[Federal Register Volume 87, Number 56 (Wednesday, March 23, 2022)]
[Rules and Regulations]
[Pages 16391-16393]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-05776]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 4

[Docket No. FDA-2022-D-0192]


Certain Ophthalmic Products: Policy Regarding Compliance With 21 
CFR Part 4; Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notification of availability.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
announcing the availability of a final guidance for industry entitled 
``Certain Ophthalmic Products: Policy Regarding Compliance With 21 CFR 
part 4.'' This guidance describes FDA's compliance policy with respect 
to the requirements of FDA regulations that are now applicable to 
ophthalmic drugs that are packaged with eye cups, eye droppers, and 
other dispensers intended for ophthalmic use.

DATES: The announcement of the guidance is published in the Federal 
Register on March 23, 2022.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances at any time as follows:

Electronic Submissions

    Submit electronic comments in the following way:

[[Page 16392]]

     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-2022-D-0192 for ``Certain Ophthalmic Products: Policy Regarding 
Compliance With 21 CFR part 4.'' Received comments will be placed in 
the docket and, except for those submitted as ``Confidential 
Submissions,'' publicly viewable at https://www.regulations.gov or at 
the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through 
Friday, 240-402-7500.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852, 240-402-7500.
    You may submit comments on any guidance at any time (see Sec.  
10.115(g)(5) (21 CFR 10.115(g)(5))).
    Submit written requests for single copies of the guidance to the 
Division of Drug Information, Center for Drug Evaluation and Research, 
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale 
Building, 4th Floor, Silver Spring, MD 20993-0002; Office of 
Communication, Outreach and Development, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002; or 
Office of Policy, Center for Devices and Radiological Health, Food and 
Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 5431, 
Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to 
assist that office in processing your requests. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT: John Barlow Weiner, Office of 
Combination Products, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 32, Rm. 5129, Silver Spring, MD 20993-0002, 301-796-8930, 
[email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Certain Ophthalmic Products: Policy Regarding Compliance 
With 21 CFR part 4.'' We are implementing this guidance without prior 
public comment because we have determined that prior public 
participation is not feasible or appropriate (Sec.  10.115(g)(2)). We 
made this determination because FDA needs to communicate its compliance 
policy in a timely manner given the urgency of these issues following 
the decision from the U.S. Court of Appeals for the District of 
Columbia Circuit in Genus Medical Technologies LLC v. U.S. Food and 
Drug Administration (Genus), 994 F.3d 631 (D.C. Cir. 2021). Although 
this guidance document is immediately in effect, it remains subject to 
comment in accordance with FDA's good guidance practices (GGP) 
regulation and FDA will consider all comments received and determine 
whether revisions to the guidance document are appropriate (Sec.  
10.115(g)(3)).
    In accordance with Sec.  200.50(c) (21 CFR 200.50(c)), eye cups, 
eye droppers, and other dispensers intended for ophthalmic use 
(collectively referred to as ophthalmic dispensers) have been regulated 
as drugs when packaged together with the ophthalmic drug with which 
they were intended to be used. Therefore, products consisting of an 
ophthalmic drug packaged with an ophthalmic dispenser were not 
regulated as combination products as defined in Sec.  3.2(e) (21 CFR 
3.2(e)) and were not subject to the requirements of part 4 (21 CFR part 
4). This practice is a departure from how FDA generally regulates other 
devices that are packaged with the drugs with which they are intended 
to be used. Specifically, when a device is packaged together with the 
drug with which it is intended to be used, FDA regulates that drug and 
the device together as a combination product (see Sec.  3.2(e)).
    On April 16, 2021, the U.S. Court of Appeals for the District of 
Columbia Circuit issued its decision in Genus. The Genus court stated 
``[e]xcepting combination products, . . . devices must be regulated as 
devices and drugs--if they do not also satisfy the device definition--
must be regulated as drugs.'' \1\ In implementing this decision, FDA 
has determined that the language in Sec.  200.50(c) indicating that eye 
cups,

[[Page 16393]]

eye droppers, and ophthalmic dispensers are regulated as drugs when 
packaged with ophthalmic drugs is now obsolete, because these articles 
meet the ``device'' definition. Accordingly, an ophthalmic dispenser 
that meets the definition of device in section 201(h) of the Federal 
Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 321(h)) and that is 
packaged together with an ophthalmic drug is now regulated as a device 
constituent part (see Sec.  3.2(e)), and, as such, is subject to the 
requirements in part 4. Because the drug constituent part provides the 
primary mode of action of these combination products, generally FDA's 
Center for Drug Evaluation and Research (CDER) will have primary 
jurisdiction over these products.
---------------------------------------------------------------------------

