Federal Register Vol. 80, No.130,

Background

On February 14, 2013, Pratt and Whitney Canada applied for an amendment to Type Certificate No. E00083EN-E to include the new PW210A engine model. The PW210A, which is a derivative of the PW210S currently approved under E00083EN-E, is intended for rotorcraft use. For their PW210A engine model, Pratt and Whitney Canada requests an additional OEI rating that combines the 30-second and 2-minute OEI rating into a single rating to satisfy the rotorcraft requirements for increased power in OEI scenarios. This additional OEI rating is named “Flat 30-second and 2-minute OEI.”

These special conditions are necessary because the applicable airworthiness regulations do not contain adequate or appropriate safety standards for combining the requirements of the flat 30-second and 2-minute OEI rating.

Under the provisions of § 21.101, Pratt and Whitney Canada must show that the PW210A meets the applicable provisions of 14 CFR part 33, as amended by Amendments 33-1 through 33-30. These regulations will be incorporated into Type Certificate No. E00083EN after type certification approval of the PW210A. The regulations incorporated by reference in the type certificate are commonly referred to as the “original type certification basis.” The regulations incorporated by reference in Type Certificate No. E00083NE are as follows:

Title 14 of the Code of Federal Regulations (14 CFR part 33), effective February 1, 1965, Amendments 33-1 through 33-24 and two special conditions:

1. Airworthiness Standards: 14 CFR part 33, effective February 1, 1965, Amendments 33-1 through 33-30, inclusive.

2. Environmental Standards: 14 CFR part 34, effective September 10, 1990, as amended by 34-1 through 34-4 and 40 CFR part 87, effective (ICAO Annex 16, Volume II—Aircraft Engine Emissions, as amended up to and including Amendment 6).

In addition, the certification basis includes other regulations, special conditions and exemptions that are not relevant to these special conditions. Type Certificate No. E00083EN will be updated to include a complete description of the certification basis for this model engine.

If the Administrator finds that the applicable airworthiness regulations (i.e., 14 CFR part 33) do not contain adequate or appropriate safety standards for the PW210A because of a novel or unusual design feature, special conditions are prescribed under the provisions of § 21.16.

Special conditions are initially applicable to the model for which they are issued. Should the type certificate for that model be amended later to include any other model that incorporates the same or similar novel or unusual design feature, or should any other model already included on the same type certificate be modified to incorporate the same or similar novel or unusual design feature, the special conditions would also apply to the other model under § 21.101.

Accordingly, should type certificate E00083EN be amended to include another model that incorporates the “Flat 30-second and 2-minute OEI,” the special conditions as defined would apply to models whose certification basis is amendment 33-25 or later.

The FAA issues special conditions, as defined in 14 CFR 11.19, in accordance with § 11.38, and they become part of the type-certification basis under § 21.17(a)(2).

The PW210A will incorporate the following novel or unusual design features: The design feature is a “Flat 30-second and 2-minute” one engine inoperative (OEI) rating. The Flat 30-second and 2-minute OEI rating represents a case where the power levels and associated operating limitations for the 30-second OEI and 2-minute OEI ratings (defined in Part 33) are the same.

These special conditions are necessary because current part 33 regulations do not contain airworthiness standards for extending the 2-minute OEI rating for 30-seconds. These special conditions extend the time dependent requirements applicable to the 30-second OEI or 2-minute OEI to the 2.5 minutes time duration of the “Flat 30-second and 2-minute OEI” Power.

The 2.5 minutes time duration for the rating may affect the engine's structural and operational characteristics that are time dependent, such as the values for transients, time duration for stabilization to steady state, and part growth due to deformation. To address these aspects, we propose special conditions based on revised requirements of §§ 33.27, 33.87(a)(7), and 33.88(b).

The 2.5 minutes time duration for the rating affects the test conducted for the endurance test. For the 30-second OEI and 2-minute OEI the test schedule of § 33.87(f) is divided among the two ratings. We propose special conditions based on revised requirements of § 33.87(f) to ensure the test will be run for 2.5 minutes duration with no interruption.

The 2.5 minutes time duration for the rating necessitates extending the time duration requirement of § 33.28(k) applicable to the 30-second OEI rating from 30 seconds to 2.5 minutes. This requirement is for automatic availability and control of the engine for the entire duration of the rating's usage.

The 2.5 minutes time duration for the rating necessitates extending the requirements of § 33.29(c) that are applicable to 30-second OEI and 2-minute OEI ratings to the single Flat 30-second and 2-minute OEI Power rating. We propose special conditions to ensure that the instrumentation requirements normally reserved for 30-second OEI and 2-minute OEI ratings are applied to the Flat 30-second and 2-minute OEI Power rating over its whole duration. The pilot does not have to be alerted at the end of 30 seconds use of the Flat 30-second and 2-minute OEI Power rating, only after the entire 2 minutes 30 seconds has expired. Paragraph 2.(e)(3) of these special conditions states that the engine must provide means or provision of means to alert maintenance of use of the Flat 30-second and 2-minute OEI Power rating, `alert' means after the aircraft lands, so any required maintenance actions can be completed before next flight.

As discussed above, these special conditions are applicable to the PW210A. Should Pratt and Whitney Canada apply at a later date for a change to the type certificate to include another model incorporating the same novel or unusual design feature, the special conditions would apply to that model as well.

This action affects only the Flat 30-second and 2-minute OEI design features on the PW210A engine model. It is not a rule of general applicability and applies only to Pratt and Whitney Canada, who requested FAA approval of this engine feature.

The authority citation for these special conditions is as follows:

Accordingly, pursuant to the authority delegated to me by the Administrator, the following special conditions are issued as part of the type certification basis for Pratt and Whitney Canada PW210A engine model.

“Rated Flat 30-second and 2-minute One Engine Inoperative (OEI) Power,” with respect to rotorcraft turbine engines, means (1) a single rating for which the shaft horsepower and associated operating limitations of the 30-second OEI and 2-minute OEI ratings are equal, and (2) the shaft horsepower is that developed under static conditions at the altitude and temperature for the hot day, and within the operating limitations established under Part 33. The rating is for continuation of flight operation after the failure or shutdown of one engine in multiengine rotorcraft, for up to three periods of use no longer than 2.5 minutes each in any one flight, and followed by mandatory inspection and prescribed maintenance action.

(a) The airworthiness standards in Part 33 Amendment 30 for the 30-second OEI and 2-minute OEI ratings are applicable to the Flat 30-second and 2-minute OEI Power rating. In addition the following special conditions apply;

(b) Section 33.7 Engine ratings and operating limitations. Flat 30-second and 2-minute OEI Power rating and operating limitations are established for power, torque, rotational speed, gas temperature, and time duration.

(c) Section 33.27 Turbine, compressor, fan, and turbosupercharger rotor overspeed. The requirements of § 33.27, except that following the test, the rotor may not exhibit conditions such as cracking or distortion which preclude continued safe operation.

(d) Section 33.28 Engine controls systems. Must incorporate a means, or a provision for a means, for automatic availability and automatic control of the Flat 30-second and 2-minute OEI Power within the declared operating limitations.

(e) Section 33.29 Instrument Connection. In lieu of the requirements of 33.29(c) the PW210A must incorporate a means or a provision for a means to:

(1) Alert the pilot when the engine is at the Flat 30-second and 2-minute OEI Power level, when the event begins, and when the time interval expires;

(2) Automatically record each usage and duration of power at the Flat 30-second and 2-minute OEI Power rating;

(3) Following each flight when the Flat 30-second and 2-minute OEI Power rating is used, alert maintenance personnel in a positive manner that the engine has been operated at the Flat 30-second and 2-minute OEI Power level, and permit retrieval of the recorded data; and

(4) Enable routine verification of the proper operation of the above means.

(f) Section 33.87 Endurance test. The requirements applicable to 30-second and 2-minute OEI ratings, except for:

(1) The test of § 33.87(a)(7) for the purposes of temperature stabilization, must be run with a test period time of 2.5 minutes.

(2) The tests in § 33.87(f)(2) and (3) must be run continuously for the duration of 2.5 minutes, and

(3) The tests in § 33.87(f)(6) and (7) must be run continuously for the duration of 2.5 minutes.

(g) Section 33.88 Engine overtemperature test. The requirements of § 33.88(b) except that the test time is 5 minutes instead of 4 minutes.

Table of Contents Executive Summary Purpose of the Rule Summary of the Major Provisions of the Rule Summary of the Costs and Benefits of the Rule I. Introduction II. The Proposed Rule III. Description of the Final Rule A. Persons Subject to the Rule B. Products Covered by the Rule C. Notification of a Permanent Discontinuance or an Interruption in Manufacturing IV. Comments on the Proposed Rule A. Persons Subject to the Rule B. Products Covered by the Rule C. Notification of a Permanent Discontinuance or an Interruption in Manufacturing D. Other Issues Raised V. Legal Authority VI. Economic Analysis of Impacts A. Introduction B. Summary VII. Paperwork Reduction Act of 1995 VIII. Federalism IX. Environmental Impact X. References Executive Summary Purpose of the Rule

FDASIA (Pub. L. 112-144) significantly amended provisions in the FD&C Act related to drug shortages. Among other things, FDASIA amended section 506C of the FD&C Act (21 U.S.C. 356c) to require all manufacturers of certain drugs to notify FDA of a permanent discontinuance or an interruption in manufacturing of these drugs 6 months in advance of the permanent discontinuance or interruption in manufacturing, or as soon as practicable. FDASIA also added section 506E to the FD&C Act (21 U.S.C. 356e), requiring FDA to maintain a current list of drugs that are determined by FDA to be in shortage in the United States and to include on that public list certain information about those shortages. Finally, FDASIA permits FDA to apply section 506C to biological products by regulation and requires FDA to issue a final rule implementing certain drug shortages provisions in FDASIA by January 9, 2014. FDA believes this final rule will improve FDA's ability to identify potential drug shortages and to prevent or mitigate the impact of these shortages.

The rule modifies FDA's regulations to implement sections 506C and 506E of the FD&C Act as amended by FDASIA. Sections 310.306, 314.81(b)(3)(iii), and 600.82 (21 CFR 310.306, 314.81(b)(3)(iii), and 600.82) require all applicants of certain approved drugs or biological products,1 including applicants of blood or blood components 2 for transfusion (“blood or blood components”) that manufacture a significant percentage of the U.S. blood supply, and all manufacturers of certain drugs marketed without an approved application (“unapproved drug manufacturers”), to notify FDA electronically of a permanent discontinuance or an interruption in manufacturing of the product that is likely to lead to a meaningful disruption in supply (for drugs and biological products other than blood or blood components) or a significant disruption in supply (for blood or blood components) of the product in the United States. Applicants 3 are required to notify FDA of a permanent discontinuance or an interruption in supply if the drug or biological product is a prescription product that is life supporting, life sustaining, or intended for use in the prevention or treatment of a debilitating disease or condition, including any such drug used in emergency medical care or during surgery, and excluding radiopharmaceutical products (referred to in this document as “covered” drugs or biological products). The rule requires notification to FDA at least 6 months prior to date of the permanent discontinuance or interruption in manufacturing, or, if 6 months' advance notice is not possible, as soon as practicable thereafter, but in no case later than 5 business days after the permanent discontinuance or interruption in manufacturing occurs.

The rule also provides that FDA will issue a noncompliance letter to an applicant for failure to notify FDA under the rule; specifies minimum information that must be included in the notification; codifies FDA's current practice of publicly disseminating information on shortages and maintaining public lists of drugs and biological products in shortage (subject to certain confidentiality protections); and defines the terms “drug shortage,” “biological product shortage,” “meaningful disruption,” “significant disruption,” “life supporting or life sustaining,” and “intended for use in the prevention or treatment of a debilitating disease or condition.”

Finally, the rule includes a technical revision to § 20.100 (21 CFR 20.100) (public disclosure regulations) to include a cross-reference to the disclosure provisions in §§ 310.306, 314.81, and 600.82; and removes § 314.91 related to reducing the 6-month notification period for “good cause,” since it is no longer applicable under section 506C of the FD&C Act as amended by FDASIA.

The rule imposes annual reporting costs of up to $16,827 on those applicants affected by the rule, and up to $441,000 on FDA in review costs. Undertaking mitigation strategies, as measured by labor resources, is estimated to cost FDA between $1.85 and $5.94 million, and industry between $2.97 and $9.55 million. We also estimate annual costs for industry between $9.57 and $30.97 million associated with increasing production. Estimated total annual costs of the interactions between industry and FDA range between $14.54 and $46.92 million. Discounting over 20 years, annualized quantified benefits from avoiding the purchase of alternative products, managing product shortages, and life-years gained, would range from $30.45 million to $98.65 million using a 3 percent discount rate, and from $30.39 million to $98.42 million using a 7 percent discount rate. The public health benefits, mostly nonquantified, include the value of information that would assist FDA, manufacturers, health care providers, and patients in evaluating, mitigating, and preventing shortages of drugs and biological products that could otherwise result in delayed patient treatment or interruption in clinical trial development.

Recent experience with shortages of drugs and biological products in the United States has shown the serious and immediate effects they can have on patients and health care providers. According to information from FDA's drug and biological product shortages databases, the number of drug and biological product shortages quadrupled from approximately 61 in 2005 to more than 250 shortages in 2011. Although the number of new drug shortages significantly decreased in 2012 to 117 shortages, in 2013 to 44 shortages, and stayed at 44 new shortages in 2014, drug and biological product shortages still represent an ongoing challenge to public health.4 Shortages can involve critical drugs used to treat cancer, to provide required parenteral nutrition, or to address other serious medical conditions and can delay or deny needed care for patients. Shortages can also result in providers prescribing second-line alternatives, which may be less effective or higher risk than first-line therapies.

In response to the increasing concerns about the impact of shortages on health care in the United States, on October 31, 2011, President Obama issued Executive Order 13588 directing FDA to “take steps that will help to prevent and reduce current and future disruptions in the supply of lifesaving medicines” and noting that “one important step is ensuring that FDA and the public receive adequate advance notice of shortages whenever possible” (Ref. 1). In response to the Executive Order's directive to address the growing problem of drug shortages, FDA published an interim final rule (IFR) on December 19, 2011 (effective January 18, 2012), modifying the regulation at § 314.81 related to drug shortages (76 FR 78530).

As a result of the Executive order and IFR, early notifications to FDA of potential shortages increased from an average of 10 a month before the Executive order to approximately 60 a month in the months after the IFR. This dramatic increase in early notifications enabled FDA to work with manufacturers and other stakeholders to successfully prevent numerous shortages by using tools such as:

• Working with manufacturers to resolve manufacturing and quality issues contributing to short supply.

• Expediting FDA inspections and reviews of submissions from manufacturers to prevent and/or alleviate shortages.

• Identifying and working with manufacturers willing to initiate or increase production to cover expected gaps in supply.

• Exercising regulatory flexibility and discretion in appropriate circumstances, if this would not cause undue risk to patients.

In July 2012, FDASIA amended the FD&C Act to modify existing drug shortages requirements and to add new drug shortages provisions. Section 506C(i) of the FD&C Act, added by FDASIA, directs FDA to adopt a final rule to implement the drug shortages provisions. The final rule supersedes the IFR.

In the Federal Register of November 4, 2013 (78 FR 65904), FDA published a proposed rule to implement certain drug shortages provisions of the FD&C Act, as amended by FDASIA.5 The preamble to the proposed rule explained that section 1001 of FDASIA made substantial changes to section 506C of the FD&C Act related to reporting and addressing “permanent discontinuances” or “interruptions in manufacturing” of certain drug products. Most significantly, section 506C of the FD&C Act as amended:

• Requires all manufacturers of a prescription drug that is life supporting, life sustaining, or intended for use in the prevention or treatment of a debilitating disease or condition, including any such drug used in emergency medical care or during surgery, and excluding radiopharmaceutical products, to notify FDA of a permanent discontinuance in the manufacture of the drug or an interruption in the manufacturing of the drug that is likely to lead to a meaningful disruption in the supply of that drug in the United States at least 6 months prior to the date of the permanent discontinuance or interruption in manufacturing, or, if that is not possible, as soon as practicable.

• Requires the manufacturer to include in the notification the reason for the permanent discontinuance or interruption in manufacturing.

• Requires FDA to issue a letter to a “person” who fails to comply with the notification requirements in section 506C.

• Defines the terms “drug,” “drug shortage,” and “meaningful disruption,” and requires FDA to define the terms “life supporting,” “life sustaining,” and “intended for use in the prevention or treatment of a debilitating disease or condition.”

• Permits FDA to apply section 506C to biological products, including vaccines and plasma-derived products and their recombinant analogs, if FDA determines the inclusion would benefit public health, taking into account existing supply reporting programs and aiming to reduce duplicative notifications.

• Requires FDA to distribute information on drug shortages to the public, to the maximum extent possible, subject to certain confidentiality protections.

In addition to modifying section 506C, FDASIA added several new drug shortage-related sections to the FD&C Act, including section 506E. Section 506E of the FD&C Act requires FDA to maintain an up-to-date list of drugs that are determined by FDA to be in shortage, including the names and the National Drug Codes (NDCs) of such drugs in shortage, the name of each manufacturer of the drug, the reason for each shortage as determined by FDA (choosing from a list of reasons enumerated in the statute), and the estimated duration of each shortage. Section 506E of the FD&C Act also includes confidentiality provisions.

The Agency proposed to implement sections 506C and 506E of the FD&C Act by amending § 314.81(b)(3)(iii) (permanent discontinuance or interruption in manufacturing of approved prescription drugs) and § 20.100 (cross-reference to disclosure provisions); adding new § 310.306 (permanent discontinuance or interruption in manufacturing of marketed prescription unapproved new drugs) and § 600.82 (permanent discontinuance or interruption in manufacturing of prescription biological products); and removing § 314.91 (reduction in the discontinuance notification period) (see 78 FR 65904).

FDA provided 60 days for public comment on the proposed rule. Based on the comments received and FDA's experience to date receiving notifications, maintaining public lists of drug and biological product shortages, and working with manufacturers and stakeholders to prevent and mitigate drug and biological product shortages, the Agency is finalizing the rule as proposed.

Sections 310.306, 314.81(b)(3)(iii), and 600.82 require notification to FDA of a permanent discontinuance or an interruption in manufacturing of a covered drug or biological product. The following persons are subject to these notification requirements:

• All applicants with an approved NDA or ANDA for a covered drug product (§ 314.81(b)(3)(iii)).

• All applicants with an approved BLA for a covered biological product, other than blood or blood components (§ 600.82(a)(1)).

• Applicants with an approved BLA for blood or blood components, if the applicant is a manufacturer of a significant percentage of the U.S. blood supply (§ 600.82(a)(2)).

• All manufacturers of a covered drug product marketed without an approved NDA or ANDA (§ 310.306, which applies § 314.81(b)(3)(iii) in its entirety to covered drug products marketed without an approved NDA or ANDA).

Section 506C of the FD&C Act as amended by FDASIA requires a “manufacturer” to notify FDA of a permanent discontinuance or an interruption in manufacturing. The rule requires the ANDA, NDA, or BLA applicant (for approved drugs or biological products) or the unapproved drug manufacturer (for marketed, unapproved drugs) to notify FDA of a permanent discontinuance or an interruption in manufacturing.

For purposes of section 506C of the FD&C Act, under the rule an ANDA, NDA, or BLA applicant is considered the manufacturer of an approved, covered product, even if the ANDA, NDA, or BLA applicant contracts that function out to another entity. In other words, the rule makes clear that for approved, covered drugs and biological products, the ANDA, NDA, or BLA applicant bears the responsibility for reporting to FDA a permanent discontinuance or an interruption in manufacturing, whether the product is manufactured by the applicant itself or for the applicant under contract with one or more different entities. As such, the ANDA, NDA, or BLA applicant should establish a process with any relevant contract manufacturer, active pharmaceutical ingredient (API) supplier, or other non-applicant entity that ensures the applicant's compliance with this rule.

Section 506C(i)(3) of the FD&C Act, as amended by FDASIA, directs FDA to “take into account any supply reporting programs [for biological products] and . . . aim to reduce duplicative notification” in applying section 506C to biological products by regulation. Accordingly, with respect to blood or blood components, the rule applies only to applicants that are manufacturers of a “significant percentage of the United States blood supply.” As described more fully in sections III.B.2.c and III.C.1.b.ii, FDA believes that this approach with respect to blood or blood components will ensure that the Agency receives information that is essential to preventing shortages of these products, without unnecessarily duplicating existing systems and without being unduly burdensome for industry. FDA intends to consider an applicant that holds a BLA for blood or blood components to be a manufacturer of a “significant percentage” of the U.S. blood supply if the applicant manufactures 10 percent or more of the U.S. blood supply.6

The rule applies to all prescription drug products approved under an NDA or ANDA (§ 314.81(b)(3)(iii)), all marketed unapproved prescription drug products (§ 310.306), and all prescription biological products approved under a BLA (§ 600.82) that are:

• Life supporting; life sustaining; or intended for use in the prevention or treatment of a debilitating disease or condition, including any such product used in emergency medical care or during surgery; and

• Not radiopharmaceutical products.7

FDASIA does not define the terms “life supporting,” “life sustaining,” or “intended for use in the prevention or treatment of a debilitating disease or condition,” but instead requires FDA to define them (section 506C(i)(2) of the FD&C Act). Sections 314.81(b)(3)(iii)(f) and 600.82(f) define a “life supporting or life sustaining” drug or biological product as one that is “essential to, or that yields information that is essential to, the restoration or continuation of a bodily function important to the continuation of human life.” As explained in the preamble to the proposed rule (78 FR 65904 at 65909), this definition of “life supporting or life sustaining” is consistent with language used to describe this term in the preamble to the final rule implementing pre-FDASIA section 506C (72 FR 58993 at 58994, October 18, 2007), and in medical device regulations (see 21 CFR 821.3(g)).

The final rule defines “intended for use in the prevention or treatment of a debilitating disease or condition” to mean “intended for use in the prevention or treatment of a disease or condition associated with mortality or morbidity that has a substantial impact on day-to-day functioning” (§§ 314.81(b)(3)(iii)(f) and 600.82(f)). FDA equates “debilitating disease or condition” with “serious disease or condition” under this definition, and we have defined it according to the definition of “serious” found in § 312.300 (21 CFR 312.300), which governs expanded access to investigational new drugs. This definition of “intended for use in the prevention or treatment of a debilitating disease or condition” is also consistent with our discussion of the term in the preamble to the proposed rule implementing the pre-FDASIA section 506C (65 FR 66665 at 66666, November 7, 2000).

It is important to note that the definitions of “life supporting or life sustaining” and “intended for use in the prevention or treatment of a debilitating disease or condition” are, in important respects, different than FDA's definition of “medically necessary” as used in the context of the existing Center for Drug Evaluation and Research (CDER) Manual of Policies and Procedures (MAPP) on shortages of CDER-regulated products (CDER MAPP 4190.1 Rev. 2) (Ref. 2) and the existing Center for Biologics Evaluation and Research (CBER) Standard Operating Policy and Procedure (SOPP) on shortages of CBER-regulated products (CBER SOPP 8506) (Ref. 3). In general, FDA considers a product to be medically necessary under the internal MAPP and SOPP if there is no other product that is judged by CDER or CBER medical staff to be an appropriate substitute or there is an inadequate supply of an acceptable alternative, as determined by appropriate CDER and CBER personnel. In contrast, under this rule, an applicant is required to notify FDA of a permanent discontinuance or an interruption in manufacturing of a drug or biological product that is life supporting, life sustaining, or intended for use in the prevention or treatment of debilitating disease or condition, whether or not the product is considered “medically necessary” under the MAPP or SOPP. Under the MAPP and SOPP, FDA uses the definition of medically necessary to prioritize the Agency's response to specific shortages or potential shortages and to allocate resources appropriately.

Section 506C of the FD&C Act, as amended, states that for purposes of section 506C, the term “drug” does not include biological products as defined in section 351(i) of the Public Health Service Act, unless the Secretary of Health and Human Services (HHS) (the Secretary) applies section 506C to such products by regulation. Section 506C(i)(3) of the FD&C Act provides that FDA may, by regulation, apply section 506C to biological products, “including plasma products derived from human plasma protein and their recombinant analogs” if “the Secretary determines that such inclusion would benefit the public health,” taking into account “any [existing] supply reporting programs” and aiming to reduce “duplicative notification.” Additionally, FDA may apply section 506C of the FD&C Act to vaccines, but the Secretary must determine whether notification of a vaccine shortage to the Centers for Disease Control and Prevention (CDC) under its “vaccine shortage notification program” could satisfy a vaccine manufacturer's obligation to notify FDA of a permanent discontinuance or an interruption in manufacturing under section 506C.

As proposed, FDA is applying section 506C of the FD&C Act to all biological products, including recombinant therapeutic proteins, monoclonal antibody products, vaccines, allergenic products, plasma-derived products and their recombinant analogs, blood or blood components, and cellular and gene therapy products. Shortages of biological products can have serious negative consequences for patients who rely on these products for their treatment. FDA anticipates that early notification of a permanent discontinuance or an interruption in the manufacturing of biological products will allow the Agency to address, prevent, or mitigate a shortage of these products, greatly benefiting the public health. In addition, we have determined that requiring manufacturers of biological products to notify FDA under this rule will not duplicate the existing reporting programs of which we are aware.

a. Plasma-derived products and their recombinant analogs. Under § 600.82(a), the requirements of section 506C of the FD&C Act apply to all biological products, including plasma products derived from human plasma protein and their recombinant analogs (referred to in this document as plasma-derived products and their recombinant analogs). As explained in the preamble to the proposed rule (78 FR 65904 at 65910), with respect to plasma-derived products and their recombinant analogs, FDA recognizes that the Plasma Protein Therapeutics Association (PPTA) has developed a voluntary data system that captures the distribution and supply of five plasma product groups in the United States: Plasma-Derived Factor VIII, Recombinant Factor VIII, Immune Globulin (Ig), Albumin 5%, and Albumin 25%. The PPTA, in consultation with a third party, voluntarily submits a monthly report to FDA of aggregate distribution data for these five product groups. This information provides a picture of the total supply and distribution of these five products in any given month as compared to the last 12 months.

FDA recognizes and greatly appreciates the efforts by PPTA to provide plasma product supply information to FDA and the public. However, as described in detail in the preamble to the proposed rule (78 FR 65904 at 65910), FDA concluded that it would benefit the public health for the Agency to receive direct notification under this rule from all manufacturers of these products. Because the PPTA program does not serve the same purpose as notification under this rule, including plasma-derived products and their recombinant analogs in this rule will not duplicate the PPTA system. FDA believes that including these products within the scope of the rule is essential to FDA's efforts to identify permanent discontinuances and interruptions in manufacturing of these products, and consequently, essential to our efforts to address, prevent, or mitigate shortages of these products.

b. Vaccines. Under section 506C(i)(3)(B) of the FD&C Act, if FDA applies section 506C to vaccines, the Secretary must specifically consider whether the notification requirement may be satisfied by submitting a notification to CDC under CDC's “vaccine shortage notification program.”

