New Drugs Regulatory Program Modernization: Improving Approval Package Documentation and Communication, 30733-30736 [2019-13751]
Download as PDF
<![CDATA[
Federal Register / Vol. 84, No. 124 / Thursday, June 27, 2019 / Notices
INFORMATION section for electronic
access to the guidance document.
FOR FURTHER INFORMATION CONTACT:
Regarding the guidance: Brian Booth,
Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 51, Rm. 2186, Silver Spring,
MD 20993–0002, 301–796–1508; 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.
Regarding the ICH: Amanda Roache,
Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 51, Rm. 6364, Silver Spring,
MD 20993–0002, 301–796–4548.
SUPPLEMENTARY INFORMATION:
jspears on DSK30JT082PROD with NOTICES
I. Background
In recent years, regulatory authorities
and industry associations from around
the world have participated in many
important initiatives to promote
international harmonization of
regulatory requirements under the ICH.
FDA has participated in several ICH
meetings designed to enhance
harmonization, and FDA is committed
to seeking scientifically based
harmonized technical procedures for
pharmaceutical development. One of
the goals of harmonization is to identify
and reduce differences in technical
requirements for drug development
among regulatory agencies.
ICH was established to provide an
opportunity for harmonization
initiatives to be developed with input
from both regulatory and industry
representatives. FDA also seeks input
from consumer representatives and
others. ICH is concerned with
harmonization of technical
requirements for the registration of
pharmaceutical products for human use
among regulators around the world. The
six founding members of the ICH are the
European Commission; the European
Federation of Pharmaceutical Industries
Associations; FDA; the Japanese
Ministry of Health, Labour, and Welfare;
the Japanese Pharmaceutical
Manufacturers Association; and the
Pharmaceutical Research and
Manufacturers of America. The
Standing Members of the ICH
Association include Health Canada and
Swissmedic. Any party eligible as a
Member in accordance with the ICH
Articles of Association can apply for
membership in writing to the ICH
Secretariat. The ICH Secretariat, which
coordinates the preparation of
VerDate Sep<11>2014
20:15 Jun 26, 2019
Jkt 247001
documentation, operates as an
international nonprofit organization and
is funded by the Members of the ICH
Association.
The ICH Assembly is the overarching
body of the Association and includes
representatives from each of the ICH
members and observers. The Assembly
is responsible for the endorsement of
draft guidelines and adoption of final
guidelines. FDA publishes ICH
guidelines as FDA guidance.
In November 2018, the ICH Assembly
endorsed the draft guideline entitled
‘‘M10 Bioanalytical Method Validation’’
and agreed that the guideline should be
made available for public comment. The
draft guideline is the product of the M10
Expert Working Group of the ICH.
Comments about this draft will be
considered by FDA and the ICH M10
Expert Working Group.
The draft guidance provides guidance
on the validation of bioanalytical assays
that support regulatory submissions.
The draft guidance describes the various
elements and expectations of method
validation for assays in nonclinical and
clinical studies of new drugs and
generic drugs and applies to
chromatographic and ligand-binding
assays for parent drug and active
metabolites in biological matrices such
as plasma, blood, or serum.
This draft guidance has been left in
the original ICH format. The final
guidance will be reformatted and edited
to conform with FDA’s good guidance
practices regulation (21 CFR 10.115) and
style before publication. The draft
guidance, when finalized, will represent
the current thinking of FDA on ‘‘M10
Bioanalytical Method Validation.’’ 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. This guidance is not subject
to Executive Order 12866.
II. Electronic Access
Persons with access to the internet
may obtain the draft guidance at https://
www.regulations.gov, https://www
.fda.gov/Drugs/GuidanceCompliance
RegulatoryInformation/Guidances/
default.htm, or https://www.fda.gov/
BiologicsBloodVaccines/
GuidanceComplianceRegulatory
Information/Guidances/default.htm.
Dated: June 24, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019–13698 Filed 6–26–19; 8:45 am]
BILLING CODE 4164–01–P
PO 00000
Frm 00044
Fmt 4703
Sfmt 4703
30733
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2019–N–2012]
New Drugs Regulatory Program
Modernization: Improving Approval
Package Documentation and
Communication
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice; request for comments.
