[Federal Register Volume 84, Number 136 (Tuesday, July 16, 2019)]
[Notices]
[Pages 33949-33951]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-15103]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-N-1006]


Providing Regulatory Submissions in Electronic Format--Certain 
Human Pharmaceutical Product Applications and Related Submissions Using 
the Electronic Common Technical Document Specifications (Revision 7); 
Draft Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``Providing 
Regulatory Submissions in Electronic Format--Certain Human 
Pharmaceutical Product Applications and Related Submissions Using the 
eCTD Specifications (Revision 7).'' FDA has identified certain 
submission types that FDA believes warrant an exemption (Type III drug 
master files (DMFs)) or a long-term waiver (certain positron emission 
tomography (PET) drug products and certain Type II DMFs supporting PET 
drugs or noncommercial submissions or applications) from the 
requirement to submit to the Agency in eCTD format. In addition, this 
guidance outlines certain circumstances where FDA may determine that a 
short-term waiver from electronic common technical document (eCTD) 
submission requirements could be granted. This guidance is a revision 
of the final guidance issued on January 29, 2019, and when finalized, 
will supersede that guidance.

DATES: Submit either electronic or written comments on the draft 
guidance by September 16, 2019 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

ADDRESSES: You may submit comments on any guidance at any time as 
follows:

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-2014-N-1006 for ``Providing Regulatory Submissions in Electronic 
Format--Certain Human Pharmaceutical Product Applications and Related 
Submissions Using the eCTD Specifications (Revision 7).'' 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.
     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.gpo.gov/fdsys/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

[[Page 33950]]

and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, 
Rockville, MD 20852.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    Submit written requests for single copies of the 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 to the 
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. Send 
one self-addressed adhesive label to assist that office in processing 
your requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Ebla Ali Ibrahim, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6302, Silver Spring, MD 20993-0002, 301-
796-3691; or Stephen Ripley, Center for Biologics Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
71, Rm. 7301, Silver Spring, MD 20993-0002, 240-402-7911.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Providing Regulatory Submissions in Electronic Format--
Certain Human Pharmaceutical Product Applications and Related 
Submissions Using the eCTD Specifications (Revision 7).'' This guidance 
provides information regarding submission types that FDA believes 
warrant an exemption or long-term waiver from Agency eCTD requirements. 
In addition, this guidance outlines certain circumstances where FDA 
proposes granting short-term waivers from eCTD submission requirements. 
This revised draft guidance is intended to address current concerns 
raised to FDA regarding the burden of complying with eCTD submission 
requirements, which could have unintended public health consequences.
    In the Federal Register of January 3, 2013 (78 FR 310), FDA 
announced the availability of a draft guidance for industry entitled 
``Providing Regulatory Submissions in Electronic Format--Certain Human 
Pharmaceutical Product Applications and Related Submissions Using the 
eCTD Specifications.'' The draft guidance was announced in accordance 
with the Food and Drug Administration Safety and Innovation Act, which 
amended the Federal Food, Drug, and Cosmetic Act (FD&C Act) to require 
that certain submissions under the FD&C Act and Public Health Service 
Act be submitted in electronic format, beginning no earlier than 2 
years after publication of the final version of the draft guidance. 
That draft guidance described how FDA planned to implement the 
requirements for the electronic submission of applications for certain 
human pharmaceutical products. In the Federal Register of July 25, 2014 
(79 FR 43494), FDA announced the availability of a revised draft 
guidance for industry of the same title, which contained changes from 
the previous 2013 draft guidance on eCTD requirements. The final 
guidance (Revision 3) posted on May 5, 2015, provided a timetable of 24 
months after issuance of the final guidance for the initial 
implementation of the electronic submission requirement for new drug 
applications (NDAs), abbreviated new drug applications (ANDAs), 
biologic license applications (BLAs), and master files (May 5, 2017), 
and 36 months for commercial investigational new drug applications 
(INDs) (May 5, 2018). In April 2017, the revised guidance updated the 
timetable for compliance for required master file submissions in eCTD 
from 24 months to 36 months. In April 2018, the guidance was revised to 
include an extension for the timetable for Type III DMF submissions in 
eCTD for an additional 12 months. FDA determined that many of the 
concerns outlined in the guidance remain, and Revision 6 of the 
guidance was published to extend Type III DMF submissions in eCTD until 
May 5, 2020. Revision 6 of the guidance remains in effect until this 
draft revised version of the guidance is finalized.
    Type III DMFs. Type III DMFs are submitted to the Agency to provide 
information regarding packaging or packaging materials in support of 
NDAs, ANDAs, or BLAs. These DMFs are commonly submitted by firms that 
are not pharmaceutical manufacturers, but instead are material 
suppliers and manufacturers of packaging and packaging materials. Such 
firms are several steps removed from the NDA, ANDA, or BLA applicant in 
the supply chain. As described further below, compliance with eCTD 
submission requirements can represent a significant burden to support 
use of their packaging products for pharmaceuticals when balanced 
against their business interest in supplying their products for this 
use. In many cases, pharmaceutical packaging material is a limited 
portion of their overall business. In addition, the need to continue to 
maintain a Type III DMF to support a drug marketing application may 
occur even when the firm's packaging material or product is no longer 
actively marketed. There is a possibility that this regulatory burden 
could result in firms ending their supply of these critical materials 
to the pharmaceutical industry, which could lead to drug supply 
interruptions and drug shortages. Finally, only a small portion of Type 
III DMFs submitted to the Agency require review by FDA staff in support 
of a marketing application; in most cases, the information needed to 
support approval is already present in the marketing application. The 
burden on the Agency of allowing non-eCTD submissions for Type III DMFs 
is expected to be reasonably low. FDA reviewed the concerns expressed 
by the suppliers and manufacturers and proposes to exempt Type III DMFs 
from compliance with the eCTD submission requirement (as opposed to 
maintaining a compliance deadline of May 5, 2020). FDA continues to 
recommend use of the eCTD format for Type III DMF submissions where 
possible, but the Agency is issuing this revision to its guidance to 
propose this exemption.
    PET drug products. PET is a medical imaging method that produces a 
computerized image (scan) using a class of positron-emitting drugs, a 
unique type of radiopharmaceuticals. A PET drug or biologic is a 
radioactive agent that exhibits spontaneous disintegration of unstable 
nuclei by the emission of positrons and is used for providing dual 
photon positron emission tomographic diagnostic images (21 CFR 212.1, 
21 CFR 601.31(a)). PET is used in evaluating patients with coronary 
artery disease and in certain neurologic disorders. PET drugs are 
distinct among radiopharmaceuticals because of their unique production 
methods, and many are characterized by their short half-lives (some as 
short as 20 minutes). Many PET drug production facilities are therefore 
close in proximity to the patients to whom the drugs are administered.
    FDA's proposal to grant waivers from eCTD requirements for certain 
PET drugs is consistent with FDA's and Congress's history of 
recognizing that PET drugs can pose unique considerations. For example, 
in 1997, Congress passed the Food and Drug Administration Modernization 
Act (FDAMA) (Pub. L. 105-115), which directed FDA to regulate PET drugs

