FD&C Act (21 

U.S.C. 360e(b)) requiring premarket 

approval. 

Section 515(f) of the FD&C Act 

provides an alternative pathway for 

meeting the premarket approval 

requirement. Under section 515(f), 

manufacturers may meet the premarket 

approval requirement if they file a 

notice of completion of a product 

development protocol (PDP) approved 

under section 515(f)(4) of the FD&C Act 

and FDA declares the PDP completed 

under section 515(f)(6)(B) of the FD&C 

Act. Accordingly, the manufacturer of a 

preamendments class III device may 

comply with a call for PMAs by filing 

a PMA or a notice of completion of a 

PDP. In practice, however, the option of 

filing a notice of completion of a PDP 

has rarely been used. For simplicity, 

although the PDP option remains 

available to manufacturers in response 

to a final order under section 515(b) of 

the FD&C Act, this document will refer 

only to the requirement for filing and 

obtaining approval of a PMA. 

Section 515(b)(1) of the FD&C Act sets 

forth the process for issuing a final 

order. Specifically, prior to the issuance 

of a final order requiring premarket 

approval for a preamendments class III 

device, the following must occur: (1) 

publication of a proposed order in the 

Federal Register; (2) a meeting of a 

device classification panel described in 

section 513(b) of the FD&C Act; and (3) 

consideration of comments from all 

affected stakeholders, including 

patients, payors, and providers. 

Section 515(b)(2) of the FD&C Act 

provides that a proposed order to 

require premarket approval shall 

contain: (1) the proposed order; (2) 

proposed findings with respect to the 

degree of risk of illness or injury 

designed to be eliminated or reduced by 

requiring the device to have an 

approved PMA, and the benefit to the 

public from the use of the device; (3) an 

opportunity for the submission of 

comments on the proposed order and 

the proposed findings; and (4) an 

opportunity to request a change in the 

classification of the device based on 

new information relevant to the 

classification of the device. 

Section 515(b)(3) of the FD&C Act 

provides that FDA shall, after the close 

of the comment period on the proposed 

order,1 consideration of any comments 

received, and a meeting of a device 

classification panel described in section 

513(b) of the FD&C Act, issue a final 

order to require premarket approval or 

publish a document terminating the 

proceeding together with the reasons for 

such termination. If FDA terminates the 

proceeding, FDA is required to initiate 

reclassification of the device under 

section 513(e) of the FD&C Act, unless 

the reason for termination is that the 

device is a banned device under section 

516 of the FD&C Act (21 U.S.C. 360f). 

A preamendments class III device 

may be commercially distributed 

without a PMA until 90 days after FDA 

issues a final order requiring premarket 

approval for the device, or 30 months 

after the classification of the device in 

class III under section 513 of the FD&C 

Act becomes effective, whichever is 

later (section 501(f)(2)(B) of the FD&C 

Act (21 U.S.C. 351(f)(2)(B)). Elsewhere 

in this issue of the Federal Register, 

FDA is proposing to classify solid 

wound dressings; wound dressings 

formulated as a gel, cream, or ointment; 

and liquid wound washes containing 

antimicrobials with a high level of AMR 

(i.e., the ability of a microorganism to 

resist the effects of an antimicrobial) 

concern to class III. Therefore, if the 

proposed classification regulation and 

the order to require PMAs are finalized 

at the same time, a PMA for these 

wound dressings must be filed within 

the 30-month period because that will 

be the later of the two time periods. If 

a PMA is not timely filed for such 

devices, then the device would be 

deemed adulterated under section 501(f) 

of the FD&C Act. 

Also, a preamendments device subject 

to the order process under section 

515(b) of the FD&C Act is not required 

to have an approved investigational 

device exemption (IDE) (see part 812 (21 

CFR part 812)) contemporaneous with 

its interstate distribution until the date 

identified by FDA in the final order 

requiring the filing of a PMA for the 

device. At that time, an IDE is required 

only if a PMA has not been filed. If the 

manufacturer, importer, or other 

sponsor of the device submits an IDE 

application and FDA approves it, the 

device may be distributed for 

investigational use. If a PMA is not filed 

by the later of the two dates, and the 

device is not distributed for 

investigational use under an IDE, the 

device is deemed adulterated within the 

meaning of section 501(f)(1)(A) of the 

FD&C Act and subject to enforcement 

action. 

II. Regulatory History of the Devices 

After the enactment of the Medical 

Device Amendments of 1976, FDA 

undertook an effort to identify and 

classify all preamendments devices, in 

accordance with section 513(d) of the 

FD&C Act. Consistent with the FD&C 

Act, FDA has held multiple General and 

Plastic Surgery Devices Panel meetings 

regarding the classification of wound 

dressings: on November 27, 1998 (Ref. 

