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Rule2022-19737

Annual Summary Reporting Requirements Under the Right to Try Act

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Published

September 14, 2022

Effective

November 14, 2022

Issuing agencies

Health and Human Services DepartmentFood and Drug Administration

Abstract

The Food and Drug Administration (FDA, the Agency, or we) is issuing a final rule to specify the deadline and content for submission of an annual summary of investigational drugs supplied under the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017 (Right to Try Act) and the uses for which the investigational drugs were supplied. This final rule implements a provision in the Right to Try Act that requires sponsors and manufacturers who provide an "eligible investigational drug" under the provisions of the Right to Try Act to submit to FDA an annual summary of such use, and directs FDA to specify by regulation the deadline of submission.

Full Text

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<title>Federal Register, Volume 87 Issue 177 (Wednesday, September 14, 2022)</title>
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[Federal Register Volume 87, Number 177 (Wednesday, September 14, 2022)]
[Rules and Regulations]
[Pages 56269-56277]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-19737]

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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: Final rule.

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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
issuing a final rule to specify the deadline and content for submission
of an annual summary of investigational drugs supplied under the
Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina
Right to Try Act of 2017 (Right to Try Act) and the uses for which the
investigational drugs were supplied. This final rule implements a
provision in the Right to Try Act that requires sponsors and
manufacturers who provide an ``eligible investigational drug'' under
the provisions of the Right to Try Act to submit to FDA an annual
summary of such use, and directs FDA to specify by regulation the
deadline of submission.

DATES: This rule is effective November 14, 2022. For additional
information on the effective and compliance dates, see section V of
this document.

ADDRESSES: For access to the docket to read background documents or
comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the
docket number found in brackets in the heading of this final rule into
the ``Search'' box and follow the prompts, and/or go to the Dockets
Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852,
240-402-7500.

FOR FURTHER INFORMATION CONTACT:
With regard to the final rule: Allison Hoffman, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 32, Rm. 3138, Silver
Spring, MD 20993, 301-796-9203, <a href="/cdn-cgi/l/email-protection#dc9db0b0b5afb3b2f294b3babab1bdb29cbab8bdf2b4b4aff2bbb3aa"><span class="__cf_email__" data-cfemail="743518181d071b1a5a3c1b121219151a341210155a1c1c075a131b02">[email&#160;protected]</span></a>.
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, 301-796-5733,
<a href="/cdn-cgi/l/email-protection#48181a091b3c292e2e082e2c296620203b662f273e"><span class="__cf_email__" data-cfemail="9dcdcfdccee9fcfbfbddfbf9fcb3f5f5eeb3faf2eb">[email&#160;protected]</span></a>.

SUPPLEMENTARY INFORMATION:

Table of Contents

I. Executive Summary
A. Purpose of the Final Rule
B. Summary of the Major Provisions of the Final Rule
C. Legal Authority
D. Costs and Benefits
II. Background
A. Need for the Regulation/History of the Rulemaking
B. Summary of Comments to the Proposed Rule
C. General Overview of the Final Rule
III. Legal Authority
IV. Comments on the Proposed Rule and FDA Response
A. Introduction
B. Description of General Comments and FDA Response
C. Comments on the Submission Deadline
D. Comments on Combining Right to Try Reporting
E. Comments on Submitting Dosing Information
F. Comments on Adverse Event Reporting
G. Comments on the Definition of Manufacturer or Sponsor
H. Comments on Reporting Patient Demographic Information
I. Comments on Outcomes Reporting
J. Comments on the Clarity of the Proposed Rule
V. Effective/Compliance Date(s)
VI. Economic Analysis of Impacts
A. Introduction
B. Summary of Costs and Benefits
VII. Analysis of Environmental Impact
VIII. Paperwork Reduction Act of 1995
IX. Federalism
X. Consultation and Coordination with Indian Tribal Governments
XI. Reference

I. Executive Summary

A. Purpose of the Final Rule

The purpose of this rule is to implement provisions of the Federal
Food, Drug, and Cosmetic Act (FD&C Act), added by the Right to Try Act,
which requires sponsors and manufacturers who provide an ``eligible
investigational drug'' under the Right to Try Act to submit to FDA an
annual summary of such use, and directs FDA to specify by regulation
the deadline of submission. The rule provides information on the
necessary contents of the annual summary and the deadline for its
submission.

B. Summary of the Major Provisions of the Final Rule

The rule adds a new subpart to the regulations, to specify the
deadline and content for submission of an annual summary of
investigational drugs supplied under the Right to Try provisions of the
FD&C Act and the uses for which they were supplied. The Right to Try
Act provides that the manufacturer or sponsor of an eligible
investigational drug shall submit to FDA an annual summary of any use
of such drug supplied under 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

The enacted provisions of the Right to Try Act, in conjunction with
FDA's general rulemaking authority serve as FDA's legal authority for
this rule.