The Food and Drug
Administration (FDA or Agency) is
seeking public comment on the Clinical
Data Summary Report Pilot program as
part of the Agency’s continuous
assessment of the efficiency and
transparency of the clinical data used in
the regulatory decision-making process.
The Agency is also seeking public
feedback on a new integrated review
template for the documentation of new
drug marketing applications developed
as part of the New Drugs Regulatory
Program Modernization. The Agency
hopes to receive public feedback on
both of these efforts and on how FDA
might continue supporting our
stakeholders’ needs related to the clarity
and transparency of drug approval
decisions.
SUMMARY:
Submit either electronic or
written comments on the notice by
August 26, 2019.
ADDRESSES: You may submit comments
as follows. Please note that late,
untimely filed comments will not be
considered. Electronic comments must
be submitted on or before August 26,
2019. The https://www.regulations.gov
electronic filing system will accept
comments until 11:59 p.m. Eastern Time
at the end of August 26, 2019.
Comments received by mail/hand
delivery/courier (for written/paper
submissions) will be considered timely
if they are postmarked or the delivery
service acceptance receipt is on or
before that date.
DATES:
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
E:\FR\FM\27JNN1.SGM
27JNN1
30734
Federal Register / Vol. 84, No. 124 / Thursday, June 27, 2019 / Notices
jspears on DSK30JT082PROD with NOTICES
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–
2019–N–2012 for ‘‘New Drugs
Regulatory Program Modernization:
Improving Approval Package
Documentation and Communication.’’
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.
• 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
VerDate Sep<11>2014
20:15 Jun 26, 2019
Jkt 247001
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/201523389.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.
FOR FURTHER INFORMATION CONTACT:
Regarding the Clinical Data Summary
Pilot Program: Patrick Zhou, Center for
Drug Evaluation and Research, Food
and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 1148,
Silver Spring, MD 20993–0002, 301–
348–1817, Patrick.Zhou@fda.hhs.gov,
with the subject line ‘‘Collecting Public
Feedback on the Clinical Data Summary
Pilot Program.’’
Regarding the Integrated Review:
Kevin Bugin, Center for Drug Evaluation
and Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 22, Rm. 5128, Silver Spring,
MD 20993–0002, 301–796–2302,
Kevin.Bugin@fda.hhs.gov, with the
subject line ‘‘Collecting Public Feedback
on the Integrated Review.’’
SUPPLEMENTARY INFORMATION:
I. Background
Currently, FDA’s Center for Drug
Evaluation and Research (CDER)
provides access to action packages,
which include all discipline reviews, for
newly approved original new drug
applications (NDAs) and biologics
license applications (BLAs) by posting
these action packages on the FDA
website at www.fda.gov/drugs@FDA.
FDA posts them regardless of whether
there has been a request under the
Freedom of Information Act (FOIA), 5
U.S.C. 552.
Other approval-related information
such as review documents for
abbreviated new drug applications
(ANDAs) or NDA efficacy supplements
are posted on www.fda.gov/drugs@FDA
after they have been redacted and
PO 00000
Frm 00045
Fmt 4703
Sfmt 4703
disclosed in response to a FOIA request,
but they are not routinely posted
proactively by the Agency. While the
action packages include a significant
amount of information from the
sponsor’s application, they can reach up
to hundreds of pages and include
administrative and/or correspondencerelated documentation. As a result,
some stakeholders have difficulty
navigating the documents and using
them to gain an understanding of the
basis for FDA drug approvals. To
address this, two efforts have been
launched: (1) A pilot program referred
to as the Clinical Data Summary Pilot
Program (Pilot), launched in January
2018, through which parts of a sponsor’s
clinical study reports (CSRs) were to be
posted and (2) a new integrated
template that will be used to document
FDA’s review of new drug applications
and efficacy supplements. This
document seeks public comment on
both of these efforts.
