[Federal Register Volume 85, Number 143 (Friday, July 24, 2020)]
[Proposed Rules]
[Pages 44803-44811]
[FR Doc No: 2020-16016]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 300

[Docket No. FDA-2019-N-5553]
RIN 0910-AI36

Annual Summary Reporting Requirements Under the Right to Try Act

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: To facilitate implementation of the reporting requirements of
the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew
Bellina Right to Try Act of 2017 (Right to Try Act), the Food and Drug
Administration (FDA, the Agency, or we) is proposing to establish
requirements for the deadline and contents of submission of an annual
summary. This proposed rule, if finalized, would implement the
statutory requirement under provisions of the Right to Try Act for
submission of an annual summary by sponsors and manufacturers who
provide an eligible investigational drug for use by an eligible
patient.

DATES: Submit either electronic or written comments on the proposed
rule by September 22, 2020. Submit comments on information collection
issues under the Paperwork Reduction Act of 1995 by September 22, 2020.

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 September 22, 2020. The https://www.regulations.gov electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of September 22, 2020]. 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 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-5553 for ``Annual Summary Reporting Requirements Under the
Right to Try Act.'' 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,<PHONE_NUMBER>.
     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.govinfo.gov/content/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,<PHONE_NUMBER>.
    Submit comments on the information collection issues under the
Paperwork Reduction Act of 1995 to the Office of Management and Budget
(OMB) at https://www.reginfo.gov/public/do/PRAMain. Find this
particular information collection by selecting ``Currently under
Review--Open for Public Comments'' or by using the search function. The
title of this proposed collection is ``Annual Summary Reporting
Requirements Under the Right to Try Act.''

FOR FURTHER INFORMATION CONTACT: Kathleen Davies, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 32, Rm. 3121, Silver
Spring, MD 20993,<PHONE_NUMBER><EMAIL_ADDRESS>    With regard to the information collection: Domini Bean, Office of
Operations, Food and Drug Administration, Three White Flint North 10A-
12M, 11601 Landsdown St., North Bethesda, MD 20852,<PHONE_NUMBER>,
<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

Table of Contents

I. Executive Summary
    A. Purpose of the Proposed Rule
    B. Summary of the Major Provisions of the Proposed Rule
    C. Legal Authority
    D. Costs and Benefits
II. Background
    A. Introduction
    B. Criteria for Use Under Section 561B of the FD&C Act
III. Legal Authority
IV. Description of the Proposed Rule
    A. Scope/Applicability
    B. Definitions
    C. Proposed Deadline for Submission of Annual Summary
    D. Proposed Annual Summary Submission Contents
    E. Proposed Annual Summary Submission Location
V. Proposed Effective Date
VI. Preliminary Economic Analysis of Impacts
VII. Analysis of Environmental Impact
VIII. Paperwork Reduction Act of 1995
IX. Federalism
X. Consultation and Coordination With Indian Tribal Governments
XI. References

I. Executive Summary

A. Purpose of the Proposed Rule

    The purpose of this proposed rule is to implement section
561B(d)(1) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21
U.S.C. 360bbb-0a(d)(1)), added by the Right to Try Act, which requires
sponsors and manufacturers who provide an ``eligible investigational
drug'' under section 561B of the FD&C Act to submit to FDA an annual
summary of such use, and directs FDA to specify by regulation the
deadline of submission. The proposed rule, if finalized, would provide
information on the necessary contents of the annual summary and the
deadline for its submission.

B. Summary of the Major Provisions of the Proposed Rule

    The proposed rule would add Sec.  300.200 to part 300 (21 CFR part
300) as a new subpart D, to specify the deadline and content for
submission of an annual summary of investigational drugs supplied under
section 561B of the FD&C Act, and the uses for which they were
supplied. The manufacturer or sponsor of an eligible investigational
drug shall submit to FDA an annual summary of any use of such drug
supplied under section 561B of the FD&C Act. Per the statute, the
summary shall include the number of doses supplied, the number of
patients treated, the use for which the drug was made available, and
any known serious adverse events from use of the drug.

C. Legal Authority

    Section 561B of the FD&C Act, in conjunction with FDA's general
rulemaking authority in section 701(a) of the FD&C Act (21 U.S.C.
371(a)), serve as FDA's legal authority for this proposed rule.