D. Costs and Benefits

This final rule establishes the deadline for submission of annual
summaries of use of investigational drugs supplied under the FD&C Act.
The rule also establishes the required contents of these submissions.
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. There is no data that would allow us to
predict the magnitude of generated benefits, and thus we are unable to
quantify the expected benefits of this rule.
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

[[Page 56270]]

costs is $37,132 at a 7 percent discount rate and $45,818 at a 3
percent discount rate. The annualized cost of this rule over 10 years
is $5,287 at a 7 percent discount rate and $5,371 at a 3 percent
discount rate.

II. Background

A. Need for the Regulation/History of the Rulemaking

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 (21 U.S.C. 360bbb-0a).
The Right to Try Act amends the FD&C Act to establish an alternative
option for patients who meet certain criteria to request access to
certain unapproved drug products and for sponsors and manufacturers who
agree to provide those certain unapproved drug 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 rule does not require that
physician determinations be submitted to FDA. Manufacturers or sponsors
who provide their investigational drug under the Right to Try Act are
required to submit to FDA an annual summary of the use of their
drug(s). 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 uses 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 rule specifies
that deadline. This rule specifies that submissions must be made
electronically. Currently, this means attaching a PDF document to an
email. In the future, FDA may move to electronic submission through
other direct means.
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\1\ Information on FDA's Expanded Access Program is available at
<a href="https://www.fda.gov/news-events/public-health-focus/expanded-access">https://www.fda.gov/news-events/public-health-focus/expanded-access</a>.
\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 eligible investigational drugs and the website <a href="https://www.clinicaltrials.gov">https://www.clinicaltrials.gov</a>.
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B. Summary of Comments to the Proposed Rule

FDA received fewer than 50 comments to the proposed rule from
healthcare professionals, patient advocacy groups, regulated industry,
scientific and academic experts, and private citizens. FDA received
comments on the following: (1) the annual summary submission deadline;
(2) the definition of ``manufacturer''; (3) reporting information in
the annual report on dosing, any known serious adverse events, clinical
outcomes, patient demographic information, and the amount, if any,
charged for the product; and (4) general comments requesting
clarifications. FDA also received general comments both in support of
and against the proposed annual reporting rule as well as the entire
Right to Try Act.

C. General Overview of the Final Rule

FDA has extended the submission date for the first annual summary
report from 60 calendar days after the final rule becomes effective as
proposed to a specific date of March 31, 2023.

III. Legal Authority

The Right to Try Act amended Chapter V of the FD&C Act by inserting
section 561B. New section 561B(d)(1) of the FD&C Act 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 (21 U.S.C. 371(a)), serves
as our legal authority for this final rule.

IV. Comments on the Proposed Rule and FDA Response

A. Introduction

We describe and respond to the comments in sections IV.B through
IV.J of this document. We have numbered each comment to help
distinguish between different comments. We have grouped similar
comments together under the same number, and, in some cases, we have
separated different issues discussed in the same comment and designated
them as distinct comments for purposes of our responses. The number
assigned to each comment or comment topic is purely for organizational
purposes and does not signify the comment's value or importance or the
order in which comments were received.

B. Description of General Comments and FDA Response

(Comment 1) Some comments made general remarks supporting or
opposing the proposed reporting rule or Right to Try in general without
focusing on a particular proposed provision. These comments either
supported or opposed the proposed rule, without any suggestions for
specific changes.
(Response 1) FDA made no changes in response to these comments, as
there were no suggestions for specific changes. In regards to comments
opposing issuance of the proposed rule, we do not agree that FDA should
not issue this rule. Section 561B(d) of the FD&C Act provides that
``the Secretary shall specify by regulation'' the deadline of
submission of annual summaries. This rule implements the statutory
directive in section 561B(d) of the FD&C Act, and FDA concludes that
the rulemaking is necessary to establish deadline requirements for the
submission of annual summaries.