CDC contracts with vaccine manufacturers as part of the Vaccines for Children (VFC) program.8 FDA recognizes that CDC includes language in its contracts with vaccine manufacturers requiring the manufacturer to notify CDC of vaccine supply issues that could affect the manufacturer's ability to fulfill its contract with CDC.9 As explained in the preamble to the proposed rule (78 FR 65904 at 65910), only certain vaccines are included under the existing CDC program, and thus, only manufacturers of certain vaccines are obligated to provide notification of supply issues to CDC. Based on information from CDC, FDA estimates that approximately 30 percent of vaccines licensed in the United States are not subject to CDC notification.

Moreover, even for the vaccines that are subject to CDC notification, the information collected is not adequate for purposes of this rule, because the existing CDC program does not require vaccine manufacturers to provide notice 6 months in advance of a permanent discontinuance or interruption in manufacturing. Early notice of permanent discontinuances and interruptions is critically important to the prevention of drug shortages. Although FDA and its HHS partners work together closely on vaccine supply issues, and the current framework for CDC notification is useful for contractual purposes, FDA has determined that including vaccines within the scope of this rule is necessary to fully support FDA's efforts to identify, address, prevent, or mitigate a vaccine shortage and would not be duplicative of existing notification systems.

c. Blood or blood components for transfusion. The rule applies section 506C of the FD&C Act to blood or blood components, but in a more limited manner than for other biological products (§ 600.82(a)(2)). The rule requires blood or blood component applicants (i.e., blood collection establishments subject to licensure) that manufacture a significant percentage of the U.S. blood supply to notify FDA of a permanent discontinuance or an interruption in manufacturing that is likely to lead to a “significant disruption” in the applicant's supply of blood or blood components. The rule is intended to require reporting of large-scale, permanent discontinuances, or interruptions in manufacturing of blood or blood components.

FDA anticipates that the rule will ensure that FDA receives information essential to the Agency in preventing, mitigating, or addressing shortages of blood or blood components, while avoiding duplication with existing programs that monitor local and regional supplies of blood or blood components by ABO blood group.

As explained in detail in the preamble to the proposed rule (78 FR 65904 at 65911), we are aware of two significant efforts to monitor local and regional supplies of blood or blood components: (1) America's Blood Centers (ABC) and the Blood Availability and Safety Information System (BASIS) and (2) the Interorganizational Task Force on Domestic Disasters and Acts of Terrorism (Task Force), which is managed by the AABB (formerly the American Association of Blood Banks).

The ABC and BASIS systems monitor the supply and demand of blood or blood components on a daily and weekly basis, and in the event of a national disaster. In other words, ABC and BASIS are tools for local blood centers and hospitals to track their day-to-day inventory of blood or blood components. Unlike the notifications required under this rule, ABC and BASIS are not designed to predict large-scale or nationwide disruptions in the supply of blood or blood components. Moreover, ABC and BASIS are voluntary systems, whereas the rule requires reporting.

The Task Force was formed in January 2002 to help make certain that blood collection efforts resulting from domestic disasters and acts of terrorism are managed properly, and to deliver clear and consistent messages to the public regarding the status of the U.S. blood supply. The Task Force's efforts, although critical to public health, are focused on inventory management and are not intended to predict large-scale disruptions in the supply of blood or blood components. The Task Force coordinates the movement of blood throughout the United States and appeals to the public for blood donations, but Task Force information is not sufficient for FDA in the context of predicting a permanent discontinuance or an interruption in manufacturing of these products that would have a large-scale impact.

In short, although the information already available to FDA from the ABC, BASIS, and Task Force programs is useful, the existing frameworks are voluntary, do not result in a direct notification from an applicant to FDA, and only capture short-term, day-to-day supply and distribution information. In addition, in contrast to this rule, the existing systems are not equipped to predict large-scale, significant disruptions of blood or blood components. Accordingly, FDA has determined that including blood or blood components within the scope of this rule would benefit the public health, providing information that is essential to FDA's efforts to address shortages of these products.

However, recognizing that the existing ABC, BASIS, and Task Force programs do provide certain information concerning the supply of blood or blood components, the reporting requirements apply only to applicants of blood or blood components that manufacture a significant percentage of the U.S. blood supply, and only to a permanent discontinuance of manufacture or an interruption in manufacturing that is likely to lead to a “significant disruption” in supply of that blood or blood component, as further described in sections III.A and III.C.1.

Under this rule, “product” refers to a specific strength, dosage form, and route of administration of a drug or biological product. For example, if Applicant X experiences an interruption in manufacturing of the 50-milligram (mg) strength of a drug product that would be subject to § 314.81(b)(3)(iii), but the 100-mg strength continues to be manufactured without delay, under the rule, Applicant X must notify FDA of the interruption in manufacturing of the 50-mg strength if the interruption is likely to lead to a meaningful disruption in the applicant's supply of the 50-mg strength.

a. Permanent discontinuance. Section 506C of the FD&C Act requires manufacturers to notify FDA of a permanent discontinuance of manufacture of a covered drug. Sections 314.81(b)(3)(iii) and 600.82 require the applicant to report all permanent discontinuances of covered drugs and biological products to FDA. For purposes of this rule, we interpret a permanent discontinuance to be a decision by the applicant for business or other reasons to cease manufacturing and distributing the product indefinitely.

b. Interruption in manufacturing. In addition to permanent discontinuances, section 506C of the FD&C Act requires manufacturers to notify FDA of an interruption in manufacturing of a covered drug that is likely to lead to a meaningful disruption in supply of that drug in the United States. The statute defines “meaningful disruption” to mean a change in production that is reasonably likely to lead to a reduction in the supply of a drug by a manufacturer that is more than negligible and affects the ability of the manufacturer to fill orders or meet expected demand for its product; and does not include interruptions in manufacturing due to matters such as routine maintenance or insignificant changes in manufacturing so long as the manufacturer expects to resume operations in a short period of time.

i. Drugs and biological products other than blood or blood components. Sections 314.81(b)(3)(iii)(a) and 600.82(a)(1) require the applicant for a product other than blood or blood components to report to FDA an interruption in manufacturing of the drug or biological product that is likely to lead to a meaningful disruption in supply of that drug or biological product in the United States. Sections 314.81(b)(3)(iii)(f) and 600.82(f) adopt the statutory definition of “meaningful disruption in supply.”

Consistent with the statutory definition of meaningful disruption, the rule requires an applicant to report an interruption in manufacturing likely to lead to a meaningful disruption in its own supply of a covered drug or biological product. In other words, when evaluating whether an interruption in manufacturing is reportable to FDA under the rule, rather than considering the potential impact of the interruption on the market as a whole, the relevant question (regardless of how large or small the applicant's market share may be) is whether the interruption is likely to lead to a reduction in the applicant's supply of a covered drug or biological product that is more than negligible, and affects the ability of the applicant to fill its own orders or meet the expected demand of its clients for the covered product. Consistent with the statute, the rule does not require an applicant to predict the market-wide impact of an interruption in its own manufacturing, which can be difficult to accurately assess and could lead to inconsistent interpretation of the regulation, less accurate predictions, and under- or overreporting.

Under the rule, reportable discontinuances or interruptions in manufacturing of a covered drug or biological product include:

• A business decision to permanently discontinue manufacture of a covered drug or biological product.

• A delay in acquiring APIs or inactive ingredients that is likely to lead to a meaningful disruption in the applicant's supply of a covered drug or biological product while alternative API suppliers are located.

• Equipment failure or contamination affecting the quality of a covered drug or biological product that necessitates an interruption in manufacturing while the equipment is repaired or the contamination issue is addressed and that is likely to lead to a meaningful disruption in the applicant's supply of the product.

• Manufacturing shutdowns for maintenance or other routine matters, if the shutdown extends for longer than anticipated or otherwise is likely to lead to a meaningful disruption in the applicant's supply of a covered drug or biological product.

• A merger of firms or transfer of an application for a covered drug or biological product to a new firm, if the merger or transfer is likely to lead to a meaningful disruption in the applicant's supply of the product.

• An interruption in manufacturing (e.g., contamination of a manufacturing line) that in the applicant's view may not meaningfully disrupt the market-wide supply of the covered drug or biological product (for example, because the applicant holds only a small share of the market for the product), but that the applicant determines is likely to lead to a meaningful disruption in its own supply of the covered product.

Conversely, an applicant is not required, under the rule, to notify FDA if an interruption in manufacturing is not likely to lead to a meaningful disruption in the applicant's supply of the drug or biological product. For example, FDA does not need to be notified in the following circumstances:

• A scheduled shutdown of an applicant's manufacturing facility for routine maintenance, if the shutdown is anticipated and planned for in advance and, therefore, is not expected to lead to a meaningful disruption in the applicant's supply of a covered drug or biological product.

• An unexpected power outage that results in an unscheduled interruption in manufacturing of a covered drug or biological product, if the applicant expects to resume normal operations within a relatively short timeframe and does not expect to experience a meaningful disruption in its supply of the covered drug or biological product.

In either of these circumstances, if the interruption in manufacturing subsequently appears likely to lead to a meaningful disruption in the applicant's supply of the covered drug or biological product, then it would become a reportable interruption in manufacturing under the rule and the applicant must notify FDA.

The list of examples described in this document is intended to assist industry in understanding what would (or would not) be required to be reported under amended section 506C of the FD&C Act, but the list is not exhaustive. The rule requires that any permanent discontinuance or any interruption in manufacturing that is likely to lead to a meaningful disruption in the applicant's supply of a covered drug or biological product be reported to FDA, even if not specifically described in this preamble.

ii. Blood or blood components for transfusion. Section 600.82(a)(2) requires an applicant that manufactures a significant percentage of the U.S. blood supply to report to FDA an interruption in manufacturing of a blood or blood component that is likely to lead to a “significant disruption” in supply of that product in the United States. As explained in section III.A, FDA intends to consider an applicant that manufactures 10 percent or more of the U.S. blood supply to manufacture a significant percentage of the U.S. blood supply for purposes of this rule.10 Section 600.82(f) defines “significant disruption” as a change in production that is reasonably likely to lead to a reduction in the supply of blood or blood components by a manufacturer that substantially affects the ability of the manufacturer to fill orders or meet expected demand for its product; and does not include interruptions in manufacturing due to matters such as routine maintenance or insignificant changes in manufacturing so long as the manufacturer expects to resume operations in a short period of time. This definition of “significant disruption” closely follows, but is not identical to, the statutory and regulatory definition of “meaningful disruption.”

For purposes of the rule, FDA intends to consider an interruption in manufacturing that leads to a reduction of 20 percent or more of an applicant's own supply of blood or blood components over a 1-month period to “substantially affect” the ability of the applicant to fill orders or meet expected demand; accordingly, such an interruption would be considered a “significant disruption” in supply. Again, when determining whether an interruption in manufacturing is likely to lead to a significant disruption in supply, the blood or blood component applicant should not consider the market as a whole, but rather, should consider only its own supply of product.

The definition of “significant disruption” (interpreted to mean affecting 20 percent or more of an individual applicant's supply over a 1-month period) as applied to blood or blood components, in combination with limiting the rule only to applicants of blood or blood components that manufacture a significant percentage (10 percent or more) of the nation's blood supply, is intended to avoid duplication with existing programs to monitor the daily and weekly distribution of blood or blood components described in section III.B.2.c of this document and in the preamble to the proposed rule (78 FR 65904 at 65911). In general, existing programs maintained by ABC, BASIS, and the Task Force monitor and resolve temporary, local shortfalls of a particular ABO blood group or a particular blood component. Accordingly, the definition of “significant disruption” is intended to capture events that are likely to precipitate large-scale disruptions in an applicant's blood supply and are unlikely to be identified and corrected by the existing ABC, BASIS, and Task Force programs. The additional limitation of the rule to applicants that manufacture a significant percentage of the nation's blood supply further ensures that reporting to FDA will not unnecessarily duplicate reporting to the ABC, BASIS, and Task Force systems, but still allows FDA to receive information that is essential to the Agency in preventing large-scale shortages of these products.

Circumstances that trigger notification to FDA of a permanent discontinuance or an interruption in manufacturing of blood or blood components include the following examples. We recognize that, with the exception of the first example of a permanent discontinuance, the following interruptions are unlikely to be reasonably anticipated 6 months in advance; they would be reportable as soon as practicable, but in no case later than 5 business days after the interruption in manufacturing occurs:

• A business decision by an applicant that manufactures 10 percent or more of the nation's blood supply to permanently discontinue manufacture of blood or blood components;

• A computer system failure that causes an applicant of a blood establishment that collects 10 percent or more of the nation's blood supply to be unable to label blood for 2 weeks, resulting in a 20 percent monthly shortfall of blood for that applicant;

• An issue with blood collection bags, such that they are unavailable, causing an applicant that manufactures 10 percent or more of the nation's blood supply to experience a 20 percent monthly shortfall in normal production for that applicant;

• An issue with apheresis collection devices that causes an applicant of a blood establishment that collects 10 percent or more of the nation's blood supply to be unable to collect platelets by apheresis, resulting in a 20 percent monthly shortfall in platelet supply for that applicant;

• An explosion or fire that damages a large testing laboratory that performs blood testing for an applicant that manufactures 10 percent or more of the nation's blood supply, resulting in a 20 percent monthly shortfall of blood or blood components for that applicant.

Conversely, a covered blood or blood component applicant is not required under the rule to notify FDA if an interruption in manufacturing is not likely to lead to a significant disruption in the applicant's supply of blood or blood components. For example, FDA does not need to be notified if a covered blood or blood component applicant experiences a temporary drop in blood donations at one of its local blood donation centers, such that it is unable to fully supply its hospital customers with blood for several days, provided the donation center quickly returns to its normal donation and supply levels and the dip in blood donations is not likely to lead to a 20 percent decrease in the applicant's overall supply of blood over a 1-month period. We expect that this type of situation would be identified and resolved through the ABC, BASIS, and Task Force systems (e.g., these systems would identify the issue and locate temporary, alternative blood supplies for the applicant's customers). If such an event does lead to a significant disruption in a covered applicant's supply of blood or blood components, it must be reported to FDA under the final rule.

Again, the list of examples described in this document is intended to assist industry in understanding what must be reported under amended section 506C of the FD&C Act, but the list is not exhaustive. The rule requires any permanent discontinuance or any interruption in manufacturing that is likely to lead to a significant disruption (as defined by the rule) in a covered applicant's supply of blood or blood components to be reported to FDA, even if not specifically discussed in this preamble.

a. Timing of notification. Section 506C of the FD&C Act requires notification to FDA: (1) At least 6 months prior to the date of the permanent discontinuance or interruption in manufacturing or (2) if 6 months' advance notice is not possible, as soon as practicable. Consistent with the statute, §§ 314.81(b)(3)(iii)(b) and 600.82(b) require an applicant to notify FDA of a permanent discontinuance or an interruption in manufacturing at least 6 months in advance of the date of the permanent discontinuance or interruption in manufacturing; or, if 6 months' advance notice is not possible, as soon as practicable thereafter, but in no case later than 5 business days after the permanent discontinuance or interruption in manufacturing occurs.

The Agency's most powerful tool for addressing drug and biological product shortages is early notification, which provides lead time for FDA to work with manufacturers and other stakeholders to prevent a shortage or to mitigate the impact of an unavoidable shortage. As such, FDA expects that applicants would provide 6 months' advance notice whenever possible. In particular, FDA believes that an applicant will generally know of a permanent discontinuance at least 6 months in advance, and in that case, the applicant must provide notification of a permanent discontinuance to FDA at least 6 months in advance. We understand that an applicant may not reasonably be able to anticipate 6 months in advance certain interruptions in manufacturing that are likely to lead to a meaningful disruption. For example, if an applicant discovers fungal contamination that requires an immediate, temporary shutdown of its manufacturing plant for a covered product, the applicant will not be able to provide FDA with 6 months' advance notice of the interruption in manufacturing. Instead, the rule requires that the applicant notify FDA “as soon as practicable,” but in no case more than 5 business days after the interruption in manufacturing occurs. In this example, the applicant must notify FDA as soon as it reasonably anticipates that an interruption in manufacturing caused by fungal contamination is likely to result in a meaningful disruption in supply of the applicant's product. The applicant should not wait until it or its manufacturer begins rejecting or delaying fulfillment of orders for the product from available inventory (i.e., the applicant should not wait until the interruption in manufacturing actually begins to disrupt supply and affect patient access to the product).

In our experience, even if it is not possible for an applicant to notify the Agency before a permanent discontinuance or an interruption in manufacturing occurs, it should generally be possible for the applicant to provide notice within a day or two, and it should always be possible for the applicant to notify the Agency no later than 5 days after the permanent discontinuance or interruption occurs, even in the event of a natural disaster or some other catastrophic incident. Accordingly, the 5-day provision represents a date certain after which FDA would be able to take action under section 506C(f) of the FD&C Act against an applicant for failure to comply with the notification requirements (see section III.C.6 for further discussion of the consequences of failure to notify FDA). Additionally, it is important to note that an applicant that could have notified the Agency before 5 days had passed, but waited until the end of the 5-day period is in violation of the rule. Consistent with the statutory intent, whenever possible, applicants are required to provide us with advance notice, whether 6 months' advance notice, or “as soon as practicable” thereafter (e.g., 3 months' advance notice).

b. Submission of notification. Sections 314.81(b)(3)(iii)(b) and 600.82(b) require an applicant to notify FDA of a permanent discontinuance or an interruption in manufacturing electronically in a format FDA can process, review, and archive. Applicants must email notifications to [email protected] (for products regulated by CDER) or [email protected] (for products regulated by CBER). In the future, the Agency may consider creating an electronic notification portal linked to the Agency's internal drug shortages database to facilitate submission of these notifications. Unless and until this portal is created, however, email notifications will be used.

c. Reduction in notification period for “good cause.” As described in the preamble to the proposed rule (78 FR 65904 at 65915), under the pre-FDASIA section 506C(b), a manufacturer could seek, and FDA could grant, a reduction in the required 6-month advance notification period for “good cause.” The regulation at § 314.91 implemented the pre-FDASIA section 506C(b). Because section 506C of the FD&C Act as amended by FDASIA does not include an option for formally seeking a reduction in the 6-month advance notification period based on “good cause,” this rule eliminates § 314.91 in its entirety.

Sections 314.81(b)(3)(iii)(c) and 600.82(c) require an applicant to include the following items in notifications submitted under section 506C(a) of the FD&C Act:

• The name of the drug or biological product subject to the notification, including the NDC for the drug or biological product (or, for a biological product that does not have an NDC, an alternative standard for identification and labeling that has been recognized as acceptable by the Center Director);

• The name of the applicant of the drug or biological product;

• Whether the notification relates to a permanent discontinuance of the drug or biological product or an interruption in manufacturing of the drug or biological product;

• A description of the reason for the permanent discontinuance or interruption in manufacturing; and

• The estimated duration of the interruption in manufacturing.

FDA requires applicants to include the minimum information listed in the initial notification to assist the Agency in complying with section 506E of the FD&C Act, which requires FDA to maintain a publicly available list of drugs in shortage, as described in section III.C.4. We recognize that the duration of an interruption in manufacturing can be difficult to accurately predict. Therefore the applicant should provide FDA with its best estimate of the expected duration of the interruption in manufacturing. If, after the initial notification is submitted, the estimated duration changes, the applicant should notify FDA of the new expected duration of the interruption in manufacturing so that FDA can respond appropriately. In addition, the applicant should include a detailed, factual description of the reason for the shortage in the notification to assist FDA in responding to the notification.

Along with the required elements of the notification, applicants are encouraged to include any other information in the notification that may assist the Agency in working with the applicant to resolve the permanent discontinuance or interruption in manufacturing. This information could include the applicant's market share, inventory on hand or in distribution channels, allocation procedures and/or plans for releasing available product, copies of communications to patients and providers regarding the shortage (e.g., Dear Healthcare Professional letters), or initial proposals to prevent or mitigate the shortage. As appropriate, the Agency will also followup with the applicant after the notification is submitted to obtain additional information and to work with the applicant to facilitate resolution of any shortage or potential shortage.

Section 506E of the FD&C Act requires FDA to maintain a publicly available list of drugs and biological products (if FDA applies section 506C of the FD&C Act to biological products by regulation) that are determined by FDA to be in shortage, including providing the names and NDCs of the drugs, the name of each manufacturer of the drug, the reason(s) for the shortage, and the estimated duration of the shortage. Section 506C(h)(2) of the FD&C Act defines “drug shortage” to mean a period of time when the demand or projected demand for the drug within the United States exceeds the supply of the drug. For purposes of section 506E of the FD&C Act, under the rule, the ANDA, NDA, or BLA applicant is considered the manufacturer of an approved drug or biological product, even if the ANDA, NDA, or BLA applicant contracts that function out to another entity.

Section 506E of the FD&C Act further requires FDA to include on the drug and biological product shortages lists the reason for the shortage, choosing from the following list of categories specified in the statute:

• Requirements relating to complying with current good manufacturing practices (CGMPs);

• Regulatory delay;

• Shortage of an active ingredient;

• Shortage of an inactive ingredient component;

• Discontinuation of the manufacture of the drug;

• Delay in shipping of the drug; and

• Demand increase in the drug.

Consistent with the statute, and with FDA's current practice, under §§ 310.306(c), 314.81(b)(3)(iii)(d), and 600.82(d), FDA will maintain publicly available lists of drugs and biological products that are determined by FDA to be in shortage, whether or not FDA has received a notification under this rule concerning the product in shortage. Sections 314.81(b)(3)(iii)(f) and 600.82(f) adopt the statutory definition of drug shortage (substituting “biological product shortage” for “drug shortage” in § 600.82(f)). As specified in the rule, the shortages lists will include the following required statutory elements for drugs or biological products in shortage: Names and NDCs (or the alternative standard for certain biological products) of the drugs or biological products, names of each applicant, reason for each shortage, and estimated duration of each shortage.

If FDA has received a notification under the rule for the drug or biological product, FDA will consider the reason for the shortage supplied by the applicant in its notification and, where applicable, other relevant information before the Agency in determining how to categorize the reason for the shortage. Consistent with the statute, the Agency, not the applicant, is responsible for determining which categorical reason best fits a particular situation. In general, FDA intends to choose the categorical reason that best fits the applicant's supplied description. To facilitate FDA's determination of the categorical reason for the shortage, under the final rule we expect applicants to supply as many details and facts as possible concerning the reason for the permanent discontinuance or interruption in manufacturing when submitting a section 506C notification. This information will also assist FDA in responding quickly to the notification. If FDA has not received a notification under the rule, but becomes aware of a shortage through other means, FDA intends to consider information before the Agency when determining and choosing the reason for the shortage to be included on the public list.

In addition to the list of statutory reasons for the shortage that FDA may choose from, the final rule also adds an eighth category, entitled “Other reason.” The Agency intends to choose “Other reason” only if none of the other listed reasons is applicable. For example, an interruption in manufacturing as a result of a natural disaster or other catastrophic loss would fall into the “Other reason” category. Moreover, although FDA may choose the “Other reason” category, the public shortages list will also include a brief summary of the reason for the shortage submitted by the applicant, thus providing additional information to the public on the cause of the shortage.

The final rule codifies, consistent with FDASIA, FDA's current practice of maintaining public lists of drugs and biological products in shortage, available on FDA's Web site at http://www.fda.gov/drugs/drugsafety/drugshortages/default.htm (for products regulated by CDER) and http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/Shortages/default.htm (for products regulated by CBER).

The list of CDER-regulated products includes six categories of information about each drug product on the list: Company (manufacturer of product and contact information); Product (name, strength, formulation, dosage, and NDC); Availability and Estimated Shortage Duration; Related Information (includes applicant's submitted description of reason for shortage); Shortage Reason (FDA-determined reason for the shortage, chosen from the list in § 314.81(b)(3)(iii)(d)); and Date Updated (last date FDA updated the information for that particular product). The list of CBER-regulated products includes similar information in fields for Product Name, Reason for Shortage, and Status.

In general, as required by sections 506C(c) and 506E of the FD&C Act, and as described in this document, FDA will publicly disclose, to the maximum extent possible, information on drug shortages, including information provided by applicants in a notification of a permanent discontinuance or an interruption in manufacturing. Sections 314.81(b)(3)(iii)(d) and 600.82(d), however, specify that FDA may choose not to make information collected under the authority of the rule available to the public on the drug or biological product shortages lists or under its general obligation to disseminate drug shortage information under section 506C(c) of the FD&C Act if the Agency determines that disclosure of such information would adversely affect the public health (such as by increasing the possibility of hoarding or other disruption of the availability of the drug or biological product to patients). These provisions closely track the statutory language in sections 506C(c) and 506E(c)(3) of the FD&C Act.

In addition, §§ 310.306(c), 314.81(b)(3)(iii)(d), and 600.82(d), as finalized, state that FDA will not provide on the public drug or biological product shortages lists or under section 506C(c) of the FD&C Act information that is protected by 18 U.S.C. 1905 or 5 U.S.C. 552(b)(4), including trade secrets and commercial or financial information that is considered confidential or privileged under § 20.61. These provisions provide appropriate protection for commercial and trade secret information protected by other Federal law and are consistent with sections 506C(d) and 506E(c)(2) of the FD&C Act, which clarify that the information provisions in sections 506C and 506E do not alter or amend 18 U.S.C. 1905 or 5 U.S.C. 552(b)(4). The final rule also implements a technical amendment to § 20.100 to include a cross-reference to §§ 310.306, 314.81, and 600.82. Section 20.100 describes, by cross-reference to other regulations, the rules on public availability of certain specific categories of information.

Consistent with section 506C(f) of the FD&C Act, §§ 310.306(b), 314.81(b)(iii)(3)(e), and 600.82(e), as finalized, provide that FDA will issue a noncompliance letter to an applicant (or, for a covered, unapproved drug, to a manufacturer) who fails to submit a section 506C notification as required under §§ 314.81(b)(iii)(3)(a) and 600.82(a) within the timeframe stated in §§ 314.81(b)(iii)(3)(b) and 600.82(b). It is important to note that failure to notify FDA includes failure to timely notify FDA. For example, if FDA discovers that an applicant did not notify FDA of the permanent discontinuance of a covered drug or biological product 6 months in advance, even though the applicant anticipated the permanent discontinuance 6 months in advance, FDA will issue a noncompliance letter. Similarly, if FDA determines that an applicant experienced a reportable interruption in manufacturing that it could not reasonably anticipate 6 months in advance, but the applicant failed to notify FDA “as soon as practicable,” FDA will issue a noncompliance letter. Refer to section III.C.2.a for a discussion of the required timing for section 506C notifications.

As required by section 506C(f) of the FD&C Act, the rule provides the applicant with 30 calendar days from the date of issuance of the noncompliance letter to respond to the letter. The applicant's response must set forth the basis for noncompliance and provide the required notification with the required information. Not later than 45 calendar days after the date of issuance of the noncompliance letter, FDA will make the letter and the applicant's response public, after appropriate redaction to protect any trade secret or confidential commercial information. FDA will not make the letter and the applicant's response public if FDA determines, based on the applicant's response, that the applicant had a reasonable basis for not notifying FDA as required.