D. Costs and Benefits

    This proposed rule, if finalized, would establish the deadline for
submission of annual summaries of use of investigational drugs supplied
under the Right to Try Act. The proposed rule would also establish the
required contents of these submissions. Costs are estimated as the time
spent by firms to prepare and submit these annual summary reports. The
total estimated present value of this rule's costs is $39,991991 at a
seven percent discount rate and $49,345345 at a three percent discount
rate (in 2018 dollars). The annualized cost of this rule over 10 years
is $5,694694 at a seven percent discount rate and $5,785785 at a three
percent discount rate.
    We are unable to quantify the expected benefits of this proposed
rule because there is no data that would allow us to predict the extent
to which direct benefits would be generated. The benefits of this rule
consist of societal and public health outcomes that may accrue from the
disclosure of the use of investigational drugs and any known serious
adverse events provided in these annual summary reports. Without these
reports, FDA would not be made aware in a systematic manner of the use
of eligible drugs under the Right to Try Act and any known serious
adverse events. With these reports, there may be increased awareness of
investigational drugs, the diseases or conditions for which patients
are seeking access, and

any known serious adverse events associated with such use.
    These reporting requirements instruct firms to collect all known
serious adverse events and submit them once per year to FDA. In
addition, based on the information in these annual summaries, FDA
intends to post online an annual summary report in accordance with
section 561B(d)(2) of the FD&C Act. FDA's posting of these reports may
increase awareness about the availability of investigational drugs.

II. Background

A. Introduction

    On May 30, 2018, the Right to Try Act (Pub. L. 115-176) was signed
into law, creating section 561B of the FD&C Act. The Right to Try Act
amends the FD&C Act to establish an option for patients who meet
certain criteria to request access to certain unapproved medical
products, and for sponsors and manufacturers who agree to provide
certain unapproved medical products other than through FDA's expanded
access program.\1\ This law provides a new pathway for patients to
request, and manufacturers or sponsors to choose to provide, access to
certain unapproved, investigational drugs, including biological
products, for patients diagnosed with life-threatening diseases or
conditions (as defined in Sec.  312.81 (21 CFR 312.81)) who, as
certified by a physician, have exhausted approved treatment options and
who are unable to participate in a clinical trial involving the
investigational drug.\2\ This proposed rule is not proposing to require
that physician determinations be submitted to FDA. Manufacturers or
sponsors who provide their investigational product under the Right to
Try Act are required to submit to FDA an annual summary of the use of
their drug. Specifically, manufacturers or sponsors of an eligible
investigational drug must submit to FDA an annual summary that includes
the number of doses supplied of an eligible investigational drug, the
number of patients treated, the use for which the drug was made
available, and any known serious adverse events. Per section 561B of
the FD&C Act, FDA is required to specify, through regulation, the
deadline for such submissions (section 561B(d)(1)). This proposed rule,
if finalized, would specify that deadline.
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    \1\ FDA's Expanded Access Program Information: https://www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse/ucm20080392.htm.
    \2\ Physicians who have questions should consult with sponsors
and manufacturers of eligible investigational drugs. Resources for
determining whether there are available clinical trials include the
sponsors of an eligible investigational drug or the website https://www.clinicaltrials.gov/.
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B. Criteria for Use Under Section 561B of the FD&C Act

    The Right to Try Act provides a pathway for patients who meet
certain criteria (i.e., eligible patients) to request, and
manufacturers or sponsors to choose to provide access, to eligible
investigational drugs under certain conditions. An eligible patient, as
defined in the Right to Try Act, is a patient who has:
     Been diagnosed with a life-threatening disease or
condition, as defined in Sec.  312.81 (or any successor regulations)
(section 561B(a)(1)(A));
     Exhausted approved treatment options and is unable to
participate in a clinical trial involving the eligible investigational
drug (this must be certified by a physician who is in good standing
with their licensing organization or board and who will not be
compensated directly by the manufacturer for so certifying) (section
561B(a)(1)(B)); and
     Provided, or their legally authorized representative has
provided, to the treating physician written informed consent regarding
the eligible investigational drug (section 561B(a)(1)(C)).
    An eligible investigational drug, as defined in the Right to Try
Act, is an investigational drug, including a biological product:
     For which a Phase 1 clinical trial (as described in 21 CFR
312.21) has been completed (section 561B(a)(2)(A));
     That has not been approved or licensed for any use by FDA
(section 561B(a)(2)(B));
     For which an application has been filed with FDA, or that
is under investigation in a clinical trial that is intended to form the
primary basis of a claim of effectiveness in support of FDA approval or
licensure and is the subject of an active investigational new drug
application submitted to FDA (section 561B(a)(2)(C)); and
     Whose active development or production is ongoing, and
that has not been discontinued by the manufacturer or placed on
clinical hold by FDA (section 561B(a)(2)(D)).
    A manufacturer or sponsor is in the best position under the Right
to Try Act to determine if an investigational drug meets these
criteria. In contrast, if patients contact FDA with questions about
whether a product is eligible, FDA likely will not be able to answer
such inquiries because disclosure laws and regulations generally
prevent the Agency from publicly sharing information about the status
or existence of an investigational new drug application (IND). For
these reasons, under this proposed rule, FDA is not proposing to make
determinations about whether a particular investigational product is an
eligible investigational drug under the Right to Try Act.

