Document ID: FDA-2012-D-1197-0010
Agency: fda
Document Type: Notice
Title: Certification Process for Designated Medical Gases; Revised Draft
Guidance for Industry; Availability
Posted Date: 2015-11-25T05:00Z

[Federal Register Volume 80, Number 227 (Wednesday, November 25, 2015)]
[Notices]
[Pages 73771-73774]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-29989]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-D-1197]

Certification Process for Designated Medical Gases; Revised Draft 
Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a revised draft guidance for industry entitled 
``Certification Process for Designated Medical Gases.'' The original 
version of this draft guidance was published by FDA on December 18, 
2012. The revised draft guidance, like the original version, describes 
the certification process created by the Food and Drug Administration 
Safety and Innovation Act (FDASIA) for certain medical gases and 
explains how FDA plans to implement that process. In response to 
comments received, we have revised the draft guidance and are reissuing 
it in draft form to enable the public to review and comment before it 
is finalized.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the Agency considers your comment on this 
draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by January 25, 2016. Submit either electronic or written 
comments concerning the collection of information proposed in the draft 
guidance and attached Form 3864 by January 25, 2016.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://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 http://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): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, 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-2012-D-1197 for ``Certification Process for Designated Medical 
Gases; Revised Draft Guidance for Industry; Availability.'' Received 
comments will be placed in the docket and, except for those submitted 
as ``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management between 9 
a.m. and 4 p.m., Monday through Friday.
     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 http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. 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

[[Page 73772]]

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: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://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 Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.
    Submit written requests for single copies of this revised draft 
guidance to the Division of Drug Information, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10001 New 
Hampshire Ave., Hillandale Building, 4th Floor, Silver Spring, MD 
20993-0002; or the Communications Staff (HFV-12), Center for Veterinary 
Medicine, Food and Drug Administration, 7519 Standish Pl., Rockville, 
MD 20855. Send one self-addressed adhesive label to assist that office 
in processing your requests. See the SUPPLEMENTARY INFORMATION section 
for electronic access to the revised draft guidance document.

FOR FURTHER INFORMATION CONTACT: Michael Folkendt, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Silver Spring, MD 20993-0002, 301-796-1900; or Germaine 
Connolly, Center for Veterinary Medicine (HFV-116), Food and Drug 
Administration, 7500 Standish Pl., Rockville, MD 20855, 240-276-8331.

SUPPLEMENTARY INFORMATION: 

I. Background

    In the Federal Register of December 18, 2012 (77 FR 74852), FDA 
announced the availability of a draft guidance for industry entitled 
``Certification Process for Designated Medical Gases.'' This guidance 
was intended to help persons or entities interested in requesting 
certification of a designated medical gas under the approval process 
for designated medical gases created by the Food and Drug 
Administration Safety and Innovation Act (FDASIA) (Pub. L. 112-144).
    Title XI, subtitle B, of FDASIA added sections 575 and 576 to the 
Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 360ddd 
and 360ddd-1), which created a certification process for designated 
medical gases. Specifically, section 575 of the FD&C Act provides that 
oxygen, nitrogen, nitrous oxide, carbon dioxide, helium, carbon 
monoxide, and medical air are designated medical gases. Section 576 of 
the FD&C Act permits any person, beginning on January 5, 2013, to 
request certification of a medical gas for certain indications and 
describes when FDA will grant or deny these requests. The December 2012 
draft guidance explained how FDA planned to implement this new 
certification process. Specifically, the December 2012 draft guidance 
described the medical gases that are eligible for certification, who 
should submit a certification request, what information should be 
submitted, and how FDA will evaluate and act on the request. The 
December 2012 draft guidance also described how the new certification 
requirement will be enforced. Finally, the draft guidance included a 
draft certification request form (Form FDA 3864) and form instructions.
    This notice announces the availability of a revised draft guidance. 
In response to comments received, we have revised the discussions of 
labeling for final use containers (see section II of the revised draft 
guidance) and documentation by a person or entity that markets a 
designated medical gas but is not the original manufacturer or marketer 
of the gas (see section VI of the revised draft guidance). The December 
2012 draft guidance also contained a detailed implementation timeline, 
which has been removed in this revised version because the dates listed 
in the implementation timeline have all passed. FDA has also made small 
revisions to improve readability and address minor technical issues. We 
have not made any changes to the draft certification request form (Form 
FDA 3864) and form instructions that were attached to the 2012 draft 
guidance and are attached to this revised guidance. The revised 
guidance is being reissued in draft form to enable the public to review 
and comment before it is finalized.
    This revised draft guidance is being issued consistent with FDA's 
good guidance practices regulation (21 CFR 10.115). This revised draft 
guidance, when finalized, will represent the current thinking of FDA on 
the certification process for designated medical gases. 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

