[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]


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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.

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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

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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/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 
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://

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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?

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    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