On January 16, 2018, then-FDA
Commissioner Scott Gottlieb announced
several efforts to enhance the
transparency of the Agency’s drug
approval decisions as part of an overall
approach to enhance the efficiency and
transparency of the Agency’s drug
approval decisions. One of those efforts
included the Pilot program to evaluate
whether publicly disclosing certain
summary information included within
sponsor-submitted CSRs improves
public understanding of the basis of
FDA’s approval decisions.
The Pilot’s goals included enhancing
the understanding of information about
drug approvals to improve the accuracy
of discussions about drug approvals in
scientific publications, increasing
stakeholders’ understanding of the basis
for FDA’s approval decisions, and
informing physicians and other
healthcare providers about the clinical
trial results on which regulatory
decisions are based.
For this Pilot, FDA sought voluntary
participation from the sponsors of fewer
than ten marketing applications selected
on the basis of novelty and clinical
importance (e.g., products that are novel
including drugs that are new molecular
entities, products across a range of
disease areas, and products of scientific
interest). For any approved application
whose sponsor agreed to participate,
FDA would post, along with the
traditional action package, summary
portions of the sponsor’s CSRs for the
pivotal trials establishing the safety and
effectiveness of the drug. One sponsor
voluntarily agreed to participate. The
subsequent posting can be found on
FDA’s Clinical Data Summary Pilot
Program web page at https://
E:\FR\FM\27JNN1.SGM
27JNN1
Federal Register / Vol. 84, No. 124 / Thursday, June 27, 2019 / Notices
jspears on DSK30JT082PROD with NOTICES
www.fda.gov/drugs/development
approvalprocess/ucm589210.htm. All
other contacted sponsors declined to
participate in the Pilot. The recruitment
phase of the Pilot is now concluded.
FDA recognizes that the needs and
expectations of different stakeholders
regarding transparency of information
relating to drug approval decisions may
vary. By opening a public docket, FDA
hopes to learn from its stakeholders
more about the potential benefits or
risks, resource requirements, and
challenges of FDA publicly releasing a
limited number of sections from certain
CSRs at the time of marketing approval.
In addition to the Pilot, FDA has other
efforts that also seek to provide greater
clarity on FDA’s application review and
decision-making process. One of those
efforts is the new integrated review
process and template developed under
the New Drugs Regulatory Program
Modernization, which is part of a
multiyear, multiphase effort to enhance
the new drugs regulatory program. The
new integrated review process and
template are intended to promote more
integrated and interdisciplinary
assessments, enhance clarity of our
assessments regarding the benefits and
risks for new drug products, and
improve our communication about the
basis for new drug approvals. For more
information, please see CDER Director
Janet Woodcock’s notes of June 4, 2018,
available at https://www.fda.gov/newsevents/fda-voices-perspectives-fdaexperts/fda-proposes-processmodernization-support-new-drugdevelopment.
II. The Integrated Review Process
The new integrated review process
and documentation template, currently
being implemented, supports reviewers
in conducting a scientifically-rigorous
review that efficiently documents
regulatory decisions. The integrated
review process includes the use and
public posting, upon approval of a new
drug or biologic, of an integrated review
document that contains a summary, an
integrated assessment, and appendices.
This new review template would
replace the current documentation
where each discipline provides a
separate application review document.
The updated template would be a
collaborative document with input from
clinical, clinical pharmacology,
biostatistics, toxicology reviewers, and
other disciplines based upon the issues
raised by the application. FDA believes
this program will also meet the goal of
effectively communicating the basis for
new drug approvals. The Agency is
therefore considering whether to focus
its efforts to better communicate the
VerDate Sep<11>2014
20:15 Jun 26, 2019
Jkt 247001
basis for drug approvals on the
development of new integrated review
documents, rather than on the release of
CSRs.
The guiding principles of this
initiative are the importance of
conducting an issue-focused
assessment, enhanced communication
both within the review team and with
the applicant, and stronger
interdisciplinary collaboration. FDA
believes that the format and content of
the integrated review will provide a
clearer description of FDA’s analysis of
the scientific issues raised by the
application, and will thereby more
effectively communicate the basis for
the approval decision.