C. Comments on the Submission Deadline

(Comment 2) Several comments focused on proposed Sec.
300.200(b)(1) regarding the submission deadline. These comments
requested a change of the submission deadline for the first annual
summary from 60 calendar days after the rule becomes effective to 90
calendar days. Some comments also requested that the first annual
summary cover a 12-month time period beginning from the finalization of
the Proposed Rule onward. Some comments requested that for the initial
annual summary, the reporting period should begin on the date the final
rule is published and end on December 31 of that calendar year.
(Response 2) FDA agrees with the proposal to change the submission
deadline for the first annual summary from 60 calendar days after the
rule becomes effective to 90 calendar days. Regarding the proposals to
change the reporting periods for the first required annual summaries,
FDA disagrees that use of investigational drugs under the Right to Try
Act prior to the finalization of this rule should not be reported.
Rather than directing manufacturers or sponsors to only report Right to
Try Act uses after FDA's rulemaking is completed, the Right to Try Act
directs manufacturers or sponsors to submit to FDA an annual summary of
``any use'' of a drug under the law (section 561B(d)(1) of the FD&C
Act). Therefore, requiring submissions of Right to Try

[[Page 56271]]

Act uses since enactment of the law is consistent with the statute.
Furthermore, the information in the reports may provide relevant
information regarding the use of eligible investigational drugs. The
comment's suggestion could lead to a situation where a serious adverse
event that occurs 1 day prior to the final rule publication is not
shared with FDA but the same event that occurred 2 days later is.
Therefore, we are finalizing the proposed requirement that uses of
eligible investigational drugs under Right to Try be reported to FDA,
even if they occurred before issuance of this rule. The rule is
considered in effect 60 days after the date of publication, however the
due date for the first annual report is March 31, 2023 (see section V),
but the Right to Try Act was effective as of the date it was signed,
May 30, 2018. The rulemaking establishes the process for reporting
actions sponsors already have taken. The first annual summary should
cover all uses under the Right to Try Act since the statute has been in
effect in accordance with Sec. 300.200(b).

D. Comments on Combining Right to Try Reporting

(Comment 3) Several comments addressed combining Right to Try
reporting with other FDA regulatory reporting requirements, noting that
it may be less burdensome and facilitate FDA having all of the data on
an investigational product together. Some comments requested the
inclusion of the annual report on Right to Try uses as an addendum or
section within the investigational new drug (IND) annual report
required under Sec. 312.33 (21 CFR 312.33), in addition to a separate
report. Some comments requested aligning the Right to Try Act reporting
with the annual reporting required under the Expanded Access
regulations and aligning the reporting of known serious adverse events
under proposed Sec. 300.200(c)(5) with current serious adverse event
reporting regulations under Sec. 312.32 (21 CFR 312.32).
(Response 3) FDA disagrees with the comments requesting combining
Right to Try reporting with other FDA-required reports. The IND
reporting regulations do not capture all the information required under
Right to Try, so it is not accurate that compliance with Sec. 312.32
will provide compliance with the reporting requirements in this rule.
Consequently, the information detailed for the Right to Try submission
would have to be added to the IND annual report. Moreover, existing IND
annual reports under Sec. 312.33 are due to FDA based upon the date an
IND application was submitted to FDA. These IND annual reports are
submitted throughout the year and not at a single point in time for all
active applications, which is consistent with international
harmonization efforts. It would be extremely difficult and resource-
intensive for FDA to examine all IND annual reports for the sole
purpose of identifying those potentially few reports that have Right to
Try information so that we can compile the annual summary required by
section 561B(d)(2) of the FD&C Act. In addition, it is efficient to
have separate reporting requirements for Right to Try Act and other
investigational drug uses because section 561B(c) of the FD&C Act
limits FDA's use of clinical outcomes associated with the use of
eligible investigational drugs under the Right to Try Act in ways that
are not applicable to other uses of INDs. For these reasons, it is more
efficient to implement the annual reporting and summary requirements of
the Right to Try Act by requiring the annual reports to be submitted as
separate reports to FDA.
FDA does not intend to object if sponsors refer to their Right to
Try activities in their IND annual report required under Sec. 312.33
as long as such information is labeled as Right to Try and is also
included in the separate Right to Try annual report. The reporting
requirements in Sec. 312.33 include a provision that requires sponsors
to identify the IND numbers that correspond to the products used under
Right to Try. This will facilitate the integration into FDA systems and
allow FDA to link all information received on a particular IND or new
drug application or biologics license application.