The Agency received submissions from 34 commenters, including public health associations, pharmaceutical industry, hospital groups, consumer groups, and individuals. A summary of the comments contained in the submissions received and FDA's responses follow.

To make it easier to identify comments and our responses, the word “Comment,” in parentheses, appears before the comment's description, and the word “Response,” in parentheses, appears before our response. We have numbered each comment to help distinguish between different comments. Similar comments are grouped together under the same number. The number assigned to each comment is purely for organizational purposes and does not signify the comment's value or importance or the order in which comments were received.

(Comment 1) One comment suggested that the notification requirement should be extended to API manufacturers. The comment stated that API manufacturers are further upstream in the drug development chain and that early warning of issues at this level, before they impact manufacturers formulating the drugs, would give FDA, other manufacturers of the drug, and programs more time to prepare and prevent shortages from affecting patients.

(Response) FDA does not agree that the notification requirement should be applied to API manufacturers. While interruptions in API supply may lead to a meaningful disruption in supply of the finished drug or biological product, they do not always have this effect. Therefore, notification to FDA of disruption in API supply would be premature and would not provide information that the Agency can take definitive action on. FDA believes that the notification requirement, which is derived from section 506C of the FD&C Act, generally provides the Agency with adequate notice to allow the Agency to work with the applicant and other stakeholders to prevent a shortage. As explained in section III.A, however, it is important that the applicant establish a process with any relevant contract manufacturer, API supplier, or other non-applicant entity to ensure that the applicant complies with this rule.

(Comment 2) One comment requested clarification on how a blood establishment will know if it is subject to the reporting requirements of the rule. The comment noted that the preamble to the proposed rule (78 FR 65904 at 65908) stated that FDA intends to consider a BLA-holder for blood or blood components to be a manufacturer of a significant percentage of the U.S. blood supply if the applicant manufactures 10 percent or more of the U.S. blood supply. The comment explained that the National Blood Collection and Utilization Survey (NBCUS) supplies the best data available nationally on collection and utilization of blood in the United States, but notes that the survey is voluntary and does not occur on an annual basis. The comment stated that it is not possible for a BLA holder to know what percentage of the U.S. blood supply it is collecting. Accordingly, the comment recommended that FDA identify an annual whole blood collection number to be used as the threshold for reporting.

(Response) FDA declines to identify an annual whole blood collection number to be used as a threshold for reporting because these numbers may fluctuate year to year. Because of their coordination with other BLA holders through the ABC, BASIS, and Task Force programs, we believe that BLA holders will generally be aware of whether they manufacture a significant percentage of the U.S. blood supply. Accordingly, we do not believe there will be significant uncertainty among BLA holders about whether they are subject to the notification requirements. If an applicant is unsure of whether it is subject to the notification requirements, we recommend that the applicant contact CBER at [email protected].

(Comment 3) One comment noted that the proposed rule did not discuss the effect of the notification provision on product allocation systems. The comment explained that products with inherently limited supply have been historically put on allocation systems by manufacturers to prioritize the allocation of these products. The comment explained that these allocation systems help manage and track product supplies, curb gray market distribution, and prevent price hikes. The comment stated that section 506(D)(d) of the FD&C Act directs FDA to establish a mechanism by which health care providers and other third party organizations may report to the Agency evidence of a drug shortage. The comment requested confirmation that a notification under section 506D(d) of the FD&C Act does not extend to situations where a receiving entity (e.g., a hospital) reaches its allocation limits.

(Response) The comment is beyond the scope of this rulemaking. The final rule implements sections 506C and 506E of the FD&C Act by amending §§ 20.100 and 314.81(b)(3)(iii) and adding new §§ 310.306 and 600.82. The rule does not address section 506D of the FD&C Act. Consistent with section 506D(d), however, we do encourage patients, providers, pharmacists, and other non-applicants to communicate with FDA about potential shortages or disruptions in supply by email at [email protected] (for products regulated by CDER) or [email protected] (for products regulated by CBER), so that the Agency can take appropriate steps to address these situations.

(Comment 4) In the preamble to the proposed rule (78 FR 65904 at 65909), FDA requested comment on the proposed definitions of “life supporting or life sustaining” and “intended for use in the prevention or treatment of a debilitating disease or condition” and in particular, whether the definitions might lead to “over-notification.” The majority of commenters supported the proposed definitions and agreed that they are consistent with current understanding of these terms. Some commenters noted that there might be the potential for over-notification but agreed that more information, rather than less, will enhance FDA's ability to prevent drug and biological product shortages. One comment stated that the definitions could lead to over-notification if they are broadly interpreted but noted that it is difficult to predict whether over-notification will actually occur. The comment suggested that within 1 year of implementation of the final rule, FDA can assess whether overnotification has occurred and can revise the draft guidance for industry entitled “Notification to FDA of Issues that May Result in a Prescription Drug or Biological Product Shortage” to include additional examples of products that are or are not likely to fall within the scope of products subject to the notification provision.

(Response) FDA appreciates the commenters' input. We continue to believe that the proposed definitions provide sufficient clarity without overly restricting the categories of products subject to the rule. We have therefore finalized the definitions that were proposed and believe that these definitions will result in appropriate notifications under the rule. If, however, FDA finds that over-notification has occurred, the Agency may consider further clarification in guidance or by other suitable means.

(Comment 5) Three comments stated that the proposed definitions were overly broad, potentially encompassing the majority of approved drug and biological products, and may be subject to inconsistent interpretation. Two comments recommended using definitions based on the definitions of “immediately life-threatening disease or condition” and “serious disease or condition” in § 312.300. One of those comments specifically proposed the following definitions:

• “A life supporting or life sustaining drug product means a drug product that is essential to, or yields information that is essential to, the restoration or continuation of a bodily function associated with a stage of disease in which there is a reasonable likelihood that death will occur within a matter of months or in which premature death is likely without early treatment.”

and

• “A debilitating disease or condition means a serious disease or condition associated with morbidity that has a substantial impact on day-to-day functioning. Short-lived and self-limiting morbidity will usually not be sufficient, but the morbidity need not be irreversible, provided it is persistent or recurrent. Whether a disease or condition is serious is a matter of clinical judgment, based on its impact on such factors as survival, day-to-day functioning, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one.”

(Response) FDA does not believe it is appropriate to incorporate the comment's proposed definitions or alternative definitions based on the definitions set forth in § 312.300. As explained in section III.B.1, under §§ 314.81(b)(3)(iii)(f) and 600.82(f) of this final rule, FDA equates “debilitating disease or condition” with “serious disease or condition,” and we have defined “debilitating disease or condition” according to the definition of “serious disease or condition” found in § 312.300. In the Agency's view, the definitions suggested in the comment would be too restrictive and could exclude certain products, such as anesthetic products, that are critical to patient care and should appropriately be considered “life supporting or life sustaining” or “intended for use in the prevention or treatment of a debilitating disease or condition.” As noted in the previous response, FDA believes that the definitions in this final rule provide sufficient clarity without overly restricting the categories of products subject to the rule. If, following implementation of the rule, it appears that further clarification is necessary, FDA will consider what type of clarification may be beneficial and take appropriate steps.

(Comment 6) Three comments suggested that FDA should consider providing a list, in guidance or otherwise, of examples of drug products or classes of drug products that are likely to meet the definitions of “life supporting or life sustaining” or “intended for use in the prevention or treatment of a debilitating disease or condition.” The commenters suggested that such a list would provide greater clarity and facilitate compliance with the rule.

(Response) FDA does not believe it is appropriate to provide a list of products that are likely to meet the definitions of “life supporting or life sustaining” or “intended for use in the prevention or treatment of a debilitating disease or condition.” Such a list would be difficult to maintain and keep up to date as products come off the market and new products enter the market. We are also concerned that applicants and the public may misinterpret the list as an exhaustive list of all products that would be subject to the notification requirement, rather than as examples of drug products or classes of drug products that are likely to meet the definitions.

If an applicant is uncertain whether a particular discontinuance or interruption in manufacturing of a drug or biological product should be reported to FDA, we encourage the applicant to proceed with notification. It is important to note that, under section 1001(b) of FDASIA, submission of a notification will not be construed as: (1) An admission that any product that is the subject of the notification violates any provision of the FD&C Act or (2) evidence of an intention to promote or market the product for an unapproved use or indication.

(Comment 7) One comment requested that FDA recognize attention-deficit hyperactivity disorder (ADHD) as an example of a debilitating condition. The comment stated that FDA could do so by adding to the definition in the final rule a list of some debilitating diseases and conditions and including ADHD in that list.

(Response) FDA has recognized ADHD as an example of a debilitating condition. We note further that when products used to treat ADHD have gone into shortage, they have been included on FDA's drug shortages Web site. However, FDA declines to add a list of examples of debilitating conditions to the rule.

(Comment 8) One comment requested clarification that drugs used to treat a “debilitating disease or condition” include sedatives, anesthetics, analgesics, and anti-inflammatory drugs.

(Response) FDA has considered sedatives, anesthetics, analgesics, and anti-inflammatory drugs to be drugs that are intended for use in the prevention or treatment of a debilitating disease or condition.

(Comment 9) One comment suggested that the rule be modified to give FDA the option of including a statement in the approval letter for new NDAs, ANDAs, or BLAs indicating that the product is covered by the rule. The comment noted that this type of statement about the product's status would provide clarity and could be beneficial, especially to applicants entering the U.S. market for the first time.

(Response) FDA understands that including a statement in the approval letter that the product is covered by this rule would clarify that particular product's status. The Agency is concerned, however, that such action may create confusion about the status of other already-approved products where the approval letter does not include a statement regarding notification under this rule. Applicants and other stakeholders may believe that the notification requirement only applies with respect to products whose approval letter contains a statement about notification under this rule. Therefore, FDA does not think it would be appropriate to add a provision to the rule as suggested by the comment.

(Comment 10) One comment requested clarification that the definition of “medically necessary” in the drug shortage MAPP solely relates to the allocation of internal Agency staffing and resources and that it has no bearing on the scope of products subject to notification under the proposed rule or FDA's determination of an actual shortage and public notification of a shortage.

(Response) As explained in section IV.B.1 of this document and in the preamble to the proposed rule, under this rule, an applicant is required to notify FDA of a permanent discontinuance or an interruption in manufacturing of a drug or biological product that is life supporting, life sustaining, or intended for use in the prevention or treatment of debilitating disease or condition, whether or not the product is considered medically necessary under the MAPP. Under the MAPP, FDA uses the definition of medically necessary to prioritize the Agency's response to specific shortages or potential shortages and to allocate resources appropriately.

(Comment 11) One comment expressed support for the inclusion of prescription drug products marketed without an approved NDA or ANDA and noted that such products are often critical to patient care.

(Response) FDA agrees that prescription drug products marketed without approved applications are important in patient care and accordingly § 310.306 is being finalized as proposed to ensure that the Agency is notified of a permanent discontinuance or an interruption in manufacturing of such products, as appropriate.

(Comment 12) Three comments raised questions about off-label uses. One comment requested clarification that off-label indications are not included within the scope of “marketed unapproved prescription drugs.” Two comments noted that many prescription drug products used to treat children and nearly all prescription drug products used to treat neonates are not labeled for use in those populations. Accordingly, those two comments stated that the rule should require notification based on off-label uses in addition to the uses in the labeling.

(Response) Off-label uses of drug and biological products are not included within the scope of “marketed unapproved prescription drugs.” FDA is not requiring applicants to consider off-label uses when determining whether a product is a covered product for purposes of the notification requirement in section 506C of the FD&C Act and implemented in this rule. The Agency understands that off-label uses can, in certain circumstances, be an important part of patient care. In fact, as explained in the MAPP on drug shortages (CDER MAPP 4190.1 Rev. 2), FDA considers off-label uses when classifying products as medically necessary for purposes of prioritization. However, off-label uses are based on a practitioner's professional judgment about what will benefit an individual patient, and we do not believe it would be reasonable to expect applicants to take account of individual practitioners' therapeutic decisionmaking in assessing whether their products are subject to the notification requirement. We note that in many cases, though, products that would be covered by the rule if it applied based on an off-label use may nevertheless be covered products based on a labeled use, in which case the applicant would be subject to the notification requirement for that product.

(Comment 13) Many comments strongly supported applying section 506C of the FD&C Act to biological products. These comments expressed the view that early notification of a permanent discontinuance or an interruption in manufacturing of biological products would benefit the public health by facilitating prompt action on FDA's part to address, prevent, or mitigate a shortage of these products.

(Response) FDA appreciates these comments and agrees that extending the notification requirement to biological products will benefit the public health. Therefore, consistent with section 506C(i)(3), the Agency is finalizing § 600.82 as proposed.

(Comment 14) Two comments requested that the Agency make clear that biosimilars are subject to the provisions of section 506C of the FD&C Act. The comments stated that while the approval process for biosimilars is still under development, it is important that such products be included in the requirements of the final rule.

(Response) This rule applies to prescription biological products licensed under section 351 of the PHS Act,11 including prescription biosimilar biological products licensed under section 351(k) of the PHS Act, that are life supporting, life sustaining, or intended for use in the prevention or treatment of a debilitating disease or condition, including any such product used in emergency medical care or during surgery, and excluding radiopharmaceutical products.

(Comment 15) One comment expressed support for the inclusion of blood or blood components for transfusion but requested clarification on how FDA will determine which blood or blood components would be exempt from the rule and how FDA plans to address shortages of products determined to be exempt. In particular, the comment sought clarification on whether the rule would apply to reagents used to cross-match platelets for transfusion. The comment stated that there have been shortages of these reagents recently, which has impacted patient care.

(Response) As explained in section III.B.2.c, the notification requirement applies only to applicants of blood or blood components for transfusion that manufacture a significant percentage of the U.S. blood supply, and only when there is a permanent discontinuance of manufacture or an interruption in manufacturing that is likely to lead to a “significant disruption” in supply of that blood or blood component. As noted in footnote 1 in the Executive Summary, the rule does not apply to biological products that meet the definition of a device in section 201(h) of the FD&C Act. Accordingly, this rule does not apply to reagents or other products that CBER regulates as devices, such as products intended for screening or confirmatory clinical laboratory testing associated with blood banking practices and other testing procedures (e.g., blood typing and compatibility testing).

(Comment 16) Two comments stated that blood and blood components should not be included in the rule. The comments cited the current systems described in the preamble to the proposed rule (78 FR 65904 at 65911) that monitor local and regional supplies of blood or blood components and coordinate during domestic disasters. The comments noted that blood and blood components do not have a history of shortages and stated that given the existing reporting systems and acknowledged successful record of planning activities in the blood community, coordination among the major blood organizations, and cooperation with FDA and HHS during and following disasters, it is not necessary to add another layer of reporting that is unlikely to provide additional security.

(Response) As explained in the preamble to the proposed rule (75 FR 65904 at 65911) and in section III.B.2.c, FDA agrees that the information available from ABC and BASIS and the efforts by the Task Force are critical to public health, and the Agency appreciates the willingness of applicants to coordinate. However, there are limitations to these existing systems. These systems are voluntary, they do not result in a direct notification from an applicant to FDA, and they only capture short-term, day-to-day supply and distribution information. In addition, the existing systems are not equipped to predict large-scale, significant disruptions of blood or blood components. We believe that including blood and blood components in the final rule will allow FDA to anticipate large-scale, significant disruptions of blood or blood components and take appropriate action. Accordingly, FDA has determined that including blood and blood components within the scope of this rule will benefit the public health by ensuring that the Agency is provided with information essential to FDA's efforts to address shortages of these products without duplicating existing programs.

(Comment 17) One comment stated that cellular and gene therapy products should not be included in the rule. The comment stated these are relatively new products and that the notification requirements are not necessary for them. The comment noted that BLA holders should be reporting to FDA, at least annually, what products are being manufactured under the license, and if an applicant is experiencing difficulty manufacturing a product, the applicant can communicate with FDA. The comment stated further that it is difficult to understand the “meaningful” process FDA would initiate if a report is received from a cellular or gene therapy manufacturer, and recommended that if cellular and gene therapy products are included in the final rule, FDA should provide a specific guidance document addressing these products.

(Response) FDA does not agree that cellular and gene therapy products should be excluded from the rule, nor do we agree that periodic distribution reporting or voluntary communication with FDA regarding manufacturing difficulties are adequate to allow the Agency to address shortages of cellular and gene therapy products. Shortages of biological products can have serious health consequences for patients who rely on these products for their treatment. Early notification of a permanent discontinuance or an interruption in the manufacturing of biological products is crucial for allowing FDA to take steps to prevent, or mitigate a shortage of these products.

The required distribution reports referred to in the comment do not provide sufficient notice for FDA to anticipate a shortage or take appropriate action to address a shortage. As explained in the preamble to the proposed rule (78 FR 65904 at 65911), under § 600.81, applicants are required to submit to CBER or CDER information about the quantity of product distributed under the license, including the quantity of product distributed to distributors. As part of the safety reporting requirement, manufacturers provide distribution data to FDA every 6 months or at other intervals as may be required by FDA. Although distribution reports submitted by applicants are helpful in the analysis of safety reporting data, these reports do not include information about a permanent discontinuance or an interruption of the manufacture of a biological product that is likely to lead to a meaningful disruption in the supply of that product. In addition, any distribution data received from the applicant at 6-month intervals may not be current. Accordingly, FDA has determined that including cellular and gene therapy products within the scope of this rule would benefit the public health by ensuring that FDA is provided with information that is essential to Agency's efforts to address shortages of these products. If, following implementation of the rule, it appears that guidance or further clarification is necessary for cellular and gene therapy products, FDA will consider what type of guidance may be beneficial and take appropriate steps in accordance with good guidance practices set out in 21 CFR 10.115.

(Comment 18) Two comments recommended that the rule not be applied to vaccines. The comments stated that, in response to the unique nature of vaccines, the CDC has successfully partnered with vaccine applicants to reduce, if not eliminate completely, impacts to public health that may arise due to a supply shortage. The comments stated that CDC continues to be in the best position to monitor and manage vaccine supply. The comments suggested that the CDC should continue to act as a confidential facilitator of critical supply information that is provided by applicants or manufacturers, to maintain these data as proprietary and confidential, and to allow CDC to use the information so that other applicants or manufacturers can fill the gap in the event of an imminent shortage. In addition, the comments noted that, for over a decade, the vaccine industry has voluntarily strived to provide FDA with the requested minimum 6-month notice when making a determination to discontinue production of a particular vaccine, where such a decision was foreseeable.

Alternatively, the comments proposed that FDA consider limiting the scope of the proposed rule to cover only non-VFC vaccines since there already are effective notification and distribution systems in place under the VFC program. The comments noted that CDC maintains a stockpile of VFC vaccines as part of its vaccine shortage notification program. Due to the CDC's regular collaboration with vaccine manufacturers, this program has proven highly successful in mitigating or completely eliminating supply disruptions.

(Response) FDA does not agree with the commenters' suggestion that the rule should not apply to vaccines or, in the alternative, should only apply to non-VFC vaccines. FDA recognizes that CDC includes language in its contracts with vaccine manufacturers requiring the manufacturer to notify CDC of vaccine supply issues that could affect the manufacturer's ability to fulfill its contract with CDC. FDA does not intend this rule to disrupt the contractual process and procedures that exist between manufacturers and CDC. However, as explained in the preamble to the proposed rule (78 FR 65904 at 65910), approximately 30 percent of vaccines licensed in the United States are not subject to CDC notification, including vaccines for rabies, yellow fever, and typhoid. Even for the vaccines that are subject to CDC notification, the information collected by CDC is not adequate for purposes of this rule. The existing CDC program does not require vaccine manufacturers to provide notice 6 months in advance of a permanent discontinuance or interruption in manufacturing. Early notice of permanent discontinuances and interruptions is critically important to prevention of drug and biological product shortages. Although FDA and its HHS partners work together on vaccine supply issues, FDA believes that including vaccines within the scope of this rule is essential to fully support FDA's efforts to identify, address, prevent, or mitigate a vaccine shortage.

(Comment 19) Two comments noted that by design, influenza vaccine is a seasonal product and consequently, is unavailable for a significant portion of each year. The comments stated that for this reason, both seasonal influenza and pandemic influenza vaccines should not be covered by the rule.

(Response) We acknowledge that some vaccines, such as those for influenza, are seasonal products by design and consequently may be unavailable for a significant portion of the year. It is important to note that “meaningful disruption” is defined as a “reduction in the supply of a drug . . . that is more than negligible and affects the ability of the manufacturer to fill orders or meet expected demand for its product.” In the case of a seasonal product, we anticipate that demand would decrease during the off-season; therefore, we would not expect that an interruption in manufacture of a seasonal product would be likely to lead to a meaningful disruption in the off-season. Accordingly, we decline to exempt vaccines intended for seasonal and pandemic use. We believe shortages of biological products, including seasonal influenza vaccines, can have serious health consequences for patients who rely on these products. Early notification of a permanent discontinuance or an interruption in the manufacturing of these products will allow FDA to promptly take steps to prevent or mitigate a shortage of these products that could otherwise result in delayed patient access.

(Comment 20) Two comments noted that the proposed rule would apply individually to all strengths, dosage forms, or routes of administration for a given product regardless of the supply status for other presentations and dosages of the same product. The commenters suggested that the rule should allow greater flexibility and should not apply to a product if an alternate presentation of the same therapeutic product is available.12

(Response) FDA does not agree. As we explained in the preamble to the proposed rule (78 FR 65904 at 65912), we understand that the permanent discontinuance or interruption in manufacturing of a specific strength, dosage form, or route of administration can have a significant impact on the targeted needs of particular patients. The Agency strives to ensure the availability of appropriate treatment options for patients. We also note that shortages of a specific strength, dosage form, or route of administration may lead to a shortage of another strength, dosage form, or route of administration, thereby exacerbating difficulties in obtaining the product. Furthermore, as explained in other comments on the proposed rule (available in Docket No. FDA-2011-N-0898), requiring notification based on the status of each strength, dosage form, and route of administration helps to ensure that patients and their health care providers have the most accurate information about potential shortages, and can make treatment decisions accordingly.

If the applicant has available an alternate presentation of the same product, the applicant should include that information in the notification as a proposal to mitigate the shortage.

(Comment 21) One comment requested confirmation that notification is not required when there is a shortage of a particular “count” of product but overall the quantity of that product is not in shortage (e.g., a manufacturer is in short supply of a 50-count bottle of 10-mg pills, but there are sufficient numbers of 25-count bottles of 10-mg pills to meet patient need).

(Response) FDA would not require notification in the situation described in the example provided.

(Comment 22) One comment expressed concern about the notification requirement as applied to blood or blood components. The comment cited the proposed rule (78 FR 65904 at 65913) and stated that monthly reporting of a decrease in any blood component produced by an affected BLA holder is overly burdensome and would result in reports that are meaningless. The comment recommended that FDA provide information and recommendations in a draft guidance to more fully explain the goals of this particular data collection.

(Response) The rule requires the notification of a permanent discontinuance or an interruption in manufacturing of blood or blood components that is likely to lead to a significant disruption in supply of the product in the United States. FDA intends to consider an interruption in manufacturing that leads to a reduction of 20 percent or more of an applicant's own supply of blood or blood components over a 1-month period to “substantially affect” the ability of the applicant to fill orders or meet expected demand. Such an interruption would be considered a significant disruption in supply. The rule does not require manufacturers to submit or report monthly data. The rule, as applied to BLA holders for blood or blood components for transfusion, is intended to capture events that are likely to precipitate large-scale disruptions in an applicant's blood supply.

(Comment 23) One comment expressed concern that the requirement that applicants report an “interruption in manufacturing” that is likely to cause a disruption in the manufacturer's own supply of a drug or biological product could keep important information from being reported to FDA. The comment explained that a manufacturer that is not experiencing “an interruption in manufacturing,” but rather is experiencing a lack of available product due to an increase in demand would not be required to notify the Agency. The comment suggested that FDA consider expanding the notification requirement to include those applicants experiencing a shortage in supply due to an increase in product demand.

(Response) FDA agrees that notification by an applicant lacking available product because of an increase in demand, and not because of an interruption in manufacturing, could be helpful in anticipating and addressing potential shortages. However, such a notification requirement is beyond the scope of section 506C of the FD&C Act implemented by the final rule. FDA does encourage applicants to communicate with FDA if there is an increase in demand that the applicant is not able to meet. We also note that if an applicant experiences an increase in demand because of another applicant's permanent discontinuance or interruption in manufacturing, FDA would expect to receive notification about the situation from the applicant that has experienced the discontinuance or interruption.

(Comment 24) Two comments recommended specific modifications to the definition of “meaningful disruption,” believing it to be unclear and potentially subject to inconsistent interpretation. First, the comments stated that terms within the definition, such as “reasonably likely,” “more than negligible,” and “short period” are insufficiently precise and recommended that the terms be removed from the definition. Second, the comments stated that, under the definition, applicants would be required to notify FDA if any products are under allocation or the demand for the product exceeds the available supply. Accordingly, the comments suggested adding language to the definition with the clarification that “meaningful disruption” means that the adverse impact to supply is unable to be remediated or minimized through allocation or other means of prioritization. Last, the comments noted that many factors could potentially affect the ability of applicants to fill orders, including some that are not within an applicant's control. The comments noted that applicants do not ultimately determine, nor can they in all cases accurately predict, volumes of orders or product demand. One of the comments accordingly recommended that FDA consider including language to clarify that the definition of “meaningful disruption” is intended to reflect situations in which the availability of a product to patients would be impacted. The comment suggested that the rule should clarify whose orders the applicant needs to be able to fill, in order to distinguish between the temporary inability to fulfill an order to a wholesaler, as opposed to the inability of a patient to obtain a prescription or receive appropriate therapy.

(Response) The final rule is being issued to implement sections 506C and 506E of the FD&C Act, consistent with section 506C(i). Section 506C(h) defines “meaningful disruption” as “a change in production that is reasonably likely to lead to a reduction in the supply of a drug by a manufacturer that is more than negligible and affects the ability of the manufacturer to fill orders or meet expected demand for its product” and that “does not include interruptions in manufacturing due to matters such as routine maintenance or insignificant changes in manufacturing so long as the manufacturer expects to resume operations in a short period of time.” The final rule adopts the statutory definition. In our view, the language used in the statute provides flexibility to accommodate the wide variety of circumstances that may result in drug or biological product shortages. If there is any uncertainty about whether a particular circumstance must be reported to FDA under the rule, we encourage applicants to submit a notification. Early notification is FDA's best tool for addressing shortages. Moreover, submission of a notification will not be construed as: (1) An admission that any product that is the subject of the notification violates any provision of the FD&C Act or (2) as evidence of an intention to promote or market the product for an unapproved use or indication.

