The Commission published its original proposals in a Notice of Proposed Rulemaking (“NPRM”) on November 2, 2016. 1 The Commission had previously issued an Advance Notice of Proposed Rulemaking (“ANPRM”) on the subject. 2 The Commission received several public comments in response to both the ANPRM and the NPRM, which are available on the Commission's website at https://sers.fec.gov/fosers/search.htm (reference REG 2013-01). On September 8, 2022, the Commission requested additional comment about any technological developments relating to electronic payment processing, newer electronic payment technologies, and contributions made via prepaid cards that may have occurred following publication of the NPRM that would be relevant to the Commission's consideration of its proposed rules. 3 The Commission received several public comments in response to its Request for Additional Comment, which are available on the Commission's website at https://sers.fec.gov/fosers/search.htm (reference REG 2013-01).

The Commission presently seeks public comment with respect to one of its proposals to modernize campaign finance regulations in light of technological advances. In a separate rulemaking, the Commission changed the definition of “public communication” at 11 CFR 100.26 and adopted a new defined term— “Internet public communication”—which appears at new 11 CFR 110.11(c)(5)(i). See generally REG 2011-02: Draft Final Rule and Explanation and Justification for Internet Communications Disclaimers (Agenda Doc. 22-52-B) (“Internet Communications Rule”). The revised definition of “public communication” at § 100.26 includes those communications that are “placed for a fee on another person's website, digital device, application, or advertising platform.” Internet Communications Rule at 16. The new defined term “Internet public communication” at new § 110.11(c)(5)(i) parallels the revised definition of “public communication” at § 100.26 by defining “internet public communication” as “any public communication over the internet that is placed for a fee on another person's website, digital device, application, or advertising platform.” Internet Communications Rule at 26.

In light of the changes in the Internet Communications Rule, as well as developments in advertising practices on the Internet, the Commission seeks comments on whether the revised definition of “public communication” at § 100.26, and the new term “internet public communication” at § 110.11(c)(5)(i), should also include communications that are “promoted for a fee” on another person's website, digital device, application, or advertising platform, and whether such communications that are “promoted for a fee” should be subject to the Commission's disclaimer requirements.

The Commission also seeks comments on how general public political advertising on the internet would be affected by the inclusion of the phrase “promoted for a fee” on another person's website, digital device, application, or advertising platform in §§ 100.26 and 110.11(c)(5)(i), and whether the wide and rapidly expanding array of options available in the internet advertising market bring to bear any particular considerations or concerns of which the Commission should be mindful or that warrant a particular approach.

To this end, the Commission seeks comments about whether, both for purposes of the term “internet public communication” and the Commission's disclaimer requirements, a distinction should be made between communications over the internet where (1) a person is paid to republish content containing express advocacy or soliciting a contribution on a third party's website, digital device, application, or advertising platform in order to increase the circulation or prominence of that content; (2) a website, digital device, application, or advertising platform is paid directly to “boost” or expand the scope of viewership of content containing express advocacy or soliciting a contribution in order to increase the circulation or prominence of that content; and (3) a person is paid to create or generate content containing express advocacy or soliciting a contribution, which then appears on a third party's website, digital device, application, or advertising platform.

Finally, the Commission is soliciting comments concerning whether and how this proposed change to the definitions of “public communication” and “internet public communication” would affect regulated entities broadly, including in contexts unrelated to the required disclaimers for a given communication.

As explained above, the Commission is soliciting comments concerning the proposed addition of certain communications “promoted for a fee” to its definitions of “public communication” and “internet public communication.” The details of this proposal can be found on the Commission's website at https://sers.fec.gov/fosers/search.htm (reference REG 2011-02). The Commission's goal in this rulemaking is to promulgate final rules that are flexible enough to encompass both non-electronic and electronic forms of payments, communications, and internet advertising, and that remain relevant as new forms of information storage, communication, payment, and advertising methods and media emerge and develop in the future. Accordingly, the Commission welcomes comments on the issues and questions addressed by this rulemaking, and on any related issues.

The FAA invites you to send any written relevant data, views, or arguments about this proposal. Send your comments to an address listed under ADDRESSES . Include “Docket No. FAA-2022-1304; Project Identifier AD-2022-00347-T” at the beginning of your comments. The most helpful comments reference a specific portion of the proposal, explain the reason for any recommended change, and include supporting data. The FAA will consider all comments received by the closing date and may amend this proposal because of those comments.

Except for Confidential Business Information (CBI) as described in the following paragraph, and other information as described in 14 CFR 11.35, the FAA will post all comments received, without change, to regulations.gov, including any personal information you provide. The agency will also post a report summarizing each substantive verbal contact received about this NPRM.

CBI is commercial or financial information that is both customarily and actually treated as private by its owner. Under the Freedom of Information Act (FOIA) (5 U.S.C. 552), CBI is exempt from public disclosure. If your comments responsive to this NPRM contain commercial or financial information that is customarily treated as private, that you actually treat as private, and that is relevant or responsive to this NPRM, it is important that you clearly designate the submitted comments as CBI. Please mark each page of your submission containing CBI as “PROPIN.” The FAA will treat such marked submissions as confidential under the FOIA, and they will not be placed in the public docket of this NPRM. Submissions containing CBI should be sent to Kumar Khatri, Aerospace Engineer, Cabin Safety and Environmental Systems Section, FAA, Seattle ACO Branch, 2200 South 216th St., Des Moines, WA 98198; phone and fax: 206-231-3842; email: kumar.r.khatri@faa.gov. Any commentary that the FAA receives that is not specifically designated as CBI will be placed in the public docket for this rulemaking.

The FAA has received a non-compliance report indicating that the technical standard order installation requirements for the first observer seat in the flight deck were not followed. When the first observer seat, located in front of the supernumerary seats, is in the furthest aft position on the seat tracks, the “head path stay out zone” is compromised. This condition, if not addressed, could result in occupants seated in the right or center supernumerary seats sustaining an injury during an emergency landing.

The FAA is issuing this NPRM after determining that the unsafe condition described previously is likely to exist or develop on other products of the same type design.

The FAA reviewed Boeing Special Attention Requirements Bulletin 767-25-0589 RB, dated February 25, 2022. This service information specifies procedures for installing markers (placards) in the flight deck regarding the position of the first observer seat position during taxi, takeoff, and landing.

This service information is reasonably available because the interested parties have access to it through their normal course of business or by the means identified in ADDRESSES .

This proposed AD would require accomplishing the actions specified in the service information already described, except for any differences identified as exceptions in the regulatory text of this proposed AD. This proposed AD would also require revising the existing AFM to include procedures for briefing all occupants other than the flightcrew members regarding the first observer seat position for taxi, takeoff, and landing, as indicated by the placards installed in the flight deck.

Section 91.9 prohibits any person from operating a civil aircraft without complying with the operating limitations specified in the AFM and on installed placards. FAA regulations also require operators to furnish pilots with any changes to the AFM (14 CFR 121.137) and pilots in command to be familiar with the AFM and installed placards containing operating limitations(14 CFR 91.505).

The FAA estimates that this AD, if adopted as proposed, would affect 153 airplanes of U.S. registry. The FAA estimates the following costs to comply with this proposed AD:

Title 49 of the United States Code specifies the FAA's authority to issue rules on aviation safety. Subtitle I, section 106, describes the authority of the FAA Administrator. Subtitle VII: Aviation Programs, describes in more detail the scope of the Agency's authority.

The FAA is issuing this rulemaking under the authority described in Subtitle VII, Part A, Subpart III, Section 44701: General requirements. Under that section, Congress charges the FAA with promoting safe flight of civil aircraft in air commerce by prescribing regulations for practices, methods, and procedures the Administrator finds necessary for safety in air commerce. This regulation is within the scope of that authority because it addresses an unsafe condition that is likely to exist or develop on products identified in this rulemaking action.

The FAA determined that this proposed AD would not have federalism implications under Executive Order 13132. This proposed AD would not have a substantial direct effect 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.

For the reasons discussed above, I certify this proposed regulation:

(1) Is not a “significant regulatory action” under Executive Order 12866,

(2) Would not affect intrastate aviation in Alaska, and

(3) Would not have a significant economic impact, positive or negative, on a substantial number of small entities under the criteria of the Regulatory Flexibility Act.

Accordingly, under the authority delegated to me by the Administrator, the FAA proposes to amend 14 CFR part 39 as follows:

The FAA invites you to send any written relevant data, views, or arguments about this proposal. Send your comments to an address listed under ADDRESSES . Include “Docket No. FAA-2022-1577; Project Identifier MCAI-2022-00860-T” at the beginning of your comments. The most helpful comments reference a specific portion of the proposal, explain the reason for any recommended change, and include supporting data. The FAA will consider all comments received by the closing date and may amend this proposal because of those comments.

Except for Confidential Business Information (CBI) as described in the following paragraph, and other information as described in 14 CFR 11.35, the FAA will post all comments received, without change, to regulations.gov , including any personal information you provide. The agency will also post a report summarizing each substantive verbal contact received about this NPRM.

CBI is commercial or financial information that is both customarily and actually treated as private by its owner. Under the Freedom of Information Act (FOIA) (5 U.S.C. 552), CBI is exempt from public disclosure. If your comments responsive to this NPRM contain commercial or financial information that is customarily treated as private, that you actually treat as private, and that is relevant or responsive to this NPRM, it is important that you clearly designate the submitted comments as CBI. Please mark each page of your submission containing CBI as “PROPIN.” The FAA will treat such marked submissions as confidential under the FOIA, and they will not be placed in the public docket of this NPRM. Submissions containing CBI should be sent to Dat Le, Aerospace Engineer, Large Aircraft Section, FAA, International Validation Branch, 2200 South 216th St., Des Moines, WA 98198; telephone 516-228-7317; email dat.v.le@faa.gov. Any commentary that the FAA receives that is not specifically designated as CBI will be placed in the public docket for this rulemaking.

The FAA issued AD 2022-09-06, Amendment 39-22026 (87 FR 29654, May 16, 2022; corrected May 23, 2022 (87 FR 31123)) (AD 2022-09-06), for certain Airbus SAS Model A350-941 and -1041 airplanes. AD 2022-09-06 was prompted by MCAI originated by EASA, which is the Technical Agent for the Member States of the European Union. EASA issued AD 2021-0208, dated September 15, 2021 (EASA AD 2021-0208) (which corresponds to FAA AD 2022-09-06), to correct an unsafe condition.

AD 2022-09-06 requires revising the existing maintenance or inspection program, as applicable, to incorporate additional new or more restrictive airworthiness limitations. The FAA issued AD 2022-09-06 to address hazardous or catastrophic airplane system failures. AD 2022-09-06 specifies that accomplishing the revision required by that AD terminates certain requirements of AD 2019-20-01, Amendment 39-19754 (84 FR 55495, October 17, 2019) (AD 2019-20-01).

Since the FAA issued AD 2022-09-06, EASA superseded AD 2021-0208 and issued EASA AD 2022-0127, dated June 28, 2022 (EASA AD 2022-0127) (referred to after this as the MCAI), for certain Airbus SAS Model A350-941 and -1041 airplanes. The MCAI states that new and/or more restrictive tasks and limitations were introduced for Airbus A350 airplanes.

Airplanes with an original airworthiness certificate or original export certificate of airworthiness issued after May 2, 2022, must comply with the airworthiness limitations specified as part of the approved type design and referenced on the type certificate data sheet; this proposed AD therefore does not include those airplanes in the applicability.

The FAA is issuing this AD to address hazardous or catastrophic airplane system failures. You may examine the MCAI in the AD docket at regulations.gov under Docket No. FAA-2022-1577.

The FAA reviewed EASA AD 2022-0127. This service information specifies new or more restrictive airworthiness limitations for airplane structures and safe life limits.

This proposed AD would also require EASA AD 2021-0208, dated September 15, 2021, which the Director of the Federal Register approved for incorporation by reference as of June 21, 2022 (87 FR 29654, May 16, 2022; corrected May 23, 2022 (87 FR 31123)).

This material is reasonably available because the interested parties have access to it through their normal course of business or by the means identified in ADDRESSES .

This product has been approved by the aviation authority of another country and is approved for operation in the United States. Pursuant to the FAA's bilateral agreement with the State of Design Authority, it has notified the FAA of the unsafe condition described in the MCAI described above. The FAA is issuing this NPRM after determining that the unsafe condition described previously is likely to exist or develop in other products of the same type design.

This proposed AD would retain certain requirements of AD 2022-09-06. This proposed AD would require revising the existing maintenance or inspection program, as applicable, to incorporate additional new or more restrictive airworthiness limitations, which are specified in EASA AD 2022-0127 already described, as proposed for incorporation by reference. Any differences with EASA AD 2022-0127 are identified as exceptions in the regulatory text of this AD.

This proposed AD would require revisions to certain operator maintenance documents to include new actions ( e.g., inspections). Compliance with these actions is required by 14 CFR 91.403(c). For airplanes that have been previously modified, altered, or repaired in the areas addressed by this proposed AD, the operator may not be able to accomplish the actions described in the revisions. In this situation, to comply with 14 CFR 91.403(c), the operator must request approval for an alternative method of compliance (AMOC) according to paragraph (n)(1) of this proposed AD.

In the FAA's ongoing efforts to improve the efficiency of the AD process, the FAA developed a process to use some civil aviation authority (CAA) ADs as the primary source of information for compliance with requirements for corresponding FAA ADs. The FAA has been coordinating this process with manufacturers and CAAs. As a result, the FAA proposes to retain the IBR of EASA AD 2021-0208 and incorporate EASA AD 2022-0127 by reference in the FAA final rule. This proposed AD would, therefore, require compliance with EASA AD 2021-0208 and EASA AD 2022-0127 through that incorporation, except for any differences identified as exceptions in the regulatory text of this proposed AD. Using common terms that are the same as the heading of a particular section in EASA AD 2021-0208 or EASA AD 2022-0127 does not mean that operators need comply only with that section. For example, where the AD requirement refers to “all required actions and compliance times,” compliance with this AD requirement is not limited to the section titled “Required Action(s) and Compliance Time(s)” in EASA AD 2021-0208 or EASA AD 2022-0127. Service information required by EASA AD 2021-0208 and EASA AD 2022-0127 for compliance will be available at regulations.gov by searching for and locating Docket No. FAA-2022-1577 after the FAA final rule is published.

The FAA's process of incorporating by reference MCAI ADs as the primary source of information for compliance with corresponding FAA ADs has been limited to certain MCAI ADs (primarily those with service bulletins as the primary source of information for accomplishing the actions required by the FAA AD). However, the FAA is now expanding the process to include MCAI ADs that require a change to airworthiness limitation documents, such as airworthiness limitation sections.

For these ADs that incorporate by reference an MCAI AD that changes airworthiness limitations, the FAA requirements are unchanged. Operators must revise the existing maintenance or inspection program, as applicable, to incorporate the information specified in the new airworthiness limitation document. The airworthiness limitations must be followed according to 14 CFR 91.403(c) and 91.409(e).

The previous format of the airworthiness limitation ADs included a paragraph that specified that no alternative actions ( e.g., inspections) or intervals may be used unless the actions and intervals are approved as an AMOC in accordance with the procedures specified in the AMOCs paragraph under “Additional AD Provisions.” This new format includes a “New Provisions for Alternative Actions and Intervals” paragraph that does not specifically refer to AMOCs, but operators may still request an AMOC to use an alternative action or interval.

The FAA estimates that this AD, if adopted as proposed, would affect 30 airplanes of U.S. registry. The FAA estimates the following costs to comply with this proposed AD:

The FAA estimates the total cost per operator for the retained actions from AD 2022-09-06 to be $7,650 (90 work-hours × $85 per work-hour).

The FAA has determined that revising the existing maintenance or inspection program takes an average of 90 work-hours per operator, although the agency recognizes that this number may vary from operator to operator. Since operators incorporate maintenance or inspection program changes for their affected fleet(s), the FAA has determined that a per-operator estimate is more accurate than a per-airplane estimate.

The FAA estimates the total cost per operator for the new proposed actions to be $7,650 (90 work-hours × $85 per work-hour).

Title 49 of the United States Code specifies the FAA's authority to issue rules on aviation safety. Subtitle I, section 106, describes the authority of the FAA Administrator. Subtitle VII: Aviation Programs, describes in more detail the scope of the Agency's authority.

The FAA is issuing this rulemaking under the authority described in Subtitle VII, Part A, Subpart III, Section 44701: General requirements. Under that section, Congress charges the FAA with promoting safe flight of civil aircraft in air commerce by prescribing regulations for practices, methods, and procedures the Administrator finds necessary for safety in air commerce. This regulation is within the scope of that authority because it addresses an unsafe condition that is likely to exist or develop on products identified in this rulemaking action.

The FAA determined that this proposed AD would not have federalism implications under Executive Order 13132. This proposed AD would not have a substantial direct effect 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.

For the reasons discussed above, I certify this proposed regulation:

(1) Is not a “significant regulatory action” under Executive Order 12866,

(2) Would not affect intrastate aviation in Alaska, and

(3) Would not have a significant economic impact, positive or negative, on a substantial number of small entities under the criteria of the Regulatory Flexibility Act.

Accordingly, under the authority delegated to me by the Administrator, the FAA proposes to amend 14 CFR part 39 as follows:

The FAA invites you to send any written relevant data, views, or arguments about this proposal. Send your comments to an address listed under ADDRESSES . Include “Docket No. FAA-2022-1575; Project Identifier MCAI-2022-00859-T” at the beginning of your comments. The most helpful comments reference a specific portion of the proposal, explain the reason for any recommended change, and include supporting data. The FAA will consider all comments received by the closing date and may amend this proposal because of those comments.

Except for Confidential Business Information (CBI) as described in the following paragraph, and other information as described in 14 CFR 11.35, the FAA will post all comments received, without change, to regulations.gov, including any personal information you provide. The agency will also post a report summarizing each substantive verbal contact received about this NPRM.

CBI is commercial or financial information that is both customarily and actually treated as private by its owner. Under the Freedom of Information Act (FOIA) (5 U.S.C. 552), CBI is exempt from public disclosure. If your comments responsive to this NPRM contain commercial or financial information that is customarily treated as private, that you actually treat as private, and that is relevant or responsive to this NPRM, it is important that you clearly designate the submitted comments as CBI. Please mark each page of your submission containing CBI as “PROPIN.” The FAA will treat such marked submissions as confidential under the FOIA, and they will not be placed in the public docket of this NPRM. Submissions containing CBI should be sent to Dat Le, Aerospace Engineer, Large Aircraft Section, FAA, International Validation Branch, 2200 South 216th St., Des Moines, WA 98198; telephone 516-228-7317; email Dat.V.Le@faa.gov. Any commentary that the FAA receives that is not specifically designated as CBI will be placed in the public docket for this rulemaking.

The FAA issued AD 2020-15-20, Amendment 39-21183 (85 FR 53156, August 28, 2020) (AD 2020-15-20), for certain Airbus SAS Model A350-941 and -1041 airplanes. AD 2020-15-20 was prompted by an MCAI originated by EASA, which is the Technical Agent for the Member States of the European Union. EASA issued AD 2019-0288, dated November 28, 2019 (EASA AD 2019-0288), to correct an unsafe condition.

AD 2020-15-20 requires revising the existing maintenance or inspection program, as applicable, to incorporate new or more restrictive airworthiness limitations. The FAA issued AD 2020-15-20 to address safety-significant latent failures that would, in combination with one or more other specific failures or events, result in a hazardous or catastrophic failure condition.

Since the FAA issued AD 2020-15-20, EASA superseded AD 2019-0288 and issued EASA AD 2022-0126, dated June 28, 2022 (EASA AD 2022-0126) (referred to after this as the MCAI), for all Airbus SAS Model A350-941 and -1041 airplanes. The MCAI states that new or more restrictive airworthiness limitations have been developed. Airplanes with an original airworthiness certificate or original export certificate of airworthiness issued after May 2, 2022 must comply with the airworthiness limitations specified as part of the approved type design and referenced on the type certificate data sheet; this proposed AD therefore does not include those airplanes in the applicability.

The FAA is proposing this AD to address safety-significant latent failures that would, in combination with one or more other specific failures or events, result in a hazardous or catastrophic failure condition. You may examine the MCAI in the AD docket at regulations.gov under Docket No. FAA-2022-1575.

The FAA reviewed EASA AD 2022-0126. This service information specifies new or more restrictive airworthiness limitations for certification maintenance requirements.

This proposed AD would also require EASA AD 2019-0288, dated November 28, 2019, which the Director of the Federal Register approved for incorporation by reference as of October 2, 2020 (85 FR 53156, August 28, 2020).

This material is reasonably available because the interested parties have access to it through their normal course of business or by the means identified in ADDRESSES .

This product has been approved by the aviation authority of another country and is approved for operation in the United States. Pursuant to the FAA's bilateral agreement with the State of Design Authority, it has notified the FAA of the unsafe condition described in the MCAI described above. The FAA is issuing this NPRM after determining that the unsafe condition described previously is likely to exist or develop in other products of the same type design.

This proposed AD would retain all requirements of AD 2020-15-20. This proposed AD would also require revising the existing maintenance or inspection program, as applicable, to incorporate additional new or more restrictive airworthiness limitations, which are specified in EASA AD 2022-0126 already described, as proposed for incorporation by reference. Any differences with EASA AD 2022-0126 are identified as exceptions in the regulatory text of this AD.

This proposed AD would require revisions to certain operator maintenance documents to include new actions ( e.g., inspections). Compliance with these actions is required by 14 CFR 91.403(c). For airplanes that have been previously modified, altered, or repaired in the areas addressed by this proposed AD, the operator may not be able to accomplish the actions described in the revisions. In this situation, to comply with 14 CFR 91.403(c), the operator must request approval for an alternative method of compliance (AMOC) according to paragraph (m)(1) of this proposed AD.

In the FAA's ongoing efforts to improve the efficiency of the AD process, the FAA developed a process to use some civil aviation authority (CAA) ADs as the primary source of information for compliance with requirements for corresponding FAA ADs. The FAA has been coordinating this process with manufacturers and CAAs. As a result, the FAA proposes to retain the IBR of EASA AD 2019-0288 and incorporate EASA AD 2022-0126 by reference in the FAA final rule. This proposed AD would, therefore, require compliance with EASA AD 2022-0126 and EASA AD 2019-0288 through that incorporation, except for any differences identified as exceptions in the regulatory text of this proposed AD. Using common terms that are the same as the heading of a particular section in EASA AD 2022-0126 or EASA AD 2019-0288 does not mean that operators need comply only with that section. For example, where the AD requirement refers to “all required actions and compliance times,” compliance with this AD requirement is not limited to the section titled “Required Action(s) and Compliance Time(s)” in EASA AD 2022-0126 or EASA AD 2019-0288. Service information required by EASA AD 2022-0126 and EASA AD 2019-0288 for compliance will be available at regulations.gov by searching for and locating Docket No. FAA-2022-1575 after the FAA final rule is published.

The FAA's process of incorporating by reference MCAI ADs as the primary source of information for compliance with corresponding FAA ADs has been limited to certain MCAI ADs (primarily those with service bulletins as the primary source of information for accomplishing the actions required by the FAA AD). However, the FAA is now expanding the process to include MCAI ADs that require a change to airworthiness limitation documents, such as airworthiness limitation sections.

For these ADs that incorporate by reference an MCAI AD that changes airworthiness limitations, the FAA requirements are unchanged. Operators must revise the existing maintenance or inspection program, as applicable, to incorporate the information specified in the new airworthiness limitation document. The airworthiness limitations must be followed according to 14 CFR 91.403(c) and 91.409(e).

The previous format of the airworthiness limitation ADs included a paragraph that specified that no alternative actions ( e.g., inspections) or intervals may be used unless the actions and intervals are approved as an AMOC in accordance with the procedures specified in the AMOCs paragraph under “Additional AD Provisions.” This new format includes a “New Provisions for Alternative Actions and Intervals” paragraph that does not specifically refer to AMOCs, but operators may still request an AMOC to use an alternative action or interval.

The FAA estimates that this AD, if adopted as proposed, would affect 30 airplanes of U.S. registry. The FAA estimates the following costs to comply with this proposed AD:

The FAA estimates the total cost per operator for the retained actions from AD 2020-15-20 to be $7,650 (90 work-hours × $85 per work-hour).

The FAA has determined that revising the existing maintenance or inspection program takes an average of 90 work-hours per operator, although the agency recognizes that this number may vary from operator to operator. Since operators incorporate maintenance or inspection program changes for their affected fleet(s), the FAA has determined that a per-operator estimate is more accurate than a per-airplane estimate.

The FAA estimates the total cost per operator for the new proposed actions to be $7,650 (90 work-hours x $85 per work-hour).

Title 49 of the United States Code specifies the FAA's authority to issue rules on aviation safety. Subtitle I, section 106, describes the authority of the FAA Administrator. Subtitle VII: Aviation Programs, describes in more detail the scope of the Agency's authority.

The FAA is issuing this rulemaking under the authority described in Subtitle VII, Part A, Subpart III, Section 44701: General requirements. Under that section, Congress charges the FAA with promoting safe flight of civil aircraft in air commerce by prescribing regulations for practices, methods, and procedures the Administrator finds necessary for safety in air commerce. This regulation is within the scope of that authority because it addresses an unsafe condition that is likely to exist or develop on products identified in this rulemaking action.

The FAA determined that this proposed AD would not have federalism implications under Executive Order 13132. This proposed AD would not have a substantial direct effect 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.

For the reasons discussed above, I certify this proposed regulation:

(1) Is not a “significant regulatory action” under Executive Order 12866,

(2) Would not affect intrastate aviation in Alaska, and

(3) Would not have a significant economic impact, positive or negative, on a substantial number of small entities under the criteria of the Regulatory Flexibility Act.

Accordingly, under the authority delegated to me by the Administrator, the FAA proposes to amend 14 CFR part 39 as follows:

The FAA invites you to send any written relevant data, views, or arguments about this proposal. Send your comments to an address listed under ADDRESSES . Include “Docket No. FAA-2022-1479; Project Identifier AD-2022-00703-T” at the beginning of your comments. The most helpful comments reference a specific portion of the proposal, explain the reason for any recommended change, and include supporting data. The FAA will consider all comments received by the closing date and may amend this proposal because of those comments.

Except for Confidential Business Information (CBI) as described in the following paragraph, and other information as described in 14 CFR 11.35, the FAA will post all comments received, without change, to regulations.gov , including any personal information you provide. The agency will also post a report summarizing each substantive verbal contact received about this NPRM.

CBI is commercial or financial information that is both customarily and actually treated as private by its owner. Under the Freedom of Information Act (FOIA) (5 U.S.C. 552), CBI is exempt from public disclosure. If your comments responsive to this NPRM contain commercial or financial information that is customarily treated as private, that you actually treat as private, and that is relevant or responsive to this NPRM, it is important that you clearly designate the submitted comments as CBI. Please mark each page of your submission containing CBI as “PROPIN.” The FAA will treat such marked submissions as confidential under the FOIA, and they will not be placed in the public docket of this NPRM. Submissions containing CBI should be sent to Nicole S. Tsang, Aerospace Engineer, Cabin Safety and Environmental Systems Section, FAA, Seattle ACO Branch, 2200 South 216th St., Des Moines, WA 98198; phone: 206-231-3959; email: nicole.s.tsang@faa.gov. Any commentary that the FAA receives that is not specifically designated as CBI will be placed in the public docket for this rulemaking.

The FAA has been notified by the European Union Aviation Safety Agency (EASA), which is the Technical Agent for the Member States of the European Union, of an issue with the B/E Aerospace 117042-XX series chemical oxygen generators installed on certain Airbus airplanes. The units may fail to deliver oxygen to passengers during an emergency on the airplane. To address this issue on certain Airbus airplanes, EASA issued AD 2015-0117, dated June 24, 2015, corrected August 7, 2015, and AD 2019-0140, dated June 12, 2019. The FAA issued corresponding AD 2016-16-02, Amendment 39-18600 (81 FR 53255, August 12, 2016), and AD 2020-04-18, Amendment 39-19855 (85 FR 14409, March 12, 2020), respectively, which require the replacement of units older than 10 years and impose a 10-year life limit on all 117042-XX series generators.

The FAA released Special Airworthiness Information Bulletin NM-17-17, dated June 19, 2017, which indicated that the FAA and B/E Aerospace Systems planned to conduct further investigation of chemical oxygen generators in the 117080 series that are 10 to 15 years old since date of manufacture, to determine if these generators have an issue similar to the 117042 series generators.

The reduction of useful life was changed for 117080-02, 117080-03, and 117080-04 series chemical oxygen generators from 15 years to 10 years. Collins Aerospace has Parts Manufacturer Approval (PMA) for 117080-02, 117080-03, and 117080-04 series chemical oxygen generators on all Boeing Model 737-100, 737-200, 737-200C, 737-300, 737-400, 737-500, 737-600, 737-700, 737-700C, 737-800, 737-900, 757-200, 757-200PF, 757-200CB, 757-300, 767-200, 767-300, 767-300F, and 767-400ER series airplanes. However, the applicability of this proposed AD also includes Boeing Model 737-900ER series airplanes. The FAA determined that Boeing Model 737-900ER series airplanes are affected because there is concern that operators might mistake the 737-900ER as a sub-model of the 737-900, and the 117080-0X series of chemical oxygen generators might be installed on Boeing Model 737-900ER series airplanes.

Collins Aerospace has observed that mis-actuations are possible 10 years after the manufacturing date and increase in likelihood as the 15-year life is approached. The mis-actuations are associated with the tin-based chemistry used to manufacture the generators and specifically appear to be caused by oxidation of tin fuel added to the chemical core. Collins Aerospace's investigation and analysis concluded that the chemical core oxidizes in a manner similar to the 117042-XX series chemical oxygen generators. This condition, if not addressed, could lead to failure of the generator to activate and consequently not deliver oxygen during an emergency, possibly resulting in injury to airplane occupants.