1); August 25 and 26, 2005 (Ref. 2); and 

September 20 and 21, 2016 (the 2016 

Panel) (Ref. 3). However, only the 2016 

Panel meeting provided the class III 

recommendations. Certain solid wound 

dressings; wound dressings formulated 

as a gel, cream, or ointment; and liquid 

wound washes containing medically 

important antimicrobials (i.e., 

antimicrobial drugs that are important 

for therapeutic use in humans and 

associated with a high level of AMR 

concern) pose different risks than other 


khammond on DSKJM1Z7X2PROD with PROPOSALS4
83804 Federal Register / Vol. 88, No. 229 / Thursday, November 30, 2023 / Proposed Rules 

2Table 1 of the World Health Organization’s 

(WHO) 2018 publication ‘‘Critically important 

antimicrobials for human medicine: 6th revision’’ 

(https://www.who.int/publications/i/item/ 

9789241515528) has a list of all classes of medically 

important antimicrobials. For the purposes of this 

proposed order, an antimicrobial is considered 

medically important if, and only if, it falls within 

any of these classes regardless of the level of 

importance specified by the WHO (i.e., critically 

important, highly important, or important). 

wound dressings. Elsewhere in this 

issue of the Federal Register, FDA is 

proposing to classify certain 

unclassified, preamendments solid 

wound dressings; wound dressings 

formulated as a gel, cream, or ointment; 

and liquid wound washes containing 

medically important antimicrobials into 

class III. A PMA, in addition to general 

controls, will provide reasonable 

assurance of the safety and effectiveness 

of these devices. 

The proposed rule would also 

establish the identification, 

classification, and regulatory controls 

for certain solid wound dressings; 

wound dressings formulated as a gel, 

cream, or ointment; and liquid wound 

washes that contain antimicrobials 

acting as either protectants or 

preservatives with a medium or low 

level of AMR concern and/or other 

chemicals. These devices have been 

subject to premarket review through a 

510(k) submission and have been 

cleared for marketing if FDA considers 

the device to be substantially equivalent 

to a legally marketed predicate in 

accordance with section 513(i) of the 

FD&C Act. To date, FDA has cleared 

more than 500 of these devices and has 

cleared only one of the device types that 

we believe will be subject to the PMA 

requirements. 

On September 20 and 21, 2016, the 

2016 Panel met for the purposes of 

obtaining recommendations about the 

classification of products, including (1) 

solid wound dressings; (2) wound 

dressings formulated as a gel, cream, or 

ointment; and (3) liquid wound washes 

(Ref. 3). FDA held the 2016 Panel to 

obtain input on the risks to health and 

benefits of wound dressings and liquid 

wound washes that contain 

antimicrobials and/or other chemicals, 

as well as the clinical relevance of 

certain indications. The 2016 Panel was 

asked to recommend to FDA whether 

such wound dressings and liquid 

wound washes that contain 

antimicrobials and/or other chemicals 

should be classified into class III 

(subject to premarket approval), class II 

(subject to general and special controls), 

or class I (subject only to general 

controls). The 2016 Panel was also 

asked to discuss the types of evidence 

(including clinical evidence) that would 

be helpful to support certain 

indications, as well as appropriate 

controls necessary to mitigate the risks 

to health and assure the safety and 

effectiveness of these types of wound 

dressings and liquid wound washes. 

For solid wound dressings containing 

antimicrobials and/or other chemicals, 

the 2016 Panel reviewed the list of risks 

to health and potential mitigation 

measures provided by FDA and agreed 

that the list was acceptable. In general, 

a majority of the 2016 Panel 

recommended that solid wound 

dressings should be classified into class 

II, subject to special controls, with the 

exception of certain solid wound 

dressings containing antimicrobials, 

such as antibiotics (with similar 

consideration to antimicrobial agents 

that may select for resistance in indirect 

ways). Some of the 2016 Panel believed 

all wound dressings and liquid wound 

washes containing antimicrobials and/ 

or other chemicals should be classified 

as class III because of the absence of 

high-quality evidence of benefit; others 

recommended class III be considered for 

any product containing an antibiotic or 

an antimicrobial that may indirectly 

contribute to antibiotic resistance. 

For wound dressings containing 

antimicrobials and/or other chemicals 

formulated as a gel, cream, or ointment, 

the 2016 Panel reviewed the list of risks 

to health and potential mitigation 

measures provided by FDA and agreed 

that the list was acceptable. In general, 

a majority of the 2016 Panel 

recommended that wound dressings 

formulated as a gel, cream, or ointment 

should be classified into class II, subject 

to special controls, with the exception 

of certain wound dressings formulated 

as a gel, cream, or ointment containing 

antimicrobials, such as antibiotics (with 

similar consideration to agents that may 

select for resistance in indirect ways), 

for which some members of the 2016 

Panel recommended class III. 

For liquid wound washes containing 

antimicrobials and/or other chemicals, 

the 2016 Panel reviewed the list of risks 

to health and potential mitigation 

measures provided by FDA and agreed 

that the list was acceptable. In general, 

a majority of the 2016 Panel 

recommended that liquid wound 

washes should be classified into class I 

or class II, subject to special controls, 

depending on the toxicity of the 

product, with the exception of certain 

liquid wound washes containing 

antimicrobials, such as antibiotics (with 

similar consideration to agents that may 

select for resistance in indirect ways), 

for which some members of the 2016 

Panel recommended class III. 

