[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Draft Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``Providing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DATES: Submit either electronic or written comments on the draft
guidance by September 16, 2019 to ensure that the Agency considers your
comment on this draft guidance before it begins work on the final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