The FAA is issuing this NPRM after determining that the unsafe condition described previously is likely to exist or develop on other products of the same type design. This product has been approved by the aviation authority of another country, and is approved for operation in the United States. Pursuant to the FAA's bilateral agreement with the State of Design Authority, the FAA has been notified of the unsafe condition described in the AD and service information referenced above. The FAA is proposing this AD because the FAA evaluated all the relevant information and determined the unsafe condition described previously is likely to exist or develop on other products of the same type design.

Collins Aerospace Service Information Letter (SIL) 117080-SIL-002, dated May 4, 2022, specifies procedures for replacing affected chemical oxygen generators.

This proposed AD would require inspecting the date of manufacture of chemical oxygen generators having part numbers 117080-02, 117080-03, and 117080-04, and replacing affected generators with serviceable units. This proposed AD would also limit the installation of passenger chemical oxygen generators to serviceable units.

The FAA estimates that this AD, if adopted as proposed, would affect 3,419 airplanes of U.S. registry. The FAA estimates the following costs to comply with this proposed AD:

Title 49 of the United States Code specifies the FAA's authority to issue rules on aviation safety. Subtitle I, section 106, describes the authority of the FAA Administrator. Subtitle VII: Aviation Programs, describes in more detail the scope of the Agency's authority.

The FAA is issuing this rulemaking under the authority described in Subtitle VII, Part A, Subpart III, Section 44701: General requirements. Under that section, Congress charges the FAA with promoting safe flight of civil aircraft in air commerce by prescribing regulations for practices, methods, and procedures the Administrator finds necessary for safety in air commerce. This regulation is within the scope of that authority because it addresses an unsafe condition that is likely to exist or develop on products identified in this rulemaking action.

The FAA determined that this proposed AD would not have federalism implications under Executive Order 13132. This proposed AD would not have a substantial direct effect 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.

For the reasons discussed above, I certify this proposed regulation:

(1) Is not a “significant regulatory action” under Executive Order 12866,

(2) Would not affect intrastate aviation in Alaska, and

(3) Would not have a significant economic impact, positive or negative, on a substantial number of small entities under the criteria of the Regulatory Flexibility Act.

Accordingly, under the authority delegated to me by the Administrator, the FAA proposes to amend 14 CFR part 39 as follows:

The FAA's authority to issue rules regarding aviation safety is found in Title 49 of the United States Code. Subtitle I, Section 106 describes the authority of the FAA Administrator. Subtitle VII, Aviation Programs, describes in more detail the scope of the agency's authority. This rulemaking is promulgated under the authority described in Subtitle VII, Part A, Subpart I, Section 40103. Under that section, the FAA is charged with prescribing regulations to assign the use of airspace necessary to ensure the safety of aircraft and the efficient use of airspace. This regulation is within the scope of that authority as it would amend the Class D airspace at Mesquite Metro Airport, Mesquite, TX, and the Class E airspace extending upward form 700 feet above the surface at Mesquite Metro Airport, contained within the Dallas-Fort Worth, TX airspace legal description, to support instrument flight rule operations at this airport.

Interested parties are invited to participate in this proposed rulemaking by submitting such written data, views, or arguments, as they may desire. Comments that provide the factual basis supporting the views and suggestions presented are particularly helpful in developing reasoned regulatory decisions on the proposal. Comments are specifically invited on the overall regulatory, aeronautical, economic, environmental, and energy-related aspects of the proposal. Communications should identify both docket numbers and be submitted in triplicate to the address listed above. Commenters wishing the FAA to acknowledge receipt of their comments on this notice must submit with those comments a self-addressed, stamped postcard on which the following statement is made: “Comments to Docket No. FAA-2022-1556/Airspace Docket No. 22-ASW-25.” The postcard will be date/time stamped and returned to the commenter.

All communications received before the specified closing date for comments will be considered before taking action on the proposed rule. The proposal contained in this notice may be changed in light of the comments received. A report summarizing each substantive public contact with FAA personnel concerned with this rulemaking will be filed in the docket.

An electronic copy of this document may be downloaded through the internet at www.regulations.gov . Recently published rulemaking documents can also be accessed through the FAA's web page at www.faa.gov/air_traffic/publications/airspace_amendments/.

You may review the public docket containing the proposal, any comments received, and any final disposition in person in the Dockets Office (see the ADDRESSES section for the address and phone number) between 9:00 a.m. and 5:00 p.m., Monday through Friday, except federal holidays. An informal docket may also be examined during normal business hours at the Federal Aviation Administration, Air Traffic Organization, Central Service Center, Operations Support Group, 10101 Hillwood Parkway, Fort Worth, TX 76177.

This document proposes to amend FAA Order JO 7400.11G, Airspace Designations and Reporting Points, dated August 19, 2022, and effective September 15, 2022. FAA Order JO 7400.11G is publicly available as listed in the ADDRESSES section of this document. FAA Order JO 7400.11G lists Class A, B, C, D, and E airspace areas, air traffic service routes, and reporting points.

The FAA is proposing an amendment to 14 CFR part 71 by:

Amending the Class D airspace to within a 4.5-mile (increased from a 3.5-mile) radius of Mesquite Metro Airport, Mesquite, TX; removing the airspace extension south of the airport; removing the city associated with the airport to comply with changes to FAA Order JO 7400.2N, Procedures for Handling Airspace Matters; and replacing the outdated terms “Notice to Airmen” with “Notice to Air Missions” and “Airport/Facility Directory” with “Chart Supplement”;

And amending the Class E airspace extending upward from 700 feet above the surface to within a 7-mile (increased from a 6.5-mile) radius of Mesquite Metro Airport contained within the Dallas-Fort Worth, TX, airspace legal description; removing the Mesquite Metro: RWY 18-LOC and the associated extension from the airspace legal description; and updating the geographic coordinates of the Granbury Regional Airport, Granbury, TX, also contained within the Dallas-Fort Worth, TX, airspace legal description.

This action is the result of an airspace review conducted as part of the decommissioning of the Mesquite LOC which provided navigation information to the instrument procedures at Mesquite Metro Airport.

Class D and E airspace designations are published in paragraphs 5000 and 6005, respectively, of FAA Order JO 7400.11G, dated August 19, 2022, and effective September 15, 2022, which is incorporated by reference in 14 CFR 71.1. The Class D and E airspace designations listed in this document will be published subsequently in FAA Order JO 7400.11.

FAA Order JO 7400.11, Airspace Designations and Reporting Points, is published yearly and effective on September 15.

The FAA has determined that this regulation only involves an established body of technical regulations for which frequent and routine amendments are necessary to keep them operationally current, is non-controversial and unlikely to result in adverse or negative comments. It, therefore: (1) is not a “significant regulatory action” under Executive Order 12866; (2) is not a “significant rule” under DOT Regulatory Policies and Procedures (44 FR 11034; February 26, 1979); and (3) does not warrant preparation of a regulatory evaluation as the anticipated impact is so minimal. Since this is a routine matter that will only affect air traffic procedures and air navigation, it is certified that this rule, when promulgated, would not have a significant economic impact on a substantial number of small entities under the criteria of the Regulatory Flexibility Act.

This proposal will be subject to an environmental analysis in accordance with FAA Order 1050.1F, “Environmental Impacts: Policies and Procedures” prior to any FAA final regulatory action.

Accordingly, pursuant to the authority delegated to me, the Federal Aviation Administration proposes to amend 14 CFR part 71 as follows:

The FAA's authority to issue rules regarding aviation safety is found in Title 49 of the United States Code. Subtitle I, Section 106 describes the authority of the FAA Administrator. Subtitle VII, Aviation Programs, describes in more detail the scope of the agency's authority. This rulemaking is promulgated under the authority described in Subtitle VII, Part A, Subpart I, Section 40103. Under that section, the FAA is charged with prescribing regulations to assign the use of airspace necessary to ensure the safety of aircraft and the efficient use of airspace. This regulation is within the scope of that authority as it would amend the Class D airspace, the Class E surface airspace, and the Class E airspace extending upward from 700 feet above the surface at Topeka Regional Airport, Topeka, KS, and Philip Billard Municipal Airport, Topeka, KS, and remove the Class E airspace designated as an extension to Class D and Class E surface airspace areas at Philip Billard Municipal Airport to support instrument flight rule operations at these airports.

Interested parties are invited to participate in this proposed rulemaking by submitting such written data, views, or arguments, as they may desire. Comments that provide the factual basis supporting the views and suggestions presented are particularly helpful in developing reasoned regulatory decisions on the proposal. Comments are specifically invited on the overall regulatory, aeronautical, economic, environmental, and energy-related aspects of the proposal. Communications should identify both docket numbers and be submitted in triplicate to the address listed above. Commenters wishing the FAA to acknowledge receipt of their comments on this notice must submit with those comments a self-addressed, stamped postcard on which the following statement is made: “Comments to Docket No. FAA-2022-1557/Airspace Docket No. 22-ACE-21.” The postcard will be date/time stamped and returned to the commenter.

All communications received before the specified closing date for comments will be considered before taking action on the proposed rule. The proposal contained in this notice may be changed in light of the comments received. A report summarizing each substantive public contact with FAA personnel concerned with this rulemaking will be filed in the docket.

An electronic copy of this document may be downloaded through the internet at www.regulations.gov . Recently published rulemaking documents can also be accessed through the FAA's web page at www.faa.gov/air_traffic/publications/airspace_amendments/. You may review the public docket containing the proposal, any comments received, and any final disposition in person in the Dockets Office (see the ADDRESSES section for the address and phone number) between 9:00 a.m. and 5:00 p.m., Monday through Friday, except federal holidays. An informal docket may also be examined during normal business hours at the Federal Aviation Administration, Air Traffic Organization, Central Service Center, Operations Support Group, 10101 Hillwood Parkway, Fort Worth, TX 76177.

This document proposes to amend FAA Order JO 7400.11G, Airspace Designations and Reporting Points, dated August 19, 2022, and effective September 15, 2022. FAA Order JO 7400.11G is publicly available as listed in the ADDRESSES section of this document. FAA Order JO 7400.11G lists Class A, B, C, D, and E airspace areas, air traffic service routes, and reporting points.

The FAA is proposing an amendment to 14 CFR part 71 by:

Amending the Class D airspace at Topeka Regional Airport, Topeka, KS, by removing the Forbes Field Airport ILS and RIPLY LOM and the associated extensions from the airspace legal description; updating the header of the airspace legal description from “Topeka, Forbes Field Airport, KS” to “Topeka, KS” to comply with changes to FAA Order JO 7400.2N, Procedures for Handling Airspace Matters; removing the city associated with the airport in the airspace legal description to comply with changes to FAA Order JO 7400.2N; updating the name of the airport (previously Forbes Field Airport) to coincide with the FAA's aeronautical database; and replacing the outdated terms “Notice to Airmen” with “Notice to Air Missions” and “Airport/Facility Directory” with “Chart Supplement”;

Amending the Class D airspace at Philip Billard Municipal Airport by adding an extension 1 mile each side of the 002° bearing from the airport extending from the 4-mile radius of the airport to 4.1 miles north of the airport; adding an extension 1 mile each side of the 134° bearing from the Philip Billard Muni: RWY 13-LOC extending from the 4-mile radius of the airport to 4.1 miles southeast of the Philip Billard Muni: RWY 13-LOC; adding an extension 1 mile each side of the 314° bearing from the airport extending from the 4-mile radius of the airport to 4.2 miles northwest of the airport; updating the header of the airspace legal description from “Topeka, Philip Billard Municipal Airport, KS” to “Topeka, KS” to comply with changes to FAA Order JO 7400.2N; removing the city associated with the airport to comply with changes to FAA Order JO 7400.2N; updating the geographic coordinates of the airport to coincide with the FAA's aeronautical database; removing Forbes Field, KS, from the airspace legal description as it is not required; and replacing the outdated terms “Notice to Airmen” with “Notice to Air Missions” and “Airport/Facility Directory” with “Chart Supplement”;

Amending the Class E surface airspace at Topeka Regional Airport by removing the Forbes Field Airport ILS and RIPLY LOM and the associated extensions from the airspace legal description; updating the header of the airspace legal description from “Topeka, Forbes Field Airport, KS” to “Topeka, KS” to comply with changes to FAA Order JO 7400.2N; removing the city associated with the airport in the airspace legal description to comply with changes to FAA Order JO 7400.2N; updating the name of the airport (previously Forbes Field Airport) to coincide with the FAA's aeronautical database; and adding missing part-time language to the airspace legal description;

Amending the Class E surface airspace at Philip Billard Municipal Airport by adding an extension 1 mile each side of the 002° bearing from the airport extending from the 4-mile radius of the airport to 4.1 miles north of the airport; adding an extension 1 mile each side of the 134° bearing from the Philip Billard Muni: RWY 13-LOC extending from the 4-mile radius of the airport to 4.1 miles southeast of the Philip Billard Muni: RWY 13-LOC; adding an extension 1 mile each side of the 314° bearing from the airport extending from the 4-mile radius of the airport to 4.2 miles northwest of the airport; updating the header of the airspace legal description from “Topeka, Philip Billard Municipal Airport, KS” to “Topeka, KS” to comply with changes to FAA Order JO 7400.2N; removing the city associated with the airport to comply with changes to FAA Order JO 7400.2N; updating the geographic coordinates of the airport to coincide with the FAA's aeronautical database; removing Forbes Field, KS, from the airspace legal description as it is not required; and replacing the outdated terms “Notice to Airmen” with “Notice to Air Missions” and “Airport/Facility Directory” with “Chart Supplement”;

Removing the Class E airspace designated as an extension to Class D and Class E surface airspace area at Philip Billard Municipal Airport as it is no longer required; Amending the Class E airspace extending upward from 700 feet above the surface at Topeka Regional Airport by removing the Forbes Field ILS and associated extension from the airspace legal description; adding an extension 1 mile each side of the 040° bearing from the airport extending from the 7.4-mile radius of the airport to 12.8 miles northeast of the airport; adding an extension 3.9 miles each side of the Forbes TACAN 124° radial extending from the 7.4-mile radius of the airport to 10.4 miles southwest of the Forbes TACAN; adding an extension 1 mile each side of the 220° bearing from the airport extending from the 7.4-mile radius of the airport to 12.8 miles southwest of the airport; updating the header of the airspace legal description from “Topeka, Forbes Field Airport, KS” to “Topeka, KS” to comply with changes to FAA Order JO 7400.2N; removing the city associated with the airport in the airspace legal description to comply with changes to FAA Order JO 7400.2N; updating the name of the airport (previously Forbes Field Airport) to coincide with the FAA's aeronautical database;

And amending the Class E airspace extending upward from 700 feet above the surface at Philip Billard Municipal Airport by removing the Topeka VORTAC, BILOY LOM, and Philip Billard Municipal Airport ILS Localizer and the associated extensions from the airspace legal description; adding an extension 1.5 miles each side of the 134° bearing from the Philip Billard Muni: RWY 13-LOC extending from the 6.5-mile radius of the airport to 8.1 miles southeast of the Philip Billard Muni: RWY 13-LOC; adding an extension 3.8 miles each side of the 314° bearing from the Philip Billard Muni: RWY 13-LOC extending from the 6.5-mile radius of the airport to 10.9 miles northwest of the Philip Billard Muni: RWY 13-LOC; updating the header of the airspace legal description from “Topeka, Philip Billard Municipal Airport, KS” to “Topeka, KS” to comply with changes to FAA Order JO 7400.2N; removing the city associated with the airport to comply with changes to FAA Order JO 7400.2N; updating the geographic coordinates of the airport to coincide with the FAA's aeronautical database.

This action is necessary due to biennial airspace reviews.

Class D and E airspace designations are published in paragraphs 5000, 6002, 6004, and 6005, respectively, of FAA Order JO 7400.11G, dated August 19, 2022, and effective September 15, 2022, which is incorporated by reference in 14 CFR 71.1. The Class D and E airspace designations listed in this document will be published subsequently in FAA Order JO 7400.11. FAA Order JO 7400.11, Airspace Designations and Reporting Points, is published yearly and effective on September 15.

The FAA has determined that this regulation only involves an established body of technical regulations for which frequent and routine amendments are necessary to keep them operationally current, is non-controversial and unlikely to result in adverse or negative comments. It, therefore: (1) is not a “significant regulatory action” under Executive Order 12866; (2) is not a “significant rule” under DOT Regulatory Policies and Procedures (44 FR 11034; February 26, 1979); and (3) does not warrant preparation of a regulatory evaluation as the anticipated impact is so minimal. Since this is a routine matter that will only affect air traffic procedures and air navigation, it is certified that this rule, when promulgated, would not have a significant economic impact on a substantial number of small entities under the criteria of the Regulatory Flexibility Act.

This proposal will be subject to an environmental analysis in accordance with FAA Order 1050.1F, “Environmental Impacts: Policies and Procedures” prior to any FAA final regulatory action.

Accordingly, pursuant to the authority delegated to me, the Federal Aviation Administration proposes to amend 14 CFR part 71 as follows:

Table of Contents I. Executive Summary A. Purpose of the Proposed Rule B. Summary of the Major Provisions of the Proposed Rule C. Legal Authority D. Costs and Benefits II. Table of Abbreviations and Commonly Used Acronyms in This Document III. Background A. Definitions B. Applicability of the IND Regulations C. Guidance on Whether Clinical Investigations Can Be Conducted Without an IND D. Need for the Regulation IV. Legal Authority V. Description of the Proposed Rule A. Self-Determined Exemption (Proposed § 312.2(b)(4)) B. FDA-Determined Exemption (Proposed § 312.2(b)(5)) C. Proposed Technical and Conforming Amendments VI. Proposed Effective Date VII. Preliminary Economic Analysis of Impacts A. Introduction B. Summary of Costs and Benefits VIII. Analysis of Environmental Impact IX. Paperwork Reduction Act of 1995 X. Federalism XI. Consultation and Coordination With Indian Tribal Governments XII. References I. Executive Summary A. Purpose of the Proposed Rule

FDA is proposing to amend its IND regulations to exempt from the scope of the requirements certain clinical investigations studying drug uses of products that are lawfully marketed as foods for human consumption (including dietary supplements) or as cosmetics. The proposed rule would make it easier for sponsors and sponsor-investigators to conduct certain clinical investigations evaluating drug uses of foods or cosmetics while maintaining adequate safeguards for human subjects.

Currently, FDA regulations provide an exemption from the IND requirements for studies of lawfully marketed drug products that meet certain criteria, including that the study does not involve a route of administration, dosage level, use in a patient population, or other factor that significantly increases the risks (or decreases the acceptability of these risks) associated with the use of the drug product. However, this exemption applies only to clinical investigations of drug products lawfully marketed in the United States, and therefore generally does not apply to clinical investigations of products marketed as foods for human consumption or as cosmetics.

FDA has exercised its enforcement discretion on a case-by-case basis and has not objected to certain clinical studies evaluating a drug use of a product lawfully marketed as a food or cosmetic being conducted without an IND, based on consideration of factors such as the purpose of the investigation and whether the study raises any concerns about the health, safety, and welfare of the subjects. This proposed rule would now establish exemptions from the IND requirements for drug studies of products lawfully marketed in the United States as a food or cosmetic when the studies meet criteria similar to those in the IND exemption for certain investigations of lawfully marketed drug products.

The proposed rule would create two types of IND exemptions for drug studies of products lawfully marketed in the United States as foods or cosmetics. One exemption, the proposed “self-determined exemption,” would specify that a clinical investigation to evaluate a drug use of a product lawfully marketed in the United States as a conventional food for human consumption, a dietary supplement, or a cosmetic is exempt from the IND requirements if certain conditions are met:

• The investigation is not intended to support a drug development plan for the product (including a future IND or application for marketing approval) or a labeling change that would cause the lawfully marketed product to become an unlawfully marketed drug;

• The investigation is conducted in compliance with the requirements for IRB review and informed consent;

• The investigation is conducted in compliance with the regulations governing promotion and commercial distribution of investigational drugs;

• The route of administration of the product in the investigation is the same as that of the lawfully marketed product; and

• The investigation meets certain criteria designed to protect the health, safety, and welfare of subjects.

Under this self-determined exemption, if a clinical investigation to evaluate a drug use of a product lawfully marketed in the United States as a food or cosmetic meets these criteria, the study would be exempt from the IND regulations. Provided the criteria are met, the study's sponsor (who may also be an investigator conducting the study, i.e., a sponsor-investigator) would not be required to submit an IND for the study or request that FDA exempt the study from the IND requirements (and we would not accept an IND for a study that we had determined was exempt).

Under the second IND exemption we propose to establish, the “FDA-determined exemption,” the sponsor of a clinical investigation to evaluate a drug use of a product lawfully marketed in the United States as a food or cosmetic could ask the Agency to exempt the investigation from the IND requirements when the investigation meets the self-determined exemption criteria except for one or more of the subject health, safety, and welfare criteria, but the sponsor has concluded that the investigation nevertheless does not present a potential for significant risk to subjects. To obtain such an exemption, the sponsor would submit a written request that includes information on the sponsor, the proposed investigation, and the product to be studied, as well as a description of why the investigation does not present a potential for significant risk to the health, safety, or welfare of subjects.

Upon receiving such a request for exemption from the IND requirements, FDA would evaluate any risks to subjects and would grant an exemption if we found that the investigation did not present a potential for significant risk (or decrease the acceptability of the risks) to the health, safety, or welfare of subjects. The proposal also would authorize FDA to exempt a study from the IND requirements on our own initiative if we determined, upon review of an IND for the study, that the study met the decision criteria for an FDA-determined exemption. The FDA-determined exemption proposal also states that we may revoke an exemption if we become aware of information suggesting that the investigation: (1) could present a potential for significant risk to the health, safety, or welfare of subjects or (2) does not meet any other eligibility requirement for the exemption.

Adopting these proposed IND exemptions would reduce the burden of conducting certain clinical investigations evaluating drug uses of products lawfully marketed as foods or cosmetics, as well as the Agency's burden of reviewing such studies, without eliminating requirements that help ensure the safety of subjects and the quality of data submitted in support of drug product approval.

We are issuing this proposed rule under FDA's authority to regulate drug products under the Federal Food, Drug, and Cosmetic Act (FD&C Act) and the Public Health Service Act (PHS Act).

Quantifiable benefits of this proposed rule are cost savings that come from reducing the burden of submitting INDs to FDA for clinical investigations to evaluate a drug use of a food or cosmetic. The proposed rule would have a one-time, upfront cost for current and future sponsors and sponsor-investigators who would have to read the rule, if it is finalized. In addition, there would be costs to FDA associated with a new type of IND-related submission, a request for an FDA-determined exemption. The impact of reviewing this new submission is analyzed in section II.E of the Preliminary Economic Analysis of Impacts for this proposed rule, as a partial offset to the cost savings of the rule. Discounted over 10 years, the total net benefit of the rule is estimated to be $33 million at a 3 percent discount rate and $27 million at a 7 percent discount rate.

This proposed rule concerns the establishment of exemptions from the requirement to submit an IND before initiating certain clinical investigations evaluating drug uses of lawfully marketed food for human consumption (including both conventional foods and dietary supplements) and cosmetics. (We refer to these product categories collectively as “foods and cosmetics” in this document.) Following is a brief discussion of important terms used in this proposed rule, the applicability of the IND regulations in part 312 (21 CFR part 312) to clinical investigations of foods and cosmetics for use as drugs, and why the proposed exemptions are needed.

Before explaining the need for the proposed IND exemptions, we believe it is helpful to discuss several terms used in the proposed rule. Under § 312.3(a), the definitions and interpretations of terms contained in section 201 of the FD&C Act (21 U.S.C. 321) apply to those terms when used in the IND regulations. Therefore, the terms “food,” “dietary supplement,” “cosmetic,” and “drug” in the proposed exemptions are defined as they are in the FD&C Act.

“Food” is defined as articles used for food or drink for man or other animals, chewing gum, and articles used for components of any such article (section 201(f) of the FD&C Act). For purposes of the proposed exemptions, “food” does not include animal feed, pet food, or other food intended for consumption by animals other than humans. Examples of food include, but are not limited to, fruits, vegetables, fish, dairy products, eggs, raw agricultural commodities for use as food or as components of food, food ingredients, food additives (including substances that migrate into food from packaging and other articles that contact food), dietary supplements, dietary ingredients, infant formula, medical foods, beverages (including alcoholic beverages and bottled water), bakery goods, snack foods, candy, and canned foods.

“Dietary supplement” is defined, in part, as a product that is intended for ingestion to supplement the diet and that contains one or more dietary ingredients (section 201(ff) of the FD&C Act). Dietary ingredients include vitamins, minerals, herbs and other botanicals, amino acids, other dietary substances intended to supplement the diet by increasing the total dietary intake, and concentrates, metabolites, constituents, extracts, and combinations of the preceding types of ingredients (section 201(ff)(1) of the FD&C Act). Because dietary supplements are deemed to be food for most purposes, the term “food” includes dietary supplements (see section 201(ff) of the FD&C Act). Notably, however, dietary supplements are not deemed to be food for purposes of section 201(g) of the FD&C Act, which, as discussed below, defines “drug” for purposes of the FD&C Act (section 201(ff) of the FD&C Act).

The term “conventional food” is not defined in the FD&C Act or in FDA's regulations. In this proposed rule, we use it to mean any food that is not a dietary supplement.

A “cosmetic” is an article (other than soap) intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance, or an article intended for use as a component of any such article (section 201(i) of the FD&C Act).

The definition of “drug” includes, among other things, “articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals” and “articles (other than food) intended to affect the structure or any function of the body of man or other animals” (section 201(g)(1)(B) and (C) of the FD&C Act). This proposed rule applies only to products that are intended for investigational use as drugs in humans. A biological product subject to licensure under section 351 of the PHS Act (42 U.S.C. 262) fits within the drug definition under the FD&C Act. A “biological product” is a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein, or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings (section 351(i) of the PHS Act).

“Clinical investigation” is defined in the IND regulations as any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects (excluding use of a marketed drug in medical practice) (§ 312.3(b)). A “subject” is defined in the IND regulations as a human who participates in an investigation, either as a recipient of an investigational new drug or as a control; subjects may be healthy or have a disease (§ 312.3(b)).

A “sponsor” of a clinical investigation is an individual or entity ( e.g., pharmaceutical or other company, governmental agency, academic institution, private organization, or other organization) who takes responsibility for and initiates the investigation (§ 312.3(b)). An “investigator” is an individual who actually conducts a clinical investigation ( i.e., the investigational drug is administered or dispensed to subjects under his or her immediate direction) (§ 312.3(b)). A person may be a “sponsor-investigator,” who is an individual who initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed (§ 312.3(b)). For simplicity, we refer to sponsors and sponsor-investigators collectively as “sponsors” in this document except in the proposed regulatory text.

The new drug provisions of the FD&C Act require that a person obtain approval of a new drug application (NDA) or abbreviated new drug application (ANDA) before introducing or delivering for introduction into interstate commerce a new drug (section 505(a) of the FD&C Act (21 U.S.C. 355(a))). Similarly, the PHS Act requires that a person obtain approval of a biologics license application (BLA) before introducing or delivering for introduction into interstate commerce a biological product (section 351(a) of the PHS Act). However, these approval requirements do not apply to a drug or biological product intended solely for investigational use by experts qualified by scientific training and experience to investigate the safety and effectiveness of drugs, provided the sponsor of the study complies with the regulations in part 312 governing the use of investigational new drugs (section 505(i) of the FD&C Act). These regulations include provisions for the submission and FDA review of INDs (see, e.g., §§ 312.20, 312.40).

There are two primary objectives of IND review. First, IND review is designed to help ensure that the safety and rights of subjects of clinical investigations are protected. Second, as applied to Phase 2 and Phase 3 studies, IND review is intended to help ensure that the quality of data obtained from a clinical study is adequate to permit evaluation of the safety and effectiveness of a drug for which marketing approval is sought (§ 312.22(a)). Phase 2 studies are controlled clinical studies conducted to evaluate the effectiveness of a drug for a particular indication in patients with the disease or condition under study or to determine the short-term side effects and risks associated with the drug (§ 312.21(b)). Phase 3 studies are expanded controlled and uncontrolled trials performed after preliminary evidence suggesting a drug's effectiveness has been obtained; they are intended to gather additional information about effectiveness and safety needed to evaluate the overall benefit-risk relationship of the drug and to provide an adequate basis for physician labeling (§ 312.21(c)). Sponsor compliance with IND requirements (such as for the content and format of INDs (§ 312.23), safety reports (§ 312.32), annual progress reports (§ 312.33), and monitoring of investigations ( e.g., §§ 312.50, 312.53, and 312.56)) and FDA review of the content of INDs, protocol amendments (§ 312.30), safety reports, annual progress reports, and other IND-related information help ensure that subjects are adequately protected and that sponsors may rely on data from investigations to support applications for approval.

Section 312.2(a) states that the IND requirements apply to all clinical investigations of products that are subject to section 505 of the FD&C Act (which includes the new drug approval requirement) or the biological product licensing provisions of the PHS Act. However, there are a few exemptions from the IND requirements set forth in § 312.2(b). For the purposes of the proposed rule, the most significant of these exemptions concerns certain investigations of drug products lawfully marketed in the United States. Under § 312.2(b)(1), a clinical investigation of a drug product that is lawfully marketed in the United States is exempt from the IND regulations if all the following apply:

• The investigation is not intended to be reported to FDA as a well-controlled study in support of a new indication for use nor to support any other significant change in the labeling for the drug;

• If the drug that is undergoing investigation is lawfully marketed as a prescription drug product, the investigation is not intended to support a significant change in the advertising for the product;

• The investigation does not involve a route of administration, dosage level, use in a patient population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with use of the drug;

• The investigation is conducted in compliance with the requirements for review by an IRB in part 56 (21 CFR part 56) and the requirements for informed consent in part 50 (21 CFR part 50); and

• The investigation is conducted in compliance with the requirements in § 312.7, which govern promotion and commercial distribution of investigational new drugs, among other things.