[[Page 33951]]

(section 121(c)) by developing appropriate procedures for the approval 
of PET drugs in accordance with section 505 of the FD&C Act (21 U.S.C. 
355) and to establish current good manufacturing practice requirements 
for PET drugs. Within FDAMA, Congress recognized the unique 
characteristics of PET drugs--in particular, the special criteria and 
processes required to produce these drugs--directing the Secretary of 
Health and Human Services to take due account of any relevant 
differences between not-for profit institutions that compound the drugs 
for their patients and commercial manufacturers of the drugs. See 
section 121(c)(1)(B) of FDAMA.
    Statements like this indicate that one of Congress' goals in 
enacting section 121 of FDAMA was to promote the availability of FDA-
approved PET drug products for the patients who need them. Previously, 
FDA found that, because of the unique circumstances surrounding the 
regulation of PET drug products, assessment of an application fee on 
certain PET drugs would present a significant barrier to innovation, 
and FDA granted a waiver of application fees for certain PET drug 
products.\1\ Similarly, FDA believes that the requirement to submit 
applications in eCTD format could result in a significant burden on 
certain PET drug producers and may lead to reduced availability of 
these innovative and lifesaving diagnostic drugs. This guidance 
proposes that sponsors and applicants of PET drug products may request 
a waiver from complying with eCTD submission requirements if they meet 
certain factors set forth in the revised eCTD guidance. Although FDA 
proposes waiving eCTD requirements for these submissions, FDA continues 
to recommend use of the eCTD format for PET drug products if feasible. 
The Agency is issuing this revision to its guidance to propose this 
waiver.
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    \1\ https://www.federalregister.gov/documents/2000/03/10/00-5865/positron-emission-tomography-drug-products-safety-and-effectiveness-of-certain-pet-drugs-for.
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    Certain Type II DMFs. Type II DMFs are submitted to the Agency to 
make quality information available for Agency evaluation of the quality 
of active pharmaceutical ingredients and drug products used in 
investigational studies. Many such studies are conducted by academic, 
non-commercial sponsors where there is no commercial objective to 
support these applications. In some cases, the Type II DMF submission 
may be submitted by the academic sponsor or by a second party. For 
these academic IND sponsors, compliance with eCTD submission 
requirements can represent a significant burden and may present an 
obstacle to the conduct of research. After consideration of this 
regulatory burden and the potential negative impact on research and 
innovation, FDA proposes to waive the requirement to comply with eCTD 
submission requirements for certain Type II DMF submissions from an 
academic institution, government (State or Federal), or a non-profit 
research organization that are solely supporting a noncommercial 
application.
    Short-Term Waivers. This guidance also describes the circumstances 
in which FDA proposes granting a temporary waiver from complying with 
eCTD submission requirements and the procedures for submitting requests 
for waivers.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the current thinking of FDA on ``Providing 
Regulatory Submissions in Electronic Format--Certain Human 
Pharmaceutical Product Applications and Related Submissions Using the 
eCTD Specifications (Revision 7).''
    FDA guidances ordinarily contain standard language explaining that 
guidances should be viewed only as recommendations unless specific 
regulatory or statutory requirements are cited. FDA is not including 
this standard language in this guidance because this guidance contains 
binding provisions. In section 745A(a) of the FD&C Act (21 U.S.C. 379k-
1), Congress granted explicit authorization to FDA to specify in 
guidance the format for the electronic submissions required under that 
section and required that FDA ``shall'' issue such guidance. 
Accordingly, this guidance explains such requirements under section 
745A(a) of the FD&C Act, indicated by the use of the words must or 
required, and therefore is not subject to the usual restrictions in 
FDA's good guidance practice regulations, such as the requirement that 
guidances not establish legally enforceable responsibilities. See e.g., 
21 CFR 10.115(d).

II. Paperwork Reduction Act of 1995

    This guidance refers to previously approved collections of 
information that are subject to review by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3520). The collections of information in 21 CFR parts 312, 314, and 601 
have been approved under OMB control numbers 0910-0014, 0910-0001, 
0910-0338, and 0910-0308.

III. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
https://www.regulations.gov.

    Dated: July 10, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-15103 Filed 7-15-19; 8:45 am]
 BILLING CODE 4164-01-P