III. Legal Authority

    The Right to Try Act amended Chapter V of the FD&C Act by inserting
section 561B (21 U.S.C. 360bbb-0a). New section 561B(d)(1) (21 U.S.C.
360bbb-0a(d)(1)) requires FDA to specify by regulation the deadline of
submission of an annual summary of the use of any eligible
investigational drug under the Right to Try Act by manufacturers or
sponsors, and specifies the contents of such summaries. This section,
in conjunction with our general rulemaking authority in section 701(a)
of the FD&C Act, serves as our legal authority for this proposed rule.

IV. Description of the Proposed Rule

    We are proposing to establish a new subpart D for part 300 of Title
21 of the Code of the Federal Register. The proposed rule, if
finalized, would specify a deadline for submission of an annual summary
of use under the Right to Try Act and identify the contents for that
annual summary. Although the Right to Try Act provides that FDA may
require the submission of this annual summary in conjunction with the
annual report for an applicable investigational drug application for
such drug (as required under 21 CFR 312.33), FDA is not proposing to
require that the annual summaries be submitted in the annual report. We
concluded that a separate process will help to ensure that information
about the use of eligible investigational drugs under the Right to Try
Act is identified by FDA. We believe sponsors who provide drugs under
the Right to Try Act will appreciate this effort to keep the
information separate. This approach will also enhance FDA's ability to
quickly identify and compile this information so we can post the
required annual summary of these reports. For these reasons, we believe
that a separate process will be least burdensome overall on FDA,
sponsors who provide drugs under the Right to Try Act, and sponsors who
do not provide drugs under the Right to Try Act (for whom there will be
no obligation to review any changes with respect to the process for
annual summaries). We request comment on this assumption.

A. Scope/Applicability (Proposed Sec.  300.200)

    This proposed rule, if finalized, would apply to any manufacturer
or sponsor who provides an eligible investigational drug for use by an
eligible patient under section 561B of the FD&C Act.

B. Definitions (Proposed Sec.  300.200)

    We are proposing to define ``eligible investigational drug'' and
``eligible patient'' as those terms are defined in section 561B(a)(1)-
(2) of the FD&C Act. In addition, we are proposing to define IND as
defined in 21 CFR 312.3.
    We are proposing to define ``known serious adverse event'' as any
serious adverse event (as defined in 21 CFR 312.32) of which the
manufacturer or sponsor is aware. A manufacturer or sponsor can learn
about a serious adverse event related to use of an eligible
investigational drug by an eligible patient from a variety of sources.
The manufacturer or sponsor should review all information about the use
of an eligible investigational drug under section 561B of the FD&C Act
that is obtained or otherwise received by the manufacturer or sponsor
from any source. A serious adverse event would be considered to be
known if information about the adverse event was reported to the
manufacturer or sponsor by an eligible patient, their treating
physician or representative, or another person associated with the use
of an eligible investigational drug under the Right to Try Act. If a
sponsor or manufacturer becomes aware of serious adverse events
associated with the use of their eligible investigational drug under
section 561B of the FD&C Act through a review of reports in the
scientific literature, unpublished scientific papers, or other sources,
the sponsor would be considered aware of the event and, as a result, it
would be a known serious adverse event. Any information that the
manufacturer or sponsor receives about serious adverse events from use
outside of section 561B of the FD&C Act would not be considered ``known
serious adverse events'' for purposes of the Right to Try Act's annual
summary requirement, although they may be required to be submitted
under other applicable regulations.
    We are proposing to define the term ``manufacturer or sponsor'' as
the person who either: (1) Meets the definition of ``sponsor'' in Sec.
312.3 for the eligible investigational drug; (2) has submitted an
application for the eligible investigational drug under section 505(b)
of the FD&C Act or section 351(a) of the Public Health Service Act; or
(3) produces the eligible investigational drug on behalf of such
persons. Sponsors under Sec.  312.3 take responsibility for or initiate
the clinical investigation, so we expect that such persons would be
well-positioned to fulfill the reporting requirements for
investigational drugs provided under the Right to Try Act. Similarly,
drugs and biologics applicants also take responsibility for monitoring
the safety of their products, so we also expect such persons to be able
to meet the reporting requirements. In addition, any person who
produces the eligible investigational drug on behalf of such persons
should also be able to provide FDA with the required information. Under
the proposed definition, the manufacturer or sponsor would not be a
person who produces only a component of the eligible investigational
drug. For example, the manufacturer or sponsor would not be an
excipient manufacturer that produces an inactive pharmaceutical
ingredient but not the drug product provided to the eligible patient.
Rather, the manufacturer or sponsor would be the person who produces
the drug product that is provided to an eligible patient. Because the
Right to Try Act only applies to unapproved products, we believe that
the person who submits annual summaries should be closely connected to
the clinical investigation or approval process. We do not believe that
the reporting requirements should apply to contract manufacturers who
are not closely connected to such processes. We request comment on this
proposed definition. In particular, we request comment on our proposal
that the term ``manufacturer or sponsor'' should only encompass persons
who initiate or take responsibility for either the clinical
investigations of the product or the pending applications to FDA, or
who produce the eligible investigational drug provided to an eligible
patient on behalf of such persons. We request comment on whether other
persons would be well-positioned to provide FDA with the required
information. We also request comment on whether, for persons who
produce the eligible investigational drug on behalf of a sponsor or
applicant, the regulatory text should specify that such persons would
only meet the definition of ``manufacturer or sponsor'' if they produce
the finished dosage form provided to the eligible patient.