    Under the Paperwork Reduction Act (44 U.S.C. 3501-3520) (the PRA), 
Federal Agencies must obtain approval from the Office of Management and 
Budget (OMB) for each collection of information they conduct or 
sponsor. ``Collection of information'' is defined in 44 U.S.C. 3502(3) 
and 5 CFR 1320.3(c) and includes Agency requests or requirements that 
members of the public submit reports, keep records, or provide 
information to a third party. Section 3506(c)(2)(A) of the PRA (44 
U.S.C. 3506(c)(2)(A)) requires Federal Agencies to provide a 60-day 
notice in the Federal Register concerning each proposed collection of 
information before submitting the collection to OMB for approval. To 
comply with this requirement, FDA is publishing notice of the proposed 
collection of information set forth in this document.
    With respect to the collection of information associated with this 
draft guidance, FDA invites comments on these topics: (1) Whether the 
proposed collection of information is necessary for the proper 
performance of FDA's functions, including whether the information will 
have practical utility; (2) the accuracy of FDA's estimate of the 
burden of the proposed collection of information, including the 
validity of the methodology and assumptions used; (3) ways to enhance 
the quality, utility, and clarity of the information to be collected; 
and (4) ways to minimize the burden of the collection of information on 
respondents, including through the use of automated collection 
techniques, when appropriate, and other forms of information 
technology.
    Title: Certification Process for Designated Medical Gas.
    Description of Respondents: Respondents to this collection of 
information are original manufacturers and/or marketers and downstream 
manufacturers and/or marketers of certain medical gas drug products.
    Burden Estimate: Under section 576 of the FD&C Act and as explained 
in the revised draft guidance, the following information would be 
submitted to FDA by a person requesting certification of a designated 
medical gas product: A description of the medical gas for which 
certification is sought; the requestor's name, address, and other 
contact information; the name, address, and other contact information 
of the manufacturing facilities involved in the production of the gas; 
and certain affirmations that the gas meets applicable compendial 
standards and

[[Page 73773]]