Section 312.2(b)(1) was created during the revision of the IND regulations in the 1980s (“IND Rewrite”) because it became clear that physicians, especially those affiliated with academic institutions, sought to conduct clinical investigations using marketed drugs, either to investigate new uses or to use the drug as a research tool to explore biological phenomena or disease processes (48 FR 26720, June 9, 1983). Although such clinical investigations are subject to section 505(i) of the FD&C Act, FDA reevaluated the utility of reviewing these INDs and concluded that our review of certain categories of INDs was not necessary to ensure the protection of study subjects. Accordingly, in the final rule adopting the IND Rewrite, we exempted from the IND requirements clinical investigations of lawfully marketed drugs that meet specific criteria designed to help ensure that exempted investigations do not expose subjects to new risks (52 FR 8798 at 8832, March 19, 1987) (codified in § 312.2(b)(1)). Under § 312.2(b)(1)(iv), investigators conducting exempt studies are still required to conform to all ethical principles applicable to the conduct of clinical investigations, including the statutory requirement for informed consent (section 505(i)(4) of the FD&C Act). Thus, a study's exemption is conditioned on a sponsor complying with the requirements for informed consent set forth in part 50 as well as the requirements for review and approval by an IRB set forth in part 56. Finally, the sponsor is prohibited from test marketing or commercially distributing the product and from promoting the product for its investigational use (see §§ 312.2(b)(1)(v) and 312.7).

To address questions about the applicability of the IND regulations to certain types of clinical investigations, in the Federal Register of October 14, 2010, we issued a notice of availability (75 FR 63189) of a draft guidance entitled “Guidance for Industry: Investigational New Drug Applications (INDs)—Determining Whether Human Research Studies Can Be Conducted Without an IND” (“2010 Draft IND Guidance”). In addition to explaining when the FD&C Act and FDA regulations require an IND to be submitted, the draft guidance described the types of clinical investigations that are exempt by regulation from the IND requirements and addressed a range of issues that commonly arise in inquiries to FDA about the application of those requirements.

On September 10, 2013, we issued a notice of availability (78 FR 55262) of the final version of that draft guidance, entitled “Guidance for Clinical Investigators, Sponsors, and Institutional Review Boards (IRBs) on Investigational New Drug Applications—Determining Whether Human Research Studies Can Be Conducted Without an IND” (“2013 IND Guidance” (Ref. 1)). Like the draft guidance (2010 Draft IND Guidance), the final guidance notes that a “drug” is not limited to articles intended to have a therapeutic purpose ( i.e., to diagnose, cure, mitigate, treat, or prevent a disease), but also includes articles (other than food) intended to affect the structure or function of the body. For example, an article administered to healthy individuals to prevent pregnancy or treat male pattern baldness is a drug. The 2013 IND Guidance further explained that the drug definition also includes articles used for research purposes in healthy subjects to blunt or provoke a physiologic response or study the mechanism of action or metabolism of a drug (Ref. 1 at 3).

The final guidance also explains the application of the IND regulations to studies of ingredients or products marketed as foods or cosmetics. The guidance explains that a clinical investigation assessing the use of a conventional food for a therapeutic purpose ( e.g., to relieve symptoms of Crohn's disease) would be a study to evaluate a drug use of the food and would therefore require an IND (Ref. 1 at 12-13; see also section 201(g)(1)(B) of the FD&C Act). However, a clinical study designed to evaluate the safety or tolerability of a food ingredient when ingested as food ( i.e., primarily for its taste, aroma, or nutritive value) would not be a study to evaluate a drug use, so an IND would not be required (Ref. 1 at 13-14; see also section 201(g)(1)(C) of the FD&C Act and Nutrilab v. Schweiker, 713 F.2d 335 (7th Cir. 1983)).

Regarding dietary supplements, the final guidance explains that a dietary supplement intended only to affect the structure or function of the body and not intended for a therapeutic purpose is not a drug (Ref. 1 at 12; see also sections 201(g)(1) and 403(r)(6) of the FD&C Act (21 U.S.C. 321(g)(1) and 343(r)(6)). Therefore, an IND is not required for a clinical investigation intended only to evaluate a dietary supplement's effect on the structure or function of the body. However, if a clinical investigation is intended to evaluate a dietary supplement's ability to diagnose, cure, mitigate, treat, or prevent a disease, an IND is required.

The final guidance explains that clinical investigations of ingredients or products marketed as cosmetics require an IND if the ingredient is being studied for use to affect the structure or function of the body or for a therapeutic purpose (Ref. 1 at 11). This is because section 201(g)(1)(B) and (C) of the FD&C Act defines as drugs both articles (other than food) intended to affect the structure or function of the body and articles intended to diagnose, cure, mitigate, treat, or prevent a disease.

Because FDA received multiple comments asking for further opportunity to comment on portions of the final guidance (sections VI.C and VI.D) addressing the applicability of the IND regulations to clinical investigations evaluating drug uses of foods (including dietary supplements) or cosmetics, on February 6, 2014, we reopened the comment period on those sections of the guidance (79 FR 7204). These comments raised questions about application of the IND requirements to certain clinical studies of conventional foods, dietary supplements, and cosmetics being investigated for uses covered by the drug definition in section 201(g)(1)(B) or (C) of the FD&C Act.

On October 30, 2015, we issued a notice of administrative stay of action staying parts of the final guidance to allow for further consideration of issues raised by comments received following the reopening of the comment period (80 FR 66907). Specifically, we stayed portions of section VI.D.2, “Conventional Food” (concerning clinical studies to evaluate non-nutritional effects on the structure or function of the body), and all of section VI.D.3, “Studies Intended to Support a Health Claim” (except as to studies intended to evaluate whether a food substance reduces the risk of a disease in individuals less than 12 months old, those with altered immune systems, and those with serious or life-threatening medical conditions). The stayed portion of section VI.D.2 states that under the applicable regulations, a clinical investigation intended only to evaluate the nutritional effects of a food (including medical foods) would not require an IND, but an investigation intended to evaluate other effects of a food on the structure or function of the body would require an IND. Section VI.D.3 (stayed except as to studies that include subjects in the three medically vulnerable categories previously described) states that under the applicable regulations, a clinical study designed to evaluate the relationship between a food substance and a disease, and intended to provide support for a health claim about reducing the risk of the disease, must be conducted under an IND, unless the substance-disease relationship being studied is already the subject of an authorized health claim under section 403(r)(1)(B) and (r)(3) of the FD&C Act (for a conventional food) or section 403(r)(1)(B) and (r)(5)(D) (for a dietary supplement). The notice announcing the administrative stay of portions of the final guidance states that we do not intend to enforce the IND requirement for studies in the stayed categories while the stay is in effect (80 FR 66907 at 66908 to 66909).

As previously stated, some clinical investigations of products marketed as foods and cosmetics are included among the types of studies that are required by the FD&C Act and FDA regulations to be conducted under an IND. Under the proposed rule, some of these clinical investigations would be exempt from the IND requirements if they meet the proposed exemption criteria discussed in section V of this document. At the completion of this rulemaking, we anticipate taking action to resolve related issues in the final guidance, including the stayed portions of the guidance.

In recent years, FDA has received inquiries about many clinical investigations evaluating a drug use of an article marketed as a food or cosmetic. Examples of such articles include conventional foods such as potatoes and dried fruit; dietary supplements such as soy isoflavones, vitamins, and green tea extract; and cosmetics such as lavender oil and hydroquinone (which is a cosmetic when used as a fragrance ingredient or hair colorant, but a drug when used to bleach the skin by decreasing the formation of melanin). Products in these categories have been studied to evaluate their use in treating, mitigating, curing, or preventing diseases such as asthma, diabetes, arthritis, gastrointestinal disorders, depression, cardiovascular disease, and cancer.

In some cases, the sponsor of a clinical investigation of a food or cosmetic—often, the manufacturer of the product—seeks to study the product for use in treating, mitigating, curing, or preventing a disease because the sponsor hopes to develop and obtain marketing approval of the product as a drug, has a financial relationship with an entity that hopes to obtain such marketing approval, or wishes to market the product for disease treatment or prevention without seeking approval for it as a new drug. For example, the manufacturer of a dietary supplement marketed with a claim that the product “supports digestive health” might wish to sponsor a clinical investigation designed to evaluate the product's ability to treat a digestive disorder. However, in other cases, a person or institution may have a purely scientific or medical interest in studying a conventional food, dietary supplement, or cosmetic for a drug use. For example, physicians and other researchers in hospitals and universities often explore potentially novel mechanisms of action of a food or cosmetic to understand whether such a product could have an effect on an aspect of a disease or medical condition. In many cases, such researchers have no intent to seek approval of the product as a drug or market it unlawfully for disease treatment or prevention without such approval, no financial interest in the product, and no research funding or other financial support from the product's manufacturer or other potential sponsors of an application for drug marketing approval.

Review divisions in the Center for Biologics Evaluation and Research (CBER) and the Center for Drug Evaluation and Research (CDER) frequently receive inquiries from study sponsors and investigators about whether the IND requirements apply to a planned study to evaluate a drug use of a food or cosmetic. In some cases, the sponsor asserts that the study is exempt from the IND requirements under § 312.2(b)(1). However, most of these studies are not eligible for the exemption in § 312.2(b)(1) because the study is not a clinical investigation of a drug product that is lawfully marketed in the United States. Nevertheless, in some cases, the Agency has concluded that it is not necessary or desirable to apply the IND requirements to a proposed drug study of a food or cosmetic because the study poses minimal risks to subjects and is not intended to be used in support of a drug marketing application, drug development plan, or labeling change that would cause the lawfully marketed food or cosmetic to become an unlawfully marketed drug. In such cases, we have exercised enforcement discretion regarding the submission of an IND for the study and the IND reporting requirements ( e.g., study progress and safety reports). Sponsors of such studies must still comply with FDA regulations on the protection of human subjects and IRB review (parts 50 and 56, respectively), along with the IND regulation regarding promotion and commercial distribution of investigational drugs (§ 312.7), and they are expected to notify us of any changes to the study protocol that could affect subjects' safety.

We believe that establishing IND exemptions for certain clinical investigations of drug uses of foods and cosmetics based on the principles behind the adoption of § 312.2(b)(1) would reduce regulatory and resource burdens on sponsors, investigators, and the Agency in circumstances when application of the IND requirements is not needed to ensure adequate protection of human subjects. Many of the proposed clinical investigations of foods and cosmetics that we have considered in recent years would have been eligible for either the proposed self-determined exemption or FDA-determined exemption. Codifying IND exemptions for investigations of drug uses of foods and cosmetics that meet certain criteria similar to the eligibility criteria for exempting studies of lawfully marketed drug products under § 312.2(b)(1) could result in reduced research costs for sponsors, fewer inquiries submitted to CBER and CDER review divisions, and greater numbers of clinical trials (because FDA consultation would not be needed for the self-determined exemption), without compromising the health, safety, or welfare of subjects or undermining the quality of data needed to support drug marketing approval.

This proposed rule would exempt from the IND regulations in part 312 certain clinical investigations evaluating drug uses of products lawfully marketed in the United States as foods (including dietary supplements) or cosmetics. These exemptions would track the exemption already provided in § 312.2(b)(1) for certain clinical investigations of lawfully marketed drugs.

Under section 701(a) of the FD&C Act (21 U.S.C. 371(a)), the Agency is empowered to issue regulations for the efficient enforcement of that statute. FDA's primary objective in reviewing an IND is to assure the rights, safety, and welfare of subjects (see 48 FR 26720 at 26725 and § 312.60), with a secondary objective of helping to ensure that the quality of data obtained from a Phase 2 or Phase 3 clinical study is adequate to permit evaluation of the drug's safety and effectiveness (§ 312.22(a)). Like any other clinical investigation where the intended use to be studied brings the investigational product within the drug definition, clinical investigations evaluating drug uses of foods and cosmetics are subject to section 505(i) of the FD&C Act. However, after reevaluating the utility of requiring such clinical investigations to be conducted under an IND, FDA finds that these investigations are remarkably diverse with respect to the composition and risk profile of the products studied, the health of the study subjects, and the nature of the study procedures ( e.g., invasive vs. non-invasive testing). Accordingly, we have drafted subject protection and study purpose criteria in an attempt to define categories of low-risk clinical investigations that can be exempted from the IND requirements without compromising human subject protection or the quality of data used to support drug marketing applications. FDA tentatively concludes that, for clinical investigations that meet the proposed criteria, review of an IND is not necessary for subject protection and would be an inefficient use of sponsor and Agency resources. Therefore, under our authority to issue regulations for the efficient enforcement of the FD&C Act, we are proposing to exempt clinical investigations that meet the proposed criteria from the IND requirements.

We are also issuing this proposed rule under FDA's authority to regulate unapproved new drug products under the FD&C Act (see sections 201, 301, 501, 502, 503, 505, 561, and 701) (21 U.S.C. 321, 331, 351, 352, 353, 355, 360bb, and 371) and section 351 of the PHS Act.

We are proposing to amend the IND regulations to establish two exemptions for clinical investigations evaluating a drug use of a food or cosmetic. Under the first exemption provision, a clinical investigation to evaluate a drug use of a food or cosmetic would be exempt from the IND requirements if certain criteria were met regarding: (1) the intent of the investigation; (2) compliance with requirements and restrictions regarding institutional review, informed consent, and promotion and commercial distribution of investigational drugs; (3) the route of administration of the product as used in the investigation; and (4) protection of subjects' health, safety, and welfare. Because a sponsor would self-determine whether the investigation met the criteria to be conducted without an IND, we refer to this exemption as the “self-determined exemption.”

Under the second proposed exemption, a sponsor of an investigation that did not meet one or more of the self-determined exemption's health, safety, and welfare criteria, but did meet all the other criteria for the self-determined exemption, could submit to us a written request for exemption if the sponsor concluded that the study nevertheless did not present a potential for significant risk to the health, safety, or welfare of subjects. Under this “FDA-determined exemption,” we would grant an exemption if we found that the investigation did not present a potential for significant risk. In addition to authorizing the Agency to grant an FDA-determined exemption upon the request of a sponsor, the proposed rule would allow FDA to exempt a study on our own initiative if we determined, upon review of an IND that had been submitted for the study, that the study met the decision criteria for an FDA-determined exemption. The proposed rule would also permit us to revoke an exemption we had granted if we subsequently became aware of information suggesting that the study presented a potential for significant risk to the health, safety, or welfare of subjects, or that the study did not meet any of the other requirements for the exemption.

The proposed self-determined and FDA-determined exemptions (including the FDA-initiated exemption) would be set forth in proposed § 312.2(b)(4) and (5), respectively, with existing exemptions and related provisions in current § 312.2(b)(4) through (6) to be renumbered accordingly. In addition, we propose to amend current § 312.2(b)(4), which states that we will not accept an IND for investigations exempt under § 312.2(b)(1), to specify that we also would not accept an IND for investigations exempt under proposed § 312.2(b)(4) and (5).

The following paragraphs describe the proposed self-determined and FDA-determined exemption provisions and other proposed changes to § 312.2(b).

Under proposed § 312.2(b)(4), a clinical investigation to evaluate a drug use of a product lawfully marketed in the United States as a food intended for human consumption (including as a conventional food or dietary supplement) or as a cosmetic would be exempt from the IND requirements if the following criteria are met:

• The investigation is not intended to support a drug development plan for the product, including a future IND or application for marketing approval (an application under section 505 of the FD&C Act or section 351 of the PHS Act), or to support a change in the labeling of the lawfully marketed product that would cause it to become an unlawfully marketed drug;

• The investigation is conducted in compliance with the requirements for institutional review in part 56 and the requirements for informed consent in part 50;

• The investigation is conducted in compliance with the requirements of § 312.7;

• The route of administration of the product in the investigation is the same as that of the lawfully marketed product; and

• The investigation meets the following criteria relating to the health, safety, and welfare of study subjects:

○ The investigation does not include subjects who are less than 12 months of age or subjects who are pregnant or lactating;

○ The investigation does not include subjects with a compromised immune system or a serious or life-threatening disease or condition;

○ The investigation does not restrict subjects from continuing with treatments or therapies prescribed or recommended by a healthcare provider;

○ The investigation does not involve any procedures that would increase the risks (or decrease the acceptability of the risks) to subjects beyond what they would ordinarily encounter during routine physical or psychological examinations or standard of care procedures to treat their medical condition;

○ The product is being used in the investigation consistent with its labeled conditions of use or, in the absence of labeled conditions of use, consistent with its ordinary conditions of use ( e.g., same dose range and total daily intake, same formulation, same duration of use); and

○ During the investigation, subjects are not taking and will not be treated with any other product(s) that would significantly increase the risks (or decrease the acceptability of the risks) they will encounter in the investigation ( e.g., because of drug interactions).

The following paragraphs discuss the scope and criteria of the proposed self-determined exemption in more detail.

The self-determined exemption would apply to studies of products that are lawfully marketed in the United States as foods intended for human consumption (including as a dietary supplement) or as cosmetics (proposed § 312.2(b)(4)). For purposes of the proposed self-determined exemption, “lawfully marketed” means the product is marketed in the United States as a food or cosmetic consistent with the FD&C Act and any applicable FDA regulations.

The proposed self-determined exemption would apply to clinical investigations evaluating a food or cosmetic for use as a drug (proposed § 312.2(b)(4)). The intended use of a product determines whether the product fits within the definition of a “drug” under the FD&C Act (see section III.C of this document).

The proposed self-determined exemption would not apply to a clinical investigation intended to support a drug development plan for a food or cosmetic, including a future IND or marketing approval application, or to support a change in the labeling of the food or cosmetic that would cause the product to become an unlawfully marketed drug (proposed § 312.2(b)(4)(i)). For example, this means that if the investigation were intended to support a future IND for a clinical trial investigating a drug use of the product, or a future NDA or BLA for the product, the investigation would not be eligible for the exemption.

As previously noted, the IND exemption for clinical investigations of lawfully marketed drug products in existing § 312.2(b)(1) does not apply to a study intended to be reported to FDA as a well-controlled study in support of a new indication for use or intended to be used to support any other significant change in a drug's labeling. In proposing this criterion in the 1983 IND Rewrite, FDA stated that the criterion was “aimed at helping ensure that investigations intended to be submitted to FDA for labeling or advertising changes are adequate in design to serve that purpose” (48 FR 26720 at 26733). We further stated that this is the “same reason the agency evaluates the design of Phase 2 and Phase 3 studies,” noting that this review “adds considerable efficacy to the drug development process” (48 FR 26720 at 26733). Similarly, if a clinical investigation of a food or cosmetic is intended to support a drug development plan for that product, the investigation must be conducted under an IND to help ensure that the quality of the scientific evaluation of the product is adequate to permit an evaluation of the product's effectiveness and safety when used as a drug, including whether data from the investigation can be used to support approval of the product as a drug (see § 312.22(a)).

The self-determined exemption also would not apply if the sponsor of the clinical investigation intended to use the study to support marketing of the food or cosmetic for a use that caused the product to be an unlawfully marketed drug. For example, if a sponsor sought to study a dietary supplement to support marketing it for a disease treatment use (rather than for a structure or function use), the study would not be eligible for the self-determined exemption. Similarly, the exemption would not apply to a study intended to support the addition of a drug claim to the label of a conventional food or a cosmetic.

To be eligible for the proposed self-determined exemption, the study must also be conducted in compliance with the IRB requirements in part 56 and the informed consent requirements in part 50 (proposed § 312.2(b)(4)(ii)). This criterion would mirror the provision in § 312.2(b)(1)(iv) that requires compliance with the IRB and informed consent requirements as a condition of eligibility for the IND exemption for certain studies of drug products lawfully marketed in the United States.

Another eligibility criterion for the proposed self-determined exemption matching a criterion for the exemption for lawfully marketed drugs is the proposed requirement that the investigation be conducted in compliance with § 312.7 (proposed § 312.2(b)(4)(iii)). Among other things, § 312.7 prohibits commercially distributing or test marketing an investigational new drug, as well as representing in a promotional context that an investigational new drug is safe or effective for the purposes for which it is under investigation.

Another eligibility criterion for the proposed self-determined exemption that is based on a criterion for the exemption for lawfully marketed drugs is the requirement that the route of administration of the product in the investigation be the same as that of the lawfully marketed product (proposed § 312.2(b)(4)(iv)). For example, a clinical investigation of a product lawfully marketed as a dietary supplement for oral ingestion would not qualify for the exemption if the product would be administered topically or transmucosally ( i.e., sublingually, buccally, or intranasally) when used as a drug in the investigation. Similarly, a clinical investigation of a product lawfully marketed as a cosmetic applied to the skin would not qualify for the exemption if the product would be administered subcutaneously, intravenously, or intramuscularly when used as a drug in the investigation. This requirement would ensure that the self-determined and FDA-determined exemptions are limited to investigations evaluating drug uses of foods and cosmetics when the investigational products are administered in the same way as the marketed products, thereby avoiding potential safety risks posed by atypical routes of administration ( e.g., products marketed as dietary supplements being studied as injectable drugs).

The proposed self-determined exemption includes several eligibility criteria designed to protect the health, safety, and welfare of study subjects (proposed § 312.2(b)(4)(v)). These criteria, discussed in the following paragraphs, are intended to serve the same purpose as the requirement under the lawfully marketed drug exemption that the investigation not involve a dosage level, use in a patient population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with use of the drug product (§ 312.2(b)(1)(iii)). Because of age-dependent development, immune system impairment, or other physiological differences, certain populations (described in the following paragraphs) may have the potential for a higher degree of risk or different risks compared to the general population. The proposed health, safety, and welfare criteria are especially important because, under the self-determined exemption, FDA would not have an opportunity to evaluate potential safety concerns before a proposed study begins.

a. No subjects less than 12 months of age or who are pregnant or lactating.

To be eligible for the self-determined exemption, a proposed study could not involve subjects less than 12 months of age or subjects who are pregnant or lactating (proposed § 312.2(b)(4)(v)(A)). We are proposing this criterion because foods and cosmetics that would not pose a safety concern in the general population may not be safe for study in these vulnerable populations. For example, a study to evaluate use of honey or a honey-containing product to prevent diarrhea in subjects less than 12 months of age would pose a risk of botulism if Clostridium botulinum spores were present in the honey. These medically vulnerable populations pose special safety concerns typically requiring that an investigation be conducted under the protections afforded by an IND (although it is possible that a sponsor could show, in a request for an FDA-determined exemption, that a particular investigation involving such a population does not present a potential for significant risk to subjects' health, safety, or welfare).

b. No subjects with a compromised immune system or a serious or life-threatening disease or condition.

The self-determined exemption would not apply if a proposed study included subjects with a compromised immune system or a serious or life-threatening disease or condition (proposed § 312.2(b)(4)(v)(B)). A person with an immune system impaired or weakened by disease ( e.g., diabetes, cancer), malnutrition, or drugs ( e.g., chemotherapy) may be unable to fight off an infection. For example, a study to evaluate use of a probiotic dietary supplement in adult subjects to prevent nausea associated with chemotherapy might pose a risk of mucormycosis due to fungal contamination of the probiotic.

A “serious” disease or condition is one that is associated with persistent or recurrent morbidity (a diseased condition or state) that has substantial impact on day-to-day functioning; the morbidity need not be irreversible to be “serious” if it is persistent or recurrent (see § 312.300(b)). FDA considers a disease or condition to be “life-threatening” if: (1) the likelihood of death is high unless the course of the disease is interrupted or (2) the disease or condition has a potentially fatal outcome (see § 312.81(a)). For example, a study to evaluate high doses of a vitamin in adults with insulin-dependent diabetes might pose risks of worsening kidney or heart function. Similarly, a study of the herbal product valerian, which potentiates the effects of alcohol, could be dangerous in adults with alcohol use disorder. Because the potential risks to subjects would generally warrant that the investigation be conducted under the IND requirements and their protections for subjects who have a serious or life-threatening disease, a study of a food or cosmetic to treat even a non-serious disease would not be eligible for the self-determined exemption if the study included such subjects.

c. Continuing treatments or therapies prescribed or recommended by a healthcare provider.

To be eligible for the self-determined exemption, the investigation could not restrict the subjects of the study from continuing with any treatment or therapy prescribed or recommended for them by a healthcare provider (proposed § 312.2(b)(4)(v)(C)). Healthcare providers could include, for example, physicians, physician assistants, dentists, physical therapists, and nurses. Being unable to continue a course of treatment or therapy that one's physician, therapist, or other healthcare provider has prescribed or recommended could significantly increase risks for a subject; therefore, an investigation in which this might occur usually warrants the protections of an IND.

d. No study procedures that would increase the risks to subjects beyond what are ordinarily encountered.

Another proposed eligibility criterion for the self-determined exemption is that the investigation not involve any procedures that would increase the risks (or decrease the acceptability of the risks) to subjects beyond what they would ordinarily encounter during a routine physical or psychological examination or standard of care procedures to treat their medical condition (proposed § 312.2(b)(4)(v)(D)). For example, using an invasive technique such as a biopsy to evaluate a study endpoint in subjects who ordinarily would be monitored with routine blood tests might increase risks to the subjects. Studies with the potential to expose subjects to greater risk than they would normally encounter in the course of their clinical care should not be conducted without an IND unless the sponsor can show (in a request for an FDA-determined exemption) that no such increase in risk will occur.

e. Product used consistent with labeled or ordinary conditions of use.

Another proposed criterion for eligibility for the self-determined exemption is that the product would have to be used in the investigation consistent with its labeled conditions of use when lawfully marketed as a food or cosmetic (§ 312.2(b)(4)(v)(E)). In the absence of labeled conditions of use, the product would have to be used consistent with its ordinary conditions of use as a lawfully marketed food or cosmetic ( e.g., same dose range and total daily intake, same formulation, same duration of use). This eligibility criterion would help ensure that a clinical investigation not conducted under an IND does not pose significant risks to subjects due to atypical use of the product.

For a product that does not have labeled conditions of use, the “ordinary” conditions of use would be those found in a regulation prescribing conditions of safe use ( e.g., a food additive or color additive regulation), if such a regulation exists. For products that do not have a regulation prescribing conditions of safe use (such as dietary supplements, cosmetics, and most conventional foods), the “ordinary” conditions of use could be those recommended in, for example, the following: guidelines issued by the Department of Health and Human Services, one of its components (such as the National Institutes of Health), or another Federal Agency; recommendations from a division of the National Academy of Sciences or the National Academy of Medicine; publicly available websites of medical societies and professional associations; and guidelines recognized by a professional medical society or nutrition association. For example, although vitamin D products may lack directions for use in children, the American Academy of Pediatrics has issued recommendations on vitamin D supplementation in children.

f. No other product taken by or used to treat subjects during the investigation would significantly increase the risks (or decrease acceptability of the risks) encountered in the investigation.

The last proposed eligibility criterion for the self-determined exemption would limit the exemption to clinical investigations in which the subjects are not taking and will not be treated with any other product that would significantly increase the risks (or decrease the acceptability of the risks) they will encounter in the investigation (proposed § 312.2(b)(4)(v)(F)). For example, drinking grapefruit juice can increase the bioavailability of blood pressure-lowering drugs in the body, and taking the herb ginseng can enhance the bleeding effects of heparin, aspirin, and nonsteroidal anti-inflammatory drugs such as ibuprofen (Ref. 2). Because administering a food or cosmetic as an investigational drug to study subjects who are taking or are being treated with another FDA-regulated product could significantly increase risks to these subjects, such an investigation should not be conducted without an IND unless the sponsor can show (in a request for an FDA-determined exemption) that no such increase in risk will occur.

Under the proposed self-determined exemption, a sponsor would not be required to submit a request to FDA for exemption from the IND requirements. (Moreover, as discussed in section V.C of this document, we would not accept an IND for an investigation that is exempt from the IND requirements under the self-determined exemption.) If a sponsor determines that its proposed study meets the eligibility criteria for the exemption, the sponsor may proceed with the study without having to submit an IND.

If the sponsor later revises the protocol or otherwise changes the study so that it no longer meets the eligibility criteria for the self-determined exemption, the sponsor would have to submit an IND for the study or a request for an FDA-determined exemption under proposed § 312.2(b)(5). In addition, if FDA becomes aware (such as during an IRB inspection or through communications from the sponsor, an investigator, a subject, or the IRB) that a study conducted without an IND in reliance on the self-determined exemption is ineligible for the exemption, we may issue an untitled letter or warning letter to the study sponsor and, if necessary, take appropriate enforcement action, such as seeking an injunction.

Some proposed investigations to evaluate a drug use of a food or cosmetic may not meet all the safety-related eligibility criteria for the self-determined exemption, but FDA still might conclude, under appropriate circumstances, that the study does not pose a significant risk to the health, safety, or welfare of subjects. For example, even in an investigation that included subjects with a serious disease, if the product to be studied and the study procedures were low risk, we might conclude, depending on other subject characteristics and the intended use of the investigational product, that the study did not present a potential for significant risk that would necessitate conducting the study under an IND. For example, we might conclude that an investigation evaluating the use of beetroot juice to mitigate, treat, or prevent signs and symptoms of chronic kidney disease did not present a potential for significant risk to subjects because, among other factors, subjects would continue to receive standard of care treatment for their disease. Therefore, we propose to establish an “FDA-determined exemption” under which a sponsor of a study that does not meet one or more of the subject health, safety, and welfare criteria for the self-determined exemption could request an IND exemption from FDA.

Under the FDA-determined exemption, a sponsor could request that we exempt from the IND requirements a clinical investigation to evaluate a drug use of a product lawfully marketed in the United States as a food or cosmetic when the investigation satisfies the requirements of the self-determined exemption except for one or more of the criteria related to the health, safety, or welfare of subjects (in proposed § 312.2(b)(4)(v)), but the sponsor has concluded that the study nevertheless does not present a potential for significant risk to subjects' health, safety, or welfare (proposed § 312.2(b)(5)(i)). The request would have to be in writing and would be required to contain the following information.

a. Study protocol or protocol summary.