As mentioned above, the integrated
review template has three main
components:
• Summary:
Æ Contains an executive summary of
FDA’s decision and assessment of
the application, including FDA’s
benefit-risk determination (as
currently employed in marketing
application reviews)
Æ Provides an overall Agency
assessment, including an overview
of the major decisions made during
the review process, and a brief
discussion of the basis for the
decisions
• Integrated Assessment:
Æ Promotes succinct, integrated,
focused analyses of the evidence of
benefit-risk, and therapeutic
individualization (e.g., special
populations, drug interactions)
Æ Highlights key issues in an
interdisciplinary manner that the
review team thinks are pertinent to
the decision-making process
• Appendices:
Æ Contains assessments and analyses
that are supportive or important to
key facts/data or conclusions for the
overall review
Æ Contains work that did not directly
impact the overall assessment of
benefit-risk, regulatory action,
labeling, or risk mitigation plans
The target audiences for this
document are diverse, and include the
lay public with a specific interest in the
particular application, drug sponsors,
researchers and others who are seeking
to understand the basis for FDA’s
decision. In general, the first two parts
of the integrated document would be
expected to provide a complete
explanation of FDA’s action, with the
third component (the appendices) also
available for those looking for additional
detail on the comprehensive analyses
FDA conducted in its review of the drug
application.
PO 00000
Frm 00046
Fmt 4703
Sfmt 4703
30735
As part of FDA’s internal assessment
for both of these programs, the Agency
is interested in receiving responses to
the following questions, in addition to
any general comments the public might
have. For convenience, it would be
helpful if commenters refer to the
numbered question and subject when
submitting responses and comments to
the following questions:
A. Regarding the Clinical Data
Summary Pilot Program
Please see the CSR posting available
on FDA’s Clinical Data Summary Pilot
Program web page at https://
www.fda.gov/drugs/development
approvalprocess/ucm589210.htm.
1. How did the CSR posted in this
Pilot affect or compare with your
understanding of the CSRs submitted to
FDA by drug sponsors?
2. How usable and/or accessible was
the information in the CSR that was
posted for the Pilot?
3. Did the required redactions/
removal of certain information from the
posted CSR affect your understanding or
use of the posted information?
4. How might the information/content
posted from this Pilot be used? What
other information/content would have
been helpful?
5. Given the other review documents
available (e.g., FDA’s action package),
how did the posted CSR affect your
understanding of FDA’s decisionmaking process regarding drug
applications?
6. What do you believe would be the
potential advantages and disadvantages
of posting this information routinely?
7. Is there any additional information
you would like to provide regarding the
potential benefits or risks, resource
requirements, and international
challenges of publicly releasing a
limited number of sections from certain
CSRs at the time of marketing approval?
To illustrate the new integrated
review template, the original reviews for
NDA 210806 (PIFELTRO (doravirine)
tablets, 100 milligrams (mg)) and NDA
210807 (DELSTRIGO (doravirine,
lamivudine, and tenofovir disoproxil
fumarate) tablets, 100/300/300
milligrams) have been rewritten to
provide an example. The original
multidisciplinary review for the NDAs
and the information provided in the
new integrated review template are
posted on https://www.fda.gov/
newdrugsmodernization#integrated.
B. Regarding the Integrated Review
1. How does the new format of the
integrated review inform your
knowledge of FDA’s basis for making
decisions?
E:\FR\FM\27JNN1.SGM
27JNN1
30736
Federal Register / Vol. 84, No. 124 / Thursday, June 27, 2019 / Notices
2. How does the usability and
accessibility of information in the new
integrated review compare to the
original review posted on FDA’s
website?
3. How could the information
provided in the new integrated review
format be used, if at all?
4. What do you believe would be the
potential advantages and disadvantages
of posting review documents in this
format?
5. Based on the integrated review,
were the issues that concerned the
review team clear and understandable?
If so, what helped achieve this? If not,
what can be improved?
6. Is there important information in
the integrated review that is difficult to
locate or should be added?
Dated: June 24, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019–13751 Filed 6–26–19; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Health Resources and Services
Administration
National Vaccine Injury Compensation
Program; List of Petitions Received
Health Resources and Services
Administration (HRSA), Department of
Health and Human Services (HHS).
ACTION: Notice.
