[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 [www.gpo.gov]
[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 https://www.regulations.gov 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, [email protected].
    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, 
[email protected].

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 
https://www.fda.gov/news-events/public-health-focus/expanded-access.
    \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 https://www.clinicaltrials.gov.
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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]]



--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                          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)
--------------------------------------------------------------------------------------------------------------------------------------------------------
XDX501.........................           99999           12345               5               1  Breast cancer....  1. Hip fracture..  1. Improved.
                                                                                                                    2. Joint pain....  2. Improved.
--------------------------------------------------------------------------------------------------------------------------------------------------------

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.
 
--------------------------------------------------------------------------------------------------------------------------------------------------------
Costs:
    Annualized Monetized $/year............       5,287  ..........  ..........        2020           7          10
                                                  5,371  ..........  ..........        2020           3          10
    Annualized Quantified..................  ..........  ..........  ..........  ..........           7  ..........
                                             ..........  ..........  ..........  ..........           3  ..........
                                            ------------------------------------------------------------------------------------------------------------
    Qualitative............................
 
--------------------------------------------------------------------------------------------------------------------------------------------------------
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 
https://www.fda.gov/about-fda/reports/economic-impact-analyses-fda-regulations.

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 https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/right-try 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:
     The name of the eligible investigational drug and 
applicable IND number.
     The number of doses supplied to the eligible patient.
     The number of eligible patients treated.
     The use for which the eligible investigational drug was 
made available to the eligible patient.
     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 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. Economic Analysis of Impacts (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, 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 https://www.fda.gov.

    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