E. Comments on Submitting Dosing Information

(Comment 4) Some comments made recommendations on proposed Sec.
300.200(c)(2) regarding dosing. Section 300.200(c)(2) proposed to
require that the annual summary include the total number of doses
supplied by the manufacturer or sponsor to eligible patients for use
under the Right to Try Act. We also proposed that each dose of an
eligible investigational drug supplied for an eligible patient shall be
counted as a dose supplied. Several comments recommended that FDA
require sponsors or drug manufacturers to report the number of doses
per patient, rather than the cumulative number of doses supplied of the
drug overall.
(Response 4) As noted in the proposed rule, FDA only proposed to
require reporting on the total number of doses supplied. This will make
the reporting requirements less burdensome for sponsors and is
consistent with the requirements in the Right to Try Act, which does
not require that information be submitted on a per patient basis. It is
also consistent with our public health oversight needs, because at this
time FDA does not foresee a need for more detailed information and FDA
can follow up with the submitter if more information would be useful to
FDA as it reviews the annual summary. However, sponsors may voluntarily
provide an itemized list of doses per patient in their tabular summary
when reporting any known serious adverse events; FDA encourages
sponsors to include information on the number of doses supplied per
patient when reporting on known serious adverse events even though this
rule does not require this information.
(Comment 5) One comment expressed that the example given in the
proposed rule of a tabular summary goes beyond the level of information
required by the Right to Try Act.
(Response 5) FDA disagrees with the comment, because the tabular
summary example included in the proposed rule showed information that
sponsors may choose to submit to provide context around the known
serious adverse event information. Specifically, the sample tabular
summary that FDA provided in the proposed rule included such non-
mandatory information as a field for a Patient ID number and for
grading the severity of known serious adverse events. However, we did
not propose to require that manufacturers or sponsors submit this
information (and indeed the final rule does not require submission of
such information).
To the extent the comment seeks a tabular summary example that
includes only mandatory information, the tabular summary below
highlights (bolded text) the mandatory information (although the
specific format is not required). The summary may include optional
contextual data (e.g., the time interval between the last dose received
and the onset of the known serious adverse event) in addition to the
statutorily required information, and the sponsor or manufacturer may
choose to submit this data if they believe the non-mandatory data could
provide relevant information.

[[Page 56272]]

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Serious adverse event(s)
Number of Number of Disease(s) or -------------------------------------
Eligible investigational drug IND No. Patient ID doses supplied patients condition(s) Serious adverse
treated event(s) Outcome(s)
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XDX501......................... 99999 12345 5 1 Breast cancer.... 1. Hip fracture.. 1. Improved.
2. Joint pain.... 2. Improved.
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F. Comments on Adverse Event Reporting

Some commenters made recommendations on proposed Sec.
300.200(c)(5) regarding adverse event reporting. In that provision, we
proposed to require that annual reports submitted to FDA include a
tabular summary of any known serious adverse events, including
resulting outcomes, experienced by patients treated with the eligible
investigational drug under the Right to Try Act.
(Comment 6) One comment recommended that manufacturers and sponsors
obtain data on the route of administration of the drug in the case of
an adverse event.
(Response 6) While the Agency welcomes manufacturers or sponsors to
include information they conclude is relevant to understanding a known
serious adverse event, FDA believes we can adequately fulfill our
public health role without including such a requirement; if FDA has
questions about route of administration that are relevant to our
review, we may pose such questions to manufacturers or sponsors.
FDA agrees that information on routes of administration may in some
cases aid FDA in understanding the circumstances surrounding an adverse
event. However, many drugs are not able to support multiple routes of
administration, so for these drugs FDA may not gain any helpful
information if we required reporting regarding route of administration.
(Comment 7) Some comments recommended that FDA encourage earlier
reporting of known serious adverse events prior to the required due
date for the annual summary.
(Response 7) FDA disagrees because section 561B(d)(1) of the FD&C
Act directs that the reporting be ``annual.'' Nevertheless, we note
that sponsors can always report safety data to FDA earlier than the
timeframes required by this rule in accordance with Sec. 312.32 (while
also ensuring compliance with the reporting timeframes under this
rule).
(Comment 8) One comment expressed concern with the definition of a
``known serious adverse event,'' arguing that only disclosing known
serious adverse events is too limiting and will not provide enough
information to evaluate a drug's associated risks. Instead, the comment
recommends that FDA require reporting of suspected adverse reactions.
One comment also requested that FDA require manufacturers and sponsors
to affirmatively seek information about known serious adverse events.
(Response 8) FDA disagrees with changing the proposed definition of
``known serious adverse event'' to encompass suspected serious adverse
reactions. We consider suspected adverse reactions to be adverse events
for which there is a reasonable possibility that the drug caused the
adverse event (see, e.g., Sec. 312.32(a) (defining ``suspected adverse
reaction'')). An adverse event, however, is any untoward medical
occurrence associated with the use of a drug in humans, whether or not
considered drug related (see Sec. 312.32(a)). Suspected adverse
reactions are the subset of all adverse events for which there is a
reasonable possibility that the drug caused the event. A ``serious
adverse event'' is an adverse event that is ``serious,'' as defined in
Sec. 312.32(a). A ``known serious adverse event'' is a serious adverse
event of which a manufacturer or sponsor is aware (Sec.
300.200(a)(4)). We believe it is appropriate to require that Right to
Try annual summaries only include information about known serious
adverse events for two reasons. First, Congress specifically required
reporting of such events, but did not require that annual summaries
include information about suspected adverse reactions. Second, at this
time we do not see a need to require reporting under this rule for
suspected adverse reactions because our IND safety reporting
requirements in Sec. 312.32 already require reporting of suspected
adverse reactions and reflect the need for the sponsor to evaluate the
available evidence. Accordingly, FDA receives needed information about
suspected adverse events through the IND safety reporting process.
With respect to the comment requesting that FDA require
manufacturers or sponsors to affirmatively seek information about
serious adverse events, we disagree. FDA does not seek to make this
rule more burdensome than is needed to efficiently implement the Right
to Try Act, and at this time it is not clear that any such
investigation requirement would result in relevant information for
purposes of FDA's Right to Try oversight role. Under the final rule,
known serious adverse events must be reported. Nevertheless, sponsors
are not constrained from including additional information they find to
be relevant regarding a known serious adverse event.