A request for an FDA-determined IND exemption for a drug study of a food or cosmetic would be required to include a copy of the study protocol or a detailed protocol summary that includes, at a minimum, the following: the study design and duration; proposed endpoints; the study population, including inclusion and exclusion criteria for subjects; a description of the specific product to be studied as an investigational drug, including ingredients, composition, and any labeling; the dosage form, dosing regimen, and route of administration of the investigational drug; the study procedures (including safety monitoring procedures); and planned modifications to the protocol in the event of adverse events (proposed § 312.2(b)(5)(i)(A)). This information about the proposed study is necessary to give FDA an adequate context in which to assess the potential risks to subjects and decide whether to exempt the study from the IND requirements.

b. Names of manufacturer and source of product to be studied.

A request for exemption would have to include the names of the manufacturer and the entity that is the source of the specific product to be studied in the investigation (proposed § 312.2(b)(5)(i)(B)). In cases where the product to be studied will be provided directly by the manufacturer, the manufacturer and source of the investigational product will be the same. However, in some cases, the investigational product might be obtained from someone other than the manufacturer, such as a distributor.

For foods not in package form and not labeled with the name of the manufacturer, the exemption request would only have to provide the source of the product.

c. Name and form of lawfully marketed food or cosmetic product; labeling.

A request for exemption would have to include the name (if different from the name of the product to be studied in the investigation) and form ( e.g., conventional food, liquid, tablet, lotion) of the lawfully marketed food or cosmetic product, and a copy of the product labeling (proposed § 312.2(b)(5)(i)(C)). If the product's labeling does not identify its ingredients, the sponsor would also be required to provide a description of the composition of the product.

d. Source(s) of funding for the investigation.

A request for exemption would have to include the source(s) of funding for the investigation (proposed § 312.2(b)(5)(i)(D)). This information is needed to help ensure that an investigation is not intended to support a drug development plan for the product being studied, which is a requirement for eligibility for the FDA-determined exemption. For example, if an investigation is funded by the manufacturer of the investigational product or by a trade association representing the interests of firms that manufacture that type of product, we would consider the funding source as a factor in determining whether an investigation is intended to support a drug development plan for the product.

e. Information about the sponsor.

A request for exemption would have to include the name, address, telephone number, email address, and contact name for the sponsor (proposed § 312.2(b)(5)(i)(E)). This information will, among other things, enable us to contact the sponsor if we have any questions and to provide our response to the request.

f. Description of why the investigation does not present a potential for significant risk to the health, safety, or welfare of subjects.

A request for exemption would have to include a brief description of why the investigation does not present a potential for significant risk to the health, safety, or welfare of subjects, including, where relevant, the following information regarding the subject health, safety, and welfare eligibility criteria set out in the self-determined exemption (proposed § 312.2(b)(5)(i)(F)):

• If the proposed investigation includes subjects who are less than 12 months of age or subjects who are pregnant or lactating, the exemption request would have to include information to demonstrate that the use of the investigational product does not present a potential for significant risk to the health, safety, or welfare of these subjects (proposed § 312.2(b)(5)(i)(F)( 1 )).

• If the investigation includes subjects with a compromised immune system or a serious or life-threatening disease or condition, the exemption request would have to include information to demonstrate that the use of the investigational product does not present a potential for significant risk to the health, safety, or welfare of these subjects (proposed § 312.2(b)(5)(i)(F)( 2 ));

• If participation in the investigation will preclude subjects from continuing with a treatment or therapy prescribed or recommended for them by a healthcare provider ( e.g., if some subjects randomized to the investigational product or placebo will be instructed to discontinue their current treatment), the exemption request would have to include an explanation of why this restriction would not present a potential for significant risk to the health, safety, or welfare of these subjects (proposed § 312.2(b)(5)(i)(F)( 3 ));

• If the subjects in the investigation will undergo any procedures during the investigation that would expose them to more risk than they would ordinarily encounter during routine physical or psychological examinations or standard of care procedures to treat their medical condition, the exemption request would have to include information to demonstrate that the procedures do not present a potential for significant risk to the health, safety, or welfare of these subjects (proposed § 312.2(b)(5)(i)(F)( 4 ));

• If the proposed conditions of use of the product in the investigation differ from the product's labeled or ordinary conditions of use, the exemption request would have to include an explanation of why the proposed conditions of use do not present a potential for significant risk to the health, safety, or welfare of the subjects (proposed § 312.2(b)(5)(i)(F)( 5 )); and

• If the investigational product is being used concurrently with other products that a subject is taking or being treated with, either as part of the study or as prescribed or recommended by a healthcare provider outside the study, the exemption request would have to include information to demonstrate that the investigational product has a history of safe use with those products or is otherwise not expected to have clinically significant interactions with the other products (proposed § 312.2(b)(5)(i)(F)( 6 )).

g. Other information as requested by FDA.

A request for exemption would have to include any other information requested by FDA for use in reviewing the exemption request (proposed § 312.2(b)(5)(i)(G)). This means that the sponsor would have to provide additional information if, upon reviewing the request, we found that such information was necessary to determine whether the investigation met the exemption criteria. For example, if a sponsor provided insufficient information to explain why use of the investigational product in a manner that differs from its labeled conditions of use did not present a potential for significant risk to subjects, we would ask for additional information to address concerns about the different conditions of use.

A sponsor seeking an FDA-determined exemption would have to submit a written request to CBER or CDER at the appropriate address set forth in § 312.140(a), which specifies where to send a new IND for a drug or biological product (proposed § 312.2(b)(5)(ii)). Sponsors should consult the 2013 IND Guidance (or successor guidance) to find the appropriate contact for inquiries about when the IND requirements apply (see Ref. 1). The FDA components listed in the guidance may also be consulted for help in determining the appropriate Center to which an exemption request should be submitted.

Upon receiving a complete exemption request, FDA would evaluate any risks to subjects that may result from participation in the clinical investigation (proposed § 312.2(b)(5)(iii)). We would grant an exemption from the IND regulations if we found that the investigation satisfied the requirements of § 312.2(b)(4)(i) through (iv) and did not present a potential for significant risk to the health, safety, or welfare of the subjects. We would notify the sponsor in writing whether the request for an FDA-determined exemption was granted. An exemption granted under this provision would not become effective until the sponsor received written notification that we had granted the exemption.

In addition to permitting FDA to grant an exemption following the request of a sponsor, the proposed rule would allow FDA to exempt a study from the IND requirements if we determine, after reviewing an IND for a study, that the study meets the decision criteria for an FDA-determined exemption ( i.e., the study meets the requirements in proposed § 312.2(b)(4)(i) through (iv) and the study does not present a potential for significant risk to the health, safety, or welfare of subjects). We believe there might be instances in which, although a sponsor had submitted an IND for a study and had not requested an exemption, we might conclude, upon reviewing the IND, that the study meets the decision criteria for an FDA-determined exemption. (We also might conclude that a study for which an IND has been submitted meets all the criteria for a self-determined exemption. If so, we would simply refuse to accept the IND under § 312.2(b)(4) (redesignated in the proposed rule as § 312.2(b)(6)), as we do when we receive an IND for a study of a lawfully marketed drug product that meets the exemption criteria in § 312.2(b)(1).) Exempting on our own initiative a study that meets the criteria for an FDA-determined exemption would reduce the regulatory burden on both the sponsor and FDA without causing harm to the health, safety, or welfare of study subjects. Therefore, proposed § 312.2(b)(5)(iv) provides that FDA may grant an exemption from the IND requirements on our own initiative after reviewing an IND and determining that the clinical investigation for which the IND was submitted satisfies the requirements of § 312.2(b)(4)(i) through (iv) and does not present a potential for significant risk to the health, safety, or welfare of subjects. Proposed § 312.2(b)(5)(iv) further states that if FDA decides to grant an exemption under § 312.2(b)(5)(iv), we will notify the sponsor or sponsor-investigator of the exemption in writing, and that the exemption will become effective when the sponsor or sponsor-investigator receives written notification that we have granted the exemption.

Under proposed § 312.2(b)(5)(v), we could revoke a previously granted exemption (whether requested by a sponsor under proposed § 312.2(b)(5)(i) or initiated by FDA under proposed § 312.2(b)(5)(iv)) if we become aware of information suggesting that the clinical investigation presents a potential for significant risk to the health, safety, or welfare of study subjects, or that the investigation does not meet any other requirement for the FDA-determined exemption (such as the requirement that the route of administration of the product in the investigation be the same as that of the lawfully marketed product). For example, we might revoke an exemption if we learn that subjects are experiencing clinically significant adverse events associated with the investigational product or if we learn of an interaction between the investigational product and another product prescribed for or dispensed to study subjects. If we learn of something that creates a potential for significant risk to subjects, we may conclude that the study must be conducted in accordance with the IND requirements to provide adequate protection to subjects. If we decided to revoke an exemption, we would notify the sponsor of the reason for revoking the exemption and, if appropriate, direct the sponsor to suspend the investigation and/or cease recruiting new subjects to the investigation.

In accordance with the proposed addition of the self-determined exemption in § 312.2(b)(4) and the FDA-determined exemptions in § 312.2(b)(5), we propose to renumber the existing provisions in § 312.2(b)(4) through (b)(6) as § 312.2(b)(6) through (b)(8).

We also propose to make a conforming amendment to existing § 312.2(b)(4) (to be renumbered as § 312.2(b)(6)), which states that FDA will not accept an application (IND) for an investigation that is exempt from the IND requirements under § 312.2(b)(1). We propose to include investigations exempted under the self-determined and FDA-determined exemption provisions among those for which we will not accept an IND.

We propose that any final rule resulting from this rulemaking become effective 30 days after the date of its publication in the Federal Register .

We have examined the impacts of the proposed 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 believe that this proposed 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 this proposed rule would create net cost savings for the affected industry by reducing the number of INDs that must be submitted to FDA, we propose to certify that the proposed rule will not have a significant economic impact on a substantial number of small entities.

The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires us to prepare a written statement, which includes an assessment of anticipated costs and benefits, before proposing “any rule that includes any Federal mandate that may result in the expenditure by State, local, and tribal governments, in the aggregate, or by the private sector, of $100,000,000 or more (adjusted annually for inflation) in any one year.” The current threshold after adjustment for inflation is $165 million, using the most current (2021) Implicit Price Deflator for the Gross Domestic Product. This proposed rule would not result in an expenditure in any year that meets or exceeds this amount.

Quantifiable benefits of this proposed rule are cost savings that come from reducing the burden of submitting INDs to FDA for clinical investigations evaluating drug uses of foods for human consumption (including dietary supplements) and cosmetics. The cost savings go to sponsors and sponsor-investigators (collectively, “sponsors”), typically physicians and other researchers at hospitals and academic institutions, who would no longer need to submit as many INDs because the proposed rule provides exemptions for qualifying drug studies of products lawfully marketed as a food or cosmetic. The proposed rule would also provide cost savings to FDA, which would not need to evaluate and monitor as many INDs. We expect the average present value of the benefits to be $28 million at a 7 percent discount rate and $34 million at a 3 percent discount rate over a 10-year time horizon.

If this proposed rule is finalized, sponsors would incur a one-time cost because they, or lawyers or consultants acting on their behalf, would have to spend time reading the rule to understand what studies are eligible for exemption and how to request an FDA-determined exemption. We estimate that 557 sponsors would read the rule the first year and 279 additional sponsors would read the rule in subsequent years. We estimate the cost of reading the rule to be $153 per sponsor. We expect the average present value of the reading cost to be $418,000 at a 3 percent discount rate and $364,000 at a 7 percent discount rate over a 10-year time horizon. In addition, there would be costs to FDA associated with a new type of IND-related submission, a request for an FDA-determined exemption. We have analyzed this cost as a partial offset to the cost savings of the rule. The total net benefit of the rule is estimated to be $33 million at a 3 percent discount rate and $27 million at a 7 percent discount rate.

Table 1 provides annualized values for the estimated benefits and costs of the proposed rule:

FDA is proposing to replace the current annual reporting requirement under § 312.33 (21 CFR 312.33), Annual reports, with a new requirement under § 312.33, Development safety update reports. Current § 312.33 requires sponsors that have an IND in effect to submit an annual report that must contain individual study information, which generally includes brief summaries of the status of each ongoing study and of each study completed during the previous year. The proposed annual FDA DSUR regulation would require these sponsors to provide an annual report that is more comprehensive and informative than the IND annual report currently required under FDA regulations—such as the requirement for an integrated overall safety analysis and a summary of cumulative pertinent safety information. In light of the increasing complexity of clinical studies, requiring a DSUR that offers a more comprehensive and informative assessment of risk than the current annual report would provide an important tool for FDA and sponsors to identify and manage potential risks and therefore reduce exposure of human subjects to unnecessary risks. Furthermore, because FDA intends that the DSUR be consistent with the format and content of submission of the DSUR supported by ICH, the annual reporting process for sponsors would be more efficient by supporting one format for submission to FDA and multiple regulatory authorities in the European Union (EU) and other countries and regions. This action is consistent with FDA's overarching goal of fostering international harmonization of regulatory requirements to the extent appropriate and feasible. If ICH updates its DSUR guidelines, FDA may evaluate the proposed regulation to determine if any corresponding updates are necessary.

The following is a brief summary of the proposed revisions to the current requirements for IND annual reporting that are made by the proposed annual FDA DSUR regulation:

• Expands the scope to require comprehensive information and allow for a thorough assessment by FDA of clinical investigations conducted anywhere in the world on behalf of the sponsor evaluating the drug (proposed § 312.33(a)(1)).

• Provides that a sponsor-investigator for a clinical investigation that is not intended to support a marketing application is only required to submit information obtained from that clinical investigation ( e.g., information that is part of that sponsor-investigator's protocol for the IND) (proposed § 312.33(a)(2)).

• Requires an executive summary (proposed § 312.33(c)).

• Requires a description of all actions relevant to the safety of the drug that were taken during the reporting period by any regulatory authority or by the sponsor, if known (proposed § 312.33(g)).

• Provides that the investigator brochure would serve as the reference safety information during the reporting period. If a sponsor is not required to submit an investigator brochure, the FDA-approved prescribing information would serve as the reference safety information. If the sponsor uses another source as the reference safety information, the regulation would require the sponsor to identify the reference safety information used (proposed § 312.33(h)(1)).

• Requires sponsors to provide a list of all safety-related changes to the reference safety information, if applicable, for the investigational drug during the reporting period. (proposed § 312.33(h)(2)).

• Requires that the report provide the clinical trial phase, the date the first participant provided informed consent, a brief description of the clinical investigation, and a brief description of the dose and regimen of the investigational drug and any comparators as part of an inventory of clinical investigations conducted during the reporting period. Also expands the requirement for information on study subjects to include the cumulative number of subjects enrolled in all treatment arms of each clinical investigation (or an estimate), the countries or regions in which each investigation was conducted, and the total number of subjects planned to be enrolled in each clinical investigation (proposed § 312.33(i)).

• Adds the requirement to include the cumulative number of subjects exposed to the investigational drug and comparators during clinical investigations that are conducted on behalf of the sponsor (proposed § 312.33(j)).

• Adds the requirement that sponsors provide line listings of all serious suspected adverse reactions (as defined in § 312.32(a)) that occurred during the reporting period , including treatment assignment. Adds the requirement that the line listings of all serious suspected adverse reactions identify those that are unexpected (serious and unexpected suspected adverse reaction) as defined in § 312.32(a).

• Adds the requirement to include a cumulative summary tabulation of serious adverse events (as defined in § 312.32(a)) obtained from all clinical investigations conducted on behalf of the sponsor that occurred since the date the IND went into effect (proposed § 312.33(k)(1)(ii)).

• Requires identifying each event omitted from the listings and tabulations of safety data required under proposed § 312.33(k)(1) because the event is a study endpoint or a component of a study endpoint (proposed § 312.33(k)(2)).

• Requires a brief summary of safety and effectiveness findings from clinical investigations of the investigational drug conducted on behalf of the sponsor that are obtained during the reporting period (proposed § 312.33(l)).

• Adds the requirement that the sponsor submit a brief summary of key safety findings obtained from other sources during the reporting period (proposed § 312.33(m)).

• Requires sponsors to provide a summary of significant chemistry, manufacturing, and control changes, including microbiological changes (if applicable), made to the investigational drug during the reporting period, as well as a brief description of the safety significance of the identified changes (proposed § 312.33(n)).

• Requires a concise, integrated evaluation of all new clinical, nonclinical, and epidemiological safety information obtained about the drug by the sponsor during the reporting period relative to the sponsor's prior knowledge of the drug (proposed § 312.33(s)).

• Requires providing a cumulative listing and brief description of all important known risks and potential risks associated with the use of the drug identified by the sponsor throughout the course of studies of the drug conducted on behalf of the sponsor (proposed § 312.33(t)).

• Requires a conclusion that briefly summarizes changes to the sponsor's previous knowledge of the investigational drug's efficacy and safety resulting from information obtained during this reporting period, in addition to an outline of actions by the sponsor that have been taken during the current reporting or will be taken in the future to address emerging safety findings (proposed § 312.33(u)).

FDA is issuing this proposed rule under sections 201, 301, 501, 502, 503, 505, and 701 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 321, 331, 351, 352, 353, 355, and 371) and under section 351 of the Public Health Service Act (PHS Act) (42 U.S.C. 262).

The estimated benefits would result from savings in labor costs for sponsors who may no longer have to prepare a different type of periodic safety report for submission to certain other countries or regions in which a drug might be studied. Moreover, FDA would receive safety data on investigational new drugs that is more comprehensive, which would enhance our ability to oversee the progress and safety of clinical investigations. The estimate of annualized benefits over 10 years ranges from $47.86 million to $117.99 million with a primary value of $86.46 million at a 7 percent discount rate and from $49.24 million to $121.01 million with a primary value of $88.79 million at a 3 percent discount rate. The primary estimate of the present value of benefits over 10 years is $607.29 million at a 7 percent discount rate and $757.38 million at a 3 percent discount rate. Costs would arise from increased labor associated with preparing and submitting a periodic safety report that is more comprehensive to meet the proposed requirements. Costs to government would arise from increased FDA resources being used to review the more comprehensive report. The estimate of annualized costs over 10 years ranges from $40.43 million to $101.34 million at a 7 percent discount rate with a primary value of $61.11 million. Using a 3 percent discount rate, the annualized costs range from $40.89 million to $102.48 million with a primary value of $61.81 million. The primary estimate of the present value of costs over 10 years is $429.20 million at a 7 percent discount rate and $527.21 million at a 3 percent discount rate.

FDA is proposing to replace the current annual reporting requirement with a new annual reporting requirement. The proposed action would require IND sponsors to submit an annual FDA DSUR—a report that retains the general aspects of the current annual report but includes information that is more comprehensive and is generally consistent with the format and content of the E2F DSUR (available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/e2f-development-safety-update-report ). The proposed annual FDA DSUR is similar to the annual safety reporting requirements in certain other countries and regions in which a drug might be studied. Promulgation of a rule containing requirements that are similar to the DSUR recommendations developed by ICH (see E2F DSUR) is also consistent with FDA's overarching goal of fostering international harmonization of regulatory requirements to the extent appropriate and feasible. Therefore, FDA expects that some of the additional regulatory burden associated with preparing a report for FDA that is more comprehensive than previously required will be offset by the mitigation of the previous regulatory burden on those sponsors who submit multiple different reports to regulatory authorities in other countries or regions.

FDA is proposing this action because of the advantages that the proposed annual FDA DSUR would provide over the current IND annual report. The advantages include: (1) enabling FDA to more efficiently identify and review new safety signal information; (2) creating a more efficient reporting process for certain sponsors by supporting a more comprehensive format for submission to FDA and multiple regulatory authorities worldwide; and (3) allowing regulatory authorities worldwide to have access to the same data within the same timeframes. For example, the DSUR includes a section that tracks knowledge about each specific safety issue through time, facilitating efficient identification and review of any new safety signal information. The integration of data from a development program with postmarketing data provides a powerful means to facilitate identification and review of any new safety signals. As discussed in section III.D.3, the proposed annual FDA DSUR will provide a more comprehensive and detailed safety summary than the IND annual report, which will facilitate reviewers' ability to efficiently identify and review new safety signal information.

The proposed annual FDA DSUR would better capture and characterize the evolving safety profile of the investigational drug and would better describe new safety findings that could have an impact on the protection of study subjects. Simply accumulating and reporting data for a given time period, as required under the current IND annual report, without considering all previously available data from clinical trials and other sources, may delay identification of important risks. DSURs specifically include a section that tracks knowledge about each specific safety issue through time, facilitating efficient identification and review of any new safety signal information.

Furthermore, a requirement for investigational drug reporting similar to the reporting done in the EU could help sponsors who need to satisfy annual reporting requirements in different countries and regions and would help prevent sponsors from sending duplicative information in different formats to different regulatory authorities. A similar annual reporting requirement would also help provide authorities in different countries with a common description of the evolving safety profile of a drug, and thus, could help ensure greater consistency and predictability in regulatory actions. We expect that the proposed annual FDA DSUR would help harmonize FDA's requirements for IND annual reporting with the E2F DSUR.

We have received support for the proposed annual FDA DSUR through public comments submitted in response to documents published in the Federal Register . For example, in response to a request for public comment in the Federal Register of April 27, 2011 (76 FR 23520), a trade organization representing major biotechnology companies urged FDA to update its regulations to reflect current practice and to be consistent with the language in the E2F DSUR. (See Docket No. FDA-2011-N-0259.) In the Federal Register of August 5, 2008 (73 FR 45462), FDA requested public comment on the E2F DSUR draft guidance for industry. In response, FDA received comments from pharmaceutical manufacturers and a trade association. (See Docket No. FDA-2008-D-0386.) Some comments proposed certain modifications to the DSUR as described in the draft guidance but were generally supportive of the draft guidance and noted that the use of the E2F DSUR would help harmonize annual reporting of clinical trials, thus enhancing efficiency and providing regulators, investigators, patients, and industry with valuable, consolidated safety information. Other comments expressed a preference for the use of the E2F DSUR to minimize discrepancies, which are, at the present time, common in the information different regulators receive. Taken together, the public comments expressed support for requiring a single reporting format for periodic safety reporting under an IND and a preference for use of the format, content, and timing of the E2F DSUR.

The IND regulations in part 312 contain procedures and requirements governing the use of investigational drugs, including biological products that do not also meet the definition of device under the FD&C Act (s ee 21 U.S.C. 321(g) through (h), 42 U.S.C. 262(i) through (j); see also 21 CFR 601.21) and contain procedures and requirements for the submission of INDs to FDA and for FDA's review of those INDs. Under the IND regulations in part 312, sponsors are required to have an IND in effect to support the use of an investigational drug in clinical trials or for expanded access uses. The IND regulations also provide various mechanisms for continued FDA oversight of clinical investigations conducted under an IND. The IND annual report currently required under § 312.33 is intended to serve as the means for reporting the status of studies being conducted under the IND and for providing the general investigational plan and safety-related changes to the investigational plan for the coming year. This proposed rule focuses on § 312.33, Annual report.

In the Federal Register of March 19, 1987 (52 FR 8798, as amended at 52 FR 23031, June 17, 1987; 63 FR 6854, February 11, 1998; and 67 FR 9584, March 4, 2002), FDA published regulations for new drug, antibiotic, and biologic drug products as part of an overall revision of the IND regulations (known as the IND Rewrite). These regulations, in part, require each sponsor to submit an annual report providing an update on the progress of clinical investigations conducted under its IND. The annual report must contain individual study information, which generally includes brief summaries of the status of each ongoing study and of each study completed during the previous year. These summaries are required to include, among other things: (1) a brief description of available results of each study completed during the previous year and interim results of ongoing clinical investigations and (2) information on the number of subjects included in each study (see § 312.33(a)). The annual report must also include summarized information about the clinical investigations conducted under the IND during the previous year, including the following, for example:

• A summary showing the most frequent and most serious adverse experiences (§ 312.33(b)(1)).

• A summary of all IND safety reports submitted during the previous year (§ 312.33(b)(2)).

• A list of preclinical studies completed or in progress during the previous year, including a summary of the major preclinical findings (§ 312.33(b)(6)).

• A summary of any significant manufacturing or microbiological changes made during the past year (§ 312.33(b)(7)).

Since the publication of the IND Rewrite, the increasing size and scope of clinical investigations have created the need for information and analyses that are more comprehensive, as well as the need for information to be presented in a format that is more useful for FDA, clinical investigators, sponsors, and others using the data included in the reports. Such comprehensive analyses will assist FDA in evaluating the safety profile of an investigational drug during its development and will assist in identifying safety signals while the clinical trials are ongoing. Because of the increasing complexity of clinical trials, having periodic reporting and consistent information reported are of increased importance for protecting human subjects from unnecessary risks. Additionally, there have been concerns about differences in the content and objectives between the current IND annual report and the annual safety report that is being used in other countries, as well as concerns about the burden associated with preparing different periodic safety reports for different regulatory authorities. These concerns led to an international effort to develop a common periodic safety report that could be used globally to satisfy reporting requirements.

In the Federal Register of October 11, 1995 (60 FR 53078), FDA published a notice entitled “International Harmonization, Policy on Standards” that described FDA's policy for working with other countries to achieve greater harmonization of regulatory requirements and guidelines. It also described FDA's views on international harmonization and collaboration as a way to enhance regulatory effectiveness by providing more consumer protection without added expenditure of government resources. Harmonization and collaboration can also increase worldwide consumer access to safe, effective, and high-quality products.

International harmonization has been facilitated through the development of ICH guidelines via a process of scientific consensus with regulatory and industry experts participating in multinational working groups. In 2006, the Center for Biologics Evaluation and Research (CBER) and the Center for Device Evaluation and Research (CDER) participated in a working group sponsored by the Council for International Organizations of Medical Sciences (CIOMS), referred to as CIOMS VII (Ref. 1). CIOMS is an international, nongovernmental, nonprofit organization established by the World Health Organization and the United Nations Educational, Scientific, and Cultural Organization that covers drug safety topics through working groups (Refs. 2 and 3). The CIOMS VII working group proposed that ICH develop a guideline on periodic reporting of safety information from clinical trials (which it termed the development safety update report (DSUR)) that would harmonize guidelines and requirements from the various regulatory agencies (Ref. 1).

The CIOMS report was the starting point for the ICH initiative (Ref. 4). In June 2008, the draft ICH guideline for the E2F DSUR was approved by the ICH steering committee (Ref. 5). In the Federal Register of August 5, 2008, FDA announced the availability of the draft ICH guidance for industry (E2F DSUR) (available at https://www.regulations.gov/document?D=FDA-2008-D-0386-0002) for public comment, which was the guideline prepared under the auspices of the ICH. After consideration of the comments received on the draft guidance for industry, the ICH steering committee approved a final draft of the guideline to be adopted by the United States, Japan, and participating European countries entitled “Development Safety Update Report, E2F,” dated August 17, 2010 (Ref. 5). In the Federal Register of August 23, 2011 (76 FR 52667), FDA issued this guideline as a final ICH guidance for industry (the E2F DSUR) that discusses the format, content, and timing of submission of a DSUR as developed by the ICH.

The E2F DSUR provides the recommended content and format of a drug safety update report that sponsors can use to satisfy the EU requirements for annual safety reports and FDA's requirements for IND annual reports, despite the differences between the EU requirements and FDA's requirements. Specifically, the annual safety report required under the EU Clinical Trial Directive 2001/20EC contains significant differences in the purpose, content, and timing of submission compared to FDA's IND annual report (Refs. 6 and 7). As a result, sponsors developing a drug in both jurisdictions are required to submit different annual reports each year to each regulatory authority. For example, the IND annual report is intended to provide only summaries of clinical studies conducted under the IND and requires a narrative or tabular summary of the most frequent and most serious adverse experiences. In contrast, the EU annual safety report is intended to be a clinical trial safety report and requires a cumulative summary tabulation of all serious adverse reactions (Refs. 6 and 7). With regard to timing, the required date for submission of the IND annual report is based on the anniversary of the effective date of the IND under § 312.40(b), whereas the date for submission of the EU annual safety report is the anniversary of the development international birth date, which is the date on which the sponsor was first authorized to conduct a clinical trial in any country or region (Ref. 1). The differences in the purpose, content, and timing of annual reporting in the EU and the United States result in study sponsors sending duplicative information to regulators, as well as regulatory authorities receiving inconsistent safety information.

The E2F DSUR provides recommendations with respect to periodic safety reporting during clinical development, offers guidance on providing meaningful information to regulators, and facilitates consistency among sponsors and regulators (Ref. 4). The E2F DSUR emphasizes high-value activities, such as data interpretation, while ensuring that the regulatory authorities that use the E2F DSUR have access to the same data in similar timeframes (Ref. 4). Following are overarching objectives enabled by the use of the E2F DSUR:

• Examining whether the information obtained by the sponsor during the reporting period aligns with prior knowledge of the safety of the investigational drug.

• Describing new safety findings that could have an impact on the protection of study subjects.

• Summarizing the current understanding and management of identified and potential risks.

• Providing an update on the status of the clinical investigation/development program and study results.

Use of the E2F DSUR provides important advantages for safety evaluation as compared to FDA's IND annual report. First, the E2F DSUR includes additional safety information to help enhance the safety of subjects. For example, the E2F DSUR specifically includes a description of significant, safety-related changes to the investigator brochure and an evaluation of the significance of the identified changes for the safety of subjects. For some drugs, this increased safety reporting requirement could potentially help characterize a safety signal and associated risks, and lead to timely action to protect subjects such as earlier termination of a study or withdrawal of a drug from the market due to safety concerns (as mentioned previously). In contrast, the IND annual report is a general update on the progress of the investigational drug's clinical development, which includes a description of the revisions made to the investigator brochure and a copy of the new brochure, if revised, and a summary of all IND safety reports submitted during the year, but no additional analysis is conducted by the sponsor.