AGENCY:
HRSA is publishing this
notice of petitions received under the
National Vaccine Injury Compensation
Program (the Program), as required by
Section 2112(b)(2) of the Public Health
Service (PHS) Act, as amended. While
the Secretary of HHS is named as the
respondent in all proceedings brought
by the filing of petitions for
compensation under the Program, the
United States Court of Federal Claims
(the Court) is charged by statute with
responsibility for considering and acting
upon the petitions.
FOR FURTHER INFORMATION CONTACT: For
information about requirements for
filing petitions, and the Program in
general, contact Lisa L. Reyes, Clerk of
Court, United States Court of Federal
Claims, 717 Madison Place NW,
Washington, DC 20005, (202) 357–6400.
For information on HRSA’s role in the
Program, contact the Director, National
Vaccine Injury Compensation Program,
5600 Fishers Lane, Room 08N146B,
Rockville, Maryland 20857; (301) 443–
6593, or visit our website at: https://
jspears on DSK30JT082PROD with NOTICES
SUMMARY:
VerDate Sep<11>2014
20:15 Jun 26, 2019
Jkt 247001
www.hrsa.gov/vaccinecompensation/
index.html.
The
Program provides a system of no-fault
compensation for certain individuals
who have been injured by specified
childhood vaccines. Subtitle 2 of Title
XXI of the PHS Act, 42 U.S.C. 300aa–
10 et seq., provides that those seeking
compensation are to file a petition with
the United States Court of Federal
Claims and to serve a copy of the
petition to the Secretary of HHS, who is
named as the respondent in each
proceeding. The Secretary has delegated
this responsibility under the Program to
HRSA. The Court is directed by statute
to appoint special masters who take
evidence, conduct hearings as
appropriate, and make initial decisions
as to eligibility for, and amount of,
compensation.
A petition may be filed with respect
to injuries, disabilities, illnesses,
conditions, and deaths resulting from
vaccines described in the Vaccine Injury
Table (the Table) set forth at 42 CFR
100.3. This Table lists for each covered
childhood vaccine the conditions that
may lead to compensation and, for each
condition, the time period for
occurrence of the first symptom or
manifestation of onset or of significant
aggravation after vaccine
administration. Compensation may also
be awarded for conditions not listed in
the Table and for conditions that are
manifested outside the time periods
specified in the Table, but only if the
petitioner shows that the condition was
caused by one of the listed vaccines.
Section 2112(b)(2) of the PHS Act, 42
U.S.C. 300aa–12(b)(2), requires that
‘‘[w]ithin 30 days after the Secretary
receives service of any petition filed
under section 2111 the Secretary shall
publish notice of such petition in the
Federal Register.’’ Due to an
administrative error, publication of the
notice covering February 2019 was
delayed. Set forth below is a list of
petitions received by HRSA on February
1, 2019, through February 28, 2019. This
list provides the name of petitioner, city
and state of vaccination (if unknown
then city and state of person or attorney
filing claim), and case number. In cases
where the Court has redacted the name
of a petitioner and/or the case number,
the list reflects such redaction.
Section 2112(b)(2) also provides that
the special master ‘‘shall afford all
interested persons an opportunity to
submit relevant, written information’’
relating to the following:
1. The existence of evidence ‘‘that
there is not a preponderance of the
evidence that the illness, disability,
SUPPLEMENTARY INFORMATION:
PO 00000
Frm 00047
Fmt 4703
Sfmt 4703
injury, condition, or death described in
the petition is due to factors unrelated
to the administration of the vaccine
described in the petition,’’ and
2. Any allegation in a petition that the
petitioner either:
a. ‘‘[S]ustained, or had significantly
aggravated, any illness, disability,
injury, or condition not set forth in the
Vaccine Injury Table but which was
caused by’’ one of the vaccines referred
to in the Table, or
b. ‘‘[S]ustained, or had significantly
aggravated, any illness, disability,
injury, or condition set forth in the
Vaccine Injury Table the first symptom
or manifestation of the onset or
significant aggravation of which did not
occur within the time period set forth in
the Table but which was caused by a
vaccine’’ referred to in the Table.