C. Proposed Deadline for Submission of Annual Summary

    We are proposing that manufacturers or sponsors submit the annual
summary to FDA no later than March 31 of each year. The summary must
include data for the preceding calendar year on the use of an eligible
investigational drug in eligible patients under the Right to Try Act.
The ``preceding calendar year'' is the period of January 1 through
December 31. For example, if a sponsor provides one eligible patient
with one eligible investigational drug during the period between
January 1, 2021, and December 31, 2021, the sponsor would be required
to submit the annual summary with information about that Right to Try
Act activity no later than March 31, 2022. We propose that the first
annual summary submitted by a manufacturer or sponsor under this
section must cover the period from enactment of section 561B of the
FD&C Act, May 30, 2018, through the date the final rule becomes
effective. We also propose that the deadline for submitting the annual
report will be 60 calendar days after the rule becomes effective. For
example, if the final rule becomes effective February 1, 2021, then:
(1) The first annual submission would be required to cover the period
between May 30, 2018, and February 1, 2021; and (2) the deadline for
submitting the first annual summary would be April 1, 2021. The second
annual summary would cover the remaining calendar year. Thus, using the
same example, the second annual summary would cover information about
investigational drugs provided under section 561B of the FD&C Act
between February 2, 2021, and December 31, 2021. For the second annual
summary, the deadline would be March 31, 2022.
    FDA is proposing March 31 of each year as the date of annual
summary submission in order to provide adequate time for sponsors and
manufacturers to compile the necessary data for submission to FDA after
December 31 of the preceding year. We conclude that 90 days is a
reasonable timeframe to compile the required information and send in
the annual submissions. FDA is proposing to require annual summaries
for the period between enactment of the Right to Try Act and the
effective date of the final rule in order to ensure that FDA receives
information about Right to Try Act activities during that period.

D. Proposed Annual Summary Submission Content

    The following describes how manufacturers or sponsors can meet the
statutory requirements regarding the content of the annual summary. We
conclude that this information is necessary for FDA to efficiently
carry out the requirements of the Right to Try Act.

1. The Name of the Eligible Investigational Drug and Applicable IND
Number
    FDA proposes that sponsors include the drug name and the relevant
IND number as identifiers in the annual summary for the eligible
investigational drug provided under the Right to Try Act.
2. Number of Doses Supplied
    FDA proposes that the manufacturer or sponsor submit the total
number of doses of the eligible investigational drug supplied to
patients for use under the Right to Try Act during the reporting
period. FDA proposes that the number of doses supplied is the total
number of doses supplied regardless of whether the doses are all to one
patient or to multiple patients. For example, if one patient receives
three doses of an eligible investigational drug and another patient
receives two doses of the same drug, the number of doses supplied is
five. FDA is proposing that manufacturers or sponsors submit a total
number of doses supplied and not an itemized list of doses per patient.
We believe that this will make the reporting requirements less
burdensome for sponsors. However, if sponsors choose, they may
voluntarily provide an itemized list of doses per patient.
3. Number of Patients Treated
    FDA proposes that the manufacturer or sponsor submit the total
number of patients for whom the manufacturer or sponsor provided the
eligible investigational drug for use under the Right to Try Act. FDA
proposes that each patient be counted once, regardless of the number of
doses or the number of courses of therapy they receive. For example, if
a patient receives three courses of treatment with an eligible
investigational drug during the reporting period, each time receiving
three doses, that patient is only counted once. FDA is proposing a
total number of patients treated be provided. Manufacturers and
sponsors should not list individual patients to whom the drug was
provided in the submission (other than for reporting of individual
serious adverse events, see section IV.D.5). The Right to Try Act
specifies that the annual summaries provide information about the
``number of patients treated'' (emphasis added).
4. Use for Which the Eligible Investigational Drug Was Made Available
    FDA proposes that the manufacturer or sponsor submit a tabular
summary identifying the disease or conditions for which the eligible
investigational drug was made available for use under the Right to Try
Act (i.e., a table of diseases or conditions with the number of
patients with each disease or condition). A tabular summary will
streamline reporting for sponsors and manufacturers and assist FDA in
efficiently fulfilling the Agency's responsibilities.
5. Any Known Serious Adverse Events and Outcomes.
    FDA proposes that the manufacturer or sponsor submit a tabular
summary of any known serious adverse events, including resulting
outcomes of such events, experienced by patients treated with an
eligible investigational drug under the Right to Try Act. The outcome
of the adverse event can provide important context to enable FDA to
determine if the outcomes are critical to understanding safety issues
associated with the eligible investigational drug without requesting
additional information for each event.
    When including a known serious adverse event or its resulting
outcome in the tabular summary, FDA suggests the use of medical
terminology included in the Medical Dictionary for Regulatory
Activities (medDRA).\3\
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    \3\ https://www.meddra.org/.
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    As discussed above, manufacturers or sponsors who provide an
eligible investigational drug for use under the Right to Try Act must
submit known serious adverse events associated with that use. Such
sponsors and manufacturers may consider combining the table of uses and
the table of known serious adverse events and outcomes of the serious
adverse event. An example of a tabular summary that could be used to
capture this information is provided below. To promote patient privacy,
we are not proposing to require that identifying information on
individual patients be provided in the submission. However, we suggest
that the manufacturer or sponsor should provide an ID number used only
by the manufacturer or sponsor in identifying the patient provided the
drug (which could be simply a sequential numbering to identify
individual patients). However, we are not proposing to include such a
requirement in the regulatory text.