G. Comments on the Definition of Manufacturer or Sponsor

In proposed Sec. 300.200(a)(5), we proposed to define a
``manufacturer or sponsor'' as the person who meets the definition of
``sponsor'' in Sec. 312.3 (21 CFR 312.3) for the eligible
investigational drug; has submitted an application for the eligible
investigational drug under section 505(b) of the FD&C Act (21 U.S.C.
355(b)) or section 351(a) of the Public Health Service Act (42 U.S.C.
262(a)); or produces the eligible investigational drug provided to an
eligible patient on behalf of such persons.
(Comment 9) Some commenters made recommendations on proposed Sec.
300.200(a)(5) regarding the definition of ``manufacturer or sponsor.''
One comment recommended the exclusion of contract manufacturing
organizations from the term ``manufacturer or sponsor'' because a
contract manufacturer may not possess the necessary information to
complete the annual report. One comment requested that FDA limit the
definition of ``manufacturer or sponsor'' to the treating physician
because for drugs supplied through Right to Try, treating physicians
are responsible for monitoring their patients' use of the drug and
their safety.
(Response 9) FDA agrees that a contract manufacturing organization
that is not closely connected to the clinical investigation and
approval process should not be considered a ``manufacturer or sponsor''
under this rule, and therefore we have updated the regulatory text to
specify that a contract manufacturer is not a ``manufacturer or
sponsor.'' We are making this change because we believe that only those
entities that are closely connected to the clinical investigation or
approval process should submit annual summaries, and contract
manufacturers

[[Page 56273]]

would generally not be considered such entities. A manufacturer or
sponsor is better positioned to have access to the relevant data
required for the annual summary if their role is not merely to
manufacture a drug to another entity's specifications on behalf of the
other entity. Accordingly, we generally do not consider most contract
manufacturers to be a ``manufacturer or sponsor'' for purposes of this
rule. We consider a ``contract manufacturer'' to be an entity that
merely manufactures a drug to another entity's specifications on behalf
of the other entity. We expect that whenever a drug is distributed
under Right to Try, there will be a manufacturer or sponsor with access
to the relevant data who will submit the required annual summary.
Regarding limiting the definition of ``sponsor'' to the treating
physician, FDA disagrees because we think there will be less confusion
if we use the regulatory definition of ``sponsor'' in Sec. 312.3. This
is a definition that industry and researchers are familiar with, and
one that Congress likely understood when it used the term in the Right
to Try Act. We also note that the Right to Try Act refers to
``physician[s],'' but not in the context of reporting annual summaries;
rather, section 561B(a)(1) of the FD&C Act refers to ``physician[s]''
in the context of the definition of an eligible patient--suggesting
that Congress understood ``physician'' and ``sponsor'' to not be
synonymous.
(Comment 10) One comment requested that FDA require sponsors to
include the physicians' names and the total number of patients each
physician has certified over each reporting period because of potential
pressure for physicians to provide access to drugs under Right to Try.
(Response 10) FDA disagrees. Under section 561B(a) of the FD&C Act,
the ``eligible patient'' definition provides for the certification by a
physician; FDA information about the identity of the physician is not
needed for FDA to review the annual summary data as provided in the
Right to Try Act. Therefore, FDA does not seek to require any
information related to the physician.
(Comment 11) One comment requested that manufacturers assign
patient identification numbers to track patients.
(Response 11) FDA recommends this practice only with respect to
patients who experienced a known serious adverse event that is included
in the Right to Try annual summary, to help distinguish between
patients and events included in the annual summary. However, FDA does
not believe it is necessary to require the assignment of patient
identification numbers. Manufacturers or sponsors can take steps to
ensure that they adequately track relevant safety information without
the use of patient identification numbers, and if FDA has questions
about information included in an annual summary FDA may contact the
manufacturer or sponsor to clarify.