(Comment 25) One comment noted that the preamble to the proposed rule (78 FR 65904 at 65912 and 65913) provides a number of examples of reportable discontinuances or interruptions in manufacturing of a covered drug or biological product. The comment stated that not all of the examples would result in a shortage of product to patients and may result in industry “over-reporting” events to the Agency. Accordingly, the comment requested that FDA further clarify the requisite link between the examples provided and an actual “meaningful disruption” in supply.

(Response) The list of examples provided in the preamble to the proposed rule are intended to assist applicants in understanding what must be reported under section 506C of the FD&C Act. As implemented by the final rule, section 506C requires that applicants notify FDA of a permanent discontinuance in the manufacture of a covered drug or biological product or an interruption of the manufacture of the drug or biological product that is likely to lead to a meaningful disruption in the supply of that product in the United States, and the reasons for such discontinuance or interruption. The list of examples is not intended to include only situations that will necessarily result in a meaningful disruption in supply. The list includes examples of events (i.e., permanent discontinuance and interruption in manufacturing) that are likely to lead to a meaningful disruption in supply and therefore must be reported to the Agency.

(Comment 26) One comment suggested that FDA amend the rule to require blood component manufacturers to report a decrease in donations when it is due to their own decision to close donation sites versus the natural ebb and flow of blood donation cycles. The comment stated that companies have the ability to create shortages with the purpose of increasing prices by closing donation sites.

(Response) FDA does not agree the suggested change is necessary or appropriate. As explained in the preamble to the proposed rule (78 FR 65904 at 65913), FDA need not be notified if a covered blood or blood component applicant experiences a temporary drop in blood donations at one of its local blood donation centers, such that it is unable to fully supply its hospital customers with blood for several days, provided the donation center quickly returns to its normal donation and supply levels and the dip in blood donations is not likely to lead to a 20 percent decrease in the applicant's overall supply of blood over a 1-month period. We expect that this type of situation would be identified and resolved through the existing programs that coordinate local and regional supplies of blood or blood components (e.g., these systems would identify the issue and locate temporary, alternative blood supplies for the applicant's customers). If such an event does lead to a significant disruption in a covered applicant's supply of blood or blood components, it would need to be reported to FDA under this rule.

(Comment 27) One comment noted that some of the quality issues subject to notification under the rule also would be subject to reporting under Field Alert Reports for drugs and Biological Product Deviation Reports for biological products. In an effort to avoid dual reporting requirements, the comment suggested that FDA attempt to coordinate these reports and the Agency's followup in order to minimize the burden on both FDA and applicants.

(Response) FDA recognizes that some quality issues that result in interruptions in manufacturing subject to this rule could also be subject to reporting under Field Alert Reports (FARs) for drugs and Biological Product Deviation Reports (BPDRs) for biological products. However, FARs and BPDRs are not supply reporting programs and do not serve the same purpose as notification under this rule. Applicants with approved NDAs and ANDAs are required to submit FARs to FDA if they find any significant problems with an approved drug; the purpose of the Field Alert Program is to quickly identify drug products that pose potential safety threats. Similarly, BPDRs are used by biological product manufacturers to report biological product deviations that may affect the safety, purity, or potency of a distributed product. Problems reported through FARs and BPDRs may not lead to a shortage. Moreover, we note that the timing of these reports and the information provided in them may not be adequate for FDA to address potential shortages. Therefore, we have determined that requiring manufacturers of drugs and biological products to notify FDA under this rule will not duplicate existing reporting programs and will provide the Agency with necessary information and lead time to take appropriate action to prevent or mitigate a shortage.

(Comment 28) One comment proposed that additional factors be taken into consideration and used as “filters” when manufacturers report drug and biologics shortages in order to limit the reporting of potential supply chain disruptions that are not “true drug shortage” events. The comment stated that these factors might include market dynamics and duration of supply chain shortage. With regard to market dynamics, the comment stated that FDA should consider the number of active suppliers and the percentage of the market supplied by such active suppliers. The comment stated that using this as a filter would help alert FDA to identify suppliers that are providing a significant percent of the market and that truly have the potential to create a drug shortage. For example, a market supplied by 10 active suppliers of equal market share would not likely experience a drug shortage if 1 of the active suppliers had a supply chain disruption. According to the comment, the market void could be absorbed by the nine other active suppliers via safety stock, additional production, etc. Therefore, the comment recommended the addition of a “primary suppliers” filter to separate those active suppliers who are supplying a significant percent to the market (i.e., such as 20 percent or more of the market).

In addition, the comment stated that the duration of a supply chain shortage should be taken into consideration and utilized as a filter regarding drug shortage reporting. This filter would consider the typical inventory levels carried in the retail and wholesale channels. For example, an active supplier may have a supply disruption (i.e., product out of stock) for 30 days; however, the market may not experience a drug shortage given the inventory levels in the retail and wholesale channels. Typical inventory levels within these channels could range from 30 to 60 days of supply; therefore, the comment proposed a 60-day potential supply disruption as the minimum duration for drug shortage reporting to avoid chances of inventory hoarding and artificial increases in market demand that ultimately undermine the intent of FDASIA.

(Response) FDA declines to adopt the “filters” proposed to reduce reporting under the rule. FDA does not agree that these proposed “filters” are consistent with the language or intent of FDASIA. As explained in the preamble to the proposed rule (78 FR 65904 at 65912), “meaningful disruption” means a disruption in the applicant's own supply. This interpretation avoids the problem of expecting an applicant to predict the market-wide impact of its own interruption in manufacturing, which can be difficult to assess and could lead to inconsistent interpretation and less accurate predictions.

(Comment 29) Two comments addressed the stockpile of VFC vaccines maintained by CDC as part of its vaccine shortage notification program and noted the success of the program in mitigating or completely eliminating supply disruptions. One of the comments requested that FDA permit applicants to take into consideration the existence of a CDC stockpile in assessing whether an interruption in manufacturing is reasonably likely to disrupt supply chains.

(Response) We acknowledge the importance of the stockpile of VFC vaccines maintained by CDC. CDC and HHS are required to maintain a stockpile of routinely recommended vaccines for the United States in the event of vaccine shortages or other unanticipated supply problems. The national pediatric vaccines stockpile currently maintains 14 pediatric vaccines that protect infants, children, and adolescents from 15 vaccine-preventable diseases excluding influenza.13 Where appropriate, FDA and the manufacturers work together with CDC and take into consideration the existence of a CDC stockpile in assessing the impact of supply disruptions and the likelihood of a shortage. However, for the purposes of reporting under this rule, we do not agree that applicants should be permitted to take into consideration the existence of the CDC stockpile. As explained in section III.C.1.b.i, consistent with the statutory definition of meaningful disruption, the rule requires an applicant to report an interruption in manufacturing that is likely to lead to a meaningful disruption in its own supply of a covered drug or biological product. The rule does not require an applicant to predict the market-wide impact of an interruption in its own manufacturing, which can be difficult to accurately assess and could lead to inconsistent interpretation of the regulation, less accurate predictions, and under- or overreporting.

(Comment 30) Three comments requested clarification of when the notification “clock” would start, in other words, exactly when the notification requirement would be triggered. Two of the comments explained that at the outset, a meaningful disruption might not appear “likely” but may become “likely” as the events progress. The comments expressed concern that the Agency and the applicant may disagree about which event would trigger the notification requirement if it was not obvious to the applicant initially that a meaningful disruption would be likely. The comments suggested that the appropriate trigger to start the notification “clock” is the date on which information becomes available to the applicant from which it could be reasonably determined that a meaningful disruption is likely to occur. Another comment noted that the notification clock could begin on the date of the event causing the interruption, or on the date the applicant becomes aware that an interruption could cause a shortage. The comment cautioned that if the latter were considered the trigger, it may be difficult to determine the exact point in time.

(Response) FDA expects that an applicant will notify FDA as soon as information becomes available to the applicant from which the applicant could reasonably determine that a meaningful disruption is likely to occur. As explained in section III.C.2.a of this document and the preamble to the proposed rule (78 FR 65904 at 65914), the applicant should not wait until the interruption in manufacturing actually begins to disrupt supply and affect patient access to the product. Early notification is the Agency's best tool for addressing shortages because it provides FDA with lead time to work with stakeholders to prevent the shortage or mitigate the impact of an unavoidable shortage. Accordingly, while not required, we encourage applicants to communicate with FDA even in situations where a meaningful disruption may appear to be possible though not necessarily likely.

We understand the commenters' concern that FDA and the applicant may disagree about which event would trigger the notification requirement. FDA has sent and intends to continue sending noncompliance letters when the Agency believes an applicant failed to notify FDA as soon as practicable or within 5 business days of the discontinuance or interruption.14 If an applicant receives a noncompliance letter but believes the failure to notify was reasonable, the applicant should provide a full explanation of the circumstances in the applicant's response to the noncompliance letter. Consistent with section 506C(f)(3) of the FD&C Act, FDA will carefully consider the explanation provided in determining whether there was a reasonable basis for not notifying the Agency. If FDA determines that there was a reasonable basis for not notifying the Agency in accordance with section 506C of the FD&C Act and this rule, we will not post the noncompliance letter or the applicant's response to FDA's Web site.

(Comment 31) Several comments addressed the proposal that if 6 months' advance notice is not possible, notification must be submitted as soon as practicable thereafter, but in no case later than 5 business days after the permanent discontinuance or interruption in manufacturing occurs. Some comments expressed concern that FDA would allow an applicant to report as late as 5 days after a permanent discontinuance or interruption in manufacturing occurs. One comment stated that this would significantly weaken the rule and limit its effectiveness. The comment further stated that for an unforeseen disruption or discontinuation, FDA should require immediate notification or should outline what situations could arise that would appropriately necessitate a 5-day reporting delay. One comment expressed the view that reporting 5 days after the interruption should only be considered acceptable in rare circumstances, such as natural disaster. Another comment stated that applicants should be required to notify FDA a minimum of 6 months prior to the discontinuance or interruption, the only exception being a natural disaster or catastrophic incident. The comment stated that the proposed language is vague and lenient and creates a loophole in mandatory reporting that ultimately serves neither the public health nor that of patients, while shielding manufacturers from their own failure to plan adequately.

In contrast, some comments expressed concern that requiring notification no later than 5 business days after the discontinuance or interruption would not provide sufficient time for applicants to investigate and get a complete understanding of the issue. The comments explained that more than 5 business days may be necessary to confirm whether actions taken in response to the interruption will affect the manufacturer's ability to fill orders or meet expected demand. One comment stated that requiring notification before a full investigation has been completed is likely to lead to overreporting and less reliable information being provided to FDA. The comment stated that the “as soon as practicable” standard set forth in FDASIA provides the necessary flexibility and should not be altered by adding a 5 business day limit. One comment recommended that, if FDA believes a definite reporting timeframe is necessary, it should be no shorter than 15 days after the permanent discontinuance or interruption in manufacturing. Another comment proposed that if a timeframe is necessary, it could be extended to 15 days along with qualifying language, such as “once it can conclusively be determined that a manufacturing issue will adversely impact supply.”

(Response) FDA's most powerful tool for addressing drug and biological product shortages is early notification, which provides lead time for the Agency to work with manufacturers and other stakeholders to prevent a shortage or to mitigate the impact of unavoidable shortages. Accordingly, we expect that applicants will provide 6 months' advance notice whenever possible. FDA understands, though, that an applicant may not reasonably be able to anticipate certain interruptions in manufacturing that are likely to lead to a meaningful disruption in supply 6 months in advance. In those situations, FDA requires notification “as soon as practicable,” but in no case more than 5 business days after the interruption in manufacturing occurs. The Agency has determined that 5 business days is adequate time for an applicant to assess whether the discontinuance or interruption in manufacturing is likely to lead to a meaningful disruption. As the situation evolves, FDA expects that applicants will provide the Agency with appropriate updates that will facilitate FDA's efforts. We believe that this timeframe appropriately balances the need for early notification and the understanding that applicants may not be able to immediately assess the impact of an interruption in manufacturing.

If notification was required only when an applicant has confirmed that a meaningful disruption will occur, then it might be appropriate to provide additional time for applicants to make this determination. However, the statute requires notification when a discontinuance or interruption in manufacturing is likely to lead to a meaningful disruption. The statute takes account of the fact that there may be a degree of uncertainty about the outcome of the discontinuance or interruption. As such, we note that the qualifying language proposed by one comment (i.e., adding “once it can conclusively be determined that a manufacturing issue will adversely impact supply” to the notification requirement) would not be consistent with the statutory requirement to notify FDA when a discontinuance or interruption is likely to lead to a meaningful disruption. FDA believes it is reasonable for an applicant to make a determination about whether an interruption is likely to lead to a meaningful disruption in supply within 5 business days of the discontinuance or interruption. The Agency does not believe that 15 business days should be necessary to make such a determination, and a delay of 15 business days in notification could have a significant impact on FDA's ability to prevent or mitigate a shortage.

We note that if an applicant receives a noncompliance letter for failure to notify the Agency within 5 business days of a discontinuance or interruption in manufacturing and believes that it would not have been reasonable to expect the applicant to determine that the event was likely to lead to a meaningful disruption, such information should be provided in the applicant's response to the noncompliance letter. The Agency, in turn, will consider that information in determining whether the applicant had a reasonable basis for not notifying FDA within the required timeframe and therefore whether the noncompliance letter should not be made public.

(Comment 32) One comment suggested that the rule should specifically include “natural disaster” as a potential trigger for notification. The comment acknowledged that the preamble to the proposed rule notes that reportable interruptions in manufacturing may include natural disasters, but the commenter was concerned that the examples provided in the proposed rule were all circumstances under the control of the manufacturer.

(Response) A wide variety of situations may lead to a reportable interruption in manufacturing (including natural disasters, equipment failure, or a delay in acquiring APIs or inactive ingredients), and FDA does not believe it is necessary or appropriate to include specific examples within the regulation itself. The Agency believes that the information and examples provided in the preamble to the proposed rule are adequate to assist applicants in determining whether a given interruption in manufacturing must be reported to FDA.

(Comment 33) One comment recommended that FDA require manufacturers to provide periodic updates on actions they are taking to bring drugs that are in shortage back to the market. The comment stated that this would help FDA understand the reasons for any continued delays in delivering drugs into the supply chain and allow the Agency to work with manufacturers in a more informed manner to reduce shortages.

(Response) Once FDA is notified of a situation that might lead to a shortage, FDA is in frequent contact with the applicant to seek ways to prevent the shortage. At this time, we do not believe that requiring periodic updates would be necessary, because we do not anticipate that requiring such updates would provide information that the Agency does not already have.

(Comment 34) Two comments provided suggestions about the electronic submission of 506C notifications to FDA. One of the comments suggested that the rule should include the specific office within FDA that notifications should be sent to. The other comment noted that applicants currently submit information in a nonspecified format via email and stated that FDA should provide greater clarity on whether this practice is intended to continue once the rule goes into effect and whether FDA will be specifying a uniform process for applicants to follow when submitting notifications.

(Response) As explained in the preamble to the proposed rule (78 FR 65904 at 65915), applicants must email notifications to [email protected] (for products regulated by CDER) and [email protected] (for products regulated by CBER). In the future, the Agency may consider creating an electronic notification portal to facilitate submission of these notifications. At that time, the Agency would provide any instructions necessary to use the portal. Because we expect that such a portal would be available on FDA's Web site, we do not believe it is necessary or appropriate to include the name of a specific receiving office in the regulation itself.

(Comment 35) Two comments recommended that information about mitigation be required in the notification. One of the comments suggested that FDA require the notification to include a description of the efforts by the applicant to prevent or mitigate the shortage. The other comment recommended that FDA require the notification to include a mitigation strategy or, at least, suggestions for mitigation.

(Response) FDA agrees that input from the applicant about ways to prevent or mitigate the shortage is crucial. The Agency, however, does not agree that it is appropriate to require information about mitigation to be included in the notification. We are concerned that there could be a delay in the notification if applicants are required to develop a mitigation strategy to include in the notification while also working to resolve the underlying issue. Instead, we have determined that it is appropriate to require basic information that is necessary for the Agency to take action and that the Agency is required to include in the shortages list under section 506E of the FD&C Act. We strongly encourage applicants to provide additional information, including proposals to prevent or mitigate the shortage, inventory on hand or in distribution channels, allocation procedures and/or plans for releasing available product, market share, or other information that may assist FDA.

(Comment 36) One comment suggested that FDA require the notification to indicate whether the drug or biological product is being used in an FDA- or National Cancer Institute-approved clinical trial. The comment explained that many clinical trials, especially for cancer treatments, are designed to test the safety and efficacy of the standard of care against, or in combination with, a new treatment being investigated. Accordingly, drug shortages have an impact on clinical trials, not just on patients undergoing standard treatment.

(Response) FDA understands that drug and biological product shortages may have an impact on clinical trials in addition to patients receiving standard treatment. However, we believe that requiring an applicant to state, in its notification, whether the product is currently being used in a clinical trial would require additional investigation by the applicant and would be unnecessarily burdensome. FDA updates the drug and biological product shortage lists regularly, and we encourage investigators to sign up for email updates or the RSS feed to make sure they are aware of the latest information regarding product shortages.

(Comment 37) One comment requested clarification on what information must be included in a notification provided by the manufacturer of a covered drug marketed without an approved application.

(Response) As required by § 310.306, manufacturers of a covered drug marketed without an approved application must provide the same information in a notification as do applicants under § 314.81(b)(3)(iii)(c).

(Comment 38) Two comments requested clarification about whether FDA will maintain a single list that includes shortages of both drugs and biological products.

(Response) At the present time, FDA intends to maintain separate lists of CDER-regulated and CBER-regulated products that are in shortage. The lists are available on FDA's Web site at http://www.fda.gov/drugs/drugsafety/drugshortages/default.htm (for products regulated by CDER) and http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/Shortages/default.htm (for products regulated by CBER).

(Comment 39) One comment expressed support for the proposed addition of “other reason” to the list of statutory reasons for the shortage that FDA could choose from. The comment noted that the seven reasons outlined in FDASIA may be difficult to apply in certain situations.

(Response) FDA agrees that the categories provided in FDASIA do not necessarily cover certain quality or manufacturing problems that may result in a shortage. Therefore, the Agency is finalizing “other reason” as an additional category that the Agency may identify.

(Comment 40) Three comments requested clarification of whether FDA would include potential drug and biological product shortages in the public lists, in addition to actual shortages. The comments expressed concern that disseminating information about potential shortages could result in unintended consequences, such as hoarding.

(Response) Under section 506E of the FD&C Act, FDA maintains an up-to-date list of drugs that are determined by FDA to be in shortage in the United States. Section 506C(h)(2) of the FD&C Act defines a shortage as “a period of time when the demand or projected demand for the drug within the United States exceeds the supply of the drug.”

(Comment 41) Two comments requested clarification on the process and criteria FDA uses to determine whether there is an actual shortage and the process and criteria FDA uses to determine whether to remove a product from the shortages list.

(Response) The MAPP on shortages of CDER-regulated products (MAPP 4190.1 Rev. 2, p. 14) and SOPP on shortages of CBER-regulated Products explain in detail the process and criteria FDA uses to verify if an actual shortage exists. The MAPP (p. 17) also explains the process and criteria FDA uses to determine whether a product should be removed from the shortages list.

(Comment 42) Several comments noted that FDA is responsible for determining whether, in fact, an actual shortage exists as well as the categorical reason for the shortage that best fits the particular situation. The comments requested that FDA consult with applicants about these determinations before making the information public. One comment noted that this has been FDA's practice and requested that the Agency continue this collaborative approach. Another comment specifically requested that FDA develop a process by which the Agency shares its intended public communication prior to posting it on FDA's Web site to allow applicants the opportunity to make corrections, including those related to unintentional disclosure of confidential or proprietary information.

(Response) FDA verifies all information with the applicants prior to posting information on FDA's Web site. Applicants also review the information posted on the Web site regularly and provide updates to FDA as new information becomes available.

(Comment 43) One comment noted that the rule does not address how the estimated shortage durations are determined. The comment stated that the estimated duration of shortages of some common medications, such as injectable calcium and phosphate preparations, listed on FDA's Web site have been inaccurate, which has made it difficult to develop strategies to prioritize care for those patients most in need of these drugs. The comment also expressed concern that there are no consequences for gross underestimations of durations of shortages. The comment recommended that FDA address these issues in the final rule.

(Response) The estimated shortage duration that is provided on FDA's Web site is intended to capture the particular applicant's anticipated recovery time and is based on information provided by the applicant. FDA communicates with applicants on a daily basis and updates the Web site with estimated recovery time as information becomes available from the applicants. The Agency makes every effort to provide as much information as possible and works closely with applicants to ensure that the Web site lists the most current information.

(Comment 44) One comment expressed concern about including each presentation of a drug product (e.g., strength, dosage form, route of administration) that is determined to be in shortage in the public shortage list when alternate presentations of the same product remain available. The comment stated that section 503B of the FD&C Act (21 U.S.C. 353b) permits a compounder to begin manufacturing a drug once it is on the section 506E shortage list. As such, the comment stated that compounders may begin manufacturing a product on the list, even if there are other available presentations that would be adequate substitutes. The comment stated that compounded products raise grave public health concerns and urged FDA to provide examples of situations in which the Agency will not list a drug or biological product because a suitable substitute is available. The comment stated that such a clarification would be consistent with the public health exception to the statutory requirement for FDA to publicly disclose, to the maximum extent possible, information on drug shortages.

(Response) The Agency does not agree that withholding particular presentations of a drug from the shortage list because other presentations are available would be appropriate or beneficial to the public health. Other comments received on the proposed rule, and our own experience, indicate the importance to health care professionals of being made aware of shortages of any presentation of a given drug product to ensure that they have the most accurate information about products in shortage and can make treatment decisions accordingly. We do not think the potential risk identified by the comment outweighs the benefit to health care providers and patients of having this information. We note further that while section 503B of the FD&C Act does permit compounding of drug products listed in the drug shortages list, only the specific presentations included in the drug shortages list may be compounded. Moreover, facilities that compound under section 503B must comply with the current good manufacturing practice requirements under section 501(a)(2)(B) of the FD&C Act (21 U.S.C. 351(a)(2)(B)).

(Comment 45) One comment suggested that FDA communicate directly with physician organizations and affected specialty societies about shortages so that the impact of the shortage can be minimized.

(Response) FDA agrees that communication about products that are in shortage is essential to ensure that health care providers have the information they need to make appropriate treatment decisions. We note that in FDA's drug and biological products shortages Web pages, individuals may sign up to receive email updates of shortage information. Drug and biological product shortage updates are also available by RSS feed.

(Comment 46) One comment recommended that FDA establish a mechanism whereby physicians can receive shortage information about specific therapeutic categories via email updates, an RSS feed, or through a smartphone application. The comment stated that these targeted communications would allow physicians to receive only the information they need.

(Response) Physicians and other interested stakeholders can receive information about specific therapeutic categories or specific products via email updates and RSS feed by signing up on FDA's Web site. In addition, in March 2015, FDA launched a mobile application (app) designed to facilitate access to information about drug shortages. The app identifies current drug shortages, resolved shortages, and discontinuances of drug products. The app allows users to search by a drug's generic name or active ingredient and also by therapeutic category. The app is available for free download via iTunes (for Apple devices) and the Google Play store (for Android devices) by searching “FDA Drug Shortages.”

(Comment 47) One comment stated that it would be helpful if the information contained in FDA's Drug Shortage Web site were categorized by specific classes of drugs in shortage that are relative to a particular area of research, such as oncology. The comment stated that by categorizing the information in this way, FDA could quickly notify researchers of drug shortages in classes frequently used by researchers in a particular specialty.

(Response) FDA's Drug Shortage Web site, which was redesigned after publication of the proposed rule, currently lists products alphabetically as well as by therapeutic category. This enables health care providers and other interested parties to access information relevant to particular specialties more easily.

(Comment 48) One comment recommended that FDA include information on the shortages Web sites indicating whether the drug or biological products listed are being utilized in an FDA-approved clinical trial. The comment also stated a link should be provided to the clinicaltrials.gov Web site for each clinical trial in which the product is being used.

(Response) FDA shares the commenter's concern about the impact that drug and biological product shortages may have on clinical trials that test investigational products against the standard of care. However, the shortages Web sites as well as clinicaltrials.gov are updated regularly, and it would not be feasible, at this time, to maintain links between the products on the shortages lists and the separate Web site that lists clinical trials in which the products may be used. FDA encourages investigators and sponsors to sign up for email updates or RSS feed and to visit FDA's Web site for the most up-to-date information about drug and biological product shortages. We also encourage sponsors to discuss with the appropriate review division any contingency plans if there is a shortage of products being used in a clinical trial.

(Comment 49) Two comments noted the provision in the proposed rule that “FDA may choose not to make information . . . available on the drug shortages list . . . if FDA determines that disclosure of such information would adversely affect the public health (such as by increasing the possibility of hoarding or other disruption of the availability of the drug to patients).” The comments stated that the provision presumes that FDA is uniquely qualified to determine the relative value and/or risk associated with public dissemination of information related to product supply and product shortages. The comments suggest that, at a minimum, FDA should incorporate applicants' input into the decisionmaking regarding public dissemination of information related to supply constraints.

(Response) The provision of the proposed rule referenced in the comment codifies section 506E(c)(3), which reflects Congress' intent that FDA should have the discretion not to make information public if the Agency determines that disclosure would adversely affect public health. We welcome stakeholder input on all shortage-related matters. However, consistent with the statute, it is ultimately FDA's determination whether disclosure of information would adversely affect public health.

(Comment 50) Three comments requested that FDA establish a process for issuing and adjudicating noncompliance letters sent to an applicant for failure to notify FDA as required by section 506C(a) of the FD&C Act. The comments expressed concern about potential disagreements between the Agency and the applicant about what constitutes timely notification and stressed the importance of a dialogue between FDA and the applicant before a noncompliance letter is issued. One comment specifically requested a process by which an applicant may appeal a decision to issue a noncompliance letter and confirmation from FDA that it will retract and remove any noncompliance letter from the Web site if the appeal is successful.

(Response) FDA believes that the process set forth in section 506C(f) of the FD&C Act (and codified in the final rule) is sufficiently clear. The Agency will send a noncompliance letter to an applicant for failure to notify FDA, which includes failure to timely notify FDA, of a permanent discontinuance or interruption in manufacture that is likely to lead to a meaningful disruption in the supply of a drug in the United States. As provided in the statute, not later than 30 calendar days following issuance, the applicant must submit a response to the noncompliance letter. If an applicant believes it received a noncompliance letter in error, the applicant should provide in its response a full explanation, including relevant dates surrounding the event in question, and any other information of which FDA should be made aware. The Agency, in turn, will consider the information provided in determining whether the noncompliance letter was issued in error or there was a reasonable basis for not notifying the Agency. If FDA determines that the original letter was issued in error or that the recipient had a reasonable basis for not notifying FDA, then the Agency will not post the noncompliance letter or response to the Web site. In light of the process and timeframes specified in section 506C(f) of the FD&C Act, FDA does not believe that a separate appeals process or any further clarification is necessary at this time.