--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                Outcome--e.g.
                                                          Disease or  condition  Number  of    Serious  adverse    Severity--CTCAE    resolved, fatal,
  Eligible investigational drug     IND No.   Patient ID         treated            doses         event term        grade 1-4 \4\    improved, sequelae
                                                                                received                                                 unknown
--------------------------------------------------------------------------------------------------------------------------------------------------------
XDX501..........................     9999999     1234567  Breast cancer........           5  Hip fracture........              3    Improved
--------------------------------------------------------------------------------------------------------------------------------------------------------

E. Proposed Annual Summary Submission Location
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    \4\ https://evs.nci.nih.gov/ftp1/CTCAE/About.html.
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    FDA is proposing that manufacturers or sponsors submit their annual
summaries under this proposed rule, if finalized, to a designated point
of contact in the Office of the Commissioner. We propose to specify the
designated point of contact on the FDA web page (https://www.fda.gov).
We expect the designated point of contact would be an email contact or
electronic portal. We will provide a direct weblink when this rule is
finalized. All submissions of the annual summary are proposed to be
submitted to FDA in an electronic format that FDA can process, review,
and archive; however, we expect that eCTD format will not be required.
The rationale for proposing a submission process separate from the IND
submission process is to ensure that information about the use of
eligible investigational drugs under the Right to Try Act can be more
easily and more quickly identified by FDA. We also consider this
separate submission to be preferable because many sponsors submit the
same annual report to multiple regulators. By providing a separate
mechanism for submitting information that is a unique reporting
requirement for FDA is less burdensome than generating different annual
reports for different regulators. FDA requests comment on the process
proposed for submission of the required annual summaries.

V. Proposed Effective Date

    FDA proposes that any final rule that may issue based on this
proposal become effective 60 days after publication in the Federal
Register. FDA proposes that any manufacturer or

sponsor who provides an eligible investigational drug for use by an
eligible patient in accordance with the Right to Try Act include in
their first annual summary submitted under this section any use from
the time of enactment of the Right to Try Act, May 30, 2018, through
the date the final rule is effective. The first annual summary
submitted under the Right to Try Act would be required to be submitted
60 calendar days after the rule becomes effective.