In accordance with Section
2112(b)(2), all interested persons may
submit written information relevant to
the issues described above in the case of
the petitions listed below. Any person
choosing to do so should file an original
and three copies of the information with
the Clerk of the United States Court of
Federal Claims at the address listed
above (under the heading FOR FURTHER
INFORMATION CONTACT), with a copy to
HRSA addressed to Director, Division of
Injury Compensation Programs,
Healthcare Systems Bureau, 5600
Fishers Lane, 08N146B, Rockville,
Maryland 20857. The Court’s caption
(Petitioner’s Name v. Secretary of HHS)
and the docket number assigned to the
petition should be used as the caption
for the written submission. Chapter 35
of title 44, United States Code, related
to paperwork reduction, does not apply
to information required for purposes of
carrying out the Program.
Dated: June 21, 2019.
George Sigounas,
Administrator.
List of Petitions Filed
1. Tanja Wagner and Scott Wagner on
behalf of S.W., Phoenix, Arizona,
Court of Federal Claims No: 19–
0188V
2. Rebecca E. Wood, Wenatchee,
Washington, Court of Federal
Claims No: 19–0189V
3. Julianna Barmasse, Cheektowaga,
New York, Court of Federal Claims
No: 19–0190V
4. Curtis Devlin, Pittsburgh,
Pennsylvania, Court of Federal
Claims No: 19–0191V
5. Janell Ward, Reno, Nevada, Court of
Federal Claims No: 19–0192V
6. Trudy Schneidermann, Luverne,
Minnesota, Court of Federal Claims
No: 19–0193V
E:\FR\FM\27JNN1.SGM
27JNN1
]]>Agencies
[Federal Register Volume 84, Number 124 (Thursday, June 27, 2019)]
[Notices]
[Pages 30733-30736]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-13751]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2019-N-2012]
New Drugs Regulatory Program Modernization: Improving Approval
Package Documentation and Communication
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; request for comments.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or Agency) is seeking
public comment on the Clinical Data Summary Report Pilot program as
part of the Agency's continuous assessment of the efficiency and
transparency of the clinical data used in the regulatory decision-
making process. The Agency is also seeking public feedback on a new
integrated review template for the documentation of new drug marketing
applications developed as part of the New Drugs Regulatory Program
Modernization. The Agency hopes to receive public feedback on both of
these efforts and on how FDA might continue supporting our
stakeholders' needs related to the clarity and transparency of drug
approval decisions.
DATES: Submit either electronic or written comments on the notice by
August 26, 2019.
ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. Electronic comments
must be submitted on or before August 26, 2019. The https://www.regulations.gov electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of August 26, 2019. Comments
received by mail/hand delivery/courier (for written/paper submissions)
will be considered timely if they are postmarked or the delivery
service acceptance receipt is 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
[[Page 30734]]
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-2019-N-2012 for ``New Drugs Regulatory Program Modernization:
Improving Approval Package Documentation and Communication.'' 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.
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 and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT:
Regarding the Clinical Data Summary Pilot Program: Patrick Zhou,
Center for Drug Evaluation and Research, Food and Drug Administration,
10903 New Hampshire Ave., Bldg. 51, Rm. 1148, Silver Spring, MD 20993-
0002, 301-348-1817, [email protected], with the subject line
``Collecting Public Feedback on the Clinical Data Summary Pilot
Program.''
Regarding the Integrated Review: Kevin Bugin, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 5128, Silver Spring, MD 20993-0002, 301-
796-2302, [email protected], with the subject line ``Collecting
Public Feedback on the Integrated Review.''
SUPPLEMENTARY INFORMATION:
I. Background
Currently, FDA's Center for Drug Evaluation and Research (CDER)
provides access to action packages, which include all discipline
reviews, for newly approved original new drug applications (NDAs) and
biologics license applications (BLAs) by posting these action packages
on the FDA website at www.fda.gov/[email protected]. FDA posts them regardless
of whether there has been a request under the Freedom of Information
Act (FOIA), 5 U.S.C. 552.