The 2016 Panel recommended that 

wound dressings and liquid wound 

washes with medically important 

antimicrobials 2 (Ref. 4) be classified 

into class III because there was a lack of 

available evidence to determine that 

general and special controls are 

sufficient to provide reasonable 

assurance of safety and effectiveness, 

and these devices present a potential 

unreasonable risk of illness or injury. 

FDA agrees with the 2016 Panel’s 

recommendation. It is also FDA’s 

position that there is a lack of available 

evidence to determine that general and 

special controls are sufficient to provide 

reasonable assurance of the devices’ 

safety and effectiveness and that the 

devices present a potential unreasonable 

risk of illness or injury. FDA further 

agrees with the 2016 Panel’s 

recommendation that wound dressings 

and liquid wound washes with 

medically important antimicrobials and/ 

or other chemicals be classified into 

class III subject to PMA. 

III. Dates New Requirements Apply 

If FDA finalizes the proposed 

classification of certain solid wound 

dressings; wound dressings formulated 

as a gel, cream, or ointment; and liquid 

wound washes containing medically 

important antimicrobials acting as either 

protectants or preservatives, these 

devices will be classified into class III. 

In accordance with sections 501(f)(2)(B) 

and 515(b) of the FD&C Act, FDA is 

proposing to require that a PMA be filed 

with the Agency for certain solid wound 

dressings; wound dressings formulated 

as a gel, cream, or ointment; and liquid 

wound washes containing medically 

important antimicrobials acting as either 

protectants or preservatives by the last 

day of the 30th calendar month 

beginning after the month in which the 

classification of the device in class III 

became effective. 

An applicant whose product was 

legally in commercial distribution 

before May 28, 1976, or whose product 

has been found to be substantially 

equivalent to such a product, will be 

permitted to continue marketing such 

class III product during FDA’s review of 

the PMA, provided that a PMA is timely 

filed. FDA intends to review any PMA 

for the device within 180 days. FDA 

cautions that under section 

515(d)(1)(B)(i) of the FD&C Act, the 

Agency may not enter into an agreement 

to extend the review period for a PMA 

beyond 180 days, unless the Agency 

finds that ‘‘. . . the continued 

availability of the device is necessary for 

the public health.’’ 


khammond on DSKJM1Z7X2PROD with PROPOSALS4
Federal Register / Vol. 88, No. 229 / Thursday, November 30, 2023 / Proposed Rules 83805 

Moreover, manufacturers must cease 

distribution of devices upon receiving a 

not approvable or denial decision 

rendered on a PMA. In such 

circumstances, to resume distribution, 

these manufacturers must receive PMA 

approval for their devices. However, the 

product may be distributed for 

investigational use only if the 

requirements of the investigational 

device exemptions regulations in part 

812 are met. The requirements for 

investigational use of significant risk 

devices include submitting an IDE 

application to FDA for review and 

approval. An approved IDE is required 

to be in effect before an investigation of 

the device may be initiated or continued 

under 21 CFR 812.30. FDA, therefore, 

recommends that IDE applications be 

submitted to FDA at least 30 days before 

the date a PMA is required to be filed 

to avoid interrupting investigations. 

For currently marketed wound 

dressings and liquid wound washes that 

are proposed to be classified into class 

III, FDA is proposing that it does not 

intend to enforce compliance with the 

30-month deadline by which PMAs 

must be submitted, when a notice of 

intent to file a PMA is submitted within 

90 days of the effective date of the order, 

if finalized. In circumstances when a 

notice of intent to file is submitted, FDA 

is proposing that it does not intend to 

enforce compliance with the 30-month 

deadline by which PMAs must be 

submitted when a PMA is submitted 

within 90 days after the 30-month 

deadline. However, as discussed above, 

even if a notice of intent and PMA are 

submitted by these dates, manufacturers 

must cease distribution of devices upon 

receiving a not approvable or denial 

decision rendered on a PMA. 

IV. Devices Subject to This Proposal 

A solid wound dressing containing 

antimicrobials and/or other chemicals is 

used to cover and protect a wound, to 

absorb exudate, and to maintain 

appropriate moisture balance within the 

wound. Medically important 

antimicrobials that are incorporated in 

the solid wound dressing are used for 

protectant purposes only to reduce 

microbial growth within the solid 

wound dressing while in use or to 

provide an antimicrobial barrier to 

microbial penetration through the solid 

wound dressing. 

A wound dressing formulated as a gel, 

cream, or ointment containing 

antimicrobials and/or other chemicals is 

used to maintain appropriate moisture 

balance within the wound. Medically 

important antimicrobials that are 

incorporated in a wound dressing 

formulated as a gel, cream, or ointment 

are used for preservative purposes only 

to maintain shelf life for a non-sterile 

wound dressing or a multiple-use 

wound dressing for single patient use 

only. 