Second, unlike FDA's IND annual report, the E2F DSUR contains an integrated safety analysis and a summary of cumulative pertinent safety information. Simply accumulating and reporting data for a given time period, without considering all previously available data from clinical trials and other sources, may delay identification of important risks. A meaningful understanding of the evolving safety profile of an investigational drug requires a periodic analysis of all available safety information, which is crucial to the ongoing assessment of risks to subjects of clinical trials during the clinical development of an investigational drug. An integrated analysis and a summary of overall safety risks, as contained in the E2F DSUR, would help increase the usefulness of the safety data and help facilitate efforts to identify and assess important safety risks promptly. The E2F DSUR includes information on cumulative patient exposure and a summary of cumulative serious adverse events, which would further enhance risk identification and assessment.

Third, the E2F DSUR provides safety information that is more comprehensive than the IND annual report, which requires only summaries of clinical studies conducted under the IND. In contrast to the current IND annual report, the E2F DSUR contains safety information from all studies using the drug, whether conducted under an IND or not. The E2F DSUR also incorporates information from studies not initiated by the sponsor and information from other relevant sources. For example, safety findings from published literature and information from the marketing experience of the drug would be included in the E2F DSUR, but these findings are not required in the IND annual report. Some sponsors have already voluntarily submitted their IND annual reports in the E2F DSUR format to the FDA; the submitted E2F DSURs have provided the aforementioned advantages, including superior organization and more comprehensive information to facilitate review.

Finally, the ability to submit a similar annual report to regulatory authorities in multiple countries and for all investigations of the drug conducted on behalf of the sponsor could provide significant advantages to those sponsors who submit reports to multiple regulatory authorities. A similar comprehensive annual report submitted to regulatory authorities in multiple countries could help ensure consistent understanding of the safety profile of a drug and could therefore help improve consistency and predictability of regulatory actions. The use of a similar annual report in multiple countries and for all studies conducted on behalf of the sponsor in which the particular drug is studied also could help ensure that regulatory authorities for all development programs are relying on the same information about the evolving safety profile of a drug.

FDA is issuing this proposed rule under sections 201, 301, 501, 502, 503, 505, and 701 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 321, 331, 351, 352, 353, 355, and 371) and under section 351 of the PHS Act.

The proposed rule would revise current §§ 312.3 and 312.33 concerning IND annual reports. The proposed rule would require IND sponsors to submit an annual DSUR that is more comprehensive and informative than the IND Annual Report currently required under FDA regulations. The proposed annual FDA DSUR is intended to be consistent with the format and content of the E2F DSUR supported by ICH for annual reporting in certain other countries and regions. If finalized, this rule would require sponsors to submit an annual FDA DSUR in lieu of the IND Annual Report. A sponsor would be able to submit an annual DSUR containing additional information to that proposed to be required by the annual FDA DSUR, in the format recommended in the E2F DSUR, as long as the submitted DSUR complies with the requirements provided in the proposed annual FDA DSUR and FDA requirements for electronic submissions (see, e.g., section 745A(a) of the FD&C Act (21 U.S.C. 379k-1)(a)). The proposed requirements are intended to provide information that is sufficiently comprehensive to facilitate FDA's assessment of clinical investigations conducted on behalf of the IND sponsor, including the sponsor of a large, multinational clinical development program intended to support applications for marketing approval of a drug in multiple countries and regions.

The proposed rule would revise § 312.3 (Definitions and interpretations) by adding a definition for data lock point. The data lock point would be defined as the designated cutoff date for data to be included in the proposed annual FDA DSUR. The definition would establish a fixed data lock point that is 1 calendar day before the anniversary of the date the IND went into effect. We propose to require that a sponsor submit the annual FDA DSUR to FDA not later than 60 calendar days after the data lock point (see proposed § 312.33).

FDA is proposing to revise current § 312.33, Annual reports, by replacing the section with a section entitled “Development safety update reports.” Proposed § 312.33 describes the scope, format, and content of the proposed annual FDA DSUR as well as when to submit the annual report. The proposed requirements are intended to be consistent with the content recommended in the E2F DSUR to the extent possible. Some of the language used in this proposed rule differs from that in the E2F DSUR because of minor differences in terminology and for consistency with other FDA requirements. We recognize that some of the information discussed in the proposed annual FDA DSUR may not be known to sponsors, which is why the proposed annual FDA DSUR only requires sponsors to submit the information that is known to them.

Proposed § 312.33(a) states that the annual FDA DSUR is intended to provide a thorough annual assessment of the clinical investigations conducted and safety information collected during the reporting period that is related to an investigational new drug. The annual FDA DSUR is intended to: (1) be sufficiently comprehensive to cover the entire scope of a large-scale, international development program designed to support applications for marketing in multiple countries and regions and (2) capture data from all completed and ongoing clinical investigations conducted on behalf of the sponsor anywhere in the world evaluating the drug, including investigations not conducted under an IND (see § 312.33(a)(1)). Proposed § 312.33(a)(1) further provides that a sponsor must submit the same annual FDA DSUR for each IND held by the sponsor for that drug.

Under § 312.10, sponsors may request that FDA waive any applicable requirement in part 312. We expect that some sponsors will request that FDA waive the requirement under proposed § 312.33 that they must submit the annual FDA DSUR not later than 60 calendar days after a data lock point established by proposed § 312.3 (which is 1 calendar day before the anniversary of the date the IND went into effect) to allow them to coordinate the timing of the annual FDA DSUR submission with the submission of reports to regulatory agencies in other countries or regions. We also expect that some sponsors will request that FDA waive the requirement under proposed § 312.33(a)(1) that a sponsor submit the same annual FDA DSUR for each IND held by the sponsor for the drug because of substantial differences in, for example, the intended uses or populations being studied under different INDs.

As required under § 312.10(a), a waiver request must contain the following: (1) an explanation of why the sponsor's compliance with the requirement is unnecessary or cannot be achieved, (2) a description of an alternative submission or course of action that satisfies the purpose of the requirement, or (3) other information that justifies a waiver. As provided under § 312.10(b), FDA may grant a requested waiver if it finds that the sponsor's noncompliance would not pose a significant and unreasonable risk to human subjects of the investigation and that at least one of the following is met: (1) the sponsor's compliance with the requirement is unnecessary for the Agency to evaluate the application or compliance cannot be achieved, (2) the sponsor's proposed alternative satisfies the requirement, or (3) the applicant's submission otherwise justifies a waiver.

FDA expects that the waiver criteria in § 312.10(b) will likely be met when a sponsor submits a waiver request in accordance with § 312.10(a) for the following reasons: (1) an alternate data lock point would permit the sponsor to coordinate the timing of submission of an annual FDA DSUR with the sponsor's submission of the proposed annual FDA DSUR to other INDs covered by the same annual FDA DSUR ( e.g., INDs for studies investigating other indications for a drug), (2) an alternate data lock point would permit the sponsor to coordinate the timing of submission of an annual FDA DSUR with the timing of submission of other reports to regulatory agencies in other countries and regions ( e.g., to coordinate the timing of submission of an annual FDA DSUR with the date of first approval or authorization for conducting a clinical investigation in any country or region ( i.e., the development international birth date of the drug)), or (3) an alternate data lock point would permit the sponsor to coordinate the timing of submission of an annual FDA DSUR with the timing of submission of the postmarketing periodic safety report required under 21 CFR 314.80(c)(2) or 600.80(c)(2), if a sponsor is submitting both reports to FDA ( e.g., is conducting clinical investigations of a lawfully marketed drug or biological product).

FDA expects that the waiver criteria in § 312.10(b) will probably be met when a sponsor submits a waiver request in accordance with § 312.10(a) to allow a sponsor to submit individual annual FDA DSURs for INDs that cover very different dosage forms of a drug ( e.g., the same active ingredient for intravenous use for a life-threatening disease versus topical administration for a more chronic disease) on the basis that submission of the same annual FDA DSUR for each IND would not be useful to FDA because of substantial differences in, for example, the intended uses or populations being studied.

Table 1 shows the major differences between the current IND annual report and the proposed annual FDA DSUR.

FDA acknowledges that the proposed content requirements of the annual FDA DSUR are more extensive than generally would be needed for reporting the status of a sponsor-investigator IND for a single clinical investigation that is not intended to support a marketing application. Therefore, we are proposing that the report for an IND conducted by a sponsor-investigator (as defined in § 312.3) that is not intended to support a marketing application must contain the required information that is obtained from the investigation conducted by the sponsor-investigator (see § 312.33(a)(2)). The sponsor-investigator is required to submit only information that is obtained from the clinical investigation conducted by the sponsor-investigator ( e.g., information that is part of that sponsor-investigator's protocol for the IND). For example, if a commercial IND sponsor provides an investigational drug to a sponsor-investigator to conduct an investigation under the sponsor-investigator's IND, it would not be necessary for the sponsor-investigator to submit information unrelated to their study ( e.g., data concerning animal toxicity, drug manufacturing information, or safety information from investigations conducted under the commercial sponsor's IND) because the information would be submitted by the sponsor. Also, the sponsor-investigator may not have right of reference to the data. For these reasons, we do not propose requiring the sponsor-investigator to provide information in the annual FDA DSUR that is not obtained from the sponsor-investigator's own clinical investigation under an IND.

Proposed § 312.33(a)(3) provides that, in § 312.33, ongoing clinical investigations consist of all active investigations, including those that are on clinical hold; investigations that have not been terminated; and investigations for which a final study report has not been submitted but the investigation might otherwise be completed. The intent is to capture all relevant investigations conducted on behalf of the sponsor.

Proposed § 312.33(b) through (u) describe the content FDA proposes to be included in the annual FDA DSUR.

Proposed § 312.33(b) describes the content of the title page, including the IND number, report number (reports to be numbered sequentially), name of the investigational drug, reporting period, date of the report, and sponsor's name and address. The reporting period is the designated 12-month period during which information was obtained for the annual FDA DSUR and ending with the data lock point. This period would run from the previous anniversary of the date the IND went into effect under § 312.40(b) until 1 calendar day before the anniversary of the date the IND went into effect unless FDA grants a waiver pursuant to § 312.10(b) for the sponsor to designate an alternate date for the data lock point.

Proposed § 312.33(c) describes the content of the executive summary for the proposed annual FDA DSUR. Proposed § 312.33(c) would require that the executive summary contain all of the following information:

• The report number and reporting period;

• A brief description of the investigational drug, including the therapeutic class(es), pharmacological class (if applicable), and mechanism of action (if known), and the indications, doses, formulations, and routes of administration being studied on behalf of the sponsor;

• The cumulative number of subjects to whom the drug has been administered throughout the course of studies of the drug conducted on behalf of the sponsor or an estimate of these subjects if a precise number cannot be determined ( e.g., for a study that is currently enrolling subjects);

• A summary of the overall safety assessment required under proposed § 312.33(s) of the main report;

• A summary of the list of important risks required under proposed § 312.33(t) of the main report;

• A summary of actions taken for safety reasons as required under proposed § 312.33(g);

• A list of countries and regions (if a drug product is approved by a region, which may be the case in the EU) in which the drug has been approved for marketing; and

• A summary of the conclusion as required under proposed § 312.33(u) of the main report.

We are proposing to require that the report contain a table of contents with sufficient detail to direct the annual FDA DSUR reader to each of the components of the report described in paragraphs (e) through (u) of proposed § 312.33 (see proposed § 312.33(d)).

We are proposing to require a detailed introduction containing the following information: (1) identification of the reporting period; (2) a brief description of the investigational drug (including the therapeutic class(es), pharmacological class (if applicable), and the mechanism of action (if known); (3) a list of the indications, doses, formulations, and routes of administration being investigated; and (4) a list of the clinical investigations conducted on behalf of the sponsor that are referred to in the report (see § 312.33(e)).

Section 312.33(e) in this proposed rule corresponds to section 3.1 (Introduction) of the E2F DSUR. In comparing these sections, we note that section 3.1 of the E2F DSUR recommends the inclusion of certain information that is not included in FDA's proposed § 312.33(e), such as information about the Development International Birth Date; a short summary of the scope of the clinical trials covered by the report; and a brief description and explanation of all information that has not been included in the annual FDA DSUR. FDA is not requiring this information under proposed § 312.33(e) because the information is not expected to provide additional important information for FDA's safety evaluation of the drug.

Proposed § 312.33(e) would require information about the drug's therapeutic class(es) and pharmacological class (with pharmacological class included as part of the original IND per § 312.23(a)(3)) because therapeutic class is important to FDA's evaluation of drugs and biologics, and pharmacological class is important to FDA's evaluation of drugs. Also, proposed § 312.33(e) would require that the mechanism of action rather than the mode of action (the term used in the E2F DSUR) be included in the description of the drug because other FDA IND regulations already use the term mechanism of action (see, e.g., § 312.23(a)(8)(i)). Unlike the E2F DSUR recommendations, FDA does not propose to require in this section information about population or populations being studied because FDA would receive this information pursuant to proposed § 312.33(i). Lastly, FDA does not propose to require in this section a rationale for the submission of multiple annual FDA DSURs for the investigational drug because FDA proposes to require sponsors to prepare and submit a single report for a drug studied under multiple INDs. If a sponsor is unable to comply with this requirement ( e.g., the sponsor would like to submit separate annual FDA DSURs for individual INDs), the sponsor may submit a waiver request in accordance with § 312.10(a) that includes information that justifies a waiver.

We are proposing that if the drug has been approved anywhere in the world, the sponsor would be required to provide a brief summary of the status of the approved drug, including the date of first approval, the indication(s), the approved dose(s), and where approved, (see proposed § 312.33(f)). This proposed requirement is consistent with the content recommended in section 3.2 (Worldwide Marketing Approval Status) of the E2F DSUR.

We are proposing to require that the sponsor describe all actions relevant to the safety of the drug that were taken by the sponsor or by a regulatory authority during the reporting period, if known (see proposed § 312.33(g)). The sponsor's actions include any actions taken by the sponsor in response to a regulatory action or any actions taken by the sponsor following a recommendation from a Data Monitoring Committee (DMC), if one is used. Proposed § 312.33(g) would also require the sponsor to provide the reason or reasons for each action.

The corresponding section 3.3 (Actions Taken in the Reporting Period for Safety Reasons) of the E2F DSUR recommends, in addition, actions related to safety that have been taken by an ethics committee. While some countries use established ethics committees with responsibilities that differ from those of institutional review boards in the United States, FDA believes that actions taken by an ethics committee in another country would often be included in a report of actions taken by sponsors or regulatory authorities. Section 3.3 of the E2F DSUR includes a list of examples of significant actions taken for safety reasons, which is similar in concept to the list of actions in proposed § 312.33(g). As such, FDA considers the information recommended in section 3.3 of the E2F DSUR to be substantially similar to what is called for by proposed § 312.33(g). The intent of proposed § 312.33(g) is to capture actions taken for safety reasons by the sponsor and by FDA in the United States and to capture analogous actions taken by regulatory authorities in other countries or regions. The intent is also to capture only actions that are significant to the conduct of clinical investigations under the IND, including the following examples of the types of actions to be reported under the proposed requirements:

• A clinical hold order issued under § 312.42;

• Denial of authorization to initiate a clinical investigation or the suspension of the conduct of a clinical investigation involving use of the drug in another country or region ( e.g., this includes early termination of an ongoing clinical trial because of safety findings or lack of efficacy);

• A requirement to cease distribution of the drug or other action related to the quality of the drug ( e.g., recall of the drug);

• Refusal to approve any application for marketing of the drug (this includes voluntary withdrawal of an application);

• An action by a regulatory authority that places a condition or limitation on the use or development of the drug ( e.g., a requirement to conduct long-term animal testing before beginning long-term studies in humans, the need for a validated immunogenicity assay before beginning phase 3 testing, specific testing needed before initiating pediatric studies, the limitation on dosing pending additional safety data, the exclusion of a particular population from clinical investigations);

• A safety-related change in the protocol or in the investigational plan of an ongoing clinical investigation of the drug ( e.g., change in dose, change in inclusion/exclusion criteria, monitoring that is new or more intensive, limit to the duration of the trial);

• A safety-related change in the information provided to human subjects in order to obtain informed consent for a clinical investigation of the drug;

• A safety-related formulation change to the drug;

• A safety advisory communication to investigators conducting studies under the IND or to healthcare professionals concerning use of the drug;

• An investigation of the drug that is initiated or planned to evaluate a safety risk associated with use of the drug;

• If the drug is lawfully marketed, each safety-related change to its labeling, including the prescribing information;

• If the drug is lawfully marketed, a significant restriction on distribution or other risk mitigation strategy ( e.g., a risk evaluation and mitigation strategy implemented under section 505-1 of the FD&C Act (21 U.S.C. 355-1)); and

• If the drug was lawfully marketed, withdrawal or suspension of marketing approval for the drug in any country or region.

We are proposing that the investigator brochure, if required under §§ 312.23(a)(5) and 312.55, will serve as the reference safety information to be used during the clinical investigation of the investigational drug. The investigator brochure in effect at the start of the reporting period will represent the reference safety information to be used by the sponsor during that reporting period. If an investigator brochure is not required and the drug is subject to an FDA-approved marketing application, we propose that the FDA-approved prescribing information will serve as the reference safety information. If an investigator brochure is not required under §§ 312.23(a)(5) and 312.55, the drug is not FDA-approved; and if the sponsor uses another source as the reference safety information, the sponsor would be required to identify the reference safety information ( e.g., coding dictionary version(s) used or the European Summary of Product Characteristics) (see proposed § 312.33(h)(1)).

We are also proposing to require the sponsor to provide a report that lists all safety-related changes to the reference safety information, if applicable, during the reporting period. If the investigator brochure is used as the reference safety information, changes to that information would include revisions made to the investigator brochure by the sponsor as described in § 312.55(b) (see proposed § 312.33(h)(2)).

We are proposing to require the sponsor to provide an inventory of ongoing and completed clinical investigations of the investigational drug that were conducted on behalf of the sponsor during the reporting period (see proposed § 312.33(i)). The intent is to identify the universe of clinical investigations that are conducted under the IND. For each clinical investigation identified, the sponsor would be required to provide the following information:

• The protocol number.

• The clinical investigation title (or abbreviated title).

• The National Clinical Trial (NCT) number, if applicable.

• The phase of the clinical investigation ( i.e., 1, 2, 3, or postmarketing).

• The date the first subject provided informed consent.

• A brief description of the clinical investigation design and the dose and regimen of the investigational drug and any comparators.

• The cumulative number (or an estimate) of subjects enrolled in each treatment arm for all treatment arms of the clinical investigation during the reporting period.

• Countries or regions in which the clinical investigation was conducted. This would include any country or region with one or more study sites.

• A demographic breakdown of study population by age, sex, and race.

• The status of the clinical investigation (ongoing or completed).

• The total number of subjects (if any) planned to be enrolled in the clinical investigation.

We are proposing that the report identify the cumulative number of subjects exposed to the investigational drug and comparators (placebo and active controls) since the date the IND went into effect (see proposed § 312.33(j)(1)). For blinded studies, this number would be estimated. It would also require that such exposure be broken down by age, sex, and race. Proposed § 312.33(j)(2) would further require the report to estimate patients' cumulative exposure to the marketed drug in each country and region in which the sponsor has lawfully marketed the drug since the date the IND went into effect, if any, accompanied by an explanation of how that exposure was estimated. The estimate of exposure is intended to provide context ( i.e., a denominator) for the cumulative summary tabulations of serious adverse events and the overall assessment of safety.

Proposed § 312.33(k)(1) generally would require lists of safety data and other information from clinical investigations of the investigational drug conducted on behalf of the sponsor. Proposed § 312.33(k)(1) would not require information about adverse events that are study endpoints or components of study endpoints ( e.g., mortality events in an outcomes trial).

Proposed § 312.33(k)(1)(i) would require line listings of serious suspected adverse reactions as defined in § 312.32(a) that occurred during the reporting period, including the treatment associated with the serious suspected adverse reaction, as well as all serious suspected adverse reactions for any comparators, if known. The line listing would identify those serious suspected adverse reactions that are unexpected ( serious and unexpected suspected adverse reactions ), as defined in § 312.32(a). The line listing should be formatted as a detailed record of the serious suspected adverse reactions and would also be required to include the following information, if applicable:

• Study title or abbreviated title.

• Subject's clinical trial identification number.

• Sponsor's adverse reaction case reference number.

• IND Safety Report reference number.

• Country in which case occurred.

• Age and sex of trial subject.

• Treatment group; identified as “blinded” if the blind has not been broken.

• Dose and dosing interval of investigational drug and, when relevant, dosage form and route of administration.

• Date of onset and/or time to onset from administration of last dose of the most serious suspected adverse reaction.

• Dates of treatment and/or best estimate of treatment duration of serious suspected adverse reaction.

• Outcome ( e.g., resolved, fatal, improved, sequelae, unknown). This field must indicate the consequences of the reaction(s) for the trial subject, using the worst of the different outcomes for multiple reactions.

• Comments ( e.g., causality assessment if the sponsor disagrees with the reporter; concomitant medications suspected to play a role in the reactions directly or by interaction; indication treated with suspect drug(s); dechallenge/rechallenge results if available).

The study identification information included with the line listing of serious suspected adverse reactions required under proposed § 312.33(k)(1)(i) would facilitate FDA's evaluation of the drug's safety information across multiple clinical trials and INDs.

Proposed § 312.33(k)(1)(ii) would require a cumulative summary tabulation of serious adverse events as defined in § 312.32(a) for all clinical investigations conducted on behalf of the sponsor since the date the IND went into effect under § 312.40(b). This summary should be formatted as a table.

Proposed § 312.33(k)(1)(iii) would require a list of study subjects who died during the reporting period and the cause of death.

Proposed § 312.33(k)(1)(iv) would require a list of subjects who withdrew from a clinical investigation during the reporting period because of an adverse event as defined in § 312.32(a), whether the adverse event was related to the investigational drug or not.

The line listings and cumulative summary lists required under proposed § 312.33(k)(1) correspond to section 3.7 (Data in Line Listings and Summary Tabulations) of the E2F DSUR, which includes slightly different information as a result of differences in terminology in safety reporting standards. Specifically, FDA issued a final ICH guidance for industry in March 1995 entitled “E2A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting” (ICH E2A Clinical Safety Data Management guideline) (available at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073087.pdf ). The E2F DSUR cross-referenced definitions for serious adverse reaction, serious adverse event, and adverse drug reaction as defined in the ICH E2A Clinical Safety Data Management guideline. The ICH Clinical Safety Data Management guideline defines adverse drug reaction as “All noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions. The phrase `responses to medicinal products' means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e., the relationship cannot be ruled out.” However, FDA issued a final rule entitled “Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and Safety Reporting Requirements for Bioavailability and Bioequivalence Studies in Humans” on September 29, 2010 (75 FR 59935), which revised the definitions of these safety reporting terms under current § 312.32(a). As a result, instead of using the term adverse drug reaction as defined in the ICH E2A Clinical Safety Data Management guideline, we are using suspected adverse reaction, which is defined under current § 312.32(a). For the purposes of IND safety reporting, “reasonable possibility,” as it appears in § 312.32(a), means there is evidence to suggest a causal relationship between the drug and the adverse event. Suspected adverse reaction implies a lesser degree of certainty about causality than adverse reaction, which means any adverse event caused by a drug. We are also making use of the term serious adverse event or serious suspected adverse reaction as defined in § 312.32(a). In light of this revision in terminology, we are making it clear that sponsors would be required under proposed § 312.33(k)(1)(i) to provide a line listing of all serious suspected adverse reactions. We note that adverse reactions, which are defined under current § 312.32(a) as adverse events caused by a drug, are a subset of all suspected adverse reactions—for which there is reason to conclude that the drug caused the event—and, if serious, would be required to be included in the line listings for proposed § 312.33(k)(1)(i).

FDA's requirements under proposed § 312.33(k)(1) for a list of study subjects who died during the reporting period and the cause of death and for a list of subjects who withdrew from the clinical investigation during the reporting period correspond to section 3.16 (Region-Specific Information) of the E2F DSUR, which similarly includes a list of subjects who died during the reporting period, the case number, the assigned treatment, and the cause of death for each subject, as well as a list of subjects who withdrew from clinical investigations during the reporting period in association with an adverse event. The E2F DSUR states that information should include whether or not withdrawing from the investigation was thought to be drug-related.

We are further proposing that a sponsor identify each event omitted from these listings or tabulations because the event is a study endpoint or a component of a study endpoint (see proposed § 312.33(k)(2)). This provision is intended to account for study endpoints in outcome studies in which death or major morbidity is the study endpoint (an adverse outcome) and to isolate those events from other reported adverse events. For example, deaths in a cancer trial in which overall survival is the study endpoint would be identified as required in proposed § 312.33(k)(2) and omitted from the safety line listings and summary tabulations described in proposed § 312.33(k)(1). Similarly, fatal strokes that are a component of a composite primary study endpoint ( e.g., all-cause mortality) would be identified as required by proposed § 312.33(k)(2) and omitted from the listings and summary tabulations of serious adverse events described in proposed § 312.33(k)(1).

We are proposing that the report briefly summarize all safety and effectiveness findings from clinical investigations of the investigational drug conducted on behalf of the sponsor that are obtained during the reporting period (see proposed § 312.33( l )). Statistically significant differences would be an example of such a finding, but in addition, clinically meaningful differences identified in an interim analysis that were provided to the sponsor and that led to a change in the protocol or population would also be required. The report would include data from any completed trials, interim analyses of ongoing trials, or long-term follow-up of subjects after exposure to the investigational drug in a clinical trial ( e.g., for advanced therapies such as gene therapy, cell therapy, or tissue-engineered products). In certain cases, the lack of effectiveness on an endpoint compared to a comparator ( e.g., cardiovascular events) can be a safety issue. Therefore, it is important to also report on studies in which there was a lack of effectiveness or lesser effectiveness relative to an active comparator, including results obtained from any completed trials or interim analysis that influenced a decision, based on lack of efficacy, to either stop a trial or to revise the documents provided to subjects when seeking informed consent.

Proposed § 312.33(m) is intended to ensure that all information that is relevant to the safety of the drug and obtained during the reporting period from any source is considered and analyzed in the report. This proposed section would require the report to briefly summarize the following safety information, if known:

• Noninterventional studies where participants are not prospectively assigned to receive a drug or other intervention per a protocol, including observational studies, epidemiological studies, registries, and active surveillance.

• Pooled or meta-analyses of randomized clinical investigations.

• Safety findings from marketing experience, if the drug is lawfully marketed in any country or region.

• Nonclinical in vivo and in vitro studies ( e.g., carcinogenicity, reproductive toxicity, immunotoxicity studies).

• Published clinical or nonclinical investigations of the drug not conducted on behalf of the sponsor.

• Published studies of other members of the drug's pharmacological class. Section 3.13 (Literature) of the E2F DSUR provides for the inclusion of information from unpublished studies of which the sponsor has become aware during the reporting period. This section of the proposed rule would require information from published studies and does not create a requirement for sponsors to seek out unpublished studies that may be related to the drug.

• All additional significant safety findings about the drug from other sources. In addition, safety information provided by codevelopment partners or safety information from investigator-initiated trials would also be captured under this bullet and is consistent with section 3.10 (Other Clinical Trial/Study Safety Information) of the E2F DSUR.

We are proposing that the report include a summary of all significant chemistry, manufacturing, and control changes, including microbiological changes (if applicable), made to the investigational drug during the reporting period and briefly describe the safety significance of the identified changes (see proposed § 312.33(n)).

We are proposing that the report briefly describe each significant modification made to protocols in response to safety data on behalf of the sponsor for clinical investigations being conducted with the investigational drug that were not previously reported under § 312.30 (see proposed § 312.33(o)). The intent of this proposed regulation is to provide awareness of significant modifications related to safety issues in trials being conducted in another country or region and not under an IND.

We are proposing that the report contain a description of the general investigational plan for the coming year to replace the plan submitted 1 year earlier (consistent with the content of the general investigational plan described in § 312.23(a)(3)(iv)) (see proposed § 312.33(p)).

We are providing the sponsor the option of including a log of any outstanding business concerning the IND for which the sponsor requests a reply, comment, or meeting (see proposed § 312.33(q)).

We are proposing that the report describe any potentially important late-breaking safety information about the investigational drug or the studies conducted under the IND that were identified by the sponsor during preparation of the annual FDA DSUR and after the data lock point (see proposed § 312.33(r)). The types of findings or actions that would be required to be described under proposed § 312.33(r) include clinically significant new adverse event reports; important follow-up data; clinically relevant toxicological findings; and actions taken for safety reasons that, if the actions had occurred before the data lock point, would have been described as required under proposed § 312.33(g). This proposed section is intended to capture findings that would have been included in the body of the report but did not come to the sponsor's awareness until after the data lock point when the sponsor was preparing the annual FDA DSUR.

We are proposing that the report provide an overall safety assessment that is a concise, integrated evaluation of all new clinical, nonclinical, and epidemiological safety information obtained by the sponsor during the reporting period relative to previous knowledge of the drug (see proposed § 312.33(s)(1)). Proposed § 312.33(s)(1) is not intended to require a repeat of information or a summary of information presented in previous sections of the annual FDA DSUR; rather, it would require an interpretation of the information and its implications for the IND. This proposed section corresponds to section 3.18.1 (Evaluation of the Risks) of the E2F DSUR, and both provide relevant points to consider (if applicable) for evaluating the risks of the drug. The integrated evaluation required under proposed § 312.33(s)(1) would include the following: (1) cumulative experience with the drug, (2) new information about the drug that was collected during the reporting period covered by the proposed annual FDA DSUR, and (3) for drugs with a marketing approval, clinically significant postmarketing data related to the drug. This proposed section of the report would explain how safety information obtained during the reporting period integrates with what was already known about the drug ( e.g., what was in prior annual FDA DSURs). The assessment must include an evaluation of the following information potentially relevant to the risk associated with use of the drug:

• Findings that suggest a significant risk in humans exposed to the drug, with associated laboratory values and relationship to dose, duration, or time course of exposure, if known.