H. Comments on Reporting Patient Demographic Information

(Comment 12) Some commenters made recommendations regarding
inclusion of patient demographic information. Some comments requested
that the rule include a non-mandatory request for such other
information to provide a more comprehensive picture on Right to Try
use, such as the demographics of patients for whom Right to Try access
was requested; information about requests that were denied, including
reason for denial; amount charged for the product (if any); and overall
patient outcomes from the Right to Try use. Other commenters asked for
reporting of patient demographic information to be mandatory.
(Response 12) Congress specified the information FDA was to collect
for the annual summary in the Right to Try Act and did not include
demographic information. We encourage sponsors and/or manufacturers to
provide demographic data, individual patient information, and other
types of data suggested in the comments as optional additional
contextual information when submitting the annual summary.

I. Comments on Outcomes Reporting

In proposed Sec. 300.200(c)(5), we proposed to require that the
annual summary include a tabular summary of any known serious adverse
events, including resulting outcomes, experienced by patients treated
with the eligible investigational drug under the Right to Try Act.
(Comment 13) One comment requested that FDA require manufacturers
and sponsors to report all relevant clinical outcome data after
treatment.
(Response 13) FDA disagrees. Congress did not specify that
manufacturers or sponsors provide information about all treatment
outcomes, and at this time we do not see a need to require this
information in annual summaries. If FDA has questions about treatment
outcomes not associated with known serious adverse events, FDA can
request that information as appropriate.
(Comment 14) One comment disagreed with the proposed requirement
that annual summaries include information about outcome data. The
comment stated that patients who receive drugs under Right to Try are
being treated individually and not as a part of a clinical trial, so
treatment plans may vary.
(Response 14) We disagree. The proposed requirement is to report
any known serious adverse events, including resulting outcomes; the
outcomes are tied specifically to the adverse event, and not the
outcome of each individual use of an eligible drug, as the comment
suggests. Requiring information about outcomes resulting from known
serious adverse events is important so that FDA can meet the directive
in section 561B(d)(2) of the FD&C Act, that FDA shall post an annual
summary report including information specific to ``clinical outcomes.''
See section 701(a) of the FD&C Act (providing FDA with authority to
promulgate regulations for the efficient enforcement of the FD&C Act).
In addition, 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. We also note that the Agency routinely evaluates safety outcomes
outside of a clinical trial, so just because eligible patients may not
be part of a clinical trial does not mean we are unable to review
information about their outcomes.
(Comment 15) One comment requested more information on how the
Secretary of Health and Human Services would inform sponsors that the
Agency's use of a drug's clinical outcome is critical to making a
safety determination on the use of the drug.
(Response 15) This comment relates to section 561B(c) of the FD&C
Act, which includes certain restrictions on certain FDA uses of a
clinical outcome associated with Right to Try unless FDA makes a
determination that use of such clinical outcome is critical to
determining the safety of the eligible investigational drug. If FDA
makes such a determination, section 561B(c)(2) of the FD&C Act provides
that FDA ``shall provide written notice of such determination to the
sponsor, including a public health justification for such
determination, and such notice shall be made part of the administrative
record.'' FDA does not believe additional clarification is necessary
because the statute specifies that FDA's notification to the sponsor
shall be ``written.'' The

[[Page 56274]]

comment has not explained what additional clarification is needed.