Other approval-related information such as review documents for
abbreviated new drug applications (ANDAs) or NDA efficacy supplements
are posted on www.fda.gov/[email protected] after they have been redacted and
disclosed in response to a FOIA request, but they are not routinely
posted proactively by the Agency. While the action packages include a
significant amount of information from the sponsor's application, they
can reach up to hundreds of pages and include administrative and/or
correspondence-related documentation. As a result, some stakeholders
have difficulty navigating the documents and using them to gain an
understanding of the basis for FDA drug approvals. To address this, two
efforts have been launched: (1) A pilot program referred to as the
Clinical Data Summary Pilot Program (Pilot), launched in January 2018,
through which parts of a sponsor's clinical study reports (CSRs) were
to be posted and (2) a new integrated template that will be used to
document FDA's review of new drug applications and efficacy
supplements. This document seeks public comment on both of these
efforts.
On January 16, 2018, then-FDA Commissioner Scott Gottlieb announced
several efforts to enhance the transparency of the Agency's drug
approval decisions as part of an overall approach to enhance the
efficiency and transparency of the Agency's drug approval decisions.
One of those efforts included the Pilot program to evaluate whether
publicly disclosing certain summary information included within
sponsor-submitted CSRs improves public understanding of the basis of
FDA's approval decisions.
The Pilot's goals included enhancing the understanding of
information about drug approvals to improve the accuracy of discussions
about drug approvals in scientific publications, increasing
stakeholders' understanding of the basis for FDA's approval decisions,
and informing physicians and other healthcare providers about the
clinical trial results on which regulatory decisions are based.
For this Pilot, FDA sought voluntary participation from the
sponsors of fewer than ten marketing applications selected on the basis
of novelty and clinical importance (e.g., products that are novel
including drugs that are new molecular entities, products across a
range of disease areas, and products of scientific interest). For any
approved application whose sponsor agreed to participate, FDA would
post, along with the traditional action package, summary portions of
the sponsor's CSRs for the pivotal trials establishing the safety and
effectiveness of the drug. One sponsor voluntarily agreed to
participate. The subsequent posting can be found on FDA's Clinical Data
Summary Pilot Program web page at https://
[[Page 30735]]
www.fda.gov/drugs/developmentapprovalprocess/ucm589210.htm. All other
contacted sponsors declined to participate in the Pilot. The
recruitment phase of the Pilot is now concluded.
FDA recognizes that the needs and expectations of different
stakeholders regarding transparency of information relating to drug
approval decisions may vary. By opening a public docket, FDA hopes to
learn from its stakeholders more about the potential benefits or risks,
resource requirements, and challenges of FDA publicly releasing a
limited number of sections from certain CSRs at the time of marketing
approval.
In addition to the Pilot, FDA has other efforts that also seek to
provide greater clarity on FDA's application review and decision-making
process. One of those efforts is the new integrated review process and
template developed under the New Drugs Regulatory Program
Modernization, which is part of a multiyear, multiphase effort to
enhance the new drugs regulatory program. The new integrated review
process and template are intended to promote more integrated and
interdisciplinary assessments, enhance clarity of our assessments
regarding the benefits and risks for new drug products, and improve our
communication about the basis for new drug approvals. For more
information, please see CDER Director Janet Woodcock's notes of June 4,
2018, available at https://www.fda.gov/news-events/fda-voices-perspectives-fda-experts/fda-proposes-process-modernization-support-new-drug-development.
II. The Integrated Review Process
The new integrated review process and documentation template,
currently being implemented, supports reviewers in conducting a
scientifically-rigorous review that efficiently documents regulatory
decisions. The integrated review process includes the use and public
posting, upon approval of a new drug or biologic, of an integrated
review document that contains a summary, an integrated assessment, and
appendices. This new review template would replace the current
documentation where each discipline provides a separate application
review document. The updated template would be a collaborative document
with input from clinical, clinical pharmacology, biostatistics,
toxicology reviewers, and other disciplines based upon the issues
raised by the application. FDA believes this program will also meet the
goal of effectively communicating the basis for new drug approvals. The
Agency is therefore considering whether to focus its efforts to better
communicate the basis for drug approvals on the development of new
integrated review documents, rather than on the release of CSRs.