• Significant changes to the information concerning an adverse event that was contained in a previous report ( e.g., increased frequency, increased severity, identification of a population at greater risk for this adverse event).

• Deaths that were previously included in an IND safety report required under § 312.32.

• Subject withdrawals from a clinical investigation resulting from an adverse event.

• Findings that suggest a significant risk to specific populations ( e.g., pediatric, geriatric, populations with hepatic or renal impairment, pregnant or lactating women, populations differentiated by genomic or genetic characteristics).

• Overdose, misuse, and abuse cases or findings regarding the potential for abuse to occur.

• Risks associated with long-term exposure ( e.g., a drug used to treat a chronic disease).

• Risks associated with the method of administration of the drug ( e.g., drugs administered by injection or drugs administered by intravenous, intrathecal, or inhalation methods might be associated with the risk of increased local concentrations, sterility, pyrogenicity, hypersensitivity, or variations in metabolism), diagnostic procedures related to use of the drug ( e.g., an invasive sampling procedure), or procedures described in a study protocol.

• Evidence of clinically significant medication errors ( i.e., any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of a healthcare provider, patient, or consumer).

• Drug interactions ( e.g., drug-drug, drug-food).

• Any other risks that significantly affect the safety assessment of the investigational drug.

We are proposing that the overall safety assessment also describe the balance between benefits, including theoretical or anticipated benefits, and cumulative identified risks related to use of the drug (see proposed § 312.33(s)(2)). The assessment would also be required to describe all changes to the benefit-risk profile compared to the previous annual report, based on information obtained during the reporting period. Proposed § 312.33(s)(2) is not intended to require a full benefit-risk assessment of the drug.

We are proposing that the report contain a cumulative listing of all important known risks ( i.e., risks established to be related to the use of the drug) and potential risks ( i.e., risks that have a reasonable possibility of a relationship to the drug, but have not yet been established) associated with the drug that are identified by the sponsor during the course of studies of the drug conducted on behalf of the sponsor, along with a brief description of the nature of each risk (see proposed § 312.33(t)). Such risks might include, for example, toxicities known to be associated with a particular molecular structure or drug class or concerns based on accumulating nonclinical or clinical data. Risks identified in a prior reporting period would be required to be re-evaluated annually and a description of each risk updated with new risk information obtained during the current reporting period. Risks that have been fully addressed or resolved would be required to remain in the summary and be briefly described ( e.g., findings from toxicology studies or early clinical trials that were not borne out by later clinical data).

Proposed § 312.33(t) would require a summary of all important known and potential risks, whereas proposed § 312.33(s) would provide an overall safety assessment.

We are proposing that the report include a conclusion to briefly summarize the following information: (1) all changes to the sponsor's previous knowledge of efficacy and safety of the investigational drug resulting from information obtained during the reporting period, (2) an outline of actions that the sponsor has taken during the reporting period to address emerging safety findings, and (3) all additional actions that the sponsor will take to address emerging safety findings in the future (see proposed § 312.33(u)).

FDA proposes that any final rule based on this proposed rule become effective 30 days after the final rule publishes in the Federal Register . FDA is proposing that the compliance date for any final rule based on this proposed rule be 180 days after the date of publication of such final rule to give sponsors sufficient time to compile the additional information that the proposed rule would require, if finalized. We request comments specifically regarding the proposed compliance date.

We have examined the impacts of the proposed 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). The Office of Information and Regulatory Affairs has determined that this proposed rule is an economically significant regulatory action as defined by Executive Order 12866.

The Regulatory Flexibility Act requires us to analyze regulatory options that would minimize any significant impact of a rule on small entities. Because the proposed requirements are unlikely to impose a substantial burden on the affected small entities, we propose to certify that the proposed rule will not have a significant economic impact on a substantial number of small entities.

The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires us to prepare a written statement, which includes an assessment of anticipated costs and benefits, before proposing “any rule that includes any Federal mandate that may result in the expenditure by State, local, and tribal governments, in the aggregate, or by the private sector, of $100,000,000 or more (adjusted annually for inflation) in any one year.” The current threshold after adjustment for inflation is $165 million, using the most current (2021) Implicit Price Deflator for the Gross Domestic Product. This proposed rule would not result in an expenditure in any year that meets or exceeds this amount.

The proposed rule seeks to revise FDA's regulations for IND annual reporting. The proposed rule would modify the format and content of the IND annual report to be generally consistent with those of the annual DSUR standards devised by the ICH. The proposed harmonization would result in savings in labor costs for certain sponsors who may no longer have to prepare a different type of periodic safety report for submission to certain other countries or regions in which a drug might be studied. Moreover, FDA would receive safety data on investigational new drugs that is more comprehensive, which would enhance our ability to oversee the progress and safety of clinical investigations. The estimate of annualized benefits over 10 years ranges from $47.86 million to $117.99 million with a primary value of $86.46 million at a 7 percent discount rate and from $49.24 million to $121.01 million with a primary value of $88.79 million at a 3 percent discount rate. The primary estimate of the present value of benefits over 10 years is $607.29 million at a 7 percent discount rate and $757.38 million at a 3 percent discount rate.

Costs would arise from increased labor associated with preparing and submitting a periodic safety report that is more comprehensive to meet the proposed requirements. Costs to government would arise from increased FDA resources being used to review the more comprehensive report. The estimate of annualized costs over 10 years ranges from $40.43 million to $101.34 million at a 7 percent discount rate with a primary value of $61.11 million. Using a 3 percent discount rate, the annualized costs range from $40.89 million to $102.48 million with a primary value of $61.81 million. The primary estimate of the present value of costs over 10 years is $429.20 million at a 7 percent discount rate and $527.21 million at a 3 percent discount rate. The annualized estimates are presented in Table 2.

We estimate that at least 77 percent of establishments in the pharmaceutical preparations industry and at least 69 percent of establishments in the biological products industry employ fewer than 1,250 employees and are therefore also classified as small businesses. Although a large number of small businesses will face costs under the proposed rule, the costs to these firms would be relatively small. The average annual cost per IND annual report as a percentage of average value of shipments for small entities is estimated to be between 0.00 percent and 0.61 percent. We therefore conclude that this proposed rule is unlikely to have a significant impact on a substantial number of small entities.

We have developed a comprehensive Preliminary Economic Analysis of Impacts that assesses the impacts of the proposed rule. The full preliminary analysis of economic impacts is available in the docket for this proposed rule (Ref. 8) and at https://www.fda.gov/about-fda/reports/economic-impact-analyses-fda-regulations.

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.

This proposed rule contains information collection provisions that are subject to review by OMB under the PRA (44 U.S.C. 3501-3521). A description of these provisions is given in the Description section with an estimate of the annual reporting burden. Included in the estimate is the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing each collection of information.

FDA invites comments on these topics: (1) whether the proposed collection of information is necessary for the proper performance of FDA's functions, including whether the information will have practical utility; (2) the accuracy of FDA's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility, and clarity of the information to be collected; and (4) ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology.

Title: Investigational New Drug Application Annual Reporting.

Description: FDA is proposing to revise its requirements for annual reports submitted to INDs. FDA is proposing to replace the current annual reporting requirement with a new annual reporting requirement that is intended to be generally consistent with the format and content of submission of the annual DSUR devised by the ICH and described in the E2F DSUR. The proposed annual FDA DSUR would provide an annual report that is more comprehensive and informative than the IND annual report required under current § 312.33. The E2F DSUR can be used to satisfy similar annual reporting requirements in certain other countries and regions in which a drug is being studied. Therefore, the proposed implementation of an annual reporting requirement similar to the E2F DSUR in place of the IND annual report format and content is consistent with FDA's overarching goal of fostering international harmonization of regulatory requirements to the extent appropriate and feasible. With the increasing complexity of clinical studies, DSURs that are more comprehensive and informative are important tools to identify and reduce exposure of human subjects to unnecessary risks. The proposed annual FDA DSUR would also help ensure FDA's ongoing oversight of the evolving safety and efficacy profile of the drug throughout the drug development process. We anticipate an additional regulatory burden associated with preparing the proposed annual FDA DSUR. However, for sponsors that currently prepare and submit the IND annual report to FDA and the E2F DSUR to another regulatory authority in another country or region, FDA expects that the burden associated with preparing two periodic safety reports will be reduced because the sponsors might no longer have to prepare two different annual safety reports, because the annual FDA DSUR and the E2F DSUR would be generally consistent in content and format.

Description of Respondents: Sponsors of clinical investigations under an IND.

In tables 4 and 5, the estimated averages for the number of respondents and total annual responses were obtained from CDER and CBER reports and data management systems.

In the approved package for OMB control number 0910-0014, FDA estimated 360 burden hours to complete and submit an IND annual report. To complete and submit the annual FDA DSUR, FDA estimates that a sponsor would spend an additional 18 to 72 hours because of the more comprehensive information not currently required by the IND annual report. Thus, we estimate that sponsors will spend a total of 396 hours to comply with the proposed requirement. The estimated average burden hours per response was made by CDER and CBER individuals familiar with the burden associated with these reports and from estimates received from the pharmaceutical industry. For the total information collection burden for preparing and submitting an annual FDA DSUR, FDA estimates 4,590,432 hours (3,855,456 CDER hours + 734,976 CBER hours = 3,430,944). The estimated 4,590,432 total hours includes 4,173,120 total hours to submit an IND annual report and 417,312 additional total hours to provide the additional information required in the annual FDA DSUR.

This proposed rule also refers to previously approved collections of information found in FDA regulations. The collections of information in part 312 have been approved under OMB control number 0910-0014.

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

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

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

The following references marked with an asterisk (*) are on display at the Dockets Management Staff (see ADDRESSES ) and are available for viewing by interested persons between 9 a.m. and 4 p.m., Monday through Friday; they are also available electronically at https://www.regulations.gov. References without asterisks are not on public display at https://www.regulations.gov because they have copyright restriction. Some may be available at the website address, if listed. References without asterisks are available for viewing only at the Dockets Management Staff. FDA has verified the website addresses as of the date this document publishes in the Federal Register , but websites are subject to change over time.

Therefore, under the Federal Food, Drug, and Cosmetic Act and under authority delegated to the Commissioner of Food and Drugs, it is proposed that 21 CFR part 312 be amended as follows:

On November 9, 2022, the National Marine Fisheries Service published a Notice of Availability (NOA) and request for comments on Amendment 123 to the Fishery Management Plan for Groundfish of the Bering Sea and Aleutian Islands Management Area (BSAI FMP) (87 FR 67665, November 9, 2022). After inquiries from the public, NMFS realized that a supporting document containing the revised BSAI FMP text was not made available for public review with the November 9, 2022 publication of the NOA. The BSAI FMP revised text was posted to regulations.gov on December 2, 2022. With this notification, NMFS is extending the comment period on the FMP Amendment to provide 60 days from the date of publication of this notification in the Federal Register .

NMFS is soliciting public comments on proposed Amendment 123 through the end of the comment period (see DATES ). NMFS is separately seeking public comment on a proposed rule that would implement Amendment 123.

Respondents do not need to submit the same comments on Amendment 123 and the proposed rule. All relevant written comments received by the end of the applicable comment period, whether specifically directed to the BSAI FMP amendment or the proposed rule will be considered by NMFS in the approval/disapproval decision for Amendments 123 and addressed in the response to comments in the final rule. Comments received after the end of the applicable comment period will not be considered in the approval/disapproval decision on Amendment 123. To be considered, comments must be received, not just postmarked or otherwise transmitted, by the last day of the comment period (see DATES ).

NMFS manages the United States (U.S.) groundfish fisheries in the exclusive economic zone (EEZ) of the BSAI under the BSAI FMP. The North Pacific Fishery Management Council (Council) prepared, and the Secretary of Commerce (Secretary) approved, the BSAI FMP under the authority of the Magnuson-Stevens Act, 16 U.S.C. 1801 et seq. Regulations governing U.S. fisheries and implementing the BSAI FMP appear at 50 CFR parts 600 and 679. The Council is authorized to prepare and recommend an FMP amendment for the conservation and management of a fishery managed under the FMP. NMFS conducts rulemaking to implement FMP amendments and related regulatory amendments. FMP amendments and regulations developed by the Council may be implemented by NMFS only after approval by the Secretary.

A notice of availability (NOA) for Amendment 123 was published in the Federal Register on November 9, 2022, with comments invited through January 9, 2023. Comments submitted on this proposed rule by the end of the comment period (See DATES ) will be considered by NMFS and addressed in the response to comments in the final rule. Comments submitted on this proposed rule may address Amendment 123 or this proposed rule. However, all comments addressing Amendment 123 must be received by January 9, 2023, to be considered in the approval/disapproval decision on Amendment 123. Commenters do not need to submit the same comments on both the NOA and this proposed rule. All relevant written comments received by January 9, 2023, whether specifically directed to Amendment 123, this proposed rule, or both will be considered by NMFS in the approval/disapproval decision for Amendment 123 and addressed in the response to comments in the final rule.

In December 2021, the Council voted to recommend Amendment 123 to link the halibut PSC limit to halibut abundance for the Amendment 80 ( i.e., non-pollock) commercial groundfish trawl fleet in the BSAI groundfish fisheries. In recommending Amendment 123, the Council intended to minimize halibut PSC to the extent practicable as required by section 303(a)(11) and National Standard 9 of the Magnuson-Stevens Act and to continue achieving optimum yield in the BSAI groundfish fisheries on a continuing basis under National Standard 1. The Council weighed and balanced the Magnuson-Stevens Act's legal requirements, including the ten national standards. Based on public comment, the analysis prepared pursuant to the National Environmental Policy Act (NEPA), and analyses under Executive orders and related laws that were included in the NEPA documentation, the Council selected to recommend Amendment 123 to NMFS.

This action would provide incentives for the Amendment 80 fleet to minimize halibut mortality at all times. Achievement of these objectives would conserve the halibut resource by improving bycatch management and could result in additional harvest opportunities in the directed commercial and subsistence halibut fisheries. To implement Amendment 123, in this action, NMFS proposes regulations that would link the halibut PSC limit to halibut abundance for the Amendment 80 commercial groundfish trawl fleet in the BSAI groundfish fisheries.

Pacific halibut is fully utilized in Alaska as a target species in subsistence, personal use, recreational (sport), and commercial halibut fisheries. Halibut has significant social, cultural, and economic importance to fishery participants and fishing communities throughout the geographical range of the resource. Halibut is also incidentally taken as bycatch in commercial groundfish fisheries. The Magnuson-Stevens Act defines bycatch as fish that are harvested in a fishery, but are not sold or kept for personal use, and includes economic and regulatory discards. 16 U.S.C. 1802(2). The term does not include fish released alive under a recreational catch and release fishery management program.

The International Pacific Halibut Commission (IPHC) adopts regulations governing the target fishery for Pacific halibut under the Convention between the United States and Canada for the Preservation of the Halibut Fishery of the Northern Pacific Ocean and Bering Sea (Convention), signed at Ottawa, Ontario, on March 2, 1953, as amended by a Protocol Amending the Convention (signed at Washington, DC, on March 29, 1979). As provided by the Northern Pacific Halibut Act of 1982 (Halibut Act) (16 U.S.C. 773-773k), the Secretary of State, with the concurrence of the Secretary of Commerce, may accept or reject, on behalf of the United States, regulations recommended by the IPHC in accordance with the Convention. The Halibut Act provides the Secretary of Commerce with the authority and general responsibility to carry out the requirements of the Convention and the Halibut Act. After acceptance by the Secretary of State and concurrence by the Secretary of Commerce, NMFS publishes the IPHC regulations in the Federal Register as annual management measures pursuant to 50 CFR 300.62.

Section 773c(c) of the Halibut Act also provides the Council with authority to develop regulations that are in addition to, and not in conflict with, approved IPHC regulations. The Council has exercised this authority in the development of Federal regulations for the halibut fishery such as (1) subsistence halibut fishery management measures, codified at 50 CFR 300.65; (2) the limited access program for charter vessels in the guided recreational fishery, codified at 50 CFR 300.67; and (3) the Individual Fishing Quota (IFQ) Program for commercial halibut fisheries, codified at 50 CFR 679.40 through 679.45.

In recent years, catch limits for the commercial halibut fishery in the BSAI have generally declined in response to decreasing halibut spawning biomass (though the catch limits increased slightly in 2021), while limits on the maximum amount of halibut bycatch allowed in the groundfish fisheries have remained the same since 2016, when they were reduced under BSAI FMP Amendment 111. The proposed rule would set annual halibut bycatch limits, also referred to as halibut PSC limits, in the BSAI Amendment 80 sector groundfish fisheries based on halibut abundance. This proposed approach for setting halibut PSC limits is consistent with the requirements of the Magnuson-Stevens Act to minimize bycatch to the extent practicable while achieving, on a continuing basis, optimum yield from the groundfish fisheries. This section of the preamble provides background on the halibut resource, halibut management, the halibut fisheries, and halibut bycatch in the groundfish fisheries in the BSAI. Sections III and IV describe the rationale and impacts of Amendment 123 and this proposed rule.

This preamble relies on the best data available consistent with the final Environmental Impact Statement/Regulatory Impact Review (collectively referred to as the “Analysis”) prepared to support this action.

Section 4.0 of the Analysis describes the stock assessment process and IPHC management framework for halibut in Alaska. A brief summary of section 4.0 follows.

The IPHC assesses the status of the Pacific halibut stock at a coastwide level from California through the Bering Sea. The IPHC assesses female spawning biomass as one important indicator of the status of the halibut stock, including the long-term reproductive health of the halibut resource. Female spawning biomass is composed of female halibut of reproductive size. Generally, this includes female halibut that are 26 inches (66.04 centimeters) in length or greater (O26), and a small proportion of the female spawning biomass includes female halibut less than 26 inches in length (U26).

The IPHC conducts an annual stock assessment for the coastwide halibut stock. Currently, the stock assessment for halibut uses four integrated age-structured models in an ensemble resulting in a single value for the entire coast (U.S. and Canada). Migration between the halibut management areas is not modeled. The IPHC's data indicate that the Pacific halibut stock declined continuously from the late 1990s to around 2012, largely as a result of decreasing size at a given age (size-at-age), higher harvest rates in the early 2000s, and weaker recruitment (the process by which new fish are incorporated into the stock) than observed during the 1980s. From about 2013 to 2016, there was a slight increasing trend in the spawning biomass, followed by a slight decline continuing into the current assessment. In recent years, the spawning biomass projections continue to indicate slight decreases, even at low fishing levels, due to recent below-average recruitment. The stock assessment models used by the IPHC in 2020 project a decreasing female spawning biomass over the next few years assuming continued current removal rates from all sources (see Figure 4-3 in section 4.2 of the Analysis).

Notably, halibut is not a groundfish species under the BSAI FMP and is instead managed under an international agreement; therefore, halibut is not subject to provisions of the Magnuson-Stevens Act that require the establishment of an annual overfishing limit (OFL), an acceptable biological catch level (ABC), or a total allowable catch (TAC) limit.

Although halibut is not managed under an OFL, ABC, or TAC, the IPHC has developed a harvest policy to control removals based on stock abundance. In 2017, the IPHC implemented an interim spawning potential ratio (SPR)-based harvest strategy policy while a management strategy evaluation (MSE) process is underway. An SPR-based harvest policy defines a default or reference level of fishing intensity to determine mortality limits. The reference level of fishing intensity is the level of fishing that would reduce the lifetime spawning output per recruit to some percentage of the unfished level. That percent of the unfished level is also dependent on current biology, fishery characteristics, and demographics. Lower values of spawning output per recruit indicate higher fishing intensity (see section 4.4 of the Analysis). The IPHC MSE simulations found that a level of fishing intensity corresponding to an SPR of 43%, in conjunction with a control rule where the fishing intensity is reduced when the stock status is estimated to be below 30 percent and set to zero when stock status is estimated to be below 20 percent, would successfully meet the coastwide conservation and fishery objective outlined by the IPHC. Additional information on the anticipated impacts of the proposed rule on the status of halibut stock is provided in section 5.2 of the Analysis.

The IPHC's harvest control rule reduces fishing intensity linearly if the stock is estimated to have fallen below the 30 percent threshold. As described in the preceding paragraph, this harvest control rule would severely curtail removals during times of particularly poor stock conditions. To date, the harvest control rule has not been triggered, even during the most recent years of relatively low exploitable biomass (see section 3.1.1.1 and section 3.1.2.1 of the Analysis). While the harvest control rule has not been triggered, the total mortality limits established by the IPHC have decreased substantially, with the exception of 2021 (see Table 4-3 in the Analysis), corresponding to the low halibut abundance conditions.

Each year, the most recent stock assessment ensemble is presented to the IPHC as a risk-based decision matrix that combines different catch levels and various performance metrics. The IPHC uses the interim SPR-based approach to recommend to the Commission a coastwide commercial catch limit, also known as a mortality limit, considering mortality from all sources, and then distributes the mortality limit across regulatory areas using estimates of stock distribution from the IPHC fishery independent setline survey, relative harvest rates, and other pertinent information. The Commission can set total mortality limits that do not follow the harvest policy, such as to address socioeconomic considerations.

The IPHC evaluates halibut mortalities using a combination of two metrics: (1) the Total Constant Exploitation Yield (TCEY), which includes harvests and incidental discard mortalities from directed commercial fisheries, plus mortality estimates from sport, subsistence, personal use, and estimates of non-directed discard mortality of halibut over 26 inches; and, (2) Total Mortality, which includes all the above sources of mortality, plus estimates of non-directed discard mortality of halibut less than 26 inches (U26). Although U26 halibut mortality is factored into the stock assessment and harvest strategy calculations, the IPHC delineates U26 and O26 differently for the following reasons: (1) U26 Pacific halibut are highly mobile and much less likely to occur in the same regulatory area in the upcoming year in which PSC limits would apply, (2) the setline survey captures almost exclusively O26 Pacific halibut, (3) there is currently no reliable tool for describing the annual distribution of U26 halibut across the entire convention area, and (4) the mortality of U26 Pacific halibut has a differing effect on the SPR than O26 fish (they are not entirely exchangeable).

The IPHC considers the TCEY distribution among regulatory areas based on estimates of biomass from the setline survey and relative harvest rates, then considers recommendations from the IPHC's advisory boards, public input, and social and economic factors to potentially adjust the TCEYs among regulatory areas. Unlike the Magnuson-Stevens Act, the Halibut Act does not include specific provisions that require the IPHC to allocate quotas within, for example, an overfishing threshold; the IPHC's broad mandate is the conservation of the halibut stock.

Due to a combination of changing IPHC harvest policies and decisions that depart from harvest policy recommendations, the IPHC has adopted coastwide catch limits of varying fishing intensities in recent years. The IPHC has adopted TCEYs above those recommended by the harvest policy in three of the last five years (Table 4-1 of the Analysis). Estimates of fishing intensity are uncertain and may change in subsequent years based on actual mortality and new stock assessments. Further, the specific formula used by the IPHC Commissioners to distribute catch limits among regulatory areas has been different for each of the past three years.

The Fishery Constant Exploitation Yield (FCEY) represents the directed fishery limits that result from the IPHC's adopted TCEYs. To calculate the FCEYs from the TCEYs, all sources of O26 halibut mortality are considered, such as unguided recreational fisheries, subsistence/personal use fisheries, and directed and non-directed commercial fishing discard mortalities. The default projection for U26 and O26 discards is to use the three-year average of recent discard mortality to minimize the effect of interannual variability of annual discard estimates. (IPHC AM096). Section 4.4.1 of the Analysis contains additional information on the process the IPHC uses to set catch limits.

Pacific halibut is allocated among fisheries by a combination of management actions taken by the IPHC, the Council, and NMFS. The IPHC annually completes a halibut stock assessment and makes recommendations for annual management measures for the halibut fishery within Convention waters. These annual management measures include specific regulations governing the commercial halibut fishery, including area-specific catch limits, authorized gear, and fishing season dates. In the United States, the IPHC recommendations are subject to acceptance by the Secretary of State with the concurrence of the Secretary of Commerce, as described above in the “Authority for Action” section of this preamble. (See sections 1.1 and 4.4.1 of the Analysis and the 2022 annual management measures for additional information on the process for establishing commercial halibut fishery catch limits (87 FR 11626, March 02, 2022).)

Although the halibut stock is assessed at a coastwide level, commercial catch limits are established for each of the IPHC regulatory areas: 2A (Washington, Oregon, and California), 2B (British Columbia), 2C (Southeast Alaska), 3A (Central Gulf of Alaska), 3B (Western Gulf of Alaska), and 4A, 4B, 4C, 4D and 4E (BSAI). The IPHC combines Areas 4C, 4D, and 4E into Area 4CDE for purposes of establishing a commercial fishery catch limit. Areas 4A, 4C, 4D, and 4E roughly correspond to the Bering Sea Subarea defined in the FMP, with Area 4CDE encompassing most of the Bering Sea Subarea in the FMP. Area 4B roughly corresponds to the Aleutian Islands Subarea in the FMP. See Figure 15 in part 679 and Table 1-3 in section 1.5 of the Analysis for Area maps and additional information on halibut and groundfish management areas in the BSAI.

In the BSAI (Area 4) halibut is harvested primarily in directed commercial fisheries and secondarily in subsistence, personal use, and recreational fisheries. Based on harvest data from 2016 through 2019, the recreational fishery operating out of ports in the BSAI harvests approximately 12,000 lb (5.44 metric tons (mt)) in Area 4 compared to approximately 50,000 lb (22.68 mt) of subsistence and personal use harvest from Area 4, and more than 5,000,000 lb (2287.96 mt) in the Area 4 commercial fishery. This action is not likely to impact the recreational fishery. BSAI recreational effort and removals are both very limited. Therefore, this preamble does not address the recreational fishery in additional detail. (See sections 4.5, 5.4, and 5.5 of the Analysis for additional detail on subsistence, personal use, recreational, and commercial halibut harvests in Area 4.)

Subsistence halibut is caught by rural residents and members of Alaska Native tribes for direct personal or family consumption as food, sharing for personal or family consumption as food, or customary trade. Pursuant to section 773c(c) of the Halibut Act, the Council developed, and NMFS implemented, the Subsistence Halibut Program to manage subsistence harvests in Alaska. Persons fishing for subsistence halibut must obtain a Subsistence Halibut Registration Certificate. Special permits for community harvest, ceremonial, and educational purposes also are available to qualified Alaska communities and federally-recognized Alaska Native tribes. A complete description of the Subsistence Halibut Program is provided in the final rule implementing the Program (68 FR 18145, April 15, 2003).

In addition to subsistence harvest, IPHC annual management measures allow halibut caught in the commercial halibut fishery that are less than the legal size limit of 32 inches (81.28 centimeters) to be retained for personal use in the Area 4D and Area 4E Community Development Quota (CDQ) halibut fishery as long as the fish are not sold or bartered. The CDQ groups are required to report the amount of personal use halibut retained during the CDQ halibut fishery to the IPHC. Sections 4.5.1.2 and 5.4 of the Analysis contain descriptions of the personal use fishery.

The commercial halibut fishery in the BSAI is managed by NMFS under the Individual Fishing Quota (IFQ) and CDQ Programs that allocate exclusive harvest privileges. The IFQ Program was implemented in 1995 (58 FR 59375, November 9, 1993). The Council and NMFS designed the IFQ Program to end a wasteful and unsafe “race for fish” and to maintain the social and economic character of the fixed-gear fisheries and the coastal fishing communities where many of these fisheries are based. Access to the halibut and sablefish fisheries is limited to those persons holding quota share (QS). Quota shares equate to exclusive harvesting privileges that are given effect on an annual basis through the issuance of IFQ permits. An annual IFQ permit authorizes the permit holder to harvest a specified amount of IFQ halibut or sablefish in a NMFS regulatory area.

The CDQ Program was established in 1992 (57 FR 54936, November 23, 1992) and amended substantially by the Coast Guard and Maritime Transportation Act of 2006 (Pub. L. 109-241 § 416; 120 Stat. 541). Under section 305(i)(1)(D) of the Magnuson-Stevens Act, a total of 65 villages are authorized to participate in the CDQ Program. Six CDQ groups represent these villages. CDQ groups manage and administer allocations of crab, groundfish, and halibut to commercial fisheries and use the revenue derived from the harvest of these CDQ allocations to fund economic development activities and provide employment opportunities on behalf of the villages they represent. See sections 3.3.4 and 4.5.1.2 of the Analysis for additional information on the CDQ Program.

Section 305(i)(1)(B) of the Magnuson-Stevens Act specifies the proportion of crab, groundfish, and halibut in the BSAI allocated to the CDQ Program. Section 305(i)(1)(C) of the Magnuson-Stevens Act specifies the proportion of the overall CDQ Program allocations assigned to each CDQ group. Each year, NMFS publishes the specific annual allocations to each CDQ group on the NMFS Alaska Region website at: https://www.fisheries.noaa.gov/alaska/commercial-fishing/fisheries-catch-and-landings-reports-alaska. The amount of halibut for commercial harvest allocated to the CDQ Program varies by Area and ranges from 20 to 100 percent of the commercial catch limits assigned to Areas 4B, 4C, 4D, and 4E.

The combined CDQ and IFQ halibut fisheries in Area 4 were harvested by, on average, approximately 120 vessels from 2015 through 2019 (see Table 4-7 in section 4.5.1 of the Analysis). The CDQ and IFQ halibut fisheries provide revenue to vessel owners and crew members who harvest halibut. These fisheries also provide economic benefits to shore-based processors and socioeconomic benefits to BSAI fishing communities that provide support services to the halibut harvesting and processing sectors. The Analysis estimates that halibut harvests in the Area 4 CDQ and IFQ fisheries averaged 5.1 million lb (2,313.32 mt) annually and generated an average of $21 million in ex-vessel revenues annually from 2015 through 2019.