J. Comments on the Clarity of the Proposed Rule

(Comment 16) One comment requested an explicit statement from FDA
that there are no reporting requirements for sponsors or manufacturers
who choose not to grant a request to provide products under Right to
Try.
(Response 16) FDA is not sure what kind of explicit statement the
comment seeks. Neither the Right to Try Act nor this final rule require
parties to report to FDA when they have declined to distribute drugs
under the Right to Try Act. FDA notes that there is no requirement that
a manufacturer or sponsor participate in Right to Try.
(Comment 17) One comment requested clarity on whether an annual
summary is only required if new access to a drug has been granted
during the reporting period or if sponsors should also report on
ongoing use from a prior reporting period.
(Response 17) Under Sec. 300.200(c)(2), the manufacturer or
sponsor must report the total number of doses supplied. The relevant
period of time is the period of time covered by the annual summary.
Therefore, the number of doses supplied during the annual summary
period is what should be reported. For example, if Patient A started
using the drug in the previous reporting period and continues to use
that drug in the current reporting period, the manufacturer or sponsor
should report how many doses were supplied during the current reporting
period.
(Comment 18) One comment requested that FDA consider providing
criteria on how a patient would submit a request for a drug under Right
to Try.
(Response 18) The Right to Try Act does not outline a role for FDA
with respect to the process by which patients may request access to
eligible investigational drugs. Therefore the comment asks FDA to
provide information about a matter that is beyond the scope of this
rulemaking. We decline.
(Comment 19) One comment requested additional detail on FDA's
intent to post online an annual summary report and expressed interest
in how FDA's posting of the annual summary report ``may increase
awareness about the availability of investigational drugs'' as noted in
the ``Costs and Benefits'' section of the preamble to the Proposed
Rule. One comment also stated that the information FDA includes in the
annual summary report does not convey or imply any conclusions
regarding the safety or efficacy of the products provided under the
Right to Try Act, and it may also be helpful for FDA's annual summary
report website to link to additional information regarding ``Expanded
Access.''
(Response 19) FDA will follow the requirements in the Right to Try
Act regarding posting an annual summary of uses of drugs under the
statute. As stated in the preamble to the proposed rule, providing this
information will increase awareness about the availability of
investigational drugs because the report will make available data about
the use of eligible investigational drugs. With respect to the comment
stating that the information included in FDA's annual summary report
will not convey or imply any conclusions about a drug's safety or
efficacy, we agree. The information included in FDA's annual summary
reports will be purely factual and will not reflect any FDA evaluations
of the eligible investigational drugs. With respect to the comment
requesting that our website link to information about ``Expanded
Access,'' we will consider that comment when we design our website for
Right to Try annual summary reports.

V. Effective/Compliance Date(s)

This final rule becomes effective 60 days after publication in the
Federal Register. Any manufacturer or sponsor who provides an eligible
investigational drug for use by an eligible patient in accordance with
the Right to Try Act must 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 December 31, 2022. The first
annual summary submitted under the Right to Try Act will be required to
be submitted March 31, 2023.
Thus, 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 FD&C Act between the
period from enactment of section 561B (May 30, 2018) and December 31,
2022, the manufacturer or sponsor shall submit to FDA a first annual
summary covering that period no later than March 31, 2023. After this
annual report, the manufacturer or sponsor must submit a report that
covers every January 1 through December 31 annual period by no later
than March of the following year, for every year in which the
manufacturer or sponsor has supplied a drug under the Right to Try Act.
Therefore, a report submitted in March 2024, would cover the period
January 1, 2023, through December 31, 2023.

VI. Economic Analysis of Impacts

A. Introduction

We have examined the impacts of the final rule under Executive
Order 12866, Executive Order 13563, 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). We
find that this final rule is not a 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 minimally dispersed,
we certify that the final 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 issuing ``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 $165
million, using the most current (2021) Implicit Price Deflator for the
Gross Domestic Product. This final rule would not result in an
expenditure in any year that meets or exceeds this amount.

B. Summary of Costs and Benefits

This final rule 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 use. The Right to Try Act
requires FDA to specify by regulation the deadline and requires that
submissions include certain information.
The benefits of this final 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

[[Page 56275]]

in these annual summary reports. These reporting requirements instruct
firms to collect all known serious adverse events and submit them once
per year to FDA. 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.
In addition, based on the information in these annual summaries,
FDA intends to 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. In some
cases, access to such drugs may help treat future patients. There is no
data that would allow us to predict the magnitude of generated
benefits, and thus we are unable to quantify the expected benefits of
this rule.
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 $37,132 at a
7 percent discount rate and $45,818 at a 3 percent discount rate (in
2020 dollars). The annualized cost of this rule over 10 years is $5,287
at a 7 percent discount rate and $5,371 at a 3 percent discount rate.
Consistent with Executive Order 12866, table 1 provides the costs and a
description of benefits for this final rule over a 10-year period.

Table 1--Summary of Benefits, Costs, and Distributional Effects of the Final Rule
--------------------------------------------------------------------------------------------------------------------------------------------------------
Units
Primary Low High ------------------------------------
Category estimate estimate estimate Year Discount Period Notes
dollars rate (%) covered
--------------------------------------------------------------------------------------------------------------------------------------------------------
Benefits:
Annualized Monetized $/year............ .......... .......... .......... 2020 7 10
.......... .......... .......... 2020 3 10
Annualized Quantified.................. .......... .......... .......... .......... 7 ..........
.......... .......... .......... .......... 3 ..........
------------------------------------------------------------------------------------------------------------
Qualitative............................ Disclosure of known serious
adverse events and outcomes
related to investigational new
drug treatments.