VI. Preliminary Economic Analysis of Impacts

    We have examined the impacts of the proposed rule under Executive
Order 12866, Executive Order 13563, Executive Order 13771, the
Regulatory Flexibility Act (5 U.S.C. 601-612), and the Unfunded
Mandates Reform Act of 1995 (Pub. L. 104-4). Executive Orders 12866 and
13563 direct us to assess all costs and benefits of available
regulatory alternatives and, when regulation is necessary, to select
regulatory approaches that maximize net benefits (including potential
economic, environmental, public health and safety, and other
advantages; distributive impacts; and equity). Executive Order 13771
requires that the costs associated with significant new regulations
``shall, to the extent permitted by law, be offset by the elimination
of existing costs associated with at least two prior regulations.''
This proposed rule is not an economically significant regulatory action
as defined by Executive Order 12866.
    The Regulatory Flexibility Act requires us to analyze regulatory
options that would minimize any significant impact of a rule on small
entities. Because the effects are low in cost and dispersed, we propose
to certify that the proposed rule will not have a significant economic
impact on a substantial number of small entities.
    The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires
us to prepare a written statement, which includes an assessment of
anticipated costs and benefits, before proposing ``any rule that
includes any Federal mandate that may result in the expenditure by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100,000,000 or more (adjusted annually for
inflation) in any one year.'' The current threshold after adjustment
for inflation is $154 million, using the most current (2018) Implicit
Price Deflator for the Gross Domestic Product. This proposed rule would
not result in an expenditure in any year that meets or exceeds this
amount. This proposed rule, if finalized, implements a statutory
requirement in the Right to Try Act that sponsors and manufacturers who
provide an eligible investigational drug under the Right to Try Act to
eligible patients submit to FDA an annual summary of such uses. The
Right to Try Act also requires FDA to specify by regulation the
deadline for these submissions.
    The proposed rule's costs are summarized in table 1; we are unable
to quantify benefits for this rule. This analysis estimates the
incremental impacts of this proposed rule, if finalized, for drug
sponsors and these annual summary reports. Costs are calculated as the
time spent by firms to prepare and submit annual summary reports based
on participation in Right to Try Act requests from eligible patients
for investigational new treatments. The total estimated present value
of this rule's costs is $39,991 at a seven percent discount rate and
$49,345 at a three percent discount rate (in 2018 dollars). The
annualized cost of this rule over ten years is $5,694 at a seven
percent discount rate and $5,785 at a three percent discount rate.
    The benefits of this rule consist of societal and public health
outcomes that may accrue from the disclosure of the use of
investigational drugs and any known serious adverse events provided in
these annual summary reports. Without these reports, FDA would not be
made aware in a systematic manner of the use of eligible
investigational drugs under the Right to Try Act and any known serious
adverse events. With these reports, there may be increased awareness of
investigational drugs, the diseases or conditions for which patients
are seeking access, and any known serious adverse events associated
with such use.
    These reporting requirements require firms to compile information
about known serious adverse events and submit them in a streamlined
manner once per year to FDA. In addition, based on the information in
these annual summaries, FDA will post an annual summary report in
accordance with section 561B(d)(2) of the FD&C Act. FDA's posting of
these reports may increase awareness about the availability of
investigational drugs.
    Consistent with Executive Order 12866, Table 1 provides the costs
and a description of benefits for this proposed rule. In line with
Executive Order 13771, in Table 2, we estimate present and annualized
values of costs continuing over an infinite time horizon.

                                   Table 1--Summary of Benefits and Costs in 2018 Dollars Over a 10-Year Time Horizon
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                Units
                                        Primary                                    ------------------------------------------------
             Category                  estimate      Low  estimate  High  estimate                  Discount  rate      Period              Notes
                                                                                Year  dollars        (%)           covered
--------------------------------------------------------------------------------------------------------------------------------------------------------
Benefits:
    Annualized Monetized $/year...  ..............  ..............  ..............            2018               7              10
                                                                                2018               3              10
    Annualized Quantified.........  ..............  ..............  ..............  ..............               7
                                                                                3
    Qualitative...................  ..............  ..............  ..............  ..............  ..............  ..............  Disclosure of
                                                                                serious adverse
                                                                                events and outcomes
                                                                                related to
                                                                                investigational new
                                                                                drug treatments.
Costs:
    Annualized Monetized $/year...         $5,6944  ..............  ..............            2018              7%              10
                                           $5,7855                                            2018              3%              10
    Annualized Quantified.........  ..............  ..............  ..............  ..............              7%
                                                                                3%
    Qualitative...................
Transfers:
    Federal Annualized............  ..............  ..............               7
    Monetized $/year..............  ..............  ..............  ..............  ..............               3  ..............  ....................
                                   ---------------------------------------------------------------------------------------------------------------------

    From/To.......................  From:
                                    To:                                             ..............
                                   ---------------------------------------------------------------------------------------------------------------------
    Other Annualized Monetized $/   ..............  ..............  ..............  ..............              7%  ..............  ....................
     year.                                                                                3%
                                   ---------------------------------------------------------------------------------------------------------------------
    From/To.......................  From:
                                    To:                                             ..............
                                   ---------------------------------------------------------------------------------------------------------------------
    Effects.......................  State, Local or Tribal Government:
                                    Small Business:
                                    Wages:
                                    Growth:
--------------------------------------------------------------------------------------------------------------------------------------------------------

                    Table 2--E.O. 13771 Summary Table
            [in 2016 dollars, over a perpetual time horizon]
------------------------------------------------------------------------
                                           Primary  (7%)   Primary  (3%)
------------------------------------------------------------------------
Present Value of Costs..................         $63,120        $176,799
Present Value of Cost Savings...........  ..............  ..............
Present Value of Net Costs..............          63,120         176,799
Annualized Costs........................           4,418           5,304
Annualized Cost Savings.................  ..............  ..............
Annualized Net Costs....................           4,418           5,304
------------------------------------------------------------------------

    We have developed a comprehensive Preliminary Economic Analysis of
Impacts that assesses the impacts of the proposed rule. The full
preliminary analysis of economic impacts is available in the docket for
this proposed rule (Ref. 1) and at https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.