However, Area 4 halibut ex-vessel revenues declined over this period, resulting in negative economic impacts for fishery participants and affected fishing communities. Since 2015, the Area 4 ex-vessel value has declined by 32 percent from the peak value of $24.9 million in 2016 to a low of $16.9 million in 2018 due to changing market conditions, while catch levels of halibut in Area 4 have remained relatively constant. The declines in ex-vessel value of commercial halibut were greatest in Areas 4A and 4B. See section 4.5.1 of the Analysis for a more detailed description of the Area 4 commercial halibut catch, revenue, and fishery participants.

In Area 4, the specific proportion of halibut removals that are taken as catch in the commercial halibut fishery or as PSC in the groundfish fisheries has shifted over time. From 1990 to 1996 (the period prior to the recent peak and decline in removals in the halibut fishery), the commercial halibut fisheries averaged 37 percent, and PSC averaged 60 percent of total halibut removals in Area 4. From 1997 to 2011 (the period of both the greatest increase and subsequent decline in the total removals of halibut), the commercial halibut fishery removals increased as a portion of total removals; the commercial halibut fisheries averaged 57 percent and PSC averaged 41 percent of total halibut removals. From 2012 through 2014, the commercial halibut fishery removals decreased as a portion of total removals; the commercial halibut fishery averaged 41 percent and PSC averaged 55 percent of total removals. Halibut PSC limits were reduced in 2016, but since 2016 the proportion of halibut removals from the commercial halibut fishery has increased. From 2016 through 2019, the commercial halibut fishery averaged 52 percent and bycatch averaged 47 percent of total removals. See sections 3.4.1, 4.5.1 and 5.4.1 of the Analysis for additional detail.

The Magnuson-Stevens Act authorizes the Council and NMFS to manage groundfish fisheries in the Alaska EEZ that take halibut as PSC, or bycatch. Every FMP must minimize bycatch to the extent practicable, 16 U.S.C. 1853(a)(11), and be consistent with the Act's ten national standards, 16 U.S.C. 1851(a)(1)-(10). The groundfish fisheries cannot be prosecuted without some level of halibut bycatch because groundfish and halibut occur in the same areas at the same times and no fishing gear or technique has been developed that can harvest commercial quantities of groundfish while avoiding all halibut bycatch. The Council has designated Pacific halibut and several other species (herring, salmon and steelhead, king crab, and Tanner crab) as “prohibited species” (section 3.6.1 of the FMP). Regulations implement the Act's requirements and require that the operator of any vessel fishing for groundfish in the BSAI minimize the catch of prohibited species (50 CFR 679.21(a)(2)(i)).

Halibut incidental catch rates are based on NMFS-certified fisheries observers' estimates of halibut incidental catch in the groundfish fishery. Discard mortality rates (DMR) are estimates of the proportion of incidentally caught halibut that do not survive after being returned to the sea. The cumulative halibut mortality that accrues to a particular halibut PSC limit is the product of a DMR multiplied by the estimated halibut PSC. DMRs are estimated using the best scientific information available in conjunction with the annual BSAI stock assessment process. The DMR methodology and findings are included as an appendix to the annual BSAI groundfish SAFE report beginning in 2022.

Although halibut PSC results from all types of gear (trawl, hook-and-line, pot, and jig gear), halibut PSC primarily occurs in the trawl and hook-and-line groundfish fisheries. NMFS minimizes halibut bycatch to the extent practicable in the BSAI by (1) establishing halibut PSC limits for trawl and non-trawl fisheries; (2) apportioning those halibut PSC limits to groundfish sectors, fishery categories, and seasons; and (3) managing groundfish fisheries to prevent PSC from exceeding the established limits. The following sections provide additional information on the process NMFS uses to establish, apportion, and manage halibut PSC limits in the BSAI.

Halibut PSC limits in the groundfish fisheries provide a constraint on halibut PSC mortality and promote conservation of the halibut resource. With one limited exception for Atka mackerel at 50 CFR 679.21(b)(4)(i)(A), groundfish fishing is prohibited once a halibut PSC limit has been reached for a particular sector or season. Therefore, halibut PSC limits are set to balance conservation of the halibut resource with the needs of fishermen, fishing communities, and U.S. consumers who depend on both halibut and groundfish resources.

The Council and NMFS have taken a number of management actions to minimize halibut bycatch to the extent practicable in the BSAI groundfish fisheries. Most recently, the Council adopted, and NMFS approved, Amendment 111 to the FMP for Groundfish of the BSAI management area in 2016 (81 FR 24714, April 27, 2016). That amendment established the current halibut PSC limits for BSAI groundfish fisheries, which were considered to be an effective means to minimize bycatch to the extent practicable at that time. The current total annual halibut PSC limit for BSAI groundfish fisheries is 3,515 mt. From that total, 1,745 mt are apportioned to the Amendment 80 sector, which is comprised of non-pollock trawl vessels (see the next sections for more detail on the Amendment 80 sector). The BSAI trawl limited access sector, which is comprised of all other trawl catcher/processor and trawl catcher vessels, is apportioned 745 mt. The BSAI non- trawl sector, which includes primarily hook-and-line catcher/processors, is apportioned 710 mt. The remaining 315 mt are apportioned to the CDQ program, which is comprised of vessels fishing for CDQ groups.

Of those four BSAI groundfish fishery sectors, the Amendment 80 sector receives the largest proportion of halibut PSC limits in the BSAI (roughly 50 percent). Therefore, the Council recommended, and NMFS agrees, that this proposed action should focus on the halibut PSC limit for the Amendment 80 sector. Several reasons drove this decision, as discussed below.

When it took final action on Amendment 111 in December 2015 to reduce the PSC limits for all fishing sectors in the BSAI, the Council considered the methods available to the fisheries and the practicability of reducing halibut bycatch and mortality at that time. The preamble to the proposed rule to implement Amendment 111 noted that the Council and NMFS believed that more stringent PSC limit reductions than those proposed were not practicable for the groundfish sectors at that time. However, at the same meeting, the Council noted that additional halibut bycatch reduction would be needed in the future and initiated analysis of means to link halibut PSC limits to halibut abundance, thereby indicating that additional efforts would be required beyond those established by Amendment 111 and utilized by the fisheries to reduce halibut bycatch and mortality. From 2015 (when the Council requested the Amendment 80 sector to proactively reduce halibut mortality ahead of Amendment 111's regulatory PSC limit reductions expected to be implemented in 2016) through 2020, the Amendment 80 sector reduced its halibut mortality to levels well below the PSC limit of 1,745 mt established under Amendment 111. Those reductions resulted in halibut mortality levels close to or below the PSC limit that would be implemented by this proposed rule based on halibut abundance estimates derived from current survey indices described below (see section 3.4.1 of the Analysis).

Notably, the ratio of estimated halibut PSC mortality (halibut bycatch with the DMR applied) to actual halibut bycatch (described in section 3.4.4 of the analysis as effective mortality) declined from 2015 through 2019. A slight uptick in effective mortality in 2020 was an artifact of greatly reduced halibut bycatch; that is, the reduced bycatch resulted in a slight increase in the ratio of mortality to bycatch. While many variables may have contributed to that relative decline, section 3.4.1 of the Analysis provides a compelling correlation between effective mortality and halibut deck sorting effort, which allows halibut to be returned to the sea more quickly thereby reducing mortality. Deck sorting efforts were increasingly employed by the Amendment 80 sector beginning in 2015. Thus, the Council and NMFS's concerns in 2015 over a potential lack of effective tools to reduce mortality and the practicability of meeting more stringent PSC limit reductions at that time have significantly been alleviated, at least with respect to the Amendment 80 sector, as evidenced by successful halibut mortality reductions. This proposed rule and BSAI FMP Amendment 123 represent the continuation of the Council's and NMFS's intent, as envisaged at the time of adoption of Amendment 111, to further reduce halibut bycatch and mortality and link halibut PSC limits to halibut abundance.

At its February 2020 meeting, the Council elected to focus its next step in halibut bycatch reduction on the Amendment 80 fleet. The Council's rationale was based on several factors: (1) the Amendment 80 fleet halibut bycatch and mortality comprised the largest proportion of the BSAI halibut PSC; (2) halibut bycatch in some other sectors had been or was being addressed under separate actions, e.g., the trawl limited access (TLAS) halibut PSC, the second largest portion of halibut PSC, is mainly taken in the directed Pacific cod and yellowfin sole fisheries, and halibut bycatch in the BSAI TLAS yellowfin sole fishery was addressed under BSAI FMP Amendment 116 (83 FR 49994, October 4, 2018), and the Council has recommended to NMFS a Pacific Cod Trawl Cooperative Program (PCTC) which will address halibut bycatch in the directed Pacific cod fishery; (3) other sectors were removed from this action ( e.g. freezer longline, catcher vessel hook-and-line, CDQ) because they are apportioned a relatively small proportion of the annual halibut PSC limit compared to the first two sectors; and (4) a step-wise approach by sector allowed for a simplified and more efficient approach. Because this proposed action directly impacts only the Amendment 80 sector's halibut PSC, no further discussion of the other sectors is provided in this preamble. That said, the Council has indicated that it may consider additional action to reduce other sectors' halibut PSC in addition to the past and present actions noted above.

Fishing under the Amendment 80 Program began in 2008 (72 FR 52668, September 14, 2007). The Amendment 80 sector comprises trawl vessels in the BSAI active in groundfish fisheries other than Bering Sea pollock. The Amendment 80 species are identified in regulation (50 CFR 679.2) as the following six species: BSAI Atka mackerel, Aleutian Islands Pacific ocean perch, BSAI flathead sole, BSAI Pacific cod, BSAI rock sole, and BSAI yellowfin sole. The Amendment 80 Program allocates a portion of the TACs of these species between the Amendment 80 fleet and other fishery participants. The Amendment 80 Program also allocates crab and halibut PSC limits to constrain bycatch of these species while Amendment 80 vessels harvest groundfish.

At its inception, the Amendment 80 Program allocated QS for the six specified species based on the historical catch of these species by Amendment 80 vessels. The Amendment 80 Program allows and facilitates the formation of Amendment 80 cooperatives among QS holders who receive an exclusive harvest privilege. This exclusive harvest privilege allows Amendment 80 cooperative participants to collaboratively manage their fishing operations and more efficiently harvest groundfish allocations and PSC limits.

The Amendment 80 sector includes vessels that focus primarily on flatfish ( i.e., flathead sole, rock sole, and yellowfin sole) and vessels that focus on Atka mackerel. In 2020, 22 fishing permits were issued to vessels in the Amendment 80 sector. Overall, 56 percent of the Amendment 80 sector's QS units were for flatfish ( i.e., flathead sole, rock sole, and yellowfin sole), 29 percent were for Aleutian Island Pacific ocean perch or Atka mackerel, and 15 percent were for Pacific cod. Section 3.3 of the Analysis provides more detailed information on Amendment 80 sector participants, harvests, and revenues in the BSAI groundfish fisheries.

Annually, each Amendment 80 QS holder elects to participate in either a cooperative or the Amendment 80 limited access fishery. Participants in the Amendment 80 limited access fishery do not receive an exclusive harvest privilege for a portion of the TACs allocated to the Amendment 80 Program. Since 2011, the Amendment 80 sector has been prosecuted exclusively by vessels operating as part of a cooperative, and all QS holders have participated in one of two cooperatives. From 2011 to 2017 there were two cooperatives; since 2017, all active Amendment 80 vessels are part of a single cooperative, the Alaska Seafood Cooperative (AKSC).

As specified in section 3.7.5.2 of the FMP and at 50 CFR 679.91, NMFS annually establishes a halibut PSC limit of 1,745 mt for the Amendment 80 sector. This halibut PSC limit is apportioned between the Amendment 80 cooperative(s) and the Amendment 80 limited access fishery according to the process specified at 50 CFR 679.91. Amendment 80 cooperatives are responsible for coordinating members' fishing activities to ensure the cooperative halibut PSC allocation is not exceeded. 50 CFR 679.91(h)(3)(xvi) prohibits each Amendment 80 cooperative from exceeding the halibut PSC limit specified on its annual Amendment 80 Cooperative Quota (CQ) permit. The regulations further specify that each member of the Amendment 80 cooperative is jointly and severally liable for any violations of the Amendment 80 Program regulations while fishing under the authority of an Amendment 80 CQ permit.

In a year when there are vessels participating in the Amendment 80 trawl limited access fishery, NMFS apportions the halibut PSC limit for that fishery among the following six fishery categories: (1) yellowfin sole, (2) rock sole/flathead sole/“other flatfish,” (3) Greenland turbot/arrowtooth flounder/Kamchatka flounder/sablefish, (4) rockfish, (5) Pacific cod, and (6) pollock/Atka mackerel/“other species,” which includes the midwater pollock fishery (see 50 CFR 679.21(e)(3)(i)(B), (e)(3)(ii)(C), and (e)(3)(iv)).

NMFS manages the Amendment 80 trawl limited access fishery halibut PSC allowances, because participants in the Amendment 80 trawl limited access fishery do not have exclusive privileges to use a specific amount of halibut PSC. To manage halibut PSC, NMFS monitors participation and PSC use in the Amendment 80 trawl limited access fishery categories. As noted above, except for the pollock/Atka mackerel/other species fishery, NMFS is authorized to close directed fishing for a trawl fishery category in the Amendment 80 trawl limited access fishery if NMFS concludes that the fishery category will or has exceeded its halibut PSC allowance. NMFS enforces a halibut PSC allowance through the prohibition against conducting any fishing contrary to an inseason action, closure, or adjustment (50 CFR 679.7(a)(2)).

Section 3.3 of the Analysis and the final rule implementing the Amendment 80 Program (72 FR 52668, September 14, 2007) provide more detailed information on the process NMFS uses to assign Amendment 80 species and halibut PSC to each Amendment 80 cooperative and the Amendment 80 limited access fishery. The current allocations of Amendment 80 species TACs and apportionments of halibut PSC to each of the Amendment 80 cooperatives were provided in the final 2022 and 2023 harvest specifications for the BSAI groundfish fisheries (87 FR 11626, March 2, 2022).

The Amendment 80 groundfish fisheries provide revenue to Amendment 80 vessel owners and crew members who harvest and process groundfish. In addition, the fisheries provide socioeconomic benefits to communities that provide support services for Amendment 80 vessel operations. Amendment 80 groundfish harvests in the BSAI averaged 289,000 mt and generated an average of $334 million in wholesale revenues annually from 2015 through 2020. Catches of yellowfin sole and Atka mackerel provided over 50 percent of the wholesale revenue for the Amendment 80 sector from 2015 through 2020. Pacific cod, rock sole, and Pacific Ocean perch were also major sources of revenue for the Amendment 80 sector during those years. See section 3.3.2 of the Analysis for more detail on Amendment 80 catch and revenue.

The halibut PSC limit established for each BSAI groundfish sector is an upper limit on halibut PSC in that sector for each year. However, the amount of halibut PSC used by a BSAI groundfish sector is almost always less than its halibut PSC limit. Halibut PSC use is less than the halibut PSC limit due to a wide range of operational factors, including the fleet's desire to avoid a closure or an enforcement action if a PSC limit is reached. By regulation (50 CFR 679.21(b)) the current PSC limit of halibut caught while conducting any fishery in the Amendment 80 sector is an amount of halibut equivalent to 1,745 mt of halibut mortality, which includes the application of the DMR. To monitor halibut bycatch mortality, the NMFS Alaska Region uses observed halibut incidental catch rates, halibut DMRs, and estimates of groundfish catch to project when a fishery's halibut bycatch mortality allowance will be and is reached.

Table 3-19 in the Analysis compares Amendment 80 halibut catch and PSC mortality to other BSAI groundfish sectors from 2010 through 2019. In 2020, the Amendment 80 sector recorded 2,031 mt of halibut bycatch and was credited with 1,097 mt of halibut PSC mortality, which was the lower than any annual total during the analyzed period (2010 through 2019) (see section 3.4.1 and Figure 3-25 in the Analysis for more detail). Examining trends in Amendment 80 halibut PSC and PSC mortality is complicated by the fact that many variables that affect these metrics have changed in recent years. PSC limits, DMR estimation methods, and halibut handling procedures have all changed to varying degrees since 2010. Section 3.4.4 of the Analysis describes methods the Amendment 80 sector has pursued to reduce its halibut PSC mortality. Section 3.3 of the Analysis describes the annual variations in halibut PSC use. Regulations were implemented in 2019 (50 CFR 679.120) to standardize catch handling and monitoring requirements to allow halibut bycatch to be sorted on the deck of trawl catcher processors and motherships participating in the non-pollock groundfish fisheries off Alaska (84 FR 55044, October 15, 2019). Historical information shows that the Amendment 80 sector's PSC use has varied annually in response to a variety of changing conditions. NMFS anticipates that these annual variations in halibut PSC use would continue under this proposed action.

Amendment 123 and the proposed rule reflect requirements that NMFS balance several factors when establishing PSC limits. The Council and NMFS considered the detailed information provided in the Analysis, including the impacts from several action alternatives with different halibut PSC limits, on (1) the halibut stock, (2) directed halibut fishery participants and communities that are engaged in directed halibut fisheries in the BSAI and in other Areas, and (3) BSAI groundfish fishery participants, like the Amendment 80 sector, and communities that are engaged in the BSAI groundfish fisheries. In developing the proposed action, the Council and NMFS aimed to appropriately balance the Magnuson-Stevens Act's requirements and national standards, particularly the requirements to establish conservation and management measures that minimize bycatch to the extent practicable, achieve optimum yield on a continuing basis, and take into account the importance of fishery resources to fishing communities. Section 5.3.2.3.1 of the Analysis provides additional detail on the balancing of the national standards. The Council believes, and NMFS agrees, that the proposed PSC limit reductions are consistent with the national standards and other Magnuson-Stevens Act requirements.

Halibut is fully utilized in the BSAI. Therefore, consistent with the Council's purpose and need statement for this action to prevent halibut PSC from becoming a larger proportion of total halibut removals in the BSAI, the Council recommended, and NMFS agrees, that PSC limits should decline in proportion to reduced amounts of halibut available for harvest by all users. The proposed action balances the interests of the two largest halibut user groups in the BSAI, the directed commercial halibut fishery and the Amendment 80 sector, by establishing abundance-based halibut PSC limits for the Amendment 80 sector. This abundance-based approach is consistent with the IPHC management approach for the directed commercial halibut fisheries off Alaska, which establishes annual catch limits that vary with halibut abundance as discussed above.

The proposed action would specify halibut PSC limits for the Amendment 80 sector based on the combined results of the most recent annual IPHC setline survey and the NMFS Alaska Fisheries Science Center (AFSC) Eastern Bering Sea (EBS) shelf trawl survey (EBS shelf trawl survey). Results of the EBS shelf trawl survey provide up-to-date estimates of biomass, abundance, distribution, and population structure of groundfish populations in support of stock assessment and ecosystem forecast models that form the basis for groundfish and crab harvest advice. Relative abundance (catch per unit effort) and size and/or age composition data are key results from this survey. The survey covers Pacific halibut in addition to other groundfish and crab target species. Data collected on the survey are also used to improve understanding of life history of the fish and invertebrate species, as well as the ecological and physical factors affecting their distribution and abundance. The EBS shelf trawl survey is generally described in a NOAA Technical Memo (Stauffer, 2004). When used together, the EBS shelf trawl survey and IPHC setline survey indices capture abundance trends for both O26 and U26 halibut.

After considering these factors, the Council recommended, and NMFS proposes, to specify halibut PSC limits for the Amendment 80 sector linked to halibut abundance indices. In any given year, results from the most recent IPHC setline survey index for halibut in Area 4ABCDE would be categorized into one of four ranges: very low, low, medium, or high. Annual results from the EBS shelf trawl survey index for halibut would be categorized into one of two ranges: high or low.

This proposed action would establish an index table that specifies a halibut PSC limit for each of several specified halibut abundance ranges, or survey index states, that may result from the annual IPHC setline and AFSC EBS shelf trawl surveys. Each year, the intersect of the most recent results from each survey in the proposed index table would establish the annual halibut PSC limit for the Amendment 80 sector. Those limits would range from the current Amendment 80 halibut PSC limit when abundance is high in the IPHC setline survey to 35 percent below the current limit when abundance is very low in the IPHC setline survey. This is within the range of alternative halibut PSC limits analyzed for this action in the Analysis ( i.e., between 15 percent above the current limit and 45 percent below it).

To illustrate how linking PSC limits to halibut abundance would work in practice, an example using 2021 data follows. Based on the halibut abundance values from the 2021 setline and EBS shelf trawl survey abundance indices in the proposed index table, a 1,309 mt PSC limit for the Amendment 80 sector would apply. This constitutes a 25 percent reduction from the 1,745 mt limit currently in regulation and is 37 mt under the sector's average halibut PSC levels from 2016 through 2019. Use of the index table to arrive at PSC limits, as in the above example, is appropriate, because it varies the allowable halibut PSC at several intervals roughly in proportion to halibut abundance, while accounting for the inter-annual variability in the Amendment 80 sector's encounters with halibut and resulting halibut PSC mortality.

Amendment 80 “halibut encounters” is a term used to describe halibut bycatch before a DMR is applied, meaning both the amount of halibut returned to the sea that is expected to survive and the amount expected to result in mortality (halibut PSC use). Amendment 80 halibut encounters from 2016 through 2020 were between 1,965 mt and 3,067 mt, and PSC mortality was between 1,097 mt and 1,461 mt. The period from 2016 through 2020 considered in the Analysis is appropriate to evaluate halibut PSC use because it reflects Amendment 80 sector operations under the existing Halibut Avoidance Plan (an industry-developed best practices guide to aid in halibut avoidance), deck sorting, and other available tools to avoid halibut and reduce halibut mortality. PSC data for 2021 was not considered in the Analysis because Amendment 80 fishing operations, along with other fisheries in Alaska, were more greatly affected in 2021 by COVID-19 mitigation measures and international supply chain and market disruptions in harvesting, processing, and shipping than they were in 2020.

The following sections of the preamble further describe the rationale for this action and its impacts on the halibut stock, the directed halibut fishery and fishing communities, and the BSAI groundfish fishery participants and fishing communities. Sections 5.2 and 5.3 of the Analysis provide additional details.

In order to analyze the impact of the proposed rule and other alternatives considered, the Analysis is predicated on two broad ideas. First, the IPHC has a mandate under the Convention to “permit the optimum yield from the fishery and to maintain the stocks at those levels” and the IPHC's management procedures are designed to achieve that. The IPHC is not required to strictly apply its stated management procedures, and marginal, short term adjustments have been made that do not materially affect the long term sustainability of the halibut resource. The Analysis prepared for this proposed rule assumed the IPHC would maintain its stated management procedures; thus, those management procedures were used as the best available method for analyzing the effects of Amendment 123, including the preferred alternative that would be implemented under this proposed rule. That assumption was made because possible changes in those management procedures, or the specific commercial catch limits that will actually be adopted by the IPHC, cannot be known or predicted with certainty. Finally, it is reasonable to conclude that even marginal adjustments similar to the recent past would not significantly change the conclusions of the Analysis.

Second, the estimates from the EBS shelf trawl survey and the IPHC setline survey are relative indices and are not absolute estimates. The relative difference between estimates in each year ( i.e., the trend) is the important outcome of the survey estimates. Changed or improved methods in either survey, should any be employed in the future, would likely result in changes to annual estimates for the entire survey time-series. As such, absolute values derived from each survey index are dependent on the assumptions of the survey design and data analysis, whereas a standardized index that indicates the trend could show less year-to-year variability. However, basing an index table on standardized trend values would make it more difficult for stakeholders to read reported survey indices in a given year and map those onto a table to anticipate the resulting Amendment 80 PSC limit Therefore, in the interest of greater transparency to the public and in regulation, the Council and NMFS chose to use absolute values derived from the surveys, rather than a standardized index, recognizing that these historical values could change in the future. This is similar to how PSC limits for other PSC species are presently set in the BSAI.

The Council and NMFS considered the impacts the proposed rule would have on the halibut stock as detailed in the Analysis. While reducing halibut bycatch mortality is a conservation measure, the Analysis concluded that, under all the alternatives considered, the impact on exploitable, coastwide halibut biomass and the halibut female spawning biomass was not likely to be significant. This is because the halibut resource in the BSAI is fully utilized, and the Council and NMFS assume that, under this proposed action, a dynamic balance between halibut allocated to directed halibut fisheries by the IPHC on one hand and PSC limits assigned to the Amendment 80 fleet (plus fixed halibut PSC limits for other sectors) on the other, would always result in full utilization, but not over-utilization of the halibut resource. According to the Analysis section 5.2, the IPHC's SPR-based management approach is expected to conserve spawning biomass across differing patterns in fishery selectivity and/or allocation among different fisheries. As such, there is likely to be little difference among the average future halibut spawning biomass under levels of PSC anticipated across all of the alternatives considered, including the proposed action.

At the Very Low/Low and Very Low/High index states, the proposed action would reduce the Amendment 80 halibut PSC limit by 35 percent from the current limit. Should the IPHC setline survey results fall into the very low abundance state, the Council and NMFS concluded that this halibut PSC limit reduction would be important to promote conservation and equitable use of the halibut stock and consistency with the abundance-based process for establishing directed halibut fishery catch limits.

In recommending the proposed rule, the Council and NMFS considered the impacts of reducing halibut PSC limits on fishermen and fishing communities that depend on the halibut resources in the BSAI, as well as in other Areas in Alaska and the Pacific Northwest, including the commercial, subsistence, personal use, and recreational fisheries (see sections 5.4 and 5.5 of the Analysis).

Near-term benefits of the proposed action to fishermen and communities dependent on the directed fishery in the Bering Sea may include accrual of fewer O26 halibut caught as PSC by the Amendment 80 sector. The current IPHC interim harvest policy subtracts the projected O26 portion of non-directed discard mortality (bycatch) from the TCEY by Area when calculating fishing limits. A portion of these halibut would be available to the commercial halibut fishery participants in the area that the PSC mortality is forgone in subsequent years or when the fish reach the legal size limit for the commercial halibut fishery (greater than or equal to 32 inches (81.28 centimeters) in total length). But, as shown in section 3.4 of the Analysis, the relationship between the PSC limit and PSC use varies; therefore, a reduction in the PSC limit may not always generate an increase in directed fishery catch limits in the short term. Even when it does, the magnitude may vary based on the actual Amendment 80 O26 PSC mortality.

The Analysis indicates that under the assumption of a 0.5 ratio for the Amendment 80 PSC limit to the directed catch limit, which is close to the 2010 through 2019 average proportion of O26 halibut in PSC mortality (~ 45 percent), directed commercial halibut catch limits could increase by approximately 360,000 lb (163.29 mt) under the 1,309 mt Amendment 80 PSC limit that would be established under the proposed action at the low/low state (the current state of the halibut stock survey indices). NMFS assumes that directed commercial halibut catch limits could increase under the 1,134 mt PSC limit that would be established under the proposed action at the very low/low state.

Anticipated benefits to the directed commercial halibut fishery from the proposed Amendment 80 PSC limits also include longer term benefits from reductions in the U26 portion of the bycatch. Reduced mortality of smaller halibut could provide benefits for the directed fishery in the Bering Sea and elsewhere as these halibut migrate and recruit to legal size. The directed halibut fishery in Area 4CDE would have the greatest potential for experiencing any incidental reallocative effects that may occur under the proposed action. The provision of additional opportunities for the directed halibut fishery that may accompany PSC limit reductions would be determined by IPHC management processes, (see section 5.4 of the Analysis). However, there is no guarantee that this action would translate into increased opportunities for the directed fishery since the IPHC is not obligated to alter, maintain, or implement their current harvest strategies based on the outcome of this action.

Sport halibut harvests, including guided and unguided sport/recreational halibut fisheries, could indirectly benefit from the implementation of the proposed action. That is, if reducing BSAI halibut PSC limits under low abundance conditions were to ultimately result in an overall improvement in availability of halibut for sport harvest, an accompanying decrease in effort and expense in harvesting halibut for sport use, and/or an increase in interest in halibut sport fishing in the region prompted by an increasing abundance of larger halibut. These indirect benefits could occur if the overall Pacific halibut stock benefits from additional promotion of conservation of the stock under the proposed action.

The proposed action would have differing impacts on Amendment 80 companies, and changes to fishing plans and operations would be needed to adjust to the reduction in halibut PSC limits under different survey abundance index states, with more significant changes required at lower abundance states. Efforts already undertaken by the sector have shown that increases in halibut avoidance or reductions in mortality are possible with the tools that are currently available to the fleet. Additional improvements are anticipated to continue to be realized, especially if halibut limits are further reduced, although the Analysis projects that the fleet will forgo some amount of profitability to reduce halibut mortality further. Reductions in halibut mortality are expected to result from changes in fishing operations that cause the sector to increase operating costs and/or reduce efficiency. The amount of mortality reduction cannot be quantified with certainty.

When the halibut PSC limits constrain target catch and Amendment 80 firms are required to implement more measures to reduce halibut mortality, operating costs may increase and revenue may decrease making annual net revenue more volatile. This could result in increased consolidation of the Amendment 80 sector and the Cooperative Quota (CQ). Firms that are less efficient at addressing halibut bycatch experience less profitability and may sell to firms that are more efficient, derive more revenue from other fisheries to provide revenue during years halibut is a constraint, or have access to more cash reserves than the sellers. Firms that cannot remain viable under the new conditions would eventually exit the fishery. Current Amendment 80 ownership and control limits leave room for one firm to exit the fishery, because a person may not individually or collectively hold or use more than 30 percent of the aggregate Amendment 80 Quota Share units initially assigned to the sector. The number of vessels in the fishery could be reduced to a minimum of five, because an Amendment 80 vessel may not be used to catch an amount of species greater than 20 percent of the aggregate Amendment 80 sector's species initial Total Allowable Catch (ITAC). While the number of vessels could decline, NMFS does not anticipate a decrease to the vessel minimum, because the fleet would still need sufficient capacity to harvest the CQ that can be supported by the available halibut PSC mortality limit. For complete discussion of impacts to the Amendment 80 sector, see section 5.3.2 of the Analysis.