A liquid wound wash is a water-based 

solution used to mechanically irrigate 

and physically remove debris from 

external wounds. It is also used to 

moisten solid wound dressings to 

maintain appropriate moisture balance 

within the dressing. Medically 

important antimicrobials that are 

incorporated in a liquid wound wash 

are used for preservative purposes only 

to maintain shelf life for a non-sterile 

liquid wound wash or a multiple-use 

wound wash for single patient use only. 

FDA currently regulates these 

unclassified devices as devices 

requiring a 510(k) submission under 

product codes FRO, GER, MGP, MGQ, 

and EFQ. 

Elsewhere in this issue of the Federal 

Register, FDA is proposing to classify 

certain solid wound dressings; wound 

dressings formulated as a gel, cream, or 

ointment; and liquid wound washes 

containing medically important 

antimicrobials acting as either 

protectants or preservatives in class III 

and identifies these devices as follows: 

solid wound dressings containing 

antimicrobials and/or other chemicals; 

wound dressings formulated as a gel, 

cream, or ointments containing 

antimicrobials and/or other chemicals; 

and liquid wound washes. 

In accordance with section 

515(b)(2)(D) of the FD&C Act, interested 

persons are being offered the 

opportunity to comment or request a 

change on the Agency’s proposed 

classification of certain solid wound 

dressings; wound dressings formulated 

as a gel, cream, or ointment; and liquid 

wound washes containing medically 

important antimicrobials acting as either 

protectants or preservatives based on 

new information published elsewhere in 

this Federal Register. 

V. Proposed Findings With Respect to 

Risks and Benefits for Solid Wound 

Dressings; Wound Dressings 

Formulated as a Gel, Cream, or 

Ointment; and Liquid Wound Washes 

Containing Medically Important 

Antimicrobials 

As required by section 515(b) of the 

FD&C Act, FDA is publishing its 

proposed findings regarding: (1) the 

degree of risk of illness or injury 

designed to be eliminated or reduced by 

requiring that these devices have an 

approved PMA and (2) the benefits to 

the public from the use of the devices. 

These findings are based on the reports 

and recommendations of the 2016 

Panel, and any additional information 

that FDA has obtained. Additional 

information regarding the risks can be 

found below, as well as in the proposed 

rule published elsewhere in this issue of 

the Federal Register, proposing to 

classify these devices into class III. 

Based on this information, FDA has 

identified the following risks to health 

to the different categories of wound 

dressings and liquid wound washes that 

are within the scope of this proposed 

rule and classification action: 

• Solid Wound Dressings: 

Æ Adverse tissue reaction, 

immunological reaction, transmission of 

pathogens and parasites, toxicity, 

delayed wound healing, 

incompatibilities with other therapies, 

contribution to the spread of AMR, 

infection, microbial growth within the 

product, product degradation during 

stated shelf storage, loss of barrier 

function, retention of dressing material 

in wound, and negatively impacting the 

skin microbiota in the peri-wound area 

resulting in impaired wound healing. 

• Wound Dressings Formulated as a 

Gel, Cream, or Ointment: 

Æ Adverse tissue reaction, 

immunological reaction, transmission of 

pathogens and parasites, toxicity, 

delayed wound healing, 

incompatibilities with other therapies, 

contribution to the spread of AMR, 

infection, microbial growth within the 

product, product degradation during 

stated shelf storage, and negatively 

impacting the skin microbiota in the 

peri-wound area resulting in impaired 

wound healing. 

• Liquid Wound Washes: 

Æ Adverse tissue reaction, 

immunological reaction, transmission of 

pathogens and parasites, toxicity, 

delayed wound healing, 

incompatibilities with other therapies, 

contribution to the spread of AMR, 

infection, microbial growth within the 

product, product degradation during 

stated shelf storage, inability to remove 

wound debris and foreign materials, and 

negatively impacting the skin 

microbiota in the peri-wound area 

resulting in impaired wound healing. 

Below is a brief description of each of 

the identified risks to health: 

• Adverse tissue reaction: Erythema, 

irritation, inflammation of the wound or 

host tissue, immune response, and 

hemolysis can occur as a result of an 

unwanted tissue response associated 

with the materials or leachables/ 

extractables in wound dressings and 

liquid wound washes. 

• Immunological reaction: This can 

result from a device derived from a new 

animal source or protein denaturation/ 


khammond on DSKJM1Z7X2PROD with PROPOSALS4
83806 Federal Register / Vol. 88, No. 229 / Thursday, November 30, 2023 / Proposed Rules 

3Only the product code FRO was queried for the 

recall analysis as the majority of the products in 

scope for this proposed order fall under FRO. The 

types of recalls reported under FRO are expected to 

be representative of all products in scope for this 

proposed order. 

modification due to the manufacturing 

conditions. 

• Transmission of pathogens and 

parasites (e.g., bacteria, mycoplasma, 

fungi, viruses, and other transmissible 

spongiform encephalopathy agents): 

This can result from contaminated 

animal sources, feed, inadequate 

processing, and viral inactivation of the 

animal-derived materials. 