VII. Analysis of Environmental Impact

    We have determined under 21 CFR 25.30(h) that this action is of a
type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.

VIII. Paperwork Reduction Act of 1995

    This proposed rule contains information collection provisions that
are subject to review by OMB under the Paperwork Reduction Act of 1995
(44 U.S.C. 3501-3521). A description of these provisions is given in
the Description section of this document with an estimate of the annual
reporting burden. Included in the estimate is the time for reviewing
instructions, searching existing data sources, gathering and
maintaining the data needed, and completing and reviewing each
collection of information.
    FDA invites comments on these topics: (1) Whether the proposed
collection of information is necessary for the proper performance of
FDA's functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.
    Title: Annual Summary Reporting Requirements Under the Right to Try
Act--OMB Control Number 0910-NEW.
    Description: The proposed rule would establish requirements for the
deadline and contents of an annual summary for sponsors and
manufacturers who provide an eligible investigational drug for use by
an eligible patient.
    As described in Section IV.C. Proposed Deadline for Submission of
Annual Summary, sponsors and manufacturers would submit to us an annual
summary no later than March 31 of each year, including data for the
preceding calendar year, which is the period from January 1 through
December 31. The first summary under this proposed rule, if finalized,
would cover a longer period of time in order to cover the period since
enactment of the Right to Try Act. As described in Section IV.E.
Proposed Annual Summary Submission Location, we propose to specify the
designated point of contact for submissions on the FDA web page at
https://www.fda.gov. A direct link will be provided when the rule is
finalized.
    Under the proposed rule, manufacturers or sponsors would submit to
us an annual summary containing the following information:
     As described in section IV.D.1, the name of the eligible
investigational drug and applicable IND number;
     As described in section IV.D.2, the number of doses
supplied to the eligible patient;
     As described in section IV.D.3, the number of eligible
patients treated;
     As described in section IV.D.4, use for which the eligible
investigational drug was made available to the eligible patient; and
     As described in section IV.D.5, any known serious adverse
events and outcomes experienced by the eligible patient treated with an
eligible investigational drug.
    Description of Respondents: Sponsors and manufacturers who provide
an eligible investigational drug to eligible patients under the Right
to Try Act.
    We estimate that 6 sponsors and manufacturers would prepare and
submit 6 annual summaries and that it would take approximately 2.5
hours to prepare and submit each report, totaling 15 hours.
    We base our estimates for the number of sponsors and manufacturers
subject to this information collection and for

the number of hours on data and information discussed in Section VI.
Preliminary Economic Analysis of Impacts.
    In the table below, we estimate the burden of this collection of
information.

                                                     Table 3--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                              Number of
  21 CFR Citation; type of IC activity       Number of      responses per    Total annual     Average  burden per  response           Total hours
                                            respondents      respondent        responses
--------------------------------------------------------------------------------------------------------------------------------------------------------
300.200; Annual summaries from sponsors                6                 1               6  2.5 (150 minutes)...............  15
 and manufacturers under the Right to
 Try Act.
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C.
3407(d)), we have submitted the information collection provisions of
this proposed rule to OMB for review. These information collection
requirements will not be effective until FDA publishes a final rule,
OMB approves the information collection requirements, and the rule goes
into effect. FDA will announce OMB approval of these requirements in
the Federal Register.

IX. Federalism

    We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. We have determined that
this proposed rule does not contain policies that have substantial
direct effects on the States, on the relationship between the National
Government and the States, or on the distribution of power and
responsibilities among the various levels of government. Accordingly,
we conclude that the rule does not contain policies that have
federalism implications as defined in the Executive Order and,
consequently, a federalism summary impact statement is not required.

X. Consultation and Coordination With Indian Tribal Governments

    We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13175. We have tentatively
determined that the rule does not contain policies that would have a
substantial direct effect on one or more Indian Tribes, on the
relationship between the Federal Government and Indian Tribes, or on
the distribution of power and responsibilities between the Federal
Government and Indian Tribes. The Agency solicits comments from tribal
officials on any potential impact on Indian Tribes from this proposed
action.

XI. Reference

    The following reference is on display at the Dockets Management
Staff (see ADDRESSES) and is available for viewing by interested
persons between 9 a.m. and 4 p.m., Monday through Friday; it is also
available electronically at https://www.regulations.gov. FDA has
verified the website address, as of the date this document publishes in
the Federal Register, but websites are subject to change over time.

    1. Preliminary Economic Analysis, available at https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.

List of Subjects in 21 CFR Part 300

    Drugs, Prescription drugs.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, we propose
that 21 CFR part 300 be amended as follows:

PART 300--GENERAL

0
1. The authority citation for part 300 shall be revised to read as
follows:

    Authority:  21 U.S.C. 331, 351, 352, 355, 360b, 360bbb-0a, 371.