that the product is manufactured in accordance with current good 
manufacturing practice. Requestors should make certification requests 
using Form FDA 3864 and include a cover letter explaining the nature of 
the submission (as explained in the Instructions page to the form). In 
certain circumstances, FDA may ask followup questions if additional 
information is needed from the requestor to determine whether a medical 
gas qualifies for certification as a designated medical gas.
    If the original information submitted in connection with a 
certification request becomes incomplete or inaccurate at any time, 
including after the request has been granted, the requestor should 
resubmit its certification request, submitting both a complete new form 
and a cover letter clearly explaining the purpose of the resubmission 
and highlighting the updated or corrected information. All updates or 
corrections to the information originally submitted (other than adding 
a new manufacturing facility) should be submitted in this manner. If 
the update or change involves adding a new manufacturing facility, 
requestors should notify FDA of the change by submitting a ``changes 
being effected'' supplement under Sec.  314.70(c) (21 CFR 314.70(c)) or 
Sec.  514.8(b)(3) (21 CFR 514.8(b)(3)). The requestor should also 
update its registration and listing information as needed.
    As explained in the revised draft guidance, section 576 of the FD&C 
Act permits any person to file a request for certification of a medical 
gas as a designated medical gas for certain indications. Based on our 
records, 31 requesters (``number of respondents'' in table 1, row 1) 
submitted 63 certification requests (``total responses'' in table 1, 
row 1) during 2013. Based on our familiarity with the medical gas 
certification process, we estimate that preparing and submitting each 
certification request to FDA (for original submissions and 
resubmissions) takes approximately 2 hours per requestor (``average 
burden per response'' in table 1). This estimate includes the time that 
some requestors may need to reply to any followup questions by FDA. For 
subsequent years, we expect to receive approximately five certification 
requests annually (including any resubmissions) (``total responses'' in 
table 1, row 2). All certification requests include Form FDA 3864 
together with a cover letter explaining the nature of the submission.
    As stated previously, requestors should notify FDA of a change that 
adds a new manufacturing facility by submitting a ``changes being 
effected'' supplement under Sec.  314.70(c) or Sec.  514.8(b)(3). Other 
manufacturing changes, e.g., a change in ownership or closure of a 
particular manufacturing facility, should be made in accordance with 
Sec.  314.70 or Sec.  514.8 as appropriate. FDA has OMB approval under 
control number 0910-0001 for the submission of manufacturing 
supplements under Sec.  314.70. FDA has OMB approval under control 
number 0910-0032 for the submission of supplements for new animal drug 
applications under Sec.  514.8. As described in the revised draft 
guidance, requestors should also update their registration and listing 
information as appropriate. FDA has OMB approval under control number 
0910-0045 for the submission of registration and listing information 
under 21 CFR part 207.
    As described in the revised draft guidance, a person or entity that 
markets a medical gas but is neither the original manufacturer nor the 
original marketer should verify and document that the gas they receive 
is from a certified source. Documentation should include the name of 
the original manufacturer(s) or marketer(s) as well the applicable new 
drug application number or numbers associated with the gas, and the 
information should be verified by reference to the FDA database 
``Drugs@FDA.gov.'' Each downstream customer should obtain documentation 
from their immediate supplier. Proper certification by a supplier or 
suppliers should be verified initially for existing suppliers and for 
new suppliers as part of a vendor qualification process. Once a new 
vendor or existing supplier has been qualified initially and the 
certification of the gas or gases confirmed, this documentation can 
consist of an annual letter from the immediate supplier attesting or 
certifying that the gas was originally manufactured at one or more 
firms with granted certifications. Based on our knowledge of the 
medical gas marketplace, we estimate that approximately 4,000 persons 
or entities that market a medical gas (but are neither the original 
manufacturer nor the original marketer) (``number of recordkeepers'' in 
table 2) will document and record that the gas they receive is from a 
certified source. We estimate that each recordkeeper will maintain 
approximately three records per year (``number of records per 
recordkeeper'' in table 2). We also estimate that it will take 
approximately 15 minutes per record to obtain and review the 
documentation (``average burden per recordkeeping'' in table 2).
    Furthermore, we estimate that 3,500 persons or entities (``number 
of respondents'' in table 3) will provide documentation of 
certification. We estimate that each responder will provide 
approximately five disclosures per year (``frequency of disclosure'' in 
table 3). Lastly, we estimate that it will take approximately 15 
minutes per disclosure (``hours per disclosure'' in table 3). This 
burden estimate includes the time required to update the disclosure 
annually and to provide a letter, as described in the revised draft 
guidance, certifying that the gas was originally manufactured at one or 
more firms with granted certifications.
    As stated in the revised draft guidance, section 576(a)(3)(A)(ii) 
of the FD&C Act provides that the labeling requirements at sections 
503(b)(4) and 502(f) of the FD&C Act (21 U.S.C. 353(b)(4) and 352(f), 
respectively) are deemed to have been met for a designated medical gas 
if the labeling on final use containers for the medical gas bears: (1) 
The information required by section 503(b)(4); (2) a warning statement 
concerning the use of the medical gas as determined by the Secretary by 
regulation; and (3) appropriate directions and warnings concerning 
storage and handling. The revised draft guidance states that with 
regard to the warning statement referred to at section 
576(a)(3)(A)(ii)(II) of the FD&C Act, a warning statement applicable to 
carbon dioxide, helium, and nitrous oxide can be found at Sec.  
201.161(a) (21 CFR 201.161(a)). However, no regulation sets forth 
warning statements for the other designated medical gases or for 
combinations of designated medical gases. The revised draft guidance 
states that in the absence of a regulation, FDA recommends that the 
labeling for final use containers containing nitrogen, medical air, 
carbon monoxide, or any medically appropriate combination of designated 
medical gases bear the warning statement set forth at Sec.  201.161(a). 
The revised draft guidance also states that FDA recommends that the 
labeling for oxygen final use containers should convey that 
uninterrupted use of high concentrations of oxygen over a long 
duration, without monitoring its effect on oxygen content of arterial 
blood, may be harmful, and that oxygen should not be used on patients 
who have stopped breathing unless used in conjunction with 
resuscitative equipment. FDA estimates that approximately 4,000 persons 
or entities (as described in the revised draft guidance) (``number of 
respondents'' in table 3) will need to include the labeling information 
described in the revised draft guidance