• Toxicity: Local and/or systemic 

toxicity, tissue necrosis, reduced tissue 

viability, and genotoxicity can occur 

due to toxic antimicrobials or other 

chemicals in the wound dressings or 

liquid wound washes, which can result 

in adverse tissue effects, leading to 

toxicity. This also includes allergic 

reaction and sensitization, as 

individuals with known sensitivity to 

the materials in the wound dressings 

and liquid wound washes may 

experience allergic reactions, which 

may be severe depending on the degree 

of sensitivity. 

• Delayed wound healing: 

Cytotoxicity resulting in dead or 

necrotic tissue can delay healing. 

• Incompatibilities with other 

therapies: An undesirable (e.g., 

antagonistic) reaction could occur 

between the materials contained in/on 

the wound dressings or liquid wound 

washes and other therapies applied to 

the wound. 

• Contribution to the spread of AMR: 

Use of antimicrobials in wound 

dressings and liquid wound washes can 

inadvertently select for and cultivate 

antimicrobial resistant organisms in 

patients and further limit a clinician’s 

therapeutic options to treat infections. 

• Infection: Unsafe methods of 

manufacturing processes, such as 

inadequate aseptic processing, 

inadequate packaging and/or product 

storage, can result in contaminated 

product that may be a source of 

infection. This risk includes bacterial 

and fungal infections and 

superinfections, which may result from 

the use of an antimicrobial-containing 

wound dressing or liquid wound wash 

that introduces contaminating 

microorganisms to the wound or 

disrupts the natural balance of skin flora 

around the wound. 

• Microbial growth within the 

product: This can occur from 

inadequate sterilization, preservative 

effectiveness failure, unsafe methods of 

manufacturing processes, inadequate 

packaging and/or product storage. This 

can lead to a change in product 

composition or characteristics (e.g., loss 

of tensile strength, change in pH) and 

may also result in infection or adverse 

tissue reaction. 

• Product degradation during stated 

shelf storage: Inadequate packaging and/ 

or inappropriate storage of wound 

dressings or liquid wound washes can 

result in product degradation during 

storage. Product degradation can also 

change the composition or 

characteristics of the product over time 

and lead to patient harm. 

• Retention of dressing material in 

wound: This risk is generally applicable 

to solid wound dressings, which can 

occur due to a loss in solid dressing 

integrity or unintended degradation of 

solid wound dressings. It may also 

occur due to the healthcare provider 

inadvertently leaving material in the 

wound. This can lead to adverse tissue 

reaction, delay in wound healing, or 

infection. 

• Inability to remove wound debris 

and foreign materials: Ineffective 

washing of the wound can occur. Debris 

and foreign material remaining in the 

wound can delay healing or lead to 

infection. This risk is applicable to the 

liquid wound washes containing 

antimicrobials and/or other chemicals. 

• Loss of barrier function: This risk is 

applicable to solid wound dressings 

indicated as barriers to microbial 

penetration through the wound dressing 

(either via mechanical or antimicrobial 

properties). Loss of this barrier function 

can introduce microbial contamination 

from the environment into the wound 

and can lead to delay in wound healing 

or infection. 

• Impact to skin microbiota in the 

peri-wound area: This risk is applicable 

to each category of antimicrobialcontaining wound dressings. 

Inadvertent leaching of antimicrobials 

away from the dressing may negatively 

impact the skin microbiota in the periwound area by reducing the presence of 

beneficial commensal microorganisms 

that play a role in the wound healing 

cascade, resulting in impaired wound 

healing. 

A. Summary of Data 

FDA conducted queries of the 

Manufacturer and User Facility Device 

Experience database to identify adverse 

events related to use of solid wound 

dressings; wound dressings formulated 

as a gel, cream, or ointment; and liquid 

wound washes containing medically 

important antimicrobials acting as either 

protectants or preservatives. The queries 

resulted in the identification of 1,973 

Medical Device Reports (MDRs) on 

these devices as of July 21, 2022. The 

reports were received by FDA from 1994 

to July 21, 2022. The number of MDRs 

received between 1994 and 2004 were 

consistently low, at fewer than 20 per 

year. Between 2005 and 2016, the 

number of MDRs increased to an 

average of 111 reports per year with a 

peak in 2015, at 298 MDRs. MDRs 

received between 2016 and 2022 

averaged 148 ± 17 MDRs per year. 

Additionally, FDA conducted a 

comprehensive literature review to 

identify and gather relevant published 

information regarding the safety and 

effectiveness of solid wound dressings; 

wound dressings formulated as a gel, 

cream, or ointment; and liquid wound 

washes containing medically important 

antimicrobials acting as either 

protectants or preservatives. 

Consequently, FDA concludes there is 

inadequate information characterizing 

the safety and effectiveness of wound 

dressings and liquid wound washes 

containing medically important 

antimicrobials. The 510(k) clearances of 

these devices were based solely on 

nonclinical information and 

determinations of substantial 

equivalence to the preamendments 

device in accordance with section 513(i) 

of the FD&C Act, which, in light of the 

available information regarding the risks 

with no information supporting the 

benefit of these devices, is inadequate to 

support a reasonable assurance of safety 

and effectiveness for these devices. 