(Comment 51) Two comments requested that FDA establish a process to ensure that no confidential or proprietary information is released when a noncompliance letter and the applicant's response is posted to FDA's Web site.

(Response) As required by section 506C(f)(3) of the FD&C Act, appropriate redactions will be made before a noncompliance letter and the applicant's response are posted to FDA's Web site. FDA has extensive experience redacting confidential and proprietary information, e.g., from NDA and BLA approval packages, before posting documents to the Web site. We believe that the systems the Agency has in place are adequate to address the redaction of noncompliance letters and any response submitted by the applicant.

(Comment 52) One comment requested confirmation that FDA intends to address the failure to notify through the noncompliance letter process and not by GMP inspections.

(Response) If an applicant fails to notify FDA as specified in the final rule, the Agency will address such failure through the process outlined in section 506C(f) of the FD&C Act and codified in this rule.

(Comment 53) One comment suggested that FDA should provide notice of noncompliance to the major news services as well as posting the information on FDA's Web site. The comment stated that in this way, consumers, distributors, and other stakeholders will have knowledge of which companies have not complied with the notification requirement.

(Response) Consistent with section 506C(f) of the FD&C Act, FDA intends to make noncompliance letters and any response to such letters public by posting them on FDA's Web site, unless FDA determines that the noncompliance letter was issued in error or, after reviewing the applicant's response, determines that the applicant had a reasonable basis for not notifying.

(Comment 54) One comment stated that FDA should be better empowered to enforce the notification requirement, potentially by being given authority to fine companies that are noncompliant.

(Response) As explained in the comment to the previous response, FDA will address noncompliance in the manner prescribed in section 506C(f) of the FD&C Act.

(Comment 55) Multiple comments requested that FDA work with other Agencies and professional societies to develop treatment guidelines when drug and biological products are in shortage.

(Response) FDA does not typically develop treatment guidelines. We note that some professional societies, such as the American Society of Health-System Pharmacists, do provide treatment guidelines that interested parties may consult.

(Comment 56) Several comments stated that notification only of a permanent discontinuance or an interruption in manufacturing is not sufficient to address the drug shortage problem. The comments noted that steps need to be taken to address manufacturing problems that may lead to product shortages. The comments also suggested that, in addition to notification, there should be a plan in place to either import an equivalent drug from other countries or assign a firm to manufacture the drug.

(Response) FDA appreciates and shares the commenters' concern about the problem of drug and biological product shortages. However, these comments are beyond the scope of this rulemaking. The Agency is issuing the final rule to implement sections 506C and 506E of the FD&C Act, which require notification of a permanent discontinuance or an interruption in manufacturing of certain covered products and maintenance by FDA of a publicly available list of drugs that are determined by FDA to be in shortage. As explained in section I, consistent with FDA's authority under the FD&C Act, the Agency uses a variety of tools to prevent or mitigate drug and biological product shortages, and early notification is crucial to FDA's efforts. However, FDA does not have authority over an applicant's business decisions regarding the manufacture of particular products.

(Comment 57) One comment raised issues concerning the preliminary regulatory impact analysis and the Agency's assessment of the net benefit of the rulemaking.

(Response) Our response is provided in the full discussion of economic impacts available in Docket No. FDA-2011-N-0898 (Ref. 4) and at http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.

FDA is amending its regulations to implement sections 506C and 506E of the FD&C Act as amended by FDASIA. FDA's authority for this rule also derives from section 701(a) of the FD&C Act (21 U.S.C. 371(a)).

FDA has examined the impacts of the final rule under Executive Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5 U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 104-4). Executive Orders 12866 and 13563 direct Agencies 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 Agency believes that this final rule is an economically significant regulatory action as defined by Executive Order 12866.

The Regulatory Flexibility Act requires Agencies to analyze regulatory options that would minimize any significant impact of a rule on small entities. The estimated per notification cost for small business entities, $227, represents a small percentage of average annual sales (up to 0.10 percent). Although the final rule does not require specific mitigation strategies, for firms that choose to implement mitigation or prevention strategies, it is possible that additional costs of $113,000 associated with implementing mitigation strategies could be significant: 2 to 7.8 percent of average annual sales for companies with fewer than 20 employees. In FDA's experience 4 to 5 small businesses entities per year have been affected by a shortage. The Agency certifies that the final rule will not have a significant economic impact on a substantial number of small entities.

Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires that Agencies 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 $144 million, using the most current (2014) Implicit Price Deflator for the Gross Domestic Product. FDA does not expect this final rule to result in any 1-year expenditure that would meet or exceed this amount.

The final rule amends FDA's regulations to implement sections 506C and 506E of the FD&C Act, as amended by FDASIA. The final rule requires all applicants of covered, approved prescription drug or biological products other than blood or blood components for transfusion (referred to as blood or blood components), all applicants of blood or blood components that manufacture a significant percentage of the U.S. blood supply, and all manufacturers of covered prescription drugs marketed without an approved application, to notify FDA electronically of a permanent discontinuance or an interruption in manufacturing of the product that is likely to lead to a meaningful disruption in supply (or a significant disruption in supply for blood or blood components) of the product in the United States 6 months in advance of the permanent discontinuance or interruption in manufacturing, or, if that is not possible, as soon as practicable, but no later than 5 business days after the permanent discontinuance or interruption occurs. The final rule also describes how to submit such a notification, the information required to be included in such a notification, the consequences for failure to submit a required notification, the disclosure of shortage-related information, and the meaning of certain terms.

The final rule would impose annual costs of up to $40.54 million on those applicants or entities affected by the rule, and up to $6.38 million on FDA in preventive costs. Estimated total annual costs of the interactions between industry and FDA range between $14.54 million and $46.92 million. Discounting over 20 years, annual quantified benefits from avoiding the purchase of more expensive alternative products, managing product shortages, and life-years gained, would range from $30.45 million to $98.65 million using a 3 percent discount rate, and from $30.39 million to $98.42 million using a 7 percent discount rate. Annualized over 20 years, net benefits range between $15.90 million and $51.72 million using a 3 percent discount rate; they range between $15.85 million and $51.50 million using a 7 percent discount rate. The public health benefits, mostly non-quantified, include the value of information that would assist FDA, manufacturers, health care providers, and patients in evaluating, mitigating, and preventing shortages of drug and biological products that could otherwise result in non-fatal adverse events, errors, delayed patient treatment, or interruption in clinical trial development. The costs and benefits are summarized in table 1.

Under the current environment all notifications provide meaningful information to identify a shortage or to prevent one, but there is uncertainty whether the scope of the rule could result in notifications that do not provide information about any shortage and lead to additional costs.

The full discussion of economic impacts is available in Docket No. FDA-2011-N-0898 and at http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm (Ref. 4).

This final rule contains information collection requirements that are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-3520). The title, description, and respondent description of the information collection provisions are shown in the following paragraphs with an estimate of the total reporting burden. Included in the estimate is the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing each collection of information.

Title: Permanent Discontinuance or Interruption in Manufacturing of Certain Drug or Biological Products; Final Rule

Description: Under the final rule, applicants with an approved NDA or ANDA for a covered drug product, manufacturers of a covered drug product marketed without an approved application, and applicants with an approved BLA for a covered biological product (including certain applications of blood or blood components) must notify FDA in writing of a permanent discontinuance of the manufacture of the drug or biological product or an interruption in manufacturing of the drug or biological product that is likely to lead to a meaningful disruption in the applicant's supply (or a significant disruption for blood or blood components) of that product. The notification is required if the drug or biological product is life supporting, life sustaining, or intended for use in the prevention or treatment of a debilitating disease or condition, including use in emergency medical care or during surgery, and if the drug or biological product is not a radiopharmaceutical drug product.

The final rule requires that the notification include the following information: (1) The name of the drug or biological product subject to the notification, including the NDC (or, for a biological product that does not have an NDC, an alternative standard for identification and labeling that has been recognized as acceptable by the Center Director); (2) the name of each applicant of the drug or biological product; (3) whether the notification relates to a permanent discontinuance of the drug or biological product or an interruption in manufacturing of the product; (4) a description of the reason for the permanent discontinuance or interruption in manufacturing; and (5) the estimated duration of the interruption in manufacturing.

Under the final rule, the notification must be submitted to FDA electronically at least 6 months prior to the date of the permanent discontinuance or interruption in manufacturing. If 6 months' advance notice is not possible because the permanent discontinuance or interruption in manufacturing was unanticipated 6 months in advance, the applicant must notify FDA as soon as practicable, but in no case later than 5 business days after the permanent discontinuance or interruption in manufacturing occurs.

If an applicant fails to submit the required notification, FDA will issue a letter informing the applicant or manufacturer of its noncompliance. The applicant must submit to FDA, not later than 30 calendar days after FDA issues the letter, a written response setting forth the basis for noncompliance and providing the required notification.

Description of Respondents: Applicants of prescription drugs and biological products subject to an approved NDA, ANDA, or BLA, and manufacturers of prescription drug products marketed without an approved ANDA or NDA, if the product is life supporting, life sustaining, or intended for use in the prevention or treatment of a debilitating disease or condition, including use in emergency medical care or during surgery, and is not a radiopharmaceutical product. If the BLA applicant is a manufacturer of blood or blood components, it is only subject to this rule if it manufactures a significant percentage of the nation's blood supply.

Burden Estimates: Based on the number of drug and biological product shortage related notifications we have seen during the past 12 months, we estimate that annually a total of approximately 75 respondents (“Number of Respondents” in table 2) will notify us of a permanent discontinuance of the manufacture of a drug or biological product or an interruption in manufacturing of a drug or biological product that is likely to lead to a meaningful disruption in the respondent's supply of that product under the final rule. We estimate that these respondents will submit annually a total of approximately 305 notifications as required under §§ 310.306, 314.81(b)(3)(iii), and 600.82. Approximately 80 of these notifications are notifications that we currently receive under OMB control number 0910-0699 for the IFR, thus we expect to receive approximately 225 new notifications under the final rule (“Total Annual Responses” in table 2).15 We estimate three notifications per respondent, because a respondent may experience multiple discontinuances or interruptions in manufacturing in a year that require notification (“No. of Responses per Respondent” in table 2). We also estimate that preparing and submitting these notifications to FDA will take approximately 2 hours per respondent (“Hours per Response” in table 2).

We base these estimates on our experience with the reporting of similar information to FDA since the issuance of the President's Executive Order 13588 of October 31, 2011 (Ref. 1), and under the interim final rule entitled “Applications for Food and Drug Administration Approval To Market a New Drug; Revision of Postmarketing Reporting Requirements—Permanent” (76 FR 78530; December 19, 2011).

FDA estimates the burden of this collection of information as follows:

The information collection provisions of this final rule have been submitted to OMB for review, as required by section 3507(d) of the PRA. Prior to the effective date of this final rule, FDA will publish a notice in the Federal Register announcing OMB's decision to approve, modify, or disapprove the information collection provisions in this final rule. An Agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number.

FDA has analyzed this final rule in accordance with the principles set forth in Executive Order 13132. FDA has determined that the rule does not contain policies that have substantial direct effects on the States, on the relationship between the National Government and the States, or on the distribution of power and responsibilities among the various levels of government. Accordingly, the Agency concludes 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.

The Agency has 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.

The following references have been placed on display in the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, and may be seen by interested persons between 9 a.m. and 4 p.m., Monday through Friday, and are available electronically at http://www.regulations.gov. (FDA has verified all the Web site addresses in this reference section, but we are not responsible for any subsequent changes to the Web sites after this document publishes in the Federal Register.)

Therefore, under the Federal Food, Drug, and Cosmetic Act, the Public Health Service Act, and under authority delegated to the Commissioner of Food and Drugs, 21 CFR parts 20, 310, 314, and 600 are amended as follows:

The final and temporary regulations (TD 9722) that are the subject of this correction are under sections 311(b), 336(a), and 337(d) of the Internal Revenue Code.

As published, the final and temporary regulations (TD 9722) contain errors that may prove to be misleading and are in need of clarification.

Accordingly, 26 CFR part 1 is corrected by making the following correcting amendments:

Background

The final and temporary regulations (TD 9722) that are the subject of this correction are under sections 311(b), 336(a), and 337(d) of the Internal Revenue Code.

As published, the final and temporary regulations (TD 9722) contain errors that may prove to be misleading and are in need of clarification.

Accordingly, the final regulations (TD 9722), that are the subject of FR Doc. 2015-14405, are corrected as follows:

1. On page 33404, in the preamble, the first column, the tenth and eleventh lines from the top of the column, the language “that controls (within the meaning of section 304(c)) the Corporate Partner.” is corrected to read “that controls the Corporate Partner within the meaning of section 304(c), except that section 318(a)(1) and (3) shall not apply (section 304(c) control).”.

2. On page 33404, in the preamble, the first column, the eighteenth through the twentieth line from the top of the first full paragraph, the language “that controls the Corporate Partner within the meaning of section 304(c) (section 304(c) control), whereas the” is corrected to read “that possesses section 304(c) control of the Corporate Partner, whereas the”.

The Coast Guard will enforce the safety zones listed in 33 CFR 165.118 on the specified dates and times as indicated in Table 1 below.

This document is issued under authority of 33 CFR 165.118 and 5 U.S.C. 552(a). In addition to this document in the Federal Register, the Coast Guard will provide mariners with advanced notification of enforcement periods via the Local Notice to Mariners and Broadcast Notice to Mariners. If the COTP determines that the regulated areas need not be enforced for the full duration stated in this document, a Broadcast Notice to Mariners may be used to grant general permission to enter the regulated areas.

The Coast Guard will enforce the Safety Zones; Annual Events in the Captain of the Port Buffalo Zone listed in 33 CFR 165.939 for the following events:

(1) Fairport Harbor Mardi Gras Fireworks, Fairport Harbor, OH; The safety zone listed in 33 CFR 165.939(a)(22) will be enforced from 9:15 p.m. to 10:15 p.m. on July 5, 2015.

(2) Sheffield Lake Annual Community Days Fireworks, Sheffield Lake, OH; The safety zone listed in 33 CFR 165.939(a)(27) will be enforced from 9:45 p.m. to 10:35 p.m. on July 10, 2015.

Pursuant to 33 CFR 165.23, entry into, transiting, or anchoring within these safety zones during an enforcement period is prohibited unless authorized by the Captain of the Port Buffalo or his designated representative. Those seeking permission to enter one of these safety zones may request permission from the Captain of Port Buffalo via channel 16, VHF-FM. Vessels and persons granted permission to enter one of these safety zones shall obey the directions of the Captain of the Port Buffalo or his designated representative. While within a safety zone, all vessels shall operate at the minimum speed necessary to maintain a safe course.

This notice is issued under authority of 33 CFR 165.939 and 5 U.S.C. 552(a). In addition to this notice in the Federal Register, the Coast Guard will provide the maritime community with advance notification of these enforcement periods via Broadcast Notice to Mariners or Local Notice to Mariners. If the Captain of the Port Buffalo determines that one of these safety zones need not be enforced for the full duration stated in this notice he or she may use a Broadcast Notice to Mariners to grant general permission to enter the respective safety zone.

The Coast Guard will enforce the Safety Zones; Annual Events in the Captain of the Port Buffalo Zone listed in 33 CFR 165.939 for the following events:

(1) Salute to our Heroes, Hamlin Beach State Park, NY; The safety zone listed in 33 CFR 165.939(a)(16) will be enforced from 9:45 p.m. to 11:30 p.m. on July 3, 2015.

(2) North Tonawanda Fireworks, North Tonawanda, NY; The safety zone listed in 33 CFR 165.939(a)(18) will be enforced from 8:45 p.m. to 10:15 p.m. on July 4, 2015.

(3) French Festival Fireworks, Cape Vincent, NY; The safety zone listed in 33 CFR 165.939(a)(3) will be enforced from 9:15 p.m. to 11 p.m. on July 11, 2015.

(4) Village Fireworks, Sodus Point, NY; The safety zone listed in 33 CFR 165.939(a)(14) will be enforced from 9:30 p.m. to 10:30 p.m. on July 3, 2015.

Pursuant to 33 CFR 165.23, entry into, transiting, or anchoring within these safety zones during an enforcement period is prohibited unless authorized by the Captain of the Port Buffalo or his designated representative. Those seeking permission to enter one of these safety zones may request permission from the Captain of Port Buffalo via channel 16, VHF-FM. Vessels and persons granted permission to enter one of these safety zones shall obey the directions of the Captain of the Port Buffalo or his designated representative. While within a safety zone, all vessels shall operate at the minimum speed necessary to maintain a safe course.

This document is issued under authority of 33 CFR 165.939 and 5 U.S.C. 552(a). In addition to this document in the Federal Register, the Coast Guard will provide the maritime community with advance notification of these enforcement periods via Broadcast Notice to Mariners or Local Notice to Mariners. If the Captain of the Port Buffalo determines that one of these safety zones need not be enforced for the full duration stated in this document he or she may use a Broadcast Notice to Mariners to grant general permission to enter the respective safety zone.

Table of Acronyms DHS Department of Homeland Security FR Federal Register NPRM Notice of Proposed Rulemaking A. Regulatory History and Information

The Coast Guard is issuing this temporary final rule without prior notice and opportunity to comment pursuant to authority under section 4(a) of the Administrative Procedure Act (APA) (5 U.S.C. 553(b)). This provision authorizes an agency to issue a rule without prior notice and opportunity to comment when the agency for good cause finds that those procedures are “impracticable, unnecessary, or contrary to the public interest.” Under 5 U.S.C. 553(b)(B), the Coast Guard finds that good cause exists for not publishing a notice of proposed rulemaking (NPRM) with respect to this rule because publishing an NPRM would be impracticable, as delayed promulgation to accommodate a notice and comment period would endanger the safety of the maritime public and workers involved in the bridge construction.

Under 5 U.S.C. 553(d)(3), the Coast Guard finds that good cause exists for making this rule effective less than 30 days after publication in the Federal Register. Delaying the effective date until 30 days after publication would be impracticable, as doing so would endanger the safety of the maritime public and workers involved in the bridge construction.

The 520 Bridge is the longest floating bridge in the world with a span of 1.4 miles across Lake Washington supported by 33 pontoons. The 520 Bridge is being replaced in order to upgrade the bridges floating pontoons for larger ones. During the bridge replacement project the east span on the 520 Bridge will at times require construction barges to block the waterway that runs beneath that span of the bridge. As a result, the Coast Guard is establishing a temporary safety zone to ensure the safety of the maritime public and workers involved in the bridge construction when the east span is being used by construction barges.

The safety zone established in this rule encompasses all waters within 100 yards of the east span of the 520 Bridge, located on Lake Washington and is effective from June 22, 2015, through September 4, 2015, when a construction barge is present in the safety zone. Vessels wishing to enter the safety zone must request permission to do so from the Captain of the Port by contacting the Joint Harbor Operations Center at 206-217-6001 or VHF Channel 16. If permission for entry is granted, vessels must proceed at a minimum speed for safe navigation.

We developed this rule after considering numerous statutes and executive orders related to rulemaking. Below we summarize our analyses based on these statutes and executive orders.

This rule is not a significant regulatory action under section 3(f) of Executive Order 12866, Regulatory Planning and Review, as supplemented by Executive Order 13563, Improving Regulation and Regulatory Review, and does not require an assessment of potential costs and benefits under section 6(a)(3) of Executive Order 12866 or under section 1 of Executive Order 13563. The Office of Management and Budget has not reviewed it under those Orders. This rule is not a significant regulatory action as the safety zone established by it is both limited in size and duration and there is an alternative route for vessels with an air draft that permits safe passage under the west span of the bridge.

The Regulatory Flexibility Act of 1980 (RFA), 5 U.S.C. 601-612, as amended, requires federal agencies to consider the potential impact of regulations on small entities during rulemaking. The term “small entities” comprises small businesses, not-for-profit organizations that are independently owned and operated and are not dominant in their fields, and governmental jurisdictions with populations of less than 50,000. The Coast Guard certifies under 5 U.S.C. 605(b) that this rule will not have a significant economic impact on a substantial number of small entities. This rule will affect the following entities, some of which may be small entities: The owners or operators of vessels intending to transit the affected waterway during the time the safety zone is in effect. This safety zone will not have a significant economic impact on a substantial number of small entities, however, because the zone established in this rule is limited in size and duration and there is an alternative route for vessels with an air draft that permits safe passage under the west span of the bridge.

Under section 213(a) of the Small Business Regulatory Enforcement Fairness Act of 1996 (Pub. L. 104-121), we want to assist small entities in understanding this rule. If the rule would affect your small business, organization, or governmental jurisdiction and you have questions concerning its provisions or options for compliance, please contact the person listed in the FOR FURTHER INFORMATION CONTACT, above.

Small businesses may send comments on the actions of Federal employees who enforce, or otherwise determine compliance with, Federal regulations to the Small Business and Agriculture Regulatory Enforcement Ombudsman and the Regional Small Business Regulatory Fairness Boards. The Ombudsman evaluates these actions annually and rates each agency's responsiveness to small business. If you wish to comment on actions by employees of the Coast Guard, call 1-888-REG-FAIR (1-888-734-3247). The Coast Guard will not retaliate against small entities that question or complain about this rule or any policy or action of the Coast Guard.

This rule will not call for a new collection of information under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).

A rule has implications for federalism under Executive Order 13132, Federalism, if it has 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. We have analyzed this rule under that Order and determined that this rule does not have implications for federalism.

The Coast Guard respects the First Amendment rights of protesters. Protesters are asked to contact the person listed in the FOR FURTHER INTFORMATION CONTACT section to coordinate protest activities so that your message can be received without jeopardizing the safety or security of people, places or vessels.

The Unfunded Mandates Reform Act of 1995 (2 U.S.C. 1531-1538) requires Federal agencies to assess the effects of their discretionary regulatory actions. In particular, the Act addresses actions that may result in the expenditure by a State, local, or tribal government, in the aggregate, or by the private sector of $100,000,000 (adjusted for inflation) or more in any one year. Though this rule will not result in such expenditure, we do discuss the effects of this rule elsewhere in this preamble.

This rule will not cause a taking of private property or otherwise have taking implications under Executive Order 12630, Governmental Actions and Interference with Constitutionally Protected Property Rights.

This rule meets applicable standards in sections 3(a) and 3(b)(2) of Executive Order 12988, Civil Justice Reform, to minimize litigation, eliminate ambiguity, and reduce burden.

We have analyzed this rule under Executive Order 13045, Protection of Children from Environmental Health Risks and Safety Risks. This rule is not an economically significant rule and does not create an environmental risk to health or risk to safety that may disproportionately affect children.

This rule does not have tribal implications under Executive Order 13175, Consultation and Coordination with Indian Tribal Governments, because it does not 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.

This action is not a “significant energy action” under Executive Order 13211, Actions Concerning Regulations That Significantly Affect Energy Supply, Distribution, or Use.

This rule does not use technical standards. Therefore, we did not consider the use of voluntary consensus standards.

We have analyzed this rule under Department of Homeland Security Management Directive 023-01 and Commandant Instruction M16475.lD, which guide the Coast Guard in complying with the National Environmental Policy Act of 1969 (NEPA)(42 U.S.C. 4321-4370f), and have determined that this action is one of a category of actions that do not individually or cumulatively have a significant effect on the human environment. This rule establishes a temporary safety zone and is categorically excluded from further review under paragraph 34(g) of Figure 2-1 of the Commandant Instruction. An environmental analysis checklist supporting this determination and a Categorical Exclusion Determination are available in the docket where indicated under ADDRESSES.

For the reasons discussed in the preamble, the Coast Guard amends 33 CFR part 165 as follows:

Table of Acronyms COTP Captain of the Port DHS Department of Homeland Security FR Federal Register NPRM Notice of Proposed Rulemaking A. Regulatory History and Information

This rulemaking establishes thirteen safety zones for thirteen fireworks displays. Each event and its corresponding regulatory history are discussed below.

Barnum Festival, LLC (fireworks): A safety zone was established in 2014 for the Barnum Festival, LLC fireworks display by enforcing 33 CFR 165.151, Table 1, 6.1. This event has been included in this rule due to deviation from the cite date and location.

Salute to Veterans (fireworks): A safety zone was established in 2014 for the Salute to Veterans fireworks display by enforcing 33 CFR 165.151, Table 1, 6.4. This event has been included in this rule due to deviation from the cite date and location.

City of Stamford (fireworks): A safety zone was established in 2014 for the City of Stamford fireworks display by enforcing 33 CFR 165.151, Table 1, 7.12. This event has been included in this rule due to deviation from the cite date.

Freeport Chamber of Commerce (fireworks): A safety zone was established in 2014 for Freeport Chamber of Commerce fireworks display when the Coast Guard issued a temporary rule entitled, “Safety Zone; Freeport Chamber of Commerce Fireworks Display; South Bay; Freeport, NY”. This rulemaking was published on June 27, 2014 in the Federal Register (79 FR 36412).

City of Norwich (fireworks): A safety zone was established in 2014 for the City of Norwich fireworks display by enforcing 33 CFR 165.151, Table 1, 7.11. This event has been included in this rule due to deviation from the cite date and location.

Go 4th Connetquot (fireworks): This event was previously named Connetquot River Summer Fireworks. A safety zone was established in 2014 for the Connetquot River Summer Fireworks display by enforcing 33 CFR 165.151, Table 1, 7.42. This event has been included in this rule due to deviation from the cite name and location.

Madison Fireworks Organization (fireworks): A safety zone was established in 2014 for the Madison Fireworks Organization fireworks display by enforcing 33 CFR 165.151, Table 1, 7.38. This event has been included in this rule due from the cite date and location.

City of Middletown (fireworks): A safety zone was established in 2014 for the City of Middletown fireworks display by enforcing 33 CFR 165.151, Table 1, 7.9. This event has been included in this rule due to deviation from the cite date and location.

Fairfield Independence Day Celebration (fireworks): A safety zone was established in 2014 for the Fairfield Independence Day Celebration fireworks display by enforcing 33 CFR 165.151, Table 1, 7.16. This event has been included in this rule due to deviation from the cite date and location.

City of West Haven: A safety zone was established in 2014 for the City of West Haven Fireworks display by enforcing 33 CFR 165.151, Table 1, 7.13. This event has been included in this rule due to deviation from the cite location.

Village of Port Jefferson Independence Day Celebration (fireworks): This event was previously named Village of Port Jefferson Fourth of July Celebration Fireworks. A safety zone was established in 2014 for the Village of Port Jefferson Fourth of July Celebration Fireworks display by enforcing 33 CFR 165.151, Table 1, 7.25. This event has been included in this rule due to deviation from the cite name and location.

Shelter Island (fireworks): A safety zone was established in 2014 for the Shelter Island fireworks display by enforcing 33 CFR 165.151, Table 1, 7.30. This event has been included in this rule due to deviation from the cite location.