    \1\ For more information on FDA's implementation of the Genus 
decision, please see Docket No. FDA-2021-N-0843, ``Genus Medical 
Technologies LLC Versus Food and Drug Administration; Request for 
Information and Comments,'' (86 FR 43553, August 9, 2021).
---------------------------------------------------------------------------

    This change impacts products subject to pending applications,\2\ 
approved products, and products marketed pursuant to section 505G of 
the FD&C Act (21 U.S.C. 355h) without an approved application under 
section 505 of the FD&C Act (21 U.S.C. 355) (commonly referred to as 
over-the-counter monograph drugs).
---------------------------------------------------------------------------

    \2\ For the purposes of this guidance, pending applications 
include applications on which FDA has taken an action that is not an 
approval action and that are not currently pending review before the 
Agency (i.e., applications that have been tentatively approved or 
applications that have received a complete response letter) and 
applications currently pending review before the Agency (including 
supplements to approved applications).
---------------------------------------------------------------------------

    We recognize that some applicants and manufacturers may need to 
develop policies and procedures necessary to comply with the 
requirements in part 4. Therefore, we are issuing the guidance to 
communicate FDA's compliance policy with respect to these products. The 
guidance explains FDA's policy with respect to compliance with the 
requirements of part 4. Specifically, the guidance explains that FDA 
generally does not intend to take action with respect to noncompliance 
with part 820 (21 CFR part 820) as described in part 4, subpart A, with 
respect to ophthalmic products that were not previously regulated as 
combination products because of the now obsolete language in Sec.  
200.50(c) for a period of 12 months following the publication of the 
guidance. Further, the guidance explains that, with respect to 
ophthalmic products affected by the Genus decision that incorporate 
lower-risk device constituent parts, for example, eye dropper bottles/
ampules that administer the drug directly to the eye, FDA does not 
intend to take action with respect to noncompliance with any applicable 
part 820 requirements for these products until FDA further considers 
the application of these requirements to these combination products. 
Additionally, the guidance describes FDA's policy with respect to 
pending applications and how FDA will determine when compliance with 
the requirements of part 4, subpart A, must be demonstrated (i.e., 
during the review of the application or after approval). As part of 
this notice, FDA is soliciting feedback from stakeholders as to whether 
a 12-month period is sufficient for affected stakeholders to develop 
and implement the policies and procedures necessary to comply with the 
requirements of part 4, including whether different amounts of time 
should be considered with respect to compliance with subpart A and 
subpart B of part 4. Finally, in addition to the guidance for industry 
we are announcing today, FDA also encourages applicants and 
manufacturers to review other guidances for industry that apply to 
CDER-led drug-device combination products.
    This guidance is being issued consistent with FDA's GGP regulation 
(Sec.  10.115). The guidance represents the current thinking of FDA on 
``Certain Ophthalmic Products: Policy Regarding Compliance With 21 CFR 
part 4.'' It does not establish any rights for any person and is not 
binding on FDA or the public. You can use an alternative approach if it 
satisfies the requirements of the applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

    While this guidance contains no collection of information, it does 
refer to previously approved FDA collections of information. Therefore, 
clearance by the Office of Management and Budget (OMB) under the 
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not 
required for this guidance. The previously approved collections of 
information are subject to review by OMB under the PRA. The collections 
of information in 21 CFR part 314 are approved under OMB control 
numbers 0910-0001, 0910-0230, and 0910-0291. The collections of 
information in 21 CFR 600.80 and 600.81 are approved under OMB control 
number 0910-0308. The collections of information in 21 CFR 606.171 are 
approved under OMB control number 0910-0458. The collections of 
information in 21 CFR 803.50, 803.53, and 803.56 are approved under OMB 
control numbers 0910-0291 and 0910-0437. The collections of information 
in 21 CFR 806.10 and 802.20 are approved under OMB control number 0910-
0359. The collections of information in 21 CFR part 211 have been 
approved under OMB control number 0910-0139. The collections of 
information in 21 CFR part 820 are approved under OMB control number 
0910-0073. The collections of information in 21 CFR parts 606 and 640 
are approved under OMB control number 0910-0116. The collections of 
information in 21 CFR part 610 are approved under OMB control numbers 
0910-0116 and 0910-0338 (also for 21 CFR part 680 and Form FDA 356h). 
The collections of information in 21 CFR part 1271, subparts C and D, 
are approved under OMB control number 0910-0543. The collections of 
information in 21 CFR 4.102, 4.103, and 4.105 are approved under OMB 
control number 0910-0834.

III. Electronic Access

    Persons with access to the internet may obtain the document at 
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

    Dated: March 11, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-05776 Filed 3-22-22; 8:45 am]
BILLING CODE 4164-01-P