FDA also reviewed recalls reported 

under product code FRO from 2003 to 

July 2022.3 There are no recalls for solid 

wound dressings; wound dressings 

formulated as a gel, cream, or ointment; 

or liquid wound washes containing 

medically important antimicrobials 

acting as either protectants or 

preservatives. 

On September 20 and 21, 2016, FDA 

convened the General and Plastic 

Surgery Device Panel described in 

section II (Ref. 3). The majority of the 

2016 Panel members noted that there is 

a lack of clinical data to demonstrate a 

clear clinical benefit regarding the use 

of wound dressings and liquid wound 

washes containing medically important 

antimicrobials. Several of the 2016 

Panel members noted that wound 

dressings and liquid wound washes 

containing medically important 

antimicrobials, such as antibiotics, 

present an unreasonable risk of illness 

or injury to the patient (e.g., directly 

contributing to the spread of 

antimicrobial resistance, further limiting 

clinician’s therapeutic options), 

especially given the lack of probable 

benefit. Additionally, the 2016 Panel 

members discussed that special 


khammond on DSKJM1Z7X2PROD with PROPOSALS4
Federal Register / Vol. 88, No. 229 / Thursday, November 30, 2023 / Proposed Rules 83807 

4See FDA guidance, ‘‘Requests for Feedback and 

Meetings for Medical Device Submissions: The QSubmission Program; Guidance for Industry and 

Food and Drug Administration Staff.’’ June 2, 2023, 

available at https://www.fda.gov/regulatoryinformation/search-fda-guidance-documents/ 

requests-feedback-and-meetings-medical-devicesubmissions-q-submission-program. 

controls, such as testing in an animal 

model, could not be used to evaluate 

and/or mitigate the high level of AMR 

risk. As such, several panelists 

concluded that these wound dressings 

and liquid wound washes should be 

classified as class III and subject to 

increased regulatory controls to mitigate 

the high level of AMR risk. 

B. Benefits of the Device 

The purported benefit of the use of 

wound dressings and liquid wound 

washes containing medically important 

antimicrobials acting as either 

protectants or preservatives include 

maintaining a moist environment, 

providing an effective barrier to 

environmental contaminants, reducing 

microbial growth within the dressing, 

and extending the shelf life of nonsterile and/or multiple-use wound 

dressings and liquid wound washes; 

however, FDA is not aware of clinical 

evidence supporting the stated benefit 

of wound dressings and liquid wound 

washes containing medically important 

antimicrobials. FDA is proposing a PMA 

be filed to require that manufacturers 

demonstrate that a reasonable assurance 

of safety and effectiveness exists for 

solid wound dressings; wound dressings 

formulated as a gel, cream, or ointment; 

and liquid wound washes containing 

medically important antimicrobials 

acting as either protectants or 

preservatives. 

C. Risks to Health 

The unreasonable risk profile of solid 

wound dressings; wound dressings 

formulated as a gel, cream, or ointment; 

and liquid wound washes containing 

medically important antimicrobials 

acting as either protectants or 

preservatives includes adverse tissue 

reaction, immunological reaction, 

transmission of pathogens and parasites, 

toxicity, delayed wound healing, 

incompatibility with other therapies, 

contribution to the spread of AMR, 

infection, microbial growth within the 

product during use, product degradation 

during stated shelf storage, retention of 

dressing material in wound, loss of 

barrier function, inability to remove 

wound debris and foreign materials, and 

negatively impacting the skin 

microbiota in the peri-wound area 

resulting in impaired wound healing. 

FDA agrees with certain 2016 Panel 

members that wound dressings and 

liquid wound washes containing 

medically important antimicrobials 

present an unreasonable risk of illness 

or injury. FDA further agrees that 

because insufficient information exists 

to determine that general and special 

controls are sufficient to provide 

reasonable assurance of the safety and 

effectiveness, wound dressings and 

liquid wound washes containing 

medically important antimicrobials 

should be class III subject to PMA. 

VI. PMA Requirements 

A PMA for solid wound dressings; 

wound dressings formulated as gels, 

creams, and ointments; and liquid 

wound washes containing medically 

important antimicrobials acting as either 

protectants or preservatives must 

include the information required by 

section 515(c)(1) of the FD&C Act. Such 

a PMA should also include a detailed 

discussion of the risks identified in 

section V, as well as a discussion of the 

effectiveness of the product for which 

premarket approval is sought. In 

addition, a PMA must include all data 

and information on the following: (1) 

any risks known, or that should be 

reasonably known, to the applicant that 

have not been identified in this 

document; (2) the effectiveness of the 

device that is the subject of the 

application; and (3) full reports of all 

preclinical and clinical information 

from investigations on the safety and 

effectiveness of the device for which 

premarket approval is sought. 