[[Page 73774]]

on approximately 10,250 gas containers (``frequency of disclosure'' in 
table 3), resulting in approximately 41,000,000 labels (``total 
disclosures'' in table 3). FDA expects that the labeling information 
currently used by industry is already consistent with the 
recommendations in the revised draft guidance. As a result, FDA 
estimates that it will take each person or entity approximately 0.1 
hours (``hours per disclosure'' in table 3) to review the information 
to ensure that their labeling is consistent with the revised draft 
guidance.
    FDA estimates the information collection resulting from the revised 
draft guidance as follows:

                                      Table 1--Estimated Reporting Burden1
----------------------------------------------------------------------------------------------------------------
                                                                                      Average
     Form FDA 3864 and other         Number of       Number of         Total        burden per
      requested information         respondents    responses per     responses     response  (in    Total hours
                                                    respondent                        hours)
----------------------------------------------------------------------------------------------------------------
Certification Requests During                 31            2.03              63               2             126
 the First Year.................
Certification Requests Annually                5               1               5               2              10
 After the First Year...........
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............             136
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

                                    Table 2--Estimated Recordkeeping Burden1
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                                                                                  Average burden
                                     Number of       Number of                          per
                                   recordkeepers    records per    Total records   recordkeeping    Total hours
                                                   recordkeeper                     (in hours)
----------------------------------------------------------------------------------------------------------------
Verification and documentation             4,000               3          12,000            0.25           3,000
 of certified sources by persons                                                    (15 minutes)
 or entities who market a
 medical gas but are neither the
 original manufacturer nor the
 original marketer..............
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

                            Table 3--Estimated Annual Third-Party Disclosure Burden1
----------------------------------------------------------------------------------------------------------------
                                     Number of     Frequency of        Total         Hours per
                                    respondents     disclosure      disclosures     disclosure      Total hours
----------------------------------------------------------------------------------------------------------------
Providing documentation of                 3,500               5          17,500            0.25           4,375
 certification..................                                                    (15 minutes)
Labeling required under section            4,000          10,250      41,000,000             0.1       4,100,000
 576(a)(3)(A)(ii) of the FD&C                                                        (6 minutes)
 Act............................
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............       4,104,375
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

III. Electronic Access

    Persons with access to the Internet may obtain the draft guidance 
at either http://www.fda.gov/RegulatoryInformation/Guidances/default.htm or http://www.regulations.gov.

    Dated: November 19, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-29989 Filed 11-24-15; 8:45 am]
BILLING CODE 4164-01-P