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

We have developed a comprehensive Economic Analysis of Impacts that
assesses the impacts of the final rule. The full analysis of economic
impacts is available in the docket for this final rule (Ref. 1) and at
<a href="https://www.fda.gov/about-fda/reports/economic-impact-analyses-fda-regulations">https://www.fda.gov/about-fda/reports/economic-impact-analyses-fda-regulations</a>.

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 final rule contains information collection provisions that are
subject to review by the Office of Management and Budget (OMB) under
the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3521). The title,
description, and respondent description of the information collection
provisions are shown in the following paragraphs 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.
Title: Annual Summary Reporting Requirements Under the Right to Try
Act--21 CFR part 300, subpart D--OMB Control Number 0910-NEW.
Description: The final rule provides for a submission schedule and
sets forth content requirements for sponsors and manufacturers who: (1)
provide an eligible investigational drug for use by an eligible patient
and (2) submit to FDA an annual summary report by subject to the
applicable regulations.

[[Page 56276]]

Regulations in Sec. 300.200 require that sponsors and
manufacturers submit to FDA 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 report will cover
the time period between enactment of the Right to Try Act (March 30,
2018) and December 31, 2022. We will provide instruction on the FDA
Right to Try web page at <a href="https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/right-try">https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/right-try</a> regarding a
designated point of contact for submissions of Right To Try annual
reporting summaries and are currently developing a form to facilitate
submission of requisite information. Data elements included in the
annual summary are:
<bullet> The name of the eligible investigational drug and
applicable IND number.
<bullet> The number of doses supplied to the eligible patient.
<bullet> The number of eligible patients treated.
<bullet> The use for which the eligible investigational drug was
made available to the eligible patient.
<bullet> Any known serious adverse events and outcomes that the
eligible patient treated with an eligible investigational drug
experienced.
Description of Respondents: Respondents to the information
collection are sponsors and manufacturers who provide an eligible
investigational drug to eligible patients in accordance with the Right
to Try Act and will submit to FDA annual summaries.
As discussed in section II.F of the Final Regulatory Impact
Analysis, we estimate the burden of the information collection as
follows:

Table 2--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of Average burden
Activity; 21 CFR citation Number of responses per Total annual per response Total hours
respondents respondent responses (in hours)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Sponsors and manufacturers submit annual summaries in accordance 6 1 6 2.5 15
with the Right to Try Act (Sec. 300.200)........................
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

Consistent with estimates in our Final Regulatory Impact Analysis,
we estimate that six sponsors and manufacturers will prepare and submit
six annual summaries and assume it takes 2.5 hours to prepare and
submit each summary, which results in a total of 15 hours annually.
The information collection provisions in this final rule have been
submitted to OMB for review as required by section 3507(d) of the
Paperwork Reduction Act of 1995.
Before the effective date of this final rule, FDA will publish a
notice in the Federal Register announcing OMB's decision to approve,
modify, or disapprove the information collection provisions in this
final rule. An Agency may not conduct or sponsor, and a person is not
required to respond to, a collection of information unless it displays
a currently valid OMB control number.

IX. Federalism

We have analyzed this final rule in accordance with the principles
set forth in Executive Order 13132. We have determined that the 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 rule in accordance with the principles set
forth in Executive Order 13175. We have determined that the rule does
not contain policies that have substantial direct effects 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. Accordingly, we
conclude that the rule does not contain policies that have tribal
implications as defined in the Executive Order and, consequently, a
tribal summary impact statement is not required.

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, 240-402-7500;
it is also available electronically at <a href="https://www.regulations.gov">https://www.regulations.gov</a>. 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. Economic Analysis of Impacts (available at <a href="https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm">https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm</a>).

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, 21 CFR
part 300 is amended as follows:

PART 300--GENERAL

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

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

0
2. Add subpart D, 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.

(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.

[[Page 56277]]

(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
(iii) Is other than a contract manufacturer acting on behalf of a
manufacturer or sponsor, producing the eligible investigational drug
provided to an eligible patient on behalf of the persons described in
paragraph (a)(5)(i) or (ii) of this section.
(b)(1) Except as described in paragraph (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 December 31, 2022, the manufacturer or sponsor shall submit
to FDA a first annual summary covering that period no later than March
31, 2023.
(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 diseases 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
investigational new drug application. FDA will specify the designated
point of contact for submission of the annual summary on FDA's website,
as described at <a href="https://www.fda.gov">https://www.fda.gov</a>.

Dated: August 31, 2022.
Robert M. Califf,
Commissioner of Food and Drugs.
[FR Doc. 2022-19737 Filed 9-13-22; 8:45 am]
BILLING CODE 4164-01-P

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