The guiding principles of this initiative are the importance of
conducting an issue-focused assessment, enhanced communication both
within the review team and with the applicant, and stronger
interdisciplinary collaboration. FDA believes that the format and
content of the integrated review will provide a clearer description of
FDA's analysis of the scientific issues raised by the application, and
will thereby more effectively communicate the basis for the approval
decision.
As mentioned above, the integrated review template has three main
components:
Summary:
[cir] Contains an executive summary of FDA's decision and
assessment of the application, including FDA's benefit-risk
determination (as currently employed in marketing application reviews)
[cir] Provides an overall Agency assessment, including an overview
of the major decisions made during the review process, and a brief
discussion of the basis for the decisions
Integrated Assessment:
[cir] Promotes succinct, integrated, focused analyses of the
evidence of benefit-risk, and therapeutic individualization (e.g.,
special populations, drug interactions)
[cir] Highlights key issues in an interdisciplinary manner that the
review team thinks are pertinent to the decision-making process
Appendices:
[cir] Contains assessments and analyses that are supportive or
important to key facts/data or conclusions for the overall review
[cir] Contains work that did not directly impact the overall
assessment of benefit-risk, regulatory action, labeling, or risk
mitigation plans
The target audiences for this document are diverse, and include the
lay public with a specific interest in the particular application, drug
sponsors, researchers and others who are seeking to understand the
basis for FDA's decision. In general, the first two parts of the
integrated document would be expected to provide a complete explanation
of FDA's action, with the third component (the appendices) also
available for those looking for additional detail on the comprehensive
analyses FDA conducted in its review of the drug application.
As part of FDA's internal assessment for both of these programs,
the Agency is interested in receiving responses to the following
questions, in addition to any general comments the public might have.
For convenience, it would be helpful if commenters refer to the
numbered question and subject when submitting responses and comments to
the following questions:
A. Regarding the Clinical Data Summary Pilot Program
Please see the CSR posting available on FDA's Clinical Data Summary
Pilot Program web page at https://www.fda.gov/drugs/developmentapprovalprocess/ucm589210.htm.
1. How did the CSR posted in this Pilot affect or compare with your
understanding of the CSRs submitted to FDA by drug sponsors?
2. How usable and/or accessible was the information in the CSR that
was posted for the Pilot?
3. Did the required redactions/removal of certain information from
the posted CSR affect your understanding or use of the posted
information?
4. How might the information/content posted from this Pilot be
used? What other information/content would have been helpful?
5. Given the other review documents available (e.g., FDA's action
package), how did the posted CSR affect your understanding of FDA's
decision-making process regarding drug applications?
6. What do you believe would be the potential advantages and
disadvantages of posting this information routinely?
7. Is there any additional information you would like to provide
regarding the potential benefits or risks, resource requirements, and
international challenges of publicly releasing a limited number of
sections from certain CSRs at the time of marketing approval?
To illustrate the new integrated review template, the original
reviews for NDA 210806 (PIFELTRO (doravirine) tablets, 100 milligrams
(mg)) and NDA 210807 (DELSTRIGO (doravirine, lamivudine, and tenofovir
disoproxil fumarate) tablets, 100/300/300 milligrams) have been
rewritten to provide an example. The original multidisciplinary review
for the NDAs and the information provided in the new integrated review
template are posted on https://www.fda.gov/newdrugsmodernization#integrated.
B. Regarding the Integrated Review
1. How does the new format of the integrated review inform your
knowledge of FDA's basis for making decisions?
[[Page 30736]]
2. How does the usability and accessibility of information in the
new integrated review compare to the original review posted on FDA's
website?
3. How could the information provided in the new integrated review
format be used, if at all?
4. What do you believe would be the potential advantages and
disadvantages of posting review documents in this format?
5. Based on the integrated review, were the issues that concerned
the review team clear and understandable? If so, what helped achieve
this? If not, what can be improved?
6. Is there important information in the integrated review that is
difficult to locate or should be added?
Dated: June 24, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-13751 Filed 6-26-19; 8:45 am]
BILLING CODE 4164-01-P