0
2. Add subpart D to part 300, consisting of Sec.  300.200, to read as
follows:

Subpart D--Annual Summary Reporting Requirements.

Sec.
300.200 Annual summary requirements under the Right to Try Act.

Sec.  300.200   Annual summary requirements under the Right to Try Act.

    (a) Definitions. The following definitions of terms apply only to
this section:
    (1) Eligible investigational drug. An eligible investigational drug
is as defined in section 561B(a)(2) of the Federal Food, Drug, and
Cosmetic Act.
    (2) Eligible patient. An eligible patient is as defined in section
561B(a)(1) of the Federal Food, Drug, and Cosmetic Act.
    (3) Investigational New Drug (IND). An IND is as defined in Sec.
312.3 of this chapter.
    (4) Known serious adverse event. A serious adverse event (as
defined in Sec.  312.32 of this chapter) is considered ``known'' if the
manufacturer or sponsor is aware of it.
    (5) Manufacturer or sponsor. A manufacturer or sponsor is the
person who:
    (i) Meets the definition of ``sponsor'' in Sec.  312.3 of this
chapter for the eligible investigational drug;
    (ii) Has submitted an application for the eligible investigational
drug under section 505(b) of the Federal Food, Drug, and Cosmetic Act
or section 351(a) of the Public Health Service Act; or
    (ii) Produces the eligible investigational drug provided to an
eligible patient on behalf of the persons described in paragraphs
(a)(5)(i) or (ii) of this section.
    (b)(1) Except as described in (b)(2) of this section, a
manufacturer or sponsor of an eligible investigational drug shall
submit to the Food and Drug Administration (FDA), no later than March
31 of each year, an annual summary of any use of eligible
investigational drugs supplied to any eligible patient under section
561B of the Federal Food, Drug, and Cosmetic Act for the period of
January 1 through December 31 of the preceding year.
    (2) For a manufacturer or sponsor of an eligible investigational
drug that has supplied an eligible patient with an eligible
investigational drug under section 561B of the Federal Food, Drug, and
Cosmetic Act between the period from enactment of section 561B (May 30,
2018) and [DATE THE FINAL RULE BECOMES EFFECTIVE], the following
deadlines apply:
    (i) The manufacturer or sponsor shall submit to FDA a first annual
summary covering that period no later than [DATE 60 CALENDAR DAYS AFTER
THE FINAL RULE BECOMES EFFECTIVE]; and
    (ii) The manufacturer or sponsor shall submit to FDA a second
annual summary covering the period from [DATE THE FINAL RULE BECOMES
EFFECTIVE] to December 31 [YEAR THE FINAL RULE BECOMES EFFECTIVE] by
March 31 [DATE THE YEAR AFTER THE FINAL RULE

BECOMES EFFECTIVE], for any eligible investigational drugs supplied to
any eligible patients under section 561B of the Federal Food, Drug, and
Cosmetic Act.
    (c) For each eligible investigational drug, the annual summary must
include:
    (1) The name of the eligible investigational drug and applicable
IND number. The name and IND number of the eligible investigational
drug supplied by the manufacturer or sponsor for use under section 561B
of the Federal Food, Drug, and Cosmetic Act.
    (2) Number of doses supplied. The total number of doses supplied by
the manufacturer or sponsor to eligible patients for use under section
561B of the Federal Food, Drug, and Cosmetic Act. Each dose of an
eligible investigational drug supplied for an eligible patient shall be
counted as a dose supplied.
    (3) Number of patients treated. The total number of eligible
patients for whom the manufacturer or sponsor provided the eligible
investigational drug for use under section 561B of the Federal Food,
Drug, and Cosmetic Act. An eligible patient treated more than one time
or with multiple doses of an eligible investigational drug shall be
counted as a single patient.
    (4) Use for which the eligible investigational drug was made
available. A tabular summary identifying the disease or conditions for
which the eligible investigational drug was made available for use
under section 561B of the Federal Food, Drug, and Cosmetic Act.
    (5) Any known serious adverse events and outcomes. A tabular
summary of any known serious adverse events, including resulting
outcomes, experienced by patients treated with the eligible
investigational drug under section 561B of the Federal Food, Drug, and
Cosmetic Act.
    (d) Annual summaries submitted pursuant to this section shall be
submitted in an electronic format that FDA can process, review, and
archive, and shall be sent directly to a designated point of contact
for submissions made under section 561B of the Federal Food, Drug, and
Cosmetic Act. The annual summaries must be submitted to the designated
point of contact and shall not be submitted to a particular IND. FDA
will specify the designated point of contact for submission of the
annual summary on FDA's website, located at https://www.fda.gov.

    Dated: July 10, 2020.
Stephen M. Hahn,
Commissioner of Food and Drugs.
[FR Doc. 2020-16016 Filed 7-23-20; 8:45 am]
BILLING CODE 4164-01-P