Sebonack Golf Club (fireworks): This event was previously named National Golf Links Fireworks. A safety zone was established in 2014 for the National Golf Links Fireworks display by enforcing 33 CFR 165.151, Table 1, 7.44. This event has been included in this rule due to deviation from the cite name, date and location.

The Coast Guard is issuing this temporary final rule without prior notice and opportunity to comment pursuant to authority under section 4(a) of the Administrative Procedure Act (APA) (5 U.S.C. 553(b)). This provision authorizes an agency to issue a rule without prior notice and opportunity to comment when the agency for good cause finds that those procedures are “impracticable, unnecessary, or contrary to the public interest.” Under 5 U.S.C. 553(b)(B), the Coast Guard finds that good cause exists for not publishing a NPRM with respect to this rule because doing so would be impracticable. There is insufficient time to publish a NPRM and solicit comments from the public before these events take place. Thus, waiting for a comment period to run would inhibit the Coast Guard's ability to fulfill its mission to keep the ports and waterways safe.

Under 5 U.S.C. 553(d)(3), and for the same reasons stated in the preceding paragraph, the Coast Guard finds that good cause exists for making this rule effective less than 30 days after publication in the Federal Register.

The legal basis for this temporary rule is 33 U.S.C. 1231; 50 U.S.C. 191; 33 CFR 1.05-1, 6.04-1, 6.04-6, and 160.5 and Department of Homeland Security Delegation No. 0170.1 which collectively authorize the Coast Guard to define regulatory safety zones.

As discussed in the Regulatory History and Information section, thirteen fireworks displays will take place in the Coast Guard Sector LIS COTP Zone between June 26, 2015 and August 1, 2015. The COTP Long Island Sound has determined that thirteen safety zones are necessary to provide for the safety of life on navigable waterways during those events.

Barnum Festival, LLC fireworks display will be held on Bridgeport Harbor, Bridgeport, CT.

Salute to Veterans fireworks display will be held on Reynolds Channel off Hempstead, NY.

City of Stamford fireworks display will be held on Fisher's Westcott Cove, Stamford, CT.

Freeport Chamber of Commerce fireworks display will be a land launch near Guy Lombardo Marina, Freeport, NY.

City of Norwich fireworks display will be held on the Thames River, Norwich, CT.

Go 4th Connetquot fireworks display will be held on Great South Bay off Snapper Inn, Oakdale, NY.

Madison Fireworks Organization fireworks will be held on Long Island Sound off Madison Beach, Madison, CT.

City of Middletown fireworks display will be held on the Connecticut River, Middletown Harbor, Middletown, CT.

Fairfield Independence Day Celebration fireworks display will be held on Long Island Sound off Fairfield, CT.

City of West Haven fireworks display will be held on New Haven Harbor off Bradley Point, West Haven, CT.

Village of Port Jefferson Independence Day Celebration will be held on Port Jefferson Harbor, Port Jefferson, NY.

Shelter Island fireworks display will be held on Gardiner Bay, Shelter Island, NY.

Sebonack Golf Club fireworks display will be held on Peconic Bay off Southampton, NY.

The fireworks displays listed above will launch pyrotechnics from either a barge on a waterway or a landsite near a waterway. A regulated area, specifically a safety zone, is required for each of these fireworks displays to protect both spectators and participants from the safety hazards created by the fireworks displays, including unexpected pyrotechnics detonation and burning debris.

This rule establishes thirteen safety zones for thirteen fireworks displays. The location of these safety zones are as follows:

This rule prevents vessels from entering, transiting, mooring, or anchoring within areas specifically designated as safety zones and restricts vessel movement around the locations of the marine events to reduce the safety risks associated with them during the periods of enforcement unless authorized by the COTP or designated representative.

Consistent with 33 CFR 165.7, the Coast Guard will notify the public and local mariners of this safety zone through appropriate means, which may include, but are not limited to, publication in the Federal Register, the Local Notice to Mariners, and Broadcast Notice to Mariners. The specific dates, including rain dates, for the events are listed in the regulatory text.

We developed this rule after considering numerous statutes and executive orders related to rulemaking. Below we summarize our analyses based on these statutes and executive orders.

This rule is not a significant regulatory action under section 3(f) of Executive Order 12866, Regulatory Planning and Review, as supplemented by Executive Order 13563, Improving Regulation and Regulatory Review, and does not require an assessment of potential costs and benefits under section 6(a)(3) of Executive Order 12866 or under section 1 of Executive Order 13563. The Office of Management and Budget has not reviewed it under those Orders.

The Coast Guard determined that this rulemaking is not a significant regulatory action for the following reasons: The enforcement of these safety zones will be relatively short in duration. Additionally, persons or vessels desiring to enter a safety zone may do so with permission from the COTP Sector Long Island Sound or a designated representative. Furthermore, these safety zones are designed in a way to limit impacts on vessel traffic, permitting vessels to navigate in other portions of the waterways not designated as a safety zone. Finally, to increase public awareness of these safety zones, the Coast Guard will notify the public of the enforcement of this rule via appropriate means, such as Local Notice to Mariners and Broadcast Notice to Mariners.

The Regulatory Flexibility Act of 1980 (RFA), 5 U.S.C. 601-612, as amended, requires federal agencies to consider the potential impact of regulations on small entities during rulemaking. The term “small entities” comprises small businesses, not-for-profit organizations that are independently owned and operated and are not dominant in their fields, and governmental jurisdictions with populations of less than 50,000. The Coast Guard certifies under 5 U.S.C. 605(b) that this rule will not have a significant economic impact on a substantial number of small entities.

This temporary final rule will affect the following entities, some of which may be small entities: The owners or operators of vessels intending to enter, transit, anchor, or moor within a safety zone during the periods of enforcement, from June 26, 2015 to August 1, 2015. However, this temporary final rule will not have a significant economic impact on a substantial number of small entities for the same reasons discussed in the REGULATORY PLANNING AND REVIEW section. Additionally, before the effective period, public notifications will be made to local mariners through appropriate means, which may include but are not limited to, the Local Notice to Mariners as well as Broadcast Notice to Mariners.

Under section 213(a) of the Small Business Regulatory Enforcement Fairness Act of 1996 (Pub. L. 104-121), we want to assist small entities in understanding this proposed rule. If the rule would affect your small business, organization, or governmental jurisdiction and you have questions concerning its provisions or options for compliance, please contact the person listed in the FOR FURTHER INFORMATION CONTACT, above.

Small businesses may send comments on the actions of Federal employees who enforce, or otherwise determine compliance with, Federal regulations to the Small Business and Agriculture Regulatory Enforcement Ombudsman and the Regional Small Business Regulatory Fairness Boards. The Ombudsman evaluates these actions annually and rates each agency's responsiveness to small business. If you wish to comment on actions by employees of the Coast Guard, call1-888-REG-FAIR (1-888-734-3247). The Coast Guard will not retaliate against small entities that question or complain about this proposed rule or any policy or action of the Coast Guard.

This rule will not call for a new collection of information under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).

A rule has implications for federalism under Executive Order 13132, Federalism, if it has 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. We have analyzed this rule under that Order and determined that this rule does not have implications for federalism.

The Coast Guard respects the First Amendment rights of protesters. Protesters are asked to contact the person listed in the FOR FURTHER INFORMATION CONTACT section to coordinate protest activities so that your message can be received without jeopardizing the safety or security of people, places or vessels.

The Unfunded Mandates Reform Act of 1995 (2 U.S.C. 1531-1538) requires Federal agencies to assess the effects of their discretionary regulatory actions. In particular, the Act addresses actions that may result in the expenditure by a State, local, or tribal government, in the aggregate, or by the private sector of $100,000,000 (adjusted for inflation) or more in any one year. Though this rule will not result in such an expenditure, we do discuss the effects of this rule elsewhere in this preamble.

This rule will not cause a taking of private property or otherwise have taking implications under Executive Order 12630, Governmental Actions and Interference with Constitutionally Protected Property Rights.

This rule meets applicable standards in sections 3(a) and 3(b)(2) of Executive Order 12988, Civil Justice Reform, to minimize litigation, eliminate ambiguity, and reduce burden.

We have analyzed this rule under Executive Order 13045, Protection of Children from Environmental Health Risks and Safety Risks. This rule is not an economically significant rule and does not create an environmental risk to health or risk to safety that may disproportionately affect children.

This rule does not have tribal implications under Executive Order 13175, Consultation and Coordination with Indian Tribal Governments, because it does not 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.

This action is not a “significant energy action” under Executive Order 13211, Actions Concerning Regulations That Significantly Affect Energy Supply, Distribution, or Use.

This rule does not use technical standards. Therefore, we did not consider the use of voluntary consensus standards.

We have analyzed this rule under Department of Homeland Security Management Directive 023-01 and Commandant Instruction M16475.lD, which guide the Coast Guard in complying with the National Environmental Policy Act of 1969 (NEPA)(42 U.S.C. 4321-4370f), and have determined that this action is one of a category of actions that do not individually or cumulatively have a significant effect on the human environment. This temporary rule involves the establishment of safety zones. This rule is categorically excluded from further review under paragraph 34(g) of Figure 2-1 of the Commandant Instruction. An environmental analysis checklist supporting this determination and a Categorical Exclusion Determination are available in the docket where indicated under ADDRESSES. We seek any comments or information that may lead to the discovery of a significant environmental impact from this rule.

For the reasons discussed in the preamble, the Coast Guard amends 33 CFR part 165 as follows:

I. Background

The SIP is a living document which the state revises as necessary to address the unique air pollution problems in the state. Therefore, EPA from time to time must take action on SIP revisions containing new and/or revised regulations to make them part of the SIP. On May 22, 1997 (62 FR 27968), EPA revised the procedures for incorporating by reference Federally-approved SIPs, as a result of consultations between EPA and the Office of Federal Register. The description of the revised SIP document, IBR procedures and “Identification of plan” format are discussed in further detail in the May 22, 1997, Federal Register document.

On February 12, 1999, EPA published a document in the Federal Register(64 FR 7091) beginning the new IBR procedure for Kansas. On November 14, 2003 (68 FR 64532), and on April 8, 2009 (74 FR 15856), EPA published an update to the IBR material for Kansas.

In this document, EPA is publishing an updated set of tables listing the regulatory (i.e., IBR) materials in the Kansas SIP taking into account the additions, deletions, and revisions to those materials previously submitted by the state agency and approved by EPA. We are removing the EPA Headquarters Library from paragraph (b)(3), as IBR materials are no longer available at this location. In addition, EPA has found errors in certain entries listed in 40 CFR 52.870(c) and (e), as amended in the published IBR update actions listed above, and is correcting them in this document. Table (c) revisions include:

• Updating state effective date, Federal Register citation and removing outdated text in explanation column for 28-19-200

• removing outdated text in explanation column for 28-19-201

• adding text in EPA approval date column and removing outdated text in explanation column for 28-19-650

Table (e) is being revised by:

• Adding text in the explanation column for (7)-(39).

In this action, EPA is doing the following:

A. Announcing the update to the IBR material as of December 31, 2014;

B. Revising the entry in paragraph 52.870(b) to reflect the update and corrections;

C. Revising certain entries in paragraphs 52.870(c) and (e) as described above;

D. Correcting the date format in the “State effective date” or “State submittal date” and “EPA approval date” columns in paragraphs 52.870(c), (d) and (e). Dates are numerical month/day/year without additional zeros;

E. Modifying the Federal Register citation in paragraphs 52.870(c), (d) and (e) to reflect the beginning page of the preamble as opposed to the page number of the regulatory text.

EPA has determined that this rule falls under the “good cause” exemption in section 553(b)(3)(B) of the Administrative Procedures Act (APA) which, upon finding “good cause,” authorizes agencies to dispense with public participation and section 553(d)(3), which allows an agency to make a rule effective immediately (thereby avoiding the 30-day delayed effective date otherwise provided for in the APA). This rule simply codifies provisions which are already in effect as a matter of law in Federal and approved State programs. Under section 553 of the APA, an agency may find good cause where procedures are “impractical, unnecessary, or contrary to the public interest.” Public comment is “unnecessary” and “contrary to the public interest” since the codification only reflects existing law. Immediate notice in the CFR benefits the public by providing notice of the updated Kansas SIP compilation.

In this rule, EPA is finalizing regulatory text that includes incorporation by reference. In accordance with requirements of 1 CFR 51.5, EPA is finalizing the incorporation by reference of the Kansas regulations described in the amendments to 40 CFR part 52 set forth below. EPA has made, and will continue to make, these documents generally available electronically through www.regulations.gov and/or in hard copy at the appropriate EPA office (see the ADDRESSES section of this preamble for more information).

Under the CAA, the Administrator is required to approve a SIP submission that complies with the provisions of the Act and applicable Federal regulations. 42 U.S.C. 7410(k); 40 CFR 52.02(a). Thus, in reviewing SIP submissions, EPA's role is to approve state choices, provided that they meet the criteria of the CAA. Accordingly, this action merely approves state law as meeting Federal requirements and does not impose additional requirements beyond those imposed by state law. For that reason, this action:

• Is not a “significant regulatory action” under the terms of Executive Order 12866 (58 FR 51735, October 4, 1993) and is therefore not subject to review under Executive Orders 12866 and 13563 (76 FR 3821, January 21, 2011).

• does not impose an information collection burden under the provisions of the Paperwork Reduction Act (44 U.S.C. 3501 et seq.);

• is certified as not having a significant economic impact on a substantial number of small entities under the Regulatory Flexibility Act (5 U.S.C. 601 et seq.);

• does not contain any unfunded mandate or significantly or uniquely affect small governments, as described in the Unfunded Mandates Reform Act of 1995 (Pub. L. 104-4);

• does not have Federalism implications as specified in Executive Order 13132 (64 FR 43255, August 10, 1999);

• is not an economically significant regulatory action based on health or safety risks subject to Executive Order 13045 (62 FR 19885, April 23, 1997);

• is not a significant regulatory action subject to Executive Order 13211 (66 FR 28355, May 22, 2001);

• is not subject to requirements of Section 12(d) of the National Technology Transfer and Advancement Act of 1995 (15 U.S.C. 272 note) because application of those requirements would be inconsistent with the CAA; and

• does not provide EPA with the discretionary authority to address, as appropriate, disproportionate human health or environmental effects, using practicable and legally permissible methods, under Executive Order 12898 (59 FR 7629, February 16, 1994).

The SIP is not approved to apply on any Indian reservation land or in any other area where EPA or an Indian tribe has demonstrated that a tribe has jurisdiction. In those areas of Indian country, the rule does not have tribal implications and will not impose substantial direct costs on tribal governments or preempt tribal law as specified by Executive Order 13175(65 FR 67249, November 9, 2000).

The Congressional Review Act,5 U.S.C. 801 et seq., as added by the Small Business Regulatory Enforcement Fairness Act of 1996, generally provides that before a rule may take effect, the agency promulgating the rule must submit a rule report, which includes a copy of the rule, to each House of the Congress and to the Comptroller General of the United States. EPA will submit a report containing this action and other required information to the U.S. Senate, the U.S. House of Representatives, and the Comptroller General of the United States prior to publication of the rule in the Federal Register. A major rule cannot take effect until 60 days after it is published in the Federal Register. This action is not a “major rule” as defined by 5 U.S.C. 804(2).

EPA has also determined that the provisions of section 307(b)(1) of the CAA pertaining to petitions for judicial review are not applicable to this action. Prior EPA rulemaking actions for each individual component of the Kansas SIP compilations previously afforded interested parties the opportunity to file a petition for judicial review in the United States Court of Appeals for the appropriate circuit within 60 days of such rulemaking action. Thus, EPA sees no need in this action to reopen the 60-day period for filing such petitions for judicial review for this “Identification of plan” reorganization update action for the State of Kansas.

For the reasons stated in the preamble, the EPA amends 40 CFR part 52 as set forth below:

Throughout this document, “we,” “us” and “our” refer to EPA.

Throughout this document, “we,” “us” and “our” refer to the EPA.

On February 11, 2015, in 80 FR 7555, the EPA proposed a limited approval and limited disapproval of the following rule that was submitted for incorporation into the California SIP.

This rule supersedes the BCAQMD rules currently in the California SIP as listed below.

We proposed a limited approval because we determined that Rule 300 improves the SIP and is largely consistent with the relevant CAA requirements. We simultaneously proposed a limited disapproval because some rule provisions conflict with section 110 and part D of the Act. These provisions include the following:

1. Allowing the burning of rubbish under variance approved by hearing board in paragraphs 5.53 and 6.5.

2. Air Pollution Control Officer discretion to waive drying time requirements in paragraph 8.2.4.

Our proposed action contains more information on the basis for this rulemaking and on our evaluation of the submittal.

The EPA's proposed action provided a 30-day public comment period. During this period, we received no comments.

No comments were submitted. Therefore, as authorized in sections 110(k)(3) and 301(a) of the Act, the EPA is finalizing a limited approval of the submitted rule. This action incorporates the submitted rule into the California SIP, including those provisions identified as deficient. As authorized under section 110(k)(3), EPA is simultaneously finalizing a limited disapproval of the rule. As a result, sanctions will be imposed unless the EPA approves subsequent SIP revisions that correct the rule deficiencies within 18 months of the effective date of this action. These sanctions will be imposed under section 179 of the Act according to 40 CFR 52.31. In addition, the EPA must promulgate a federal implementation plan (FIP) under section 110(c) unless we approve subsequent SIP revisions that correct the rule deficiencies within 24 months. Note that the submitted rule has been adopted by the BCAQMD, and the EPA's final limited disapproval does not prevent the local agency from enforcing it. The limited disapproval also does not prevent any portion of the rule from being incorporated by reference into the federally enforceable SIP as discussed in a July 9, 1992 EPA memo found at: http://www.epa.gov/nsr/ttnnsr01/gen/pdf/memo-s.pdf.

In this rule, the EPA is finalizing regulatory text that includes incorporation by reference. In accordance with requirements of 1 CFR 51.5, the EPA is finalizing the incorporation by reference of the BCAQMD rules described in the amendments to 40 CFR part 52 set forth below. The EPA has made, and will continue to make, these documents available electronically through www.regulations.gov and in hard copy at the appropriate EPA office (see the ADDRESSES section of this preamble for more information).

The Office of Management and Budget (OMB) has exempted this regulatory action from Executive Order 12866, entitled “Regulatory Planning and Review.”

This action does not impose an information collection burden under the provisions of the Paperwork Reduction Act, 44 U.S.C. 3501 et seq. Burden is defined at 5 CFR 1320.3(b).

The Regulatory Flexibility Act (RFA) generally requires an agency to conduct a regulatory flexibility analysis of any rule subject to notice and comment rulemaking requirements unless the agency certifies that the rule will not have a significant economic impact on a substantial number of small entities. Small entities include small businesses, small not-for-profit enterprises, and small governmental jurisdictions.

This rule will not have a significant impact on a substantial number of small entities because SIP limited approvals/limited disapprovals under section 110 and subchapter I, part D of the Clean Air Act do not create any new requirements but simply approve requirements that the State is already imposing. Therefore, because this limited approval/limited disapproval action does not create any new requirements, I certify that this action will not have a significant economic impact on a substantial number of small entities.

Moreover, due to the nature of the Federal-State relationship under the Clean Air Act, preparation of flexibility analysis would constitute Federal inquiry into the economic reasonableness of State action. The Clean Air Act forbids the EPA to base its actions concerning SIPs on such grounds. Union Electric Co., v. U.S. EPA, 427 U.S. 246, 255-66 (1976); 42 U.S.C. 7410(a)(2).

Under sections 202 of the Unfunded Mandates Reform Act of 1995 (“Unfunded Mandates Act”), signed into law on March 22, 1995, the EPA must prepare a budgetary impact statement to accompany any proposed or final rule that includes a Federal mandate that may result in estimated costs to State, local, or tribal governments in the aggregate; or to the private sector, of $100 million or more. Under section 205, the EPA must select the most cost-effective and least burdensome alternative that achieves the objectives of the rule and is consistent with statutory requirements. Section 203 requires the EPA to establish a plan for informing and advising any small governments that may be significantly or uniquely impacted by the rule.

The EPA has determined that the limited approval/limited disapproval action promulgated does not include a Federal mandate that may result in estimated costs of $100 million or more to either State, local, or tribal governments in the aggregate, or to the private sector. This Federal action approves pre-existing requirements under State or local law, and imposes no new requirements. Accordingly, no additional costs to State, local, or tribal governments, or to the private sector, result from this action.

Federalism (64 FR 43255, August 10, 1999) revokes and replaces Executive Orders 12612 (Federalism) and 12875 (Enhancing the Intergovernmental Partnership). Executive Order 13132 requires the EPA to develop an accountable process to ensure “meaningful and timely input by State and local officials in the development of regulatory policies that have federalism implications.” “Policies that have federalism implications” is defined in the Executive Order to include regulations 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.” Under Executive Order 13132, the EPA may not issue a regulation that has federalism implications, that imposes substantial direct compliance costs, and that is not required by statute, unless the Federal government provides the funds necessary to pay the direct compliance costs incurred by State and local governments, or the EPA consults with State and local officials early in the process of developing the proposed regulation. The EPA also may not issue a regulation that has federalism implications and that preempts State law unless the Agency consults with State and local officials early in the process of developing the proposed regulation.

This rule will not 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, as specified in Executive Order 13132, because it merely approves a State rule implementing a Federal standard, and does not alter the relationship or the distribution of power and responsibilities established in the Clean Air Act. Thus, the requirements of section 6 of the Executive Order do not apply to this rule.

Executive Order 13175, entitled “Consultation and Coordination with Indian Tribal Governments” (65 FR 67249, November 9, 2000), requires the EPA to develop an accountable process to ensure “meaningful and timely input by tribal officials in the development of regulatory policies that have tribal implications.” This final rule does not have tribal implications, as specified in Executive Order 13175. It will not have substantial direct effects on tribal governments, 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. Thus, Executive Order 13175 does not apply to this rule.

The EPA interprets Executive Order 13045 (62 FR 19885, April 23, 1997) as applying only to those regulatory actions that concern health or safety risks, such that the analysis required under section 5-501 of the Executive Order has the potential to influence the regulation. This rule is not subject to Executive Order 13045, because it approves a State rule implementing a Federal standard.

This rule is not subject to Executive Order 13211, “Actions Concerning Regulations That Significantly Affect Energy Supply, Distribution, or Use” (66 FR 28355, May 22, 2001) because it is not a significant regulatory action under Executive Order 12866.

Section 12 of the National Technology Transfer and Advancement Act (NTTAA) of 1995 requires Federal agencies to evaluate existing technical standards when developing a new regulation. To comply with NTTAA, the EPA must consider and use “voluntary consensus standards” (VCS) if available and applicable when developing programs and policies unless doing so would be inconsistent with applicable law or otherwise impractical.

The EPA believes that VCS are inapplicable to this action. This action does not require the public to perform activities conducive to the use of VCS.

Executive Order (E.O.) 12898 (59 FR 7629 (Feb. 16, 1994)) establishes federal executive policy on environmental justice. Its main provision directs federal agencies, to the greatest extent practicable and permitted by law, to make environmental justice part of their mission by identifying and addressing, as appropriate, disproportionately high and adverse human health or environmental effects of their programs, policies, and activities on minority populations and low-income populations in the United States.

The EPA lacks the discretionary authority to address environmental justice in this rulemaking.

The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the Small Business Regulatory Enforcement Fairness Act of 1996, generally provides that before a rule may take effect, the agency promulgating the rule must submit a rule report, which includes a copy of the rule, to each House of the Congress and to the Comptroller General of the United States. The EPA will submit a report containing this rule and other required information to the U.S. Senate, the U.S. House of Representatives, and the Comptroller General of the United States prior to publication of the rule in the Federal Register. A major rule cannot take effect until 60 days after it is published in the Federal Register. This action is not a “major rule” as defined by 5 U.S.C. 804(2). This rule will be effective on August 7, 2015.

Under section 307(b)(1) of the Clean Air Act, petitions for judicial review of this action must be filed in the United States Court of Appeals for the appropriate circuit by September 8, 2015. Filing a petition for reconsideration by the Administrator of this final rule does not affect the finality of this rule for the purposes of judicial review nor does it extend the time within which a petition for judicial review may be filed, and shall not postpone the effectiveness of such rule or action. This action may not be challenged later in proceedings to enforce its requirements (see section 307(b)(2)).

Part 52, chapter I, title 40 of the Code of Federal Regulations is amended as follows:

The SIP is a living document which the state revises as necessary to address the unique air pollution problems in the state. Therefore, EPA from time to time must take action on SIP revisions containing new and/or revised regulations to make them part of the SIP. On May 22, 1997 (62 FR 27968), EPA revised the procedures for incorporating by reference Federally-approved SIPs, as a result of consultations between EPA and the Office of Federal Register (OFR). The description of the revised SIP document, IBR procedures and “Identification of plan” format are discussed in further detail in the May 22, 1997, Federal Register document.

On February 12, 1999, EPA published a document in the Federal Register (64 FR 7091) beginning the new IBR procedure for Nebraska. On December 1, 2003, (68 FR 67045) and on July 30, 2009 (74 FR 37939), EPA published updates to the IBR material for Nebraska.

In this document, EPA is publishing an updated set of tables listing the regulatory (i.e., IBR) materials in the Nebraska SIP taking into account the additions, deletions, and revisions to those materials previously submitted by the state agency and approved by EPA. We are removing the EPA Headquarters Library from paragraph (b)(3), as IBR materials are no longer available at this location. Table (e) revisions include:

• Adding text in the explanation column for (6)-(27).

In this action, EPA is doing the following:

A. Announcing the update to the IBR material as of December 31, 2014.

B. Revising the entry in § 52.1420(b) to reflect the update and corrections.

C. Revising certain entries in § 52.1420(e) as described above;

D. Correcting the date format in the “State effective date” or “State submittal date” and “EPA approval date” columns in § 52.1420(c), (d) and (e). Dates are numerical month/day/year without additional zeros;

E. Modifying the Federal Register citation in § 52.1420(c), (d) and (e) to reflect the beginning page of the preamble as opposed to the page number of the regulatory text.

EPA has determined that this rule falls under the “good cause” exemption in section 553(b)(3)(B) of the Administrative Procedures Act (APA) which, upon finding “good cause,” authorizes agencies to dispense with public participation and section 553(d)(3), which allows an agency to make a rule effective immediately (thereby avoiding the 30-day delayed effective date otherwise provided for in the APA). This rule simply codifies provisions which are already in effect as a matter of law in Federal and approved State programs. Under section 553 of the APA, an agency may find good cause where procedures are “impractical, unnecessary, or contrary to the public interest.” Public comment is “unnecessary” and “contrary to the public interest” since the codification only reflects existing law. Immediate notice in the CFR benefits the public by providing notice of the updated Nebraska SIP compilation.

In this rule, EPA is finalizing regulatory text that includes incorporation by reference. In accordance with requirements of 1 CFR 51.5, EPA is finalizing the incorporation by reference of the Nebraska regulations described in the amendments to 40 CFR part 52 set forth below. EPA has made, and will continue to make, these documents generally available electronically through www.regulations.gov and/or in hard copy at the appropriate EPA office (see the ADDRESSES section of this preamble for more information).