Multiple coastal communities in the BSAI, as well as coastal communities elsewhere in Alaska and the Pacific Northwest, participate in the BSAI groundfish fisheries in one way or another, such as being homeport to participating vessels, the location of processing activities or product transfers, the location of fishery support businesses, the home of employees in the various sectors, or as the base of ownership or operations of various participating entities. An analysis of community engagement in and dependency on the Amendment 80 fishery is provided in appendix 1 (the Social Impact Assessment) of the Analysis. An analysis of the alternatives suggests that reductions in PSC limits could constrain the Amendment 80 sector under some conditions and consequently may impact the communities that depend on those fisheries. It is also important to note that some communities are substantially engaged in or substantially dependent on both the Amendment 80 fishery and the Area 4 directed halibut fishery, and thus may experience both negative and positive effects from this action. Consequently, a simple characterization of potential incidental reallocative effects to halibut dependent communities would not capture the complexity of overall impacts to those communities, much less the range of potential impacts to individual harvesters, processors, and/or fishery support businesses in those communities which may ultimately result from changes in Amendment 80 PSC limits.

As described in section 5.5 of the Analysis, reduced halibut PSC mortality relative to the status quo may indirectly benefit fishing communities that depend upon commercial and noncommercial halibut harvest, though the magnitude of that effect is likely to be attenuated by multiple biological factors and policy steps that separate bycatch mortality savings from directed harvest opportunities. Conversely, communities engaged in the Amendment 80 sector groundfish fisheries could be adversely impacted on a more direct basis.

The Seattle-Tacoma-Bellevue Washington Metropolitan Statistical Area (Seattle MSA) is substantially engaged in the Area 4 directed halibut commercial fishery as measured by ownership address of actively participating catcher vessels, among other indicators of engagement. However, compared to Alaska communities, its engagement in the BSAI halibut fishery is not as dominant as it is in the BSAI groundfish fisheries, which are likely to be most directly affected by the proposed action alternatives. No community level adverse impacts related to the BSAI halibut fishery are anticipated to the Seattle MSA under the proposed action.

The Council and NMFS believe that linking Amendment 80 halibut PSC limits to halibut abundance levels as proposed in this rule: (1) will ensure that halibut PSC mortality in Amendment 80 fisheries does not become a greater share of overall halibut removals in the BSAI, particularly in Area 4CDE; (2) will create a more equitable approach between competing users; and (3) may increase halibut harvest opportunities in directed halibut fisheries. In short, the proposed rule is reasonably calculated to promote conservation of the halibut resource, improve its management, and create a more equitable distribution process between the directed and non-directed fisheries.

The Council and NMFS have concluded that Amendment 123 is consistent with the Magnuson-Stevens Act, including the ten national standards, and other applicable law. The Analysis contains a detailed analysis of those standards. The Council and NMFS considered the proposed action in context of balancing all the national standards. Below, we highlight four of them: National Standards 1, 4, 8, and 9.

National Standard 1. The Analysis shows that, consistent with National Standard 1, the groundfish fisheries will continue to achieve optimum yield on a continuing basis under Amendment 123. Congress set, and the BSAI FMP includes, the optimum yield (OY) range for the BSAI groundfish complex as 85 percent of the historical estimate of MSY, which results in an OY range between 1.4 and 2.0 million mt of groundfish. The Analysis indicates that, even if the Amendment 80 sector harvested no fish, overall, the groundfish fisheries would continue to harvest within this OY range in most years. Thus, under National Standard 1, despite the imposition of costs on and potential loss of a portion of harvest by the Amendment 80 sector, this action is not expected to affect the BSAI groundfish fisheries' ability to achieve OY on a continuing basis.

National Standard 4. To the extent that this action involves an allocation of fishing privileges contemplated in National Standard 4, the new PSC limits are fair and equitable. An allocation need not preserve the status quo in the fishery to qualify as “fair and equitable” if a restructuring of fishing privileges would maximize overall benefits. The Council and NMFS considered that the potential hardship imposed on the Amendment 80 fleet at low and very low survey indices was, on balance, outweighed by the potential benefits from the reduction in the Amendment 80 fleet's halibut mortality and the potential increase in halibut availability to the directed halibut fisheries. The action is also reasonably calculated to promote conservation through the reduction of halibut bycatch and mortality in the Amendment 80 fleet. Further, as the National Standard Guidelines explain, the action promotes conservation (in the sense of wise use) by optimizing yield in terms of the economic and social benefit of the product. Finally, the action does not result in the acquisition of an excessive share of any fishing privileges.

In developing this proposed action, the Council and NMFS also considered other factors identified in the National Standard 4 guidance, including economic and social consequences, food production (subsistence use), dependence on the fishery by present participants and coastal communities, efficiency of various types of gear used in the fishery, transferability of effort to and impact on other fisheries, opportunity for new or past participants to enter the fishery, and enhancement of opportunities for recreational fishing.

National Standard 8. The Magnuson-Stevens Act's National Standard 8 and the associated NMFS Guidelines provide that conservation and management measures shall, consistent with the conservation requirements of the Magnuson-Stevens Act, take into account the importance of fishery resources to fishing communities by utilizing economic and social data that are based upon the best scientific information available in order to: (1) provide for the sustained participation of such communities and (2) to the extent practicable, minimize adverse economic impacts on such communities.

When the proposed action results in lower halibut PSC mortality by the Amendment 80 fleet than would have occurred under the current limit, the proposed action is expected to have a positive effect on all directed halibut fisheries (commercial, guided and unguided recreational (sport), and subsistence), minimize adverse economic impacts to communities dependent on those directed fisheries and, thus, provide for the sustained participation of such communities. The reduction in the halibut PSC limit and potential for increased opportunities for additional halibut harvest for the directed halibut fisheries are also expected to have positive social and environmental justice impacts on the directed users of the halibut resource and halibut-dependent communities, many of which are predominantly Alaska Native communities. Those impacts are estimated in section 5.5 of the Analysis and appendix 1 to the Analysis.

The social and cultural importance of halibut (as a species) and halibut fishing (as a traditional activity) for Alaska Native tribes and ethnic groups throughout Alaska is well-documented. The cultural significance of halibut for these fishermen and their associated communities exceeds the economic value of the fishery. Minority populations of the seventeen Alaska communities considered BSAI halibut-dependent range from 65 to over 90 percent of those communities' populations. Notably, those communities' low-income populations (residents living below the poverty threshold) comprise 10 percent to over 40 percent of the community.

While the Council does not currently set catch limits in the directed halibut fishery, the economic, social, and cultural benefits to Alaska communities that may result from halibut PSC reductions is discussed in section 5.5 and appendix 1 of the Analysis. Overall positive social and environmental justice impacts on dependent halibut directed fishery communities would be expected as a result of this proposed rule. In recommending the proposed action to NMFS, the Council considered providing for the sustained participation of fishing communities and minimizing adverse economic impacts on such communities, consistent with National Standard 8.

National Standard 9. Section 303(a)(11) of the Magnuson-Stevens Act and National Standard 9 generally require FMPs to include conservation and management measures that minimize bycatch to the extent practicable. The proposed action is intended to minimize halibut PSC in the Amendment 80 sector to the extent practicable. What is practicable will be determined on a case-by-case basis. According to the Merriam-Webster Dictionary, practicable means “capable of being done or carried out.” The available technology and the potential costs of carrying out bycatch minimization measures are relevant to the practicability determination. The practicability of the proposed PSC reduction relative to the status quo is discussed in sections 3.4.5 and 5.3.2.3 of the Analysis. Under the high IPHC setline survey index value, the PSC limit remains unchanged. At lower levels of halibut abundance, some of the PSC limits may be more difficult to achieve by the Amendment 80 fleet using currently available tools, forcing the Amendment 80 sector to stop fishing before harvesting their entire groundfish allocations. However, at lower halibut abundance and PSC limits, halibut encounter rates by the Amendment 80 fleet may also be lower. The following additional factors were taken into consideration under National Standard 9:

Population effects for the bycatch species. The IPHC's SPR-based management approach is expected to conserve the halibut spawning biomass across differing patterns in fishery selectivity and/or allocation among different fisheries. As such, there is likely to be little difference in the average future halibut spawning biomass coastwide under levels of PSC anticipated through this proposed action. Although the spawning stock biomass is not expected to be affected by this action, since halibut are a fully allocated species, reductions in juvenile halibut mortality may occur as a result of the PSC limits imposed by this action, particularly at low levels of abundance, allowing greater number of larger fish to recruit into the directed fisheries. However, the degree of change in the BSAI halibut fishery per unit change in PSC cannot be reliably estimated.

Ecological effects. To the extent that the proposed action changes effort in the BSAI groundfish fisheries and reduces the bycatch of halibut in the Amendment 80 fleet, those changes are not likely to have ecological effects on other species in the ecosystem or impacts on ecosystem components. Nor are they likely to produce considerations beyond those summarized in the annual Stock Assessment and Fishery Evaluation report for the BSAI groundfish fisheries.

Effects on marine mammals and birds. The potential for incidental take, prey availability, and disturbance of marine mammals and seabirds may change from status quo under the proposed rule. If the Amendment 80 fleet reduces fishing effort in specific fisheries to conserve halibut PSC and shifts to target different species, that shift in operations may result in incrementally more or less potential for incidental take, prey availability, and disturbance of marine mammals and/or seabirds. If a groundfish fishery increases the duration of fishing in certain areas, there may be more potential for incidental take, prey availability, and disturbance in those locations if they are used by marine mammals or seabirds. The fisheries are unlikely to increase their take of marine mammals above the Potential Biological Removal (PBR) levels (the maximum number of animals, not including natural mortalities, that may be removed from a marine mammal stock while allowing that stock to reach or maintain its optimum sustainable population), since take numbers are currently well below PBR levels in BSAI groundfish fisheries and no PSC limits under the proposed action are expected to result in significant increases in total fishing effort in the BSAI.

Changes in fishing practices and behavior of fishermen. Whether PSC limits under the proposed rule will result in changes in fishing practices or fishermen's behavior is unclear. As the annual PSC limit changes in accordance with halibut abundance index states, the proposed rule may yield no change to existing levels of PSC, or a reduced PSC limit may result in the industry changing its fishing patterns to avoid halibut. This could result in reduced fishing effort as the industry chooses not to pursue fisheries associated with higher halibut encounter rates to conserve halibut PSC, or it could result in greater fishing effort at lower catch per unit effort as vessels change fishing patterns or seasonal changes in the timing of the fishing to increase halibut avoidance. A program that links the Amendment 80 sector PSC limit to halibut abundance may provide incentives for the fleet to minimize halibut mortality at all times. Shifts in the location or timing of fishing may occur as a result of this action. However, there is already considerable inter-annual variability in the patterns of fishing across the Amendment 80 sector as environmental conditions and avoidance of PSC species have caused vessels to adjust their fishing patterns. Implementation of a lower PSC limit will likely result in the fleet stopping fishing before the limit is taken to avoid penalties of exceeding the hard cap. The proposed rule also assumes that the conditions in the Amendment 80 groundfish fishery will result in years when halibut mortality rates are lower, because directed fishery species are more aggregated and avoiding halibut bycatch is easier.

Changes in research, administration, enforcement costs, and management effectiveness. By law, NMFS is required to recover the actual costs of management, data collection, and enforcement directly related to any Limited Access Privilege Program and the CDQ program. This action could change halibut PSC limits that could impact the value of fisheries subject to cost recovery. Changes to direct program costs, fishery value, or both, could alter the cost recovery fee percentage due. However, it is not possible to quantitatively estimate the potential impact of this action on cost recovery fee percentages, given the wide variety of factors that affect the direct program costs and the value of a fishery. But it is reasonable to assume that the larger the change in PSC limit from status quo under this proposed action, the greater the potential impact to fishery value and fee percentage due.

When the proposed action results in a reduction to halibut PSC limits, it may increase, among some operators, the economic incentives to attempt to bias halibut PSC data. The Alaska Division of NOAA Office of Law Enforcement (OLE) has identified recent increases in reports of harassment, intimidation, hostile work environment, and other attempts to bias observer samples of PSC in the Amendment 80 sector. The Amendment 80 sector has one of the highest rates of interpersonal issues report by observers (0.49 per assignment). A further reduction of the halibut PSC limit for this sector may result in additional coercive behavior toward observers and attempts to bias their sampling. NOAA OLE's recent outreach efforts in conjunction with the recent implementation of another recent halibut action, halibut deck sorting, could be used as a model to address these concerns. Specifically, successful outreach from NOAA OLE after the implementation of halibut deck sorting, followed by routine boardings, served as a useful way for vessels to report problems they might be having with new regulations. Those efforts appeared to encourage communication and self-reporting by the vessels, and may be employed by NOAA OLE during implementation of this proposed action.

This proposed rule would change PSC limits annually for the Amendment 80 sector based on the proposed Table 58 that would be included in regulation. Thus, the use of the table would obviate the need for the Council to take action each October or December to specify the PSC limit for the following year.

Changes in fishing, processing, disposal, and marketing costs; changes in economic, social, or cultural value of fishing activities; and changes in non-consumptive uses of fishery resources, including distribution of costs and benefits. The Analysis notes that the Amendment 80 sector will incur higher costs to avoid halibut to maximize harvest of Amendment 80 species TACs with any reduction in the halibut PSC limit, and such costs are assumed to increase as the survey index states decrease. The precise extent to which these costs would affect groundfish harvests and negatively impact the Amendment 80 sector is unknown. The analysis demonstrates that the lower halibut PSC limits may result in reduced groundfish harvests and revenues for the Amendment 80 sector. The analysis also notes that the impacts of this action on the different Amendment 80 companies are likely to vary given the diversity of their respective quota holdings of different target stocks (See section 3.3 of the Analysis). Positive impacts may occur for some Amendment 80 suppliers (fuel, excluder manufacturers, etc.) and for suppliers to the directed halibut fisheries, if the proposed rule results in increased commercial, charter, unguided sport, or subsistence harvests. Some negative impacts may occur for suppliers to the Amendment 80 fleet ( e.g., suppliers of packaging material) that lose business as a result of the action.

Overall, economic producer surplus—that is, the difference between the minimum the producer would be willing to sell for and what the producer actually sells its goods for—is expected to be negatively affected, depending on future conditions of halibut abundance, which is unknown. This is because the expected reductions in the Amendment 80 producer surpluses would not be expected to be offset by economic increases in producer surpluses due to increased catch in the directed halibut fisheries.

Changes in social, or cultural value of fishing activities, and changes in non-consumptive uses of fishery resources, including distribution of costs and benefits were considered in evaluating the proposed rule's consistency with National Standard 9. These factors are described in other sections of this preamble, including under impacts to directed halibut fisheries and communities and discussion of consistency of the proposed rule with National Standards 4 and 8.

On balance, the Council and NMFS determined that reducing halibut mortality from bycatch in the Amendment 80 fleet is warranted in light of the above factors, the Magnuson-Stevens Act's requirements, and other legal requirements. The Council and NMFS concluded that the total benefits of the halibut PSC reduction outweigh its costs.

The Council took final action to base the annual halibut PSC limit for the Amendment 80 sector on halibut abundance under Amendment 123. Here, NMFS proposes regulations to implement that amendment and establish a process to set the annual halibut PSC limit for the Amendment 80 sector, namely, by linking it to annual survey indices. This proposed rule would accomplish the following:

• Specify that BSAI halibut PSC for the Amendment 80 sector be determined annually.

• Specify that halibut biomass estimates derived from results of the most recent IPHC setline survey and the AFSC EBS shelf trawl survey be applied to a specified set of index ranges for each survey to establish the BSAI halibut PSC limit for the Amendment 80 sector for the following year.

• Specify that each year the Amendment 80 sector halibut PSC limit will be included in the proposed and final rules for the annual harvest specifications for the BSAI.

Turning to the affected regulations, 50 CFR 679.21 describes prohibited species bycatch management procedures: paragraph (b)(1) establishes BSAI halibut PSC limits for the Amendment 80 sector. To establish the annual process for determining BSAI halibut PSC limit for the Amendment 80 sector, this proposed rule would revise 50 CFR 679.21.

The proposed rule would revise paragraph (b)(1) by adding paragraphs (b)(1)(i)(A) through (C) to establish the process for determining the annual BSAI halibut PSC limits for the Amendment 80 sector, including Amendment 80 cooperatives and the Amendment 80 limited access fishery. The proposed rule would specify that halibut biomass estimates derived from results of the most recent IPHC setline and the AFSC EBS shelf trawl surveys be applied to a specified table of index ranges for each survey (proposed Table 58). The value at the intercept of those survey indices within the table would be the BSAI halibut PSC limit for the Amendment 80 sector for the following year. The annual limit would be published in the draft and final harvest specifications each year.

The proposed rule would also revise 50 CFR 679.91, which establishes Amendment 80 Program annual harvester privileges and the process for assigning halibut PSC to the Amendment 80 sector, cooperatives, and limited access fishery. The proposed rule would revise paragraphs (d)(1), (d)(2)(i), and (d)(3) to clarify that the amount of halibut PSC limit for the Amendment 80 sector for each calendar year is specified and determined according to the procedure in § 679.21(b)(1)(i), replacing the references in those paragraphs to Table 35 to this part that stipulates the annual fixed amount of 1,745 mt for the Amendment 80 sector as a whole.

NMFS would modify Table 35 to Part 679 (Apportionment of Crab PSC and Halibut PSC Between the Amendment 80 and BSAI Trawl Limited Access Sectors) to indicate that the Amendment 80 sector halibut PSC would be determined annually, rather than set at a fixed amount. NMFS would add Table 58 to Part 679—Amendment 80 Sector Annual BSAI Pacific Halibut PSC Limits to establish the IPHC setline and the AFSC EBS shelf trawl survey index ranges in a table with the corresponding PSC limit at the intercepts of each survey range.

Pursuant to sections 304(b)(1)(A) and 305(d) of the Magnuson-Stevens Act, the NMFS Assistant Administrator has determined that this proposed rule is consistent with Amendment 123, other provisions of the Magnuson-Stevens Act, and other applicable laws, subject to further consideration after public comment period.

This proposed rule has been determined to be not significant for the purposes of Executive Order (E.O.) 12866.

An RIR was prepared and incorporated in the final EIS to assess the costs and benefits of available regulatory alternatives. A copy of this analysis is available from NMFS (see ADDRESSES ). NMFS is recommending Amendment 123 and the regulatory revisions in this proposed rule to minimize potentially adverse economic impacts on benefits to the Nation. Specific aspects of the economic analysis related to the impact of this proposed rule on small entities are discussed below in the Initial Regulatory Flexibility Analysis (IRFA) section.

This IRFA was prepared for this proposed rule, as required by section 603 of the Regulatory Flexibility Act (RFA) (5 U.S.C. 603), to describe the economic impact this proposed rule, if adopted, would have on small entities. The IRFA is required to describe why this action is being proposed; the objectives and legal basis for the proposed rule; the number of small entities to which the proposed rule would apply; any projected reporting, recordkeeping, or other compliance requirements of the proposed rule; any overlapping, duplicative, or conflicting Federal rules; and any significant alternatives to the proposed rule that would accomplish the stated objectives, consistent with applicable statutes, and that would minimize any significant adverse economic impacts of the proposed rule on small entities. Descriptions of this proposed rule, its purpose, and the legal basis are contained earlier in this preamble and are not repeated here.

NMFS has determined that vessels that are members of a fishing cooperative are affiliated when classifying them for the RFA analysis. In making this determination, NMFS considered the Small Business Administration (SBA) “principles of affiliation” at 13 CFR 121.103. Specifically, in 50 CFR 121.103(f), SBA refers to “[a]ffiliation based on identity of interest,” which states that affiliation may arise among two or more persons with an identity of interest. Individuals or firms that have identical or substantially identical business or economic interests (such as family members, individuals or firms with common investments, or firms that are economically dependent through contractual or other relationships) may be treated as one party with such interests aggregated. If business entities are affiliated, then the threshold for identifying small entities is applied to the group of affiliated entities rather than on an individual entity basis. NMFS has reviewed affiliation information for Amendment 80 cooperative members that are directly regulated by this action and has determined that all directly regulated catcher/processors are large via cooperative affiliation, with one exception discussed below.

This action also affects the six Western Alaska CDQ entities that are non-profit corporations, are not dominant in the BSAI non-pollock fishery, and are specifically identified as “small” entities in the regulations implementing the RFA. The CDQ entities have made direct investments in fishing vessels by creating wholly owned for-profit fishing companies, several of which are directly regulated by this action. However, as for-profit ventures, these companies are not automatically defined as small entities due to CDQ ownership, and this analysis has determined that they are all Amendment 80 cooperative-affiliated. Thus, while this proposed action directly regulates these for-profit CDQ owned companies, they are considered to be large entities for RFA purposes.

The thresholds applied to determine if an entity or group of entities are “small” under the RFA depend on the industry classification for the entity or entities. Businesses classified as primarily engaged in commercial fishing are considered small entities if they have combined annual gross receipts not in excess of $11.0 million for all affiliated operations worldwide. 50 CFR 200.2. Businesses classified as primarily engaged in fish processing are considered small entities if they employ 750 or fewer persons on a full-time, part-time, temporary, or other basis at all affiliated operations worldwide. Since at least 1993, NMFS Alaska Region has considered catcher/processors to be predominantly engaged in fish harvesting rather than fish processing. Under this classification, the threshold of $11.0 million in annual gross receipts is appropriate.

One additional vessel, the Golden Fleece, has been identified as a potentially directly regulated small entity based on revenue analysis. The Golden Fleece is Amendment 80-eligible but has chosen not to utilize its right to an Amendment 80 permit. Thus, it is not Amendment 80 cooperative-affiliated or Amendment 80 ownership-affiliated, as it is an independent company. The Golden Fleece is a member of a marketing cooperative called Golden-Tech International, Inc. This cooperative markets the catch of several Amendment 80 catcher/processors; however, NMFS does not have access to information regarding contractual relationships necessary to determine whether membership in this marketing cooperative also affiliates the Golden Fleece with Amendment 80 vessels. Therefore, the Golden Fleece is considered to be the only small entity directly regulated by this action. However, since the Golden Fleece has not participated in the Amendment 80 fishery, it is not possible to quantify adverse impacts other than to acknowledge that the proposed rule may constrain its halibut PSC limits should it choose to do so in the future. In times of lower halibut abundance, that constraint may mean that there is not adequate PSC quota to allocate to the Amendment 80 limited access fishery to allow a directed fishery to be opened by NMFS in-season management should the Golden Fleece choose to register for that fishery. Were the Golden Fleece to register in the Amendment 80 fishery as a cooperative of one, their ability to fish would be similarly constrained by the potentially lower halibut PSC limit.

In sum, based on the foregoing analysis, NMFS preliminarily determines that there is one catcher/processor entity, the Golden Fleece, that may be considered small and would potentially be directly regulated by this action. NMFS has carefully considered whether a single entity represents a “substantial number” of directly regulated entities. When Amendment 80 was enacted, there were 27 original issuances of License Limitation Permits (LLPs). That is the same number of Amendment 80 LLPs issued currently. The Golden Fleece does not hold one of the 27 original or current LLPs issued, having, having not applied for an Amendment 80 LLP to date. Through consolidation and vessel replacement, all of the LLPs participating in the Amendment 80 fishery are presently owned by five distinct corporations that are all cooperative-affiliated large entities. NMFS acknowledges that the corporation owning the LLPs is the proper consideration for determining whether a substantial number of directly regulated entities is affected. While one of 28 does not appear to represent a substantial number of directly regulated entities, one of six directly regulated entities may give the appearance of a substantial number. Thus, NMFS has prepared this IRFA, which provides potentially affected small entities an opportunity to provide comments. NMFS will evaluate any comments received regarding the potential for significant economic impact on a substantial number of small entities in the final RFA contained within the final rule.

No small entity is subject to reporting requirements that are in addition to or different from the requirements that apply to all directly regulated entities.

Under this proposed rule, requirements for recording and reporting would not be changed. Therefore, this proposed action will not change recordkeeping and reporting costs for fishery participants or impose any additional or new costs on participants.

NMFS has not identified any duplication, overlap, or conflict between this proposed rule and existing Federal rules.

No significant alternatives were identified that would accomplish the stated objectives for implementing a halibut abundance-based management via regulation, be consistent with applicable statutes, would minimize costs to potentially affected small entities more than the proposed rule. The Council considered five alternatives for action in this proposed rule along with three sub-options that could apply to all action alternatives. Alternative 1 is the no action alternative and would continue the static annual halibut PSC limit of 1,745 mt for the Amendment 80 sector.

The Council's recommended Preferred Alternative (Alternative 5) bases the determination of the annual PSC limit on the most recent survey values for the IPHC setline survey and the EBS shelf trawl survey using an index table that links PSC limits to survey abundance index states (see Table 2-8 of the Analysis). The two abundance indices are measures of the survey estimate of halibut either in metric tons (NMFS AFSC EBS shelf trawl survey) or population-density as measured by weight per unit effort (IPHC setline survey). These indices will be used to track halibut abundance and to guide setting the PSC limit for the Amendment 80 sector. The selected indices are based on the EBS shelf trawl survey and the IPHC setline survey covering IPHC Areas 4ABCDE. Both indices represent the best available scientific information. Alternatives 2 through 4 would use the same style of index table as proposed in the Preferred Alternative but would use different ranges of halibut PSC limits for the survey index levels. Alternative 2 includes a range from the current halibut PSC limit of 1,745 mt to 1,396 mt or 20 percent below the current limit. Alternative 3 includes a range from 2,007 mt or 15 percent above the current limit to 1,222 mt or 30 percent below the current limit. Alternative 4 includes a range from the current limit of 1,745 mt to 960 mt or 45 percent below the current limit.

The Preferred Alternative reflects requirements for the Council, and NMFS, to balance several factors when establishing PSC limits, including the likely impacts on the halibut stock and affected participants in the Amendment 80 and directed halibut fisheries. The Preferred Alternative would specify halibut PSC limits that range from the current Amendment 80 halibut PSC limit to 35 percent below the current limit. This is within the range of halibut PSC limits considered for this action, which range from 15 percent above the current limit to 45 percent below the current limit. The Council has acknowledged that halibut is fully utilized in the BSAI and at the medium to very low survey index states, the Amendment 80 PSC limit should decline as halibut available for harvest for all users also declines. Under those conditions, reduced halibut mortality through lower PSC limits is likely to prevent halibut PSC from becoming a larger proportion of total removals in the BSAI, consistent with the Council's purpose and need statement.

In recommending the Preferred Alternative, the Council appropriately considered the Magnuson-Stevens Act requirements. The Preferred Alternative balances the interests of the two largest halibut user groups in the BSAI, the directed commercial halibut fishery and the Amendment 80 sector, by establishing abundance-based halibut PSC limits for the Amendment 80 sector. This abundance-based approach is similar to the IPHC's management approach for the directed halibut fisheries off Alaska, which establishes annual catch limits that vary with established measures of halibut abundance.

This proposed rule does not require any collection of information (“recordkeeping and reporting”) requirements approved by the Office of Management and Budget (OMB) under the Paperwork Reduction Act (PRA). This proposed rule does not amend existing information collections or create new information collections applicable to directly regulated entities. The Amendment 80 sector is subject to a comprehensive information collection in the form of the Economic Data Reporting (EDR) Program enacted in 2008. The Council reviewed the EDR for Amendment 80, and three other sectors, in February of 2022 and kept the Amendment 80 EDR largely intact while adopting some agency recommendations for small changes to the information collection forms to reduce respondent burden.

Send comments on these or any other aspects of the collection of information to NMFS Alaska Region at the ADDRESSES above, by email to OIRA_Submission@omb.eop.gov, or by fax to (202) 395-5806.

Notwithstanding any other provision of law, no person is required to respond to, and no person shall be subject to penalty for failure to comply with, a collection of information subject to the requirements of the PRA, unless that collection of information displays a currently valid OMB control number. All currently approved NOAA collections of information may be viewed at http://www.cio.noaa.gov/services_programs/prasubs.html.

E.O. 13175 of November 6, 2000, the Executive Memorandum of April 29, 1994, the American Indian and Alaska Native Policy of the U.S. Department of Commerce (March 30, 1995), and the Department of Commerce Tribal Consultation and Coordination policy (78 FR 33331, June 4, 2013) outline the responsibilities NMFS has for tribal consultations related to Federal policies that have tribal implications. Further, section 161 of Public Law 108-199 extends the consultation requirements of E.O. 13175 to Alaska Native corporations. Under E.O. 13175 and agency policies, NMFS is required to give the opportunity for meaningful and timely input by tribal officials and representatives of Alaska Native corporations in the development of regulatory policies that have tribal implications. To that end, NMFS will provide a copy of this proposed rule to all potentially impacted federally recognized tribal governments in Alaska and Alaska Native corporations to notify them of the opportunity to comment or request a consultation on this proposed action.

Section 5(b)(2)(B) of E.O. 13175 requires NMFS to prepare a “tribal summary impact statement” for any regulation that has tribal implications, imposes substantial direct compliance costs on Native tribal governments, and is not required by statute. The tribal summary impact statement must contain (1) a description of the extent of the agency's prior consultation with tribal officials, (2) a summary of the nature of their concerns, (3) the agency's position supporting the need to issue the regulation, and (4) a statement of the extent to which the concerns of tribal officials have been met. If the Secretary of Commerce approves this proposed action, a tribal impact summary statement that addresses the four questions above will be prepared and included in the final rule.

For reasons set out in the preamble, NMFS proposes to amend 50 CFR part 679 as follows: