Document ID: FDA-2023-N-3275-0001
Agency: fda
Document Type: Proposed Rule
Title: 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
Posted Date: 2023-11-30T05:00Z

[Federal Register Volume 88, Number 229 (Thursday, November 30, 2023)]
[Proposed Rules]
[Pages 83802-83808]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-26208]

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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.

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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.

[[Page 83803]]

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, [email protected].

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).
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    \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.
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    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

[[Page 83804]]

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.
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    \2\ Table 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).
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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.''

[[Page 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:
    [cir] 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:
    [cir] 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:
    [cir] 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/

[[Page 83806]]

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 antimicrobial-containing wound 
dressings. Inadvertent leaching of antimicrobials away from the 
dressing may negatively impact the skin microbiota in the peri-wound 
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.
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    \3\ Only 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.
---------------------------------------------------------------------------

    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

[[Page 83807]]

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 non-sterile 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 Sec.  
860.7(c)(2) (21 CFR 860.7(c)(2))). FDA defines valid scientific 
evidence in Sec.  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.
---------------------------------------------------------------------------

    \4\ See FDA guidance, ``Requests for Feedback and Meetings for 
Medical Device Submissions: The Q-Submission Program; Guidance for 
Industry and Food and Drug Administration Staff.'' June 2, 2023, 
available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-submission-program.
---------------------------------------------------------------------------

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

[[Page 83808]]

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.archive-it.org/7993/20170405192855/https://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/GeneralandPlasticSurgeryDevicesPanel/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.archive-it.org/7993/20201227032045/https://www.fda.gov/advisory-committees/general-and-plastic-surgery-devices-panel/2016-meeting-materials-general-and-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

0
1. The authority citation for part 878 continues to read as follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.

0
2. Amend Sec.  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:

Sec.  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.
0
3. Amend Sec.  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:

Sec.  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.
0
4. Amend Sec.  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:

Sec.  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