Under the CAA, the Administrator is required to approve a SIP submission that complies with the provisions of the Act and applicable Federal regulations. 42 U.S.C. 7410(k); 40 CFR 52.02(a). Thus, in reviewing SIP submissions, EPA's role is to approve state choices, provided that they meet the criteria of the CAA. Accordingly, this action merely approves state law as meeting Federal requirements and does not impose additional requirements beyond those imposed by state law. For that reason, this action:

• Is not a “significant regulatory action” under the terms of Executive Order 12866 (58 FR 51735, October 4, 1993) and is therefore not subject to review under Executive Orders 12866 and 13563 (76 FR 3821, January 21, 2011).

• does not impose an information collection burden under the provisions of the Paperwork Reduction Act (44 U.S.C. 3501 et seq.);

• is certified as not having a significant economic impact on a substantial number of small entities under the Regulatory Flexibility Act (5 U.S.C. 601 et seq.);

• does not contain any unfunded mandate or significantly or uniquely affect small governments, as described in the Unfunded Mandates Reform Act of 1995 (Pub. L. 104-4);

• does not have Federalism implications as specified in Executive Order 13132 (64 FR 43255, August 10, 1999);

• is not an economically significant regulatory action based on health or safety risks subject to Executive Order 13045 (62 FR 19885, April 23, 1997);

• is not a significant regulatory action subject to Executive Order 13211 (66 FR 28355, May 22, 2001);

• is not subject to requirements of Section 12(d) of the National Technology Transfer and Advancement Act of 1995 (15 U.S.C. 272 note) because application of those requirements would be inconsistent with the CAA; and

• does not provide EPA with the discretionary authority to address, as appropriate, disproportionate human health or environmental effects, using practicable and legally permissible methods, under Executive Order 12898 (59 FR 7629, February 16, 1994).

The SIP is not approved to apply on any Indian reservation land or in any other area where EPA or an Indian tribe has demonstrated that a tribe has jurisdiction. In those areas of Indian country, the rule does not have tribal implications and will not impose substantial direct costs on tribal governments or preempt tribal law as specified by Executive Order 13175 (65 FR 67249, November 9, 2000).

The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the Small Business Regulatory Enforcement Fairness Act of 1996, generally provides that before a rule may take effect, the agency promulgating the rule must submit a rule report, which includes a copy of the rule, to each House of the Congress and to the Comptroller General of the United States. EPA will submit a report containing this action and other required information to the U.S. Senate, the U.S. House of Representatives, and the Comptroller General of the United States prior to publication of the rule in the Federal Register. A major rule cannot take effect until 60 days after it is published in the Federal Register. This action is not a “major rule” as defined by 5 U.S.C. 804(2).

EPA has also determined that the provisions of section 307(b)(1) of the CAA pertaining to petitions for judicial review are not applicable to this action. Prior EPA rulemaking actions for each individual component of the Nebraska SIP compilations previously afforded interested parties the opportunity to file a petition for judicial review in the United States Court of Appeals for the appropriate circuit within 60 days of such rulemaking action. Thus, EPA sees no need in this action to reopen the 60-day period for filing such petitions for judicial review for this “Identification of plan” reorganization update action for the State of Nebraska.

For the reasons stated in the preamble, the EPA amends 40 CFR part 52 as set forth below:

I. General Information A. Does this action apply to me?

You may be potentially affected by this action if you are an agricultural producer, food manufacturer, or pesticide manufacturer. The following list of North American Industrial Classification System (NAICS) codes is not intended to be exhaustive, but rather provides a guide to help readers determine whether this document applies to them. Potentially affected entities may include:

• Crop production (NAICS code 111).

• Animal production (NAICS code 112).

• Food manufacturing (NAICS code 311).

• Pesticide manufacturing (NAICS code 32532).

You may access a frequently updated electronic version of EPA's tolerance regulations at 40 CFR part 180 through the Government Printing Office's e-CFR site at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.

Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an objection to any aspect of this regulation and may also request a hearing on those objections. You must file your objection or request a hearing on this regulation in accordance with the instructions provided in 40 CFR part 178. To ensure proper receipt by EPA, you must identify docket ID number EPA-HQ-OPP-2014-0346 in the subject line on the first page of your submission. All objections and requests for a hearing must be in writing, and must be received by the Hearing Clerk on or before September 8, 2015. Addresses for mail and hand delivery of objections and hearing requests are provided in 40 CFR 178.25(b).

In addition to filing an objection or hearing request with the Hearing Clerk as described in 40 CFR part 178, please submit a copy of the filing (excluding any Confidential Business Information (CBI)) for inclusion in the public docket. Information not marked confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA without prior notice. Submit the non-CBI copy of your objection or hearing request, identified by docket ID number EPA-HQ-OPP-2014-0346, by one of the following methods:

• Federal eRulemaking Portal: http://www.regulations.gov. Follow the online instructions for submitting comments. Do not submit electronically any information you consider to be CBI or other information whose disclosure is restricted by statute.

• Mail: OPP Docket, Environmental Protection Agency Docket Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC 20460-0001.

• Hand Delivery: To make special arrangements for hand delivery or delivery of boxed information, please follow the instructions at http://www.epa.gov/dockets/contacts.html.

Additional instructions on commenting or visiting the docket, along with more information about dockets generally, is available at http://www.epa.gov/dockets.

In the Federal Register of August 1, 2014 (79 FR 44729) (FRL-9911-67), EPA issued a document pursuant to FFDCA section 408(d)(3), 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 4E8264) by IR-4, IR-4 Project Headquarters, Rutgers, The State University of New Jersey, 500 College Road East, Suite 201 W, Princeton, NJ 08450. The petition requested that 40 CFR part 180 be amended by establishing tolerances for residues of the fungicide prohexadione calcium, calcium 3-oxido-5-oxo-4-propionylcyclohex-3-enecarboxylate, in or on strawberry at 0.3 parts per million (ppm) and watercress at 2.0 ppm. That document referenced a summary of the petition prepared by BASF Corporation, the registrant, which is available in the docket, http://www.regulations.gov. A comment was received on the notice of filing. EPA's response to these comments is discussed in Unit IV.C.

Based upon review of the data supporting the petition, EPA has amended the tolerance for watercress from what the petitioner requested. The reason for this change is explained in Unit IV.D.

Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a tolerance (the legal limit for a pesticide chemical residue in or on a food) only if EPA determines that the tolerance is “safe.” Section 408(b)(2)(A)(ii) of FFDCA defines “safe” to mean that “there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposures and all other exposures for which there is reliable information.” This includes exposure through drinking water and in residential settings, but does not include occupational exposure. Section 408(b)(2)(C) of FFDCA requires EPA to give special consideration to exposure of infants and children to the pesticide chemical residue in establishing a tolerance and to “ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue . . . .”

Consistent with FFDCA section 408(b)(2)(D), and the factors specified in FFDCA section 408(b)(2)(D), EPA has reviewed the available scientific data and other relevant information in support of this action. EPA has sufficient data to assess the hazards of and to make a determination on aggregate exposure for prohexadione calcium including exposure resulting from the tolerances established by this action. EPA's assessment of exposures and risks associated with prohexadione calcium follows.

EPA has evaluated the available toxicity data and considered its validity, completeness, and reliability as well as the relationship of the results of the studies to human risk. EPA has also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children.

The most sensitive effect in the prohexadione toxicity database by oral exposure is kidney toxicity in dogs both for subchronic and chronic durations. Minor hematological changes (decreased white blood cell counts in males), and fore-stomach hyperplasia were seen only at very high doses in rodents. No dermal toxicity was observed up to the limit dose of 1,000 milligram/kilogram/day (mg/kg/day). There was no evidence of neurotoxicity in either of the neurotoxicity screening batteries up to or exceeding the limit dose.

In rats and rabbits, no increased quantitative or qualitative pre- or postnatal susceptibility was observed. In rats, no maternal or developmental toxicity was observed up to the limit dose (1,000 mg/kg/day). Three developmental studies in rabbits are available in the toxicological database for prohexadione calcium. In one study, late abortions occurred during GD 24-29 at 200 mg/kg/day, with increased mortality in maternal animals (GD 15-24) also noted at this dose. In another rabbit developmental study, two premature deliveries (on GD 24 and 26) were noted at the highest dose tested (350 mg/kg/day) with no developmental effects observed. No maternal or developmental effects were seen in a third rabbit developmental study up to 150 mg/kg/day. In the 2-generation reproductive toxicity study with rats, parental toxicity (minimal mortality) occurred at a dose well below the dose that caused decreases in offspring body weight (3, 850 mg/kg/day).

Prohexadione calcium is classified as not likely to be carcinogenic to humans based on lack of evidence of carcinogenicity in rats and mice.

Specific information on the studies received and the nature of the adverse effects caused by prohexadione calcium as well as the no-observed-adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-level (LOAEL) from the toxicity studies can be found at http://www.regulations.gov in document Prohexadione Calcium. Section 3 Registration for Use on Strawberry and Watercress. Human Health Risk Assessment on pages 11-14 in docket ID number EPA-HQ-OPP-2014-0346.

Once a pesticide's toxicological profile is determined, EPA identifies toxicological points of departure (POD) and levels of concern to use in evaluating the risk posed by human exposure to the pesticide. For hazards that have a threshold below which there is no appreciable risk, the toxicological POD is used as the basis for derivation of reference values for risk assessment. PODs are developed based on a careful analysis of the doses in each toxicological study to determine the dose at which no adverse effects are observed (the NOAEL) and the lowest dose at which adverse effects of concern are identified (the LOAEL). Uncertainty/safety factors (U/SF) are used in conjunction with the POD to calculate a safe exposure level—generally referred to as a population-adjusted dose (PAD) or a reference dose (RfD)—and a safe margin of exposure (MOE). For non-threshold risks, the Agency assumes that any amount of exposure will lead to some degree of risk. Thus, the Agency estimates risk in terms of the probability of an occurrence of the adverse effect expected in a lifetime. For more information on the general principles EPA uses in risk characterization and a complete description of the risk assessment process, see http://www.epa.gov/pesticides/factsheets/riskassess.htm.

A summary of the toxicological endpoints for prohexadione calcium used for human risk assessment is shown in the Table of this unit. Since the assessment in 2011, (November 18, 2011) (76 FR 71459) (FRL-9326-4), the Agency has reevaluated the endpoints and determined that the previously identified dermal endpoints are no longer appropriate.

1. Dietary exposure from food and feed uses. In evaluating dietary exposure to prohexadione calcium, EPA considered exposure under the petitioned-for tolerances as well as all existing prohexadione calcium tolerances in 40 CFR 180.547. EPA assessed dietary exposures from prohexadione calcium in food as follows:

i. Acute exposure. Quantitative acute dietary exposure and risk assessments are performed for a food-use pesticide, if a toxicological study has indicated the possibility of an effect of concern occurring as a result of a 1-day or single exposure.

No such effects were identified in the toxicological studies for prohexadione calcium; therefore, a quantitative acute dietary exposure assessment is unnecessary.

ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data from the USDA Nationwide Health and Nutrition Examination Survey, What We Eat In America (NHANES/WWEIA) conducted from 2003-2008. As to residue levels in food, the chronic dietary analysis assumed Dietary Exposure Evaluation Model (DEEM) (ver. 7.81) default processing factors, 100 percent crop treated (PCT) and tolerance-level residues for all commodities.

iii. Cancer. Based on the data summarized in Unit III.A., EPA has concluded that prohexadione calcium does not pose a cancer risk to humans. Therefore, a dietary exposure assessment for the purpose of assessing cancer risk is unnecessary.

iv. Anticipated residue and percent crop treated (PCT) information. EPA did not use anticipated residue or PCT information in the dietary assessment for prohexadione calcium. Tolerance-level residues and/or 100 PCT were assumed for all food commodities.

2. Dietary exposure from drinking water. The Agency used screening level water exposure models in the dietary exposure analysis and risk assessment for prohexadione calcium in drinking water. These simulation models take into account data on the physical, chemical, and fate/transport characteristics of prohexadione calcium. Further information regarding EPA drinking water models used in pesticide exposure assessment can be found at http://www.epa.gov/oppefed1/models/water/index.htm.

Based on the Tier 1 Rice Model and Screening Concentration in Ground Water (SCI-GROW) model, the estimated drinking water concentrations (EDWCs) of prohexadione calcium for chronic exposures for non-cancer assessments are estimated to be 170 parts per billion (ppb) for surface water and 0.137 ppb for ground water.

Modeled estimates of drinking water concentrations were directly entered into the dietary exposure model. For chronic dietary risk assessment, the water concentration of value 170 ppb was used to assess the contribution to drinking water.

3. From non-dietary exposure. The term “residential exposure” is used in this document to refer to non-occupational, non-dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, and flea and tick control on pets).

Prohexadione calcium is currently registered for the following uses that could result in residential exposures: Residential lawns, ornamentals, athletic fields, parks, and golf courses. EPA assessed residential exposure using the following assumptions: Short-term residential handler exposures may result from adults applying prohexadione calcium to residential lawns and ornamentals. The Agency assessed inhalation exposures for adult handlers applying manually-pressurized handwand applications to bedding plants. Short-term exposure is also possible for post-application incidental oral exposures of children 1-<2 years old. The Agency assessed hand-to-mouth exposures and incidental soil ingestions from applications to turf for children. Intermediate- and long-term exposures are not expected since there are no registered or proposed uses of prohexadione calcium that result in intermediate- or long-term residential exposures. Further information regarding EPA standard assumptions and generic inputs for residential exposures may be found at http://www.epa.gov/pesticides/science/residential-exposure-sop.html.

4. Cumulative effects from substances with a common mechanism of toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider “available information” concerning the cumulative effects of a particular pesticide's residues and “other substances that have a common mechanism of toxicity.”

EPA has not found prohexadione calcium to share a common mechanism of toxicity with any other substances, and prohexadione calcium does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that prohexadione calcium does not have a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see EPA's Web site at http://www.epa.gov/pesticides/cumulative.

1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA shall apply an additional tenfold (10X) margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the database on toxicity and exposure unless EPA determines based on reliable data that a different margin of safety will be safe for infants and children. This additional margin of safety is commonly referred to as the Food Quality Protection Act Safety Factor (FQPA SF). In applying this provision, EPA either retains the default value of 10X, or uses a different additional safety factor when reliable data are available to EPA support the choice of a different factor.

2. Prenatal and postnatal sensitivity. There are no residual uncertainties for prenatal and postnatal toxicity and there is no evidence of increased qualitative or quantitative susceptibility of any kind for fetuses and offspring in both rats and rabbits.

3. Conclusion. EPA has determined that reliable data show the safety of infants and children would be adequately protected if the FQPA SF were reduced to 1X. That decision is based on the following findings:

i. The toxicity database for prohexadione calcium is complete.

ii. There is no indication that prohexadione calcium is a neurotoxic chemical and there is no need for a developmental neurotoxicity study or additional UFs to account for neurotoxicity.

iii. There is no evidence that prohexadione calcium results in increased susceptibility in in utero rats or rabbits in the prenatal developmental studies or in young rats in the 2-generation reproduction study.

iv. There are no residual uncertainties identified in the exposure databases. The dietary food exposure assessments were performed based on 100 PCT, tolerance-level residues, and DEEM (Ver 7.81) default processing factors. EPA made conservative (protective) assumptions in the ground and surface water modeling used to assess exposure to prohexadione calcium in drinking water. EPA used similarly conservative assumptions to assess post-application exposure of children as well as incidental oral exposure of toddlers. These assessments will not underestimate the exposure and risks posed by prohexadione calcium.

EPA determines whether acute and chronic dietary pesticide exposures are safe by comparing aggregate exposure estimates to the acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA calculates the lifetime probability of acquiring cancer given the estimated aggregate exposure. Short-, intermediate-, and chronic-term risks are evaluated by comparing the estimated aggregate food, water, and residential exposure to the appropriate PODs to ensure that an adequate MOE exists.

1. Acute risk. An acute aggregate risk assessment takes into account acute exposure estimates from dietary consumption of food and drinking water. No adverse effect resulting from a single oral exposure was identified and no acute dietary endpoint was selected. Therefore, prohexadione calcium is not expected to pose an acute risk.

2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that chronic exposure to prohexadione calcium from food and water will utilize 19% of the cPAD for children 1-2 years old, the population group receiving the greatest exposure. Based on the explanation in Unit III.C.3., regarding residential use patterns, chronic residential exposure to residues of prohexadione calcium is not expected.

3. Short-term risk. Short-term aggregate exposure takes into account short-term residential exposure plus chronic exposure to food and water (considered to be a background exposure level).

Prohexadione calcium is currently registered for uses that could result in short-term residential exposure, and the Agency has determined that it is appropriate to aggregate chronic exposure through food and water with short-term residential exposures to prohexadione calcium.

Using the exposure assumptions described in this unit for short-term exposures, EPA has concluded the combined short-term food, water, and residential exposures result in aggregate MOEs of 14,000 for adults and 2,100 for children. Because EPA's level of concern for prohexadione calcium is a MOE of 100 or below, these MOEs are not of concern.

4. Intermediate-term risk. Intermediate-term aggregate exposure takes into account intermediate-term residential exposure plus chronic exposure to food and water (considered to be a background exposure level).

An intermediate-term adverse effect was identified; however, prohexadione calcium is not registered for any use patterns that would result in intermediate-term residential exposure. Intermediate-term risk is assessed based on intermediate-term residential exposure plus chronic dietary exposure. Because there is no intermediate-term residential exposure and chronic dietary exposure has already been assessed under the appropriately protective cPAD (which is at least as protective as the POD used to assess intermediate-term risk), no further assessment of intermediate-term risk is necessary, and EPA relies on the chronic dietary risk assessment for evaluating intermediate-term risk for prohexadione calcium.

5. Aggregate cancer risk for U.S. population. Based on the lack of evidence of carcinogenicity in two adequate rodent carcinogenicity studies, prohexadione calcium is not expected to pose a cancer risk to humans.

6. Determination of safety. Based on these risk assessments, EPA concludes that there is a reasonable certainty that no harm will result to the general population, or to infants and children from aggregate exposure to prohexadione calcium residues.

Adequate enforcement methodology (BASF Analytical Method D9601 and 564/0) is available to enforce the tolerance expression for residues of prohexadione calcium in watercress and strawberry samples.

The method may be requested from: Chief, Analytical Chemistry Branch, Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD 20755-5350; telephone number: (410) 305-2905; email address: [email protected].

In making its tolerance decisions, EPA seeks to harmonize U.S. tolerances with international standards whenever possible, consistent with U.S. food safety standards and agricultural practices. EPA considers the international maximum residue limits (MRLs) established by the Codex Alimentarius Commission (Codex), as required by FFDCA section 408(b)(4). The Codex Alimentarius is a joint United Nations Food and Agriculture Organization/World Health Organization food standards program, and it is recognized as an international food safety standards-setting organization in trade agreements to which the United States is a party. EPA may establish a tolerance that is different from a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain the reasons for departing from the Codex level.

The Codex has not established a MRL for prohexadione calcium in/on strawberries and watercress.

One comment was received in response to the notice of filing of IR-4's petition. The commenter stated this use should be denied due to toxicity to bees and that all use of chemicals should be stopped. The comment primarily appears directed to the registration of the pesticide under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), but to the extent the comment is directed at the present tolerance action, the Agency understands the commenter's concerns and recognizes that some individuals believe that pesticides should be banned on agricultural crops. However, the existing legal framework provided by section 408 of FFDCA states that tolerances may be set when persons seeking such tolerances or exemptions have demonstrated that the pesticide meets the safety standard imposed by that statute. This citizen's comment appears to be directed at the underlying statute and not EPA's implementation of it; the citizen has made no contention that EPA has acted in violation of the statutory framework. As to bees the EPA will consider impacts to the environment and non-target species under the authority of FIFRA.

The tolerance on watercress has been revised from what was proposed in the initial petition. EPA is increasing the proposed tolerance for residues in/on watercress from 2 ppm to 4.0 ppm based on the available watercress field trial data and the OECD tolerance calculation procedure.

Therefore, tolerances are established for residues of prohexadione calcium, calcium 3-oxido-5-oxo-4-propionylcyclohex-3-enecarboxylate, in or on strawberry at 0.30 ppm and watercress at 4.0 ppm.

This action establishes tolerances under FFDCA section 408(d) in response to a petition submitted to the Agency. The Office of Management and Budget (OMB) has exempted these types of actions from review under Executive Order 12866, entitled “Regulatory Planning and Review” (58 FR 51735, October 4, 1993). Because this action has been exempted from review under Executive Order 12866, this action is not subject to Executive Order 13211, entitled “Actions Concerning Regulations That Significantly Affect Energy Supply, Distribution, or Use” (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled “Protection of Children from Environmental Health Risks and Safety Risks” (62 FR 19885, April 23, 1997). This action does not contain any information collections subject to OMB approval under the Paperwork Reduction Act (PRA) (44 U.S.C. 3501 et seq.), nor does it require any special considerations under Executive Order 12898, entitled “Federal Actions to Address Environmental Justice in Minority Populations and Low-Income Populations” (59 FR 7629, February 16, 1994).

Since tolerances and exemptions that are established on the basis of a petition under FFDCA section 408(d), such as the tolerance in this final rule, do not require the issuance of a proposed rule, the requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et seq.), do not apply.

This action directly regulates growers, food processors, food handlers, and food retailers, not States or tribes, nor does this action alter the relationships or distribution of power and responsibilities established by Congress in the preemption provisions of FFDCA section 408(n)(4). As such, the Agency has determined that this action will not have a substantial direct effect on States or tribal governments, on the relationship between the national government and the States or tribal governments, or on the distribution of power and responsibilities among the various levels of government or between the Federal Government and Indian tribes. Thus, the Agency has determined that Executive Order 13132, entitled “Federalism” (64 FR 43255, August 10, 1999) and Executive Order 13175, entitled “Consultation and Coordination with Indian Tribal Governments” (65 FR 67249, November 9, 2000) do not apply to this action. In addition, this action does not impose any enforceable duty or contain any unfunded mandate as described under Title II of the Unfunded Mandates Reform Act (UMRA) (2 U.S.C. 1501 et seq.).

This action does not involve any technical standards that would require Agency consideration of voluntary consensus standards pursuant to section 12(d) of the National Technology Transfer and Advancement Act (NTTAA) (15 U.S.C. 272 note).

Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.), EPA will submit a report containing this rule and other required information to the U.S. Senate, the U.S. House of Representatives, and the Comptroller General of the United States prior to publication of the rule in the Federal Register. This action is not a “major rule” as defined by 5 U.S.C. 804(2).

Therefore, 40 CFR chapter I is amended as follows:

I. General Information A. Does this action apply to me?

You may be potentially affected by this action if you are an agricultural producer, food manufacturer, or pesticide manufacturer. The following list of North American Industrial Classification System (NAICS) codes is not intended to be exhaustive, but rather provides a guide to help readers determine whether this document applies to them. Potentially affected entities may include:

• Crop production (N AICS code 111).

• Animal production (NAICS code 112).

• Food manufacturing (NAICS code 311).

• Pesticide manufacturing (NAICS code 32532).

You may access a frequently updated electronic version of EPA's tolerance regulations at 40 CFR part 180 through the Government Printing Office's e-CFR site at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.

Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an objection to any aspect of this regulation and may also request a hearing on those objections. You must file your objection or request a hearing on this regulation in accordance with the instructions provided in 40 CFR part 178. To ensure proper receipt by EPA, you must identify docket ID number EPA-HQ-OPP-2014-0284 in the subject line on the first page of your submission. All objections and requests for a hearing must be in writing, and must be received by the Hearing Clerk on or before September 8, 2015. Addresses for mail and hand delivery of objections and hearing requests are provided in 40 CFR 178.25(b).

In addition to filing an objection or hearing request with the Hearing Clerk as described in 40 CFR part 178, please submit a copy of the filing (excluding any Confidential Business Information (CBI)) for inclusion in the public docket. Information not marked confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA without prior notice. Submit the non-CBI copy of your objection or hearing request, identified by docket ID number EPA-HQ-OPP-2014-0284, by one of the following methods:

• Federal eRulemaking Portal: http://www.regulations.gov. Follow the online instructions for submitting comments. Do not submit electronically any information you consider to be CBI or other information whose disclosure is restricted by statute.

• Mail: OPP Docket, Environmental Protection Agency Docket Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC 20460-0001.

• Hand Delivery: To make special arrangements for hand delivery or delivery of boxed information, please follow the instructions at http://www.epa.gov/dockets/contacts.html.

Additional instructions on commenting or visiting the docket, along with more information about dockets generally, is available at http://www.epa.gov/dockets.

In the Federal Register of December 17, 2014 (79 FR 75107) (FRL-9918-90), EPA issued a document pursuant to FFDCA section 408(d)(3), 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 4E8248) by IR-4 500 College Road East, Suite 201 W, Princeton, NJ 08540, requests to establish a tolerance in 40 CFR part 180 for residues of S-metolachlor in or on the raw agricultural commodity lettuce at 1.5 parts per million (ppm); vegetable, cucurbit group 9 at 0.50 ppm; vegetable, fruiting, group 8-10, except tabasco pepper at 0.10 ppm; low growing berry subgroup 13-07G except cranberry at 0.40 ppm; and sunflower subgroup 20B at 0.50 ppm and the concurrent deletion of the existing tolerances for okra; vegetable, fruiting, group 8 except tabasco pepper; cucumber; melon subgroup 9A; pumpkin; squash, winter; and sunflower, seed. That document referenced a summary of the petition prepared by Syngenta Crop Protection, the registrant, which is available in the docket, http://www.regulations.gov. There were no comments received in response to the notice of filing.

Based upon review of the data supporting the petition, EPA has modified the levels at which some of the tolerances are being established. The reason for these changes are explained in Unit IV.C.

Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a tolerance (the legal limit for a pesticide chemical residue in or on a food) only if EPA determines that the tolerance is “safe.” Section 408(b)(2)(A)(ii) of FFDCA defines “safe” to mean that “there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposures and all other exposures for which there is reliable information.” This includes exposure through drinking water and in residential settings, but does not include occupational exposure. Section 408(b)(2)(C) of FFDCA requires EPA to give special consideration to exposure of infants and children to the pesticide chemical residue in establishing a tolerance and to “ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue. . . .”

Consistent with FFDCA section 408(b)(2)(D), and the factors specified in FFDCA section 408(b)(2)(D), EPA has reviewed the available scientific data and other relevant information in support of this action. EPA has sufficient data to assess the hazards of and to make a determination on aggregate exposure for S-metolachlor including exposure resulting from the tolerances established by this action. EPA's assessment of exposures and risks associated with S-metolachlor follows.

EPA has evaluated the available toxicity data and considered its validity, completeness, and reliability as well as the relationship of the results of the studies to human risk. EPA has also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children.