A PMA must include valid scientific 

evidence to demonstrate reasonable 

assurance of the safety and effectiveness 

of the solid wound dressing; wound 

dressing formulated as gels, creams, and 

ointments; or liquid wound wash 

containing medically important 

antimicrobials acting as either 

protectants or preservatives for its 

intended use (see § 860.7(c)(2) (21 CFR 

860.7(c)(2))). FDA defines valid 

scientific evidence in § 860.7(c)(2). 

To present reasonable assurance of 

safety and effectiveness of solid wound 

dressings; wound dressings formulated 

as gels, creams, and ointments; and 

liquid wound washes containing 

medically important antimicrobials 

acting as either protectants or 

preservatives, FDA tentatively 

concludes that manufacturers should 

submit performance testing to support 

PMA approval. Existing published 

clinical literature relevant to the 

product may also be leveraged as part of 

the PMA submission. In addition, FDA 

strongly encourages manufacturers to 

meet with the Agency early through the 

Q-Submission Program 4 for any 

assistance in preparation of their PMA. 

VII. Analysis of Environmental Impact 

We have determined under 21 CFR 

25.34(b) that this action is of a type that 

does not individually or cumulatively 

have a significant effect on the human 

environment. Therefore, neither an 

environmental assessment nor an 

environmental impact statement is 

required. 

VIII. Paperwork Reduction Act of 1995 

While this proposed order 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 814, 

subparts A through E, have been 

approved under OMB control number 

0910–0231; and the collections of 

information in part 812 have been 

approved under OMB control number 

0910–0078. 

IX. Proposed Effective Date 

FDA is proposing that any final order 

based on this proposal become effective 

on the date of its publication in the 

Federal Register or at a later date if 

stated in the final order. 

X. Opportunity To Request a Change in 

Classification 

Before requiring the filing of a PMA 

or notice of completion of a PDP for a 

device, FDA is required by section 

515(b)(2)(D) of the FD&C Act to provide 

an opportunity for interested persons to 

request a change in the classification of 

the device based on new information 

relevant to the classification of the 

device. A request for a change in the 

classification of solid wound dressings; 

wound dressings formulated as gels, 

creams, and ointments; and liquid 

wound washes containing medically 

important antimicrobials acting as either 

protectants or preservatives, as 

described in this document, should be 

provided in response to the proposed 

rule issued elsewhere in this issue of the 

Federal Register and contain the 

information required by 21 CFR 

860.123, including new information 

relevant to the classification of the 

device. 

XI. References 

The following references marked with 

an asterisk (*) are on display at the 

Dockets Management Staff (see 

ADDRESSES) and are available for 


khammond on DSKJM1Z7X2PROD with PROPOSALS4
83808 Federal Register / Vol. 88, No. 229 / Thursday, November 30, 2023 / Proposed Rules 

viewing by interested persons between 

9 a.m. and 4 p.m., Monday through 

Friday; they also are available 

electronically at https://

www.regulations.gov. References 

without asterisks are not on public 

display at https://www.regulations.gov 

because they have copyright restriction. 

Some may be available at the website 

address, if listed. References without 

asterisks are available for viewing only 

at the Dockets Management Staff. FDA 

has verified the website addresses, as of 

the date this document publishes in the 

Federal Register, but websites are 

subject to change over time. 

* 1. General and Plastic Surgery Devices 

Panel, ‘‘Transcript of the FDA General 

and Plastic Surgery Devices Panel 

meeting—November 17, 1998.’’ 

Available at https://web.archive.org/web/ 

20180125235924/https://www.fda.gov/ 

ohrms/dockets/ac/98/transcpt/ 

3483t1.pdf. 

* 2. General and Plastic Surgery Devices 

Panel, ‘‘Brief Summary from the General 

and Plastic Surgery Devices Panel 

Meeting—August 25–26, 2005.’’ 

Available at https://wayback.archiveit.org/7993/20170405192855/https://

www.fda.gov/AdvisoryCommittees/ 

CommitteesMeetingMaterials/ 

MedicalDevices/MedicalDevicesAdvisory

Committee/Generaland

PlasticSurgeryDevicesPanel/ 

ucm124755.htm. 

* 3. General and Plastic Surgery Devices 

Panel, ‘‘2016 Meeting Materials of the 

General and Plastic Surgery Advisory 

Panel—September 20–21, 2016.’’ 

Available at https://wayback.archiveit.org/7993/20201227032045/https://

www.fda.gov/advisory-committees/ 

general-and-plastic-surgery-devicespanel/2016-meeting-materials-generaland-plastic-surgery-advisory-panel. 

4. WHO, Critically Important Antimicrobials 

for Human Medicine. 2018. Available at 

https://www.who.int/publications/i/ 

item/9789241515528. 

List of Subjects in 21 CFR Part 878 

Medical devices. 

Therefore, under the Federal Food, 

Drug, and Cosmetic Act and under 

authority delegated to the Commissioner 

of Food and Drugs, we propose that 21 

CFR part 878 be amended as follows: 

PART 878—GENERAL AND PLASTIC 

SURGERY DEVICES 

■ 1. The authority citation for part 878 

continues to read as follows: 

Authority: 21 U.S.C. 351, 360, 360c, 360e, 

360j, 360l, 371. 

■ 2. Amend § 878.4016, as proposed to 

be added in FR 2023–26209, published 

elsewhere in this issue of the Federal 

Register, by adding paragraph (c) to read 

as follows: 

§ 878.4016 Solid wound dressings 

containing antimicrobials and/or other 

chemicals. 

* * * * * 

(c) Date premarket approval 

application (PMA) or notice of 

completion of product development 

protocol (PDP) is required. A PMA or 

notice of completion of a PDP is 

required to be filed with the Food and 

Drug Administration on or before 

[DATE OF THE LAST DAY OF THE 

30TH FULL CALENDAR MONTH 

AFTER EFFECTIVE DATE OF FINAL 

RULE], for any solid wound dressing, as 

identified in paragraph (a) of this 

section, that either contains one or more 

medically important antimicrobials 

acting as protectants and was in 

commercial distribution before May 28, 

1976, or has, on or before [DATE OF 

THE LAST DAY OF THE 30TH FULL 

CALENDAR MONTH AFTER 

EFFECTIVE DATE OF FINAL RULE], 

been found to be substantially 

equivalent to any solid wound dressing, 

as identified in paragraph (a) of this 

section, that contains one or more 

medically important antimicrobials 

acting as protectants and that was in 

commercial distribution before May 28, 

1976. Any other solid wound dressing, 

as identified in paragraph (a) of this 

section, that contains one or more 

medically important antimicrobials 

acting as protectants shall have an 

approved PMA or declared completed 

PDP in effect before being placed in 

commercial distribution. 

■ 3. Amend § 878.4017, as proposed to 

be added in FR 2023–26209, published 

elsewhere in this issue of the Federal 

Register, by adding paragraph (c) to read 

as follows: 

§ 878.4017 Wound dressings formulated 

as a gel, cream, or ointment containing 

antimicrobials and/or other chemicals. 

* * * * * 

(c) Date premarket approval 

application (PMA) or notice of 

completion of product development 

protocol (PDP) is required. A PMA or 

notice of completion of a PDP is 

required to be filed with the Food and 

Drug Administration on or before 

[DATE OF THE LAST DAY OF THE 

30TH FULL CALENDAR MONTH 

AFTER EFFECTIVE DATE OF FINAL 

RULE], for any wound dressing 

formulated as a gel, cream, or ointment, 

as identified in paragraph (a) of this 

section, that either contains one or more 

medically important antimicrobials 

acting as preservatives and was in 

commercial distribution before May 28, 

1976, or has, on or before [A DATE OF 

THE LAST DAY OF THE 30TH FULL 

CALENDAR MONTH AFTER 

EFFECTIVE DATE OF FINAL RULE], 

been found to be substantially 

equivalent to any wound dressings 

formulated as a gel, cream, or ointment, 

as identified in paragraph (a) of this 

section, that contains one or more 

medically important antimicrobials 

acting as preservatives and that was in 

commercial distribution before May 28, 

1976. Any other wound dressing 

formulated as a gel, cream, or ointment, 

as identified in paragraph (a) of this 

section, that contains one or more 

medically important antimicrobials 

acting as preservatives shall have an 

approved PMA or declared completed 

PDP in effect before being placed in 

commercial distribution. 

■ 4. Amend § 878.4019, as proposed to 

be added in FR 2023–26209, published 

elsewhere in this issue of the Federal 

Register, by adding paragraph (c) to read 

as follows: 

§ 878.4019 Liquid wound washes. 

* * * * * 

(c) Date premarket approval 

application (PMA) or notice of 

completion of product development 

protocol (PDP) is required. A PMA or 

notice of completion of a PDP is 

required to be filed with the Food and 

Drug Administration on or before 

[DATE OF THE LAST DAY OF THE 

30TH FULL CALENDAR MONTH 

AFTER EFFECTIVE DATE OF THE 

FINAL RULE], for any liquid wound 

wash, as identified in paragraph (a) of 

this section, that either contains one or 

more medically important 

antimicrobials acting as preservatives 

and was in commercial distribution 

before May 28, 1976, or has, on or before 

[DATE OF THE LAST DAY OF THE 

30TH FULL CALENDAR MONTH 

AFTER EFFECTIVE DATE OF THE 

FINAL RULE], been found to be 

substantially equivalent to any liquid 

wound wash, as identified in paragraph 

(a) of this section, that contains one or 

more medically important 

antimicrobials acting as preservatives 

and that was in commercial distribution 

before May 28, 1976. Any other liquid 

wound wash, as identified in paragraph 

(a) of this section, that contains one or 

more medically important 

antimicrobials acting as preservatives 

shall have an approved PMA or 

declared completed PDP in effect before 

being placed in commercial 

distribution. 

Dated: November 22, 2023. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2023–26208 Filed 11–29–23; 8:45 am] 

BILLING CODE 4164–01–P 


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