The existing toxicological database is primarily comprised of studies conducted with metolachlor. However, bridging studies indicate that the metolachlor toxicology database can be used to assess toxicity for S-metolachlor. In subchronic (metolachlor and S-metolachlor) and chronic (metolachlor) toxicity studies in dogs and rats decreased body weight and body weight (bw) gain were the most commonly observed effects. No systemic toxicity was observed in rabbits when metolachlor was administered dermally. There was no evidence of neurotoxic effects in the available toxicity studies, and there is no evidence of Immunotoxicity in the submitted mouse Immunotoxicity study.

Prenatal developmental studies in the rat and rabbit with both metolachlor and S-metolachlor revealed no evidence of a qualitative or quantitative susceptibility in fetal animals. A 2-generation reproduction study with metolachlor in rats showed no evidence of parental or reproductive toxicity. There are no residual uncertainties with regard to pre- and/or postnatal toxicity.

Metolachlor has been evaluated for carcinogenic effects in the mouse and the rat. Metolachlor did not cause an increase in tumors of any kind in mice. In rats, metolachlor caused an increase in benign liver tumors in rats, but this increase was seen only at the highest dose tested and was statistically significant compared to controls only in females. There was no evidence of mutagenic or cytogenetic effects in vivo or in vitro. Based on this evidence, EPA has concluded that metolachlor does not have a common mechanism of carcinogenicity with acetochlor and alachlor, compounds that are structurally similar to metolachlor. Metolachlor has been classified as a Group C, possible human carcinogen, based on liver tumors in rats at the highest dose tested (HDT).

Taking into account the qualitatively weak evidence on carcinogenic effects and the fact that the increase in benign tumors in female rats occurs at a dose 1,500 times the chronic reference dose (cRfD), EPA has concluded that the cRfD is protective of any potential cancer effect.

Specific information on the studies received and the nature of the adverse effects caused by S-metolachlor as well as the no-observed-adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-level (LOAEL) from the toxicity studies can be found at http://www.regulations.gov in the document “S-metolachlor—Risk Assessment for Establishment of Tolerances for New Uses on Lettuce, Low Growing Berry Subgroup 13-07G, except Cranberry; Vegetable, Cucurbit, Group 9; Sunflower subgroup 20B; Vegetable, Fruiting, Group 8-10; except Tabasco Pepper and Okra” on pp. 40 in docket ID number EPA-HQ-OPP-2014-0284.

Once a pesticide's toxicological profile is determined, EPA identifies toxicological points of departure (POD) and levels of concern to use in evaluating the risk posed by human exposure to the pesticide. For hazards that have a threshold below which there is no appreciable risk, the toxicological POD is used as the basis for derivation of reference values for risk assessment. PODs are developed based on a careful analysis of the doses in each toxicological study to determine the dose at which the NOAEL and the LOAEL are identified. Uncertainty/safety factors are used in conjunction with the POD to calculate a safe exposure level—generally referred to as a population-adjusted dose (PAD) or a reference dose (RfD)—and a safe margin of exposure (MOE). For non-threshold risks, the Agency assumes that any amount of exposure will lead to some degree of risk. Thus, the Agency estimates risk in terms of the probability of an occurrence of the adverse effect expected in a lifetime. For more information on the general principles EPA uses in risk characterization and a complete description of the risk assessment process, see http://www.epa.gov/pesticides/factsheets/riskassess.htm.

A summary of the toxicological endpoints for S-metolachlor used for human risk assessment is shown in Table 1 of this unit.

1. Dietary exposure from food and feed uses. In evaluating dietary exposure to S-metolachlor, EPA considered exposure under the petitioned-for tolerances as well as all existing S-metolachlor tolerances in 40 CFR 180.368. EPA assessed dietary exposures from S-metolachlor in food as follows:

i. Acute exposure. Quantitative acute dietary exposure and risk assessments are performed for a food-use pesticide, if a toxicological study has indicated the possibility of an effect of concern occurring as a result of a 1-day or single exposure.

Such effects were identified for S-metolachlor. In estimating acute dietary exposure, EPA used food consumption information from the United States Department of Agriculture's (USDA) National Health and Nutrition Examination Survey/What We Eat in America, (NHANES/WWEIA). As to residue levels in food, EPA assumed tolerance level residues and 100 percent crop treated (PCT).

ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data from the USDA's NHANES/WWEIA. As to residue levels in food, EPA assumed tolerance level residues and 100 PCT.

iii. Cancer. Based on the data summarized in Unit III.A., EPA has concluded that a nonlinear RfD approach is appropriate for assessing cancer risk to S-metolachlor. Therefore, a separate quantitative cancer exposure assessment is unnecessary since the chronic dietary risk estimate will be protective of potential cancer risk.

iv. Anticipated residue and PCT information. EPA did not use anticipated residue or PCT information in the dietary assessment for S-metolachlor. Tolerance level residues and 100 PCT were assumed for all food commodities.

2. Dietary exposure from drinking water. The Agency used screening level water exposure models in the dietary exposure analysis and risk assessment for S-metolachlor in drinking water. These simulation models take into account data on the physical, chemical, and fate/transport characteristics of S-metolachlor. Further information regarding EPA drinking water models used in pesticide exposure assessment can be found at http://www.epa.gov/oppefed1/models/water/index.htm.

The Agency assessed parent metolachlor, and the metabolites CGA-51202 (metolachlor-OA), CGA-40172, and CGA-50720 together in the drinking water assessment using a total toxic residues (TTR) approach where half-lives were recalculated to collectively account for the parent and the combined residues of concern.

Based on the Surface Water Concentration Calculator (SWCC), the Pesticide Root Zone Model Ground Water (PRZM GW), and the Screening Concentration in Ground Water (SCI-GROW), the estimated drinking water concentrations (EDWCs) of S-metolachlor and its metabolites for acute exposures are estimated to be 371 parts per billion (ppb) for surface water and 1,060 ppb for ground water, and for chronic exposures are estimated to be 43.70 ppb for surface water and 14.3 ppb in ground water.

Modeled estimates of drinking water concentrations were directly entered into the dietary exposure model. For acute dietary risk assessment, the water concentration value of 1,060 ppb was used to assess the contribution to drinking water. For chronic dietary risk assessment, the water concentration of value 43.70 ppb was used to assess the contribution to drinking water.

3. From non-dietary exposure. The term “residential exposure” is used in this document to refer to non-occupational, non-dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticide, and flea and tick control on pets).

S-metolachlor is currently registered for the following uses that could result in residential exposures: On commercial (sod farm) and residential warm-season turf grasses and other non-crop land including golf courses, sports fields, and ornamental gardens. EPA assessed residential exposure using the following assumptions: For residential handlers, short-term inhalation exposure is expected. The following scenarios were evaluated:

• Mixing/loading/applying gardens/trees with manually-pressurized hand wand, hose-end sprayer, backpack, and sprinkler can equipment.

• Mixing/loading/applying lawns/turf with manually-pressurized hand wand, hose-end sprayer, backpack, and sprinkler can equipment.

For residential post-application, there is the potential for short-term incidental oral exposure for individuals exposed as a result of being in an environment that has been previously treated with S-metolachlor. The quantitative exposure/risk assessment for residential post-application exposures is based on the following scenario:

• Hand-to-mouth incidental oral exposure of children 1-2 years old playing on turf treated with S-metolachlor.

Further information regarding EPA standard assumptions and generic inputs for residential exposures may be found at http://www.epa.gov/pesticides/science/residential-exposure-sop.html.

4. Cumulative effects from substances with a common mechanism of toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider “available information” concerning the cumulative effects of a particular pesticide's residues and “other substances that have a common mechanism of toxicity.”

EPA has not found S-metolachlor to share a common mechanism of toxicity with any other substances, and S-metolachlor does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that S-metolachlor does not have a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see EPA's Web site at http://www.epa.gov/pesticides/cumulative.

1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA shall apply an additional tenfold (10×) margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the database on toxicity and exposure unless EPA determines based on reliable data that a different margin of safety will be safe for infants and children. This additional margin of safety is commonly referred to as the Food Quality Protection Act Safety Factor (FQPA SF). In applying this provision, EPA either retains the default value of 10×, or uses a different additional safety factor when reliable data available to EPA support the choice of a different factor.

2. Prenatal and postnatal sensitivity. There was no evidence of increased quantitative or qualitative fetal susceptibility in the prenatal developmental studies in rats and rabbits or in the reproductive toxicity study in rats, with either metolachlor or S-metolachlor. In general, significant developmental toxicity was not seen in rats or rabbits with either compound. The only effects observed in fetal animals were in the rat prenatal developmental study and included slightly decreased number of implantations per dam, decreased number of live fetuses/dam, increased number of resorptions/dam and significant decrease in mean fetal bw. These effects occurred at maternally toxic doses (1,000 milligram/kilogram/day (mg/kg/day)).

3. Conclusion. EPA has determined that reliable data show the safety of infants and children would be adequately protected if the FQPA SF were reduced to 1× for all scenarios except inhalation. For inhalation scenarios a 10× database uncertainty factor (UF) still applies. This decision is based on the following findings:

i. The toxicology database for metolachlor and S-metolachlor is complete, with the exception of a required subchronic inhalation study for metolachlor. As noted above, a 10× data base UF will be applied only for assessing risk for inhalation exposure scenarios.

ii. There is no indication that S-metolachlor is a neurotoxic chemical and there is no need for a developmental neurotoxicity study or additional UFs to account for neurotoxicity.

iii. There is no evidence that S-metolachlor results in increased susceptibility in in utero rats or rabbits in the prenatal developmental studies or in young rats in the 2-generation reproduction study.

iv. There are no residual uncertainties identified in the exposure databases. The dietary food exposure assessments were performed based on 100 PCT and tolerance-level residues. EPA made conservative (protective) assumptions in the ground and surface water modeling used to assess exposure to S-metolachlor in drinking water. EPA used similarly conservative assumptions to assess post-application incidental oral exposure of children 1<2 years old. These assessments will not underestimate the exposure and risks posed by S-metolachlor.

EPA determines whether acute and chronic dietary pesticide exposures are safe by comparing aggregate exposure estimates to the acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA calculates the lifetime probability of acquiring cancer given the estimated aggregate exposure. Short-, intermediate-, and chronic-term risks are evaluated by comparing the estimated aggregate food, water, and residential exposure to the appropriate PODs to ensure that an adequate MOE exists.

1. Acute risk. Using the exposure assumptions discussed in this unit for acute exposure, the acute dietary exposure from food and water to S-metolachlor will occupy 6.1% of the aPAD for all infants (less than 1 year old), the population group receiving the greatest exposure.

2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that chronic exposure to S-metolachlor from food and water will utilize 6.8% of the cPAD for children 1-2 years old, the population group receiving the greatest exposure. Based on the explanation in Unit III.C.3., regarding residential use patterns, chronic residential exposure to residues of S-metolachlor is not expected.

3. Short-term risk. Short-term aggregate exposure takes into account short-term residential exposure plus chronic exposure to food and water (considered to be a background exposure level).

S-metolachlor is currently registered for uses that could result in short-term residential exposure, and the Agency has determined that it is appropriate to aggregate chronic exposure through food and water with short-term residential exposures to S-metolachlor. Potential short-term residential risk scenarios anticipated include adult inhalation handler exposure to turf via backpack sprayer and post-application incidental oral exposure of children playing on treated lawns.

Using the exposure assumptions described in this unit for short-term exposures, EPA has concluded the combined short-term food, water, and residential exposures result in aggregate MOEs of 10,400 for adults and 1,100 for children 1-2 years old. Because EPA's levels of concern for S-metolachlor is a MOE of 1,000 or below for inhalation scenarios (adults) and 100 or below for incidental oral scenarios (children 1-2 years old), these MOEs are not of concern.

4. Intermediate-term risk. Intermediate-term aggregate exposure takes into account intermediate-term residential exposure plus chronic exposure to food and water (considered to be a background exposure level).

An intermediate-term adverse effect was identified; however, S-metolachlor is not registered for any use patterns that would result in intermediate-term residential exposure. Because there is no intermediate-term residential exposure and chronic dietary exposure has already been assessed under the appropriately protective cPAD (which is at least as protective as the POD used to assess intermediate-term risk), no further assessment of intermediate-term risk is necessary, and EPA relies on the chronic dietary risk assessment for evaluating intermediate-term risk for S-metolachlor.

5. Aggregate cancer risk for U.S. population. As discussed in Unit III.A, the chronic dietary risk assessment is protective of any potential cancer effects. Based on the results of that assessment, EPA concludes that S-metolachlor is not expected to pose a cancer risk to humans.

6. Determination of safety. Based on these risk assessments, EPA concludes that there is a reasonable certainty that no harm will result to the general population, or to infants and children from aggregate exposure to S-metolachlor residues.

Adequate methodology is available for enforcing the established and recommended tolerances. PAM Vol. II, Pesticide Regulation Section 180.368, lists a gas chromatography with nitrogen-phosphorus detector (GC/NPD) method (Method I) for determining residues in/on plant commodities and a gas chromatography with mass selective detector (GC/MSD) method (Method II) for determining residues in livestock commodities. These methods determine residues of metolachlor and its metabolites as either CGA-37913 or CGA-49751 following acid hydrolysis. Adequate data are also available on the recovery of metolachlor through FDA's Multiresidue Method Testing Protocols which indicate that metolachlor is completely recovered through Method 302.

In making its tolerance decisions, EPA seeks to harmonize U.S. tolerances with international standards whenever possible, consistent with U.S. food safety standards and agricultural practices. EPA considers the international maximum residue limits (MRLs) established by the Codex Alimentarius Commission (Codex), as required by FFDCA section 408(b)(4). The Codex Alimentarius is a joint United Nations Food and Agriculture Organization/World Health Organization food standards program, and it is recognized as an international food safety standards-setting organization in trade agreements to which the United States is a party. EPA may establish a tolerance that is different from a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain the reasons for departing from the Codex level.

The Codex has not established a MRL for S-metolachlor.

The tolerance being established for the sunflower subgroup 20B is 1.0 ppm, not 0.50 ppm as proposed. This is due to the Agency using the Organization for Economic Cooperation and Development (OECD) Tolerance Calculation procedures, which determined that a tolerance of 1.0 ppm is appropriate based on entry of the 4 field trials for pre-emergence application.

Therefore, tolerances are established for residues of S-metolachlor in or on lettuce at 1.5 ppm; the low growing berry subgroup 13-07G, except cranberry at 0.40 ppm; the sunflower subgroup 20B at 1.0 ppm; the vegetable, cucurbit group 9 at 0.50 ppm; and the vegetable, fruiting, group 8-10, except tabasco pepper at 0.10 ppm. Additionally, due to the establishment of the tolerances listed above, the existing tolerances for vegetable, fruiting, group 8, except tabasco pepper; cucumber; melon subgroup 9A; okra; pumpkin; squash, winter; and sunflower, seed are removed as they are unnecessary.

This action establishes tolerances under FFDCA section 408(d) in response to a petition submitted to the Agency. The Office of Management and Budget (OMB) has exempted these types of actions from review under Executive Order 12866, entitled “Regulatory Planning and Review” (58 FR 51735, October 4, 1993). Because this action has been exempted from review under Executive Order 12866, this action is not subject to Executive Order 13211, entitled “Actions Concerning Regulations That Significantly Affect Energy Supply, Distribution, or Use” (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled “Protection of Children from Environmental Health Risks and Safety Risks” (62 FR 19885, April 23, 1997). This action does not contain any information collections subject to OMB approval under the Paperwork Reduction Act (PRA) (44 U.S.C. 3501 et seq.), nor does it require any special considerations under Executive Order 12898, entitled “Federal Actions to Address Environmental Justice in Minority Populations and Low-Income Populations” (59 FR 7629, February 16, 1994).

Since tolerances and exemptions that are established on the basis of a petition under FFDCA section 408(d), such as the tolerance in this final rule, do not require the issuance of a proposed rule, the requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et seq.), do not apply.

This action directly regulates growers, food processors, food handlers, and food retailers, not States or tribes, nor does this action alter the relationships or distribution of power and responsibilities established by Congress in the preemption provisions of FFDCA section 408(n)(4). As such, the Agency has determined that this action will not have a substantial direct effect on States or tribal governments, on the relationship between the national government and the States or tribal governments, or on the distribution of power and responsibilities among the various levels of government or between the Federal Government and Indian tribes. Thus, the Agency has determined that Executive Order 13132, entitled “Federalism” (64 FR 43255, August 10, 1999) and Executive Order 13175, entitled “Consultation and Coordination with Indian Tribal Governments” (65 FR 67249, November 9, 2000) do not apply to this action. In addition, this action does not impose any enforceable duty or contain any unfunded mandate as described under Title II of the Unfunded Mandates Reform Act (UMRA) (2 U.S.C. 1501 et seq.).

This action does not involve any technical standards that would require Agency consideration of voluntary consensus standards pursuant to section 12(d) of the National Technology Transfer and Advancement Act (NTTAA) (15 U.S.C. 272 note).

Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.), EPA will submit a report containing this rule and other required information to the U.S. Senate, the U.S. House of Representatives, and the Comptroller General of the United States prior to publication of the rule in the Federal Register. This action is not a “major rule” as defined by 5 U.S.C. 804(2).

Therefore, 40 CFR chapter I is amended as follows:

Background

On March 9, 2015, NMFS published a proposed rule in the Federal Register (80 FR 12375) to revise regulations at 50 CFR part 300, subpart C, to implement Resolution C-14-06, “Measures for the Conservation and Management of Bluefin Tuna in the Eastern Pacific Ocean, 2015-2016.” This resolution was adopted by the IATTC at its 88th meeting in October 2014. The public comment period was open until April 8, 2015, and NMFS accepted public comment at a hearing held at the NMFS West Coast Region Long Beach office on March 26, 2015. Additionally, NMFS solicited public comment on the proposed trip limits, which are a new management tool in U.S. West Coast management of fisheries for Pacific bluefin tuna. The proposed trip limits were based on a recommendation from the Pacific Fishery Management Council (Council) at its November 2014 meeting.

The final rule is implemented under the authority of the Tuna Conventions Act (16 U.S.C. 951 et seq.), which directs the Secretary of Commerce, after approval by the Secretary of State, to promulgate regulations as may be necessary to implement resolutions adopted by the IATTC. This authority has been delegated to NMFS.

The proposed rule contains additional background information, including information on the IATTC, the international obligations of the United States as an IATTC member, and the need for regulations. Additional information on changes since the proposed rule is included below.

This final rule establishes catch limits for U.S. commercial vessels that catch Pacific bluefin tuna in the Convention Area (defined as the waters of the eastern Pacific Ocean (EPO)) for 2015 and 2016. Since 1998, conservation resolutions adopted by the IATTC have further defined the Convention Area as the area bounded by the coast of the Americas, the 50° N. and 50° S. parallels, and the 150° W. meridian. In 2015, the catch limit for the entire U.S. fleet is 425 metric tons (mt) with an initial trip limit 1 of 25 mt per vessel. When NMFS anticipates that the total catch for the fleet has reached 375 mt, NMFS will impose a 2-mt trip limit for each vessel that will be in effect until the total catch for 2015 reaches 425 mt. For calendar year 2016, NMFS will announce the catch limit in a Federal Register notice; NMFS will calculate the 2016 catch limit to ensure compliance with Resolution C-14-06 (i.e., not to exceed 425 mt in either year and if catch exceeds 300 mt in 2015, then catch will be limited to 200 mt in 2016). The 2016 catch limit will be calculated as the remainder from the 2015 catch limit (i.e., how much of 425 mt was not caught) added to 175 mt, except as follows: (1) If 175 mt or less is caught in 2015, then the 2016 catch limit is 425 mt; (2) if greater than 300 mt and up to 400 mt are caught in 2015, then the catch limit in 2016 will be 200 mt; or (3) if greater than 425 mt is caught in 2015, then the catch limit in 2016 will be further reduced by the amount in excess of 425 mt (i.e., the remainder of the 600 mt limit for 2015-2016). The fishery in 2016 will also be subject to an initial 25-mt trip limit until catch is within 50 mt of the 2016 catch limit, after which a 2-mt trip limit will be imposed.

When NMFS determines that the catch limit is expected to be reached in 2015 or 2016 (based on landings receipts, data submitted in logbooks, and other available fishery information), NMFS will prohibit commercial fishing for, or retention of, Pacific bluefin tuna for the remainder of the calendar year. NMFS will publish a notice in the Federal Register announcing that the targeting, retaining, transshipping or landing for Pacific bluefin tuna will be prohibited on a specified effective date through the end of that calendar year. Upon that effective date, a commercial fishing vessel of the United States may not be used to target, retain on board, transship, or land Pacific bluefin tuna captured in the Convention Area during the period specified in the announcement, with the exception that any Pacific bluefin tuna already on board a fishing vessel on the effective date may be retained on board, transshipped, and/or landed, to the extent authorized by applicable laws and regulations, provided that they are landed within 14 days after the effective date.

NMFS will provide updates on Pacific bluefin tuna catches in the Convention Area to the public via the IATTC listserv and the West Coast Region Web site: http://www.westcoast.fisheries.noaa.gov/fisheries/migratory_species/bluefin_tuna_harvest_status.html. Additionally, NMFS will report preliminary estimates of Pacific bluefin tuna catch between monthly intervals if and when commercial catches approach the limits to help participants in the U.S. commercial fishery plan for the possibility of catch limits being reached. NMFS will notify industry when catch approaches 250 mt in 2015.

In 2015, NMFS will publish up to two Federal Register notices after the final rule is issued, imposing inseason management measures. First, NMFS will publish a notice when the commercial 2-mt trip limit is imposed (i.e., catch is expected to reach 375 mt). Second, NMFS will publish a notice closing the entire commercial fishery when NMFS determines that the catch limit is expected to be met.

In 2016, NMFS will publish up to three notices in the Federal Register. The first notice will announce the 2016 catch limit. A second notice will announce the 2-mt trip limit, when NMFS determines that the commercial catch is expected to be within 50 mt of the catch limit. NMFS will publish a third notice in the Federal Register when NMFS determines that the catch limit is expected to be reached.

NMFS received eight written public comments and additional comments from attendees to a public hearing held on March 26, 2015, at the NMFS West Coast Region Long Beach office. Comments received were in regard to more than one aspect of the rule and some comments were very similar; therefore, NMFS is responding to the common themes/topics. The responses are summarized below. NMFS did not receive any comments objecting to the 2-mt trip limit when catch is within 50 mt of the catch limit in either 2015 or 2016. One commenter generally supported restrictions on commercial fishing and did not express support or objections to specific measures of the proposed rule.

Comments that were beyond the scope of this rulemaking are not addressed here. Nonetheless, some of those comments are valuable and NMFS will consider them for future management planning.

Comment 1: The rule should not include a trip limit (e.g., an initial 20-mt trip limit proposed), or should have a higher trip limit (e.g., up to 50 mt), because it will lead to discards. In support for this point, a commenter noted that a recent record of per trip catches from one vessel exceeded the proposed trip limit. The commenter also stated that fish in excess of the trip limit that are encircled and then released would not survive; therefore, the trip limits do not promote management measures to reduce fishing mortality. Additionally, the ability of vessel operators to catch a small quantity is uncertain. If only large schools are present, the vessel operators may have to forgo catching Pacific bluefin tuna. A comment received at the public hearing also recommended a higher trip limit.

Response: NMFS agrees that an increase in the trip limit from 20 mt to 25 mt is warranted (for an explanation of the rationale, please see the next section, Changes from the Proposed Rule). NMFS anticipates that increasing the trip limit from the proposed 20 mt to 25 mt will reduce the potential for discards while still sufficiently reducing the rate of harvest to meet the management objectives of providing access to, without exceeding, the full catch limit. Increasing the trip limit beyond 25 mt would make monitoring and timely closure more difficult. Regarding mortality of released fish, other comments received suggest vessel operators could target smaller schools and fish could survive brailing operations. NMFS is unaware of any studies that refute this anecdotal information.

Comment 2: NMFS should adopt an initial trip limit (e.g., 20-mt trip limit) as proposed because it may alleviate derby-style fishing pressures and the potential for excess supply of Pacific bluefin tuna, and therefore, could make fishery more profitable. In particular, slowing the harvest rate could support development of a local fresh-frozen market for Pacific bluefin tuna in California, whereas large sets are only suitable for canning. Commenters also specifically supported 20 mt as the initial trip limit. The 20-mt trip limit is a good an inseason management tool to ensure that catch limits are not exceeded and reduce the potential for a fishery closure that could require discarding of incidentally caught PBF. A skilled purse seine captain can estimate the size of a set, and release fish alive during the brailing operation, if needed. One commenter suggested trip limits should only be imposed for the short-term, while the overall catch limit is so low.

Response: NMFS agrees that the initial trip limit (e.g., 20 mt) is a useful management tool in this situation. As explained in the Response to Comment 1, NMFS is implementing an initial trip limit of 25 mt, rather than 20 mt as originally proposed, to address concerns about discards; the higher trip limit is expected to meet the management objectives, including alleviating derby-style fishing pressure. Further, the 2-mt trip limit when catch is within 50 mt of the 2015 or 2016 limit is intended to prevent discards of incidentally caught PBF in non-directed fisheries (e.g. troll and line, drift gillnet). Additionally, the catch and trip limits in this rule are only applicable to 2015 and 2016. If the IATTC adopts subsequent resolutions on the conservation and management of Pacific bluefin tuna, NMFS will evaluate whether trip limits are appropriate management measures at that time.

Comment 3: Current monitoring and enforcement is inadequate to enforce catch and trip limits, and ensure the biennial catch limits are not exceeded. The proposed trip limit—NMFS assumes this refers to the 20-mt trip limit and not the 2-mt trip limit— incentivizes discards. Further, misreporting could undermine accurate estimates of fishing mortality. Vessel operators should be required to record discards to ensure that the United States does not exceed the catch limits. Without observer coverage, NMFS should estimate the portion of catch discarded dead and include it in the estimate of total U.S. catch of Pacific bluefin tuna. The fishery should be closely monitored to ensure the catch limit is not exceeded.

Response: NMFS acknowledges that monitoring and enforcement of trip limits can be a problem for fisheries management, but has determined that an initial trip limit of 25 mt can be adequately monitored and enforced. Vessel operators are required to fill out logbooks, which includes all catch, whether kept or returned to sea, and to submit the logbooks to NMFS within 30 days of each landing or transshipment (see 50 CFR 660.708). All catch, including discards, will count toward the catch limits. NMFS intends to work closely with California Department of Fish and Wildlife (CDFW) and vessel operators, as it did in 2014, to monitor catches and landings to ensure limits are not exceeded. In 2014, NMFS received near real-time landings data from CDFW and vessel operators.

Comment 4: The proposed rule fails to address an objective in ResolutionC-14-06 that only 50 percent of the total catch be comprised of fish less than 30 kilograms (kg). Furthermore, the United States should limit catches even further to 250 mt per year, a level comparable to the 30 percent reduction considered for the recreational fishery.

Response: Regarding size limits,C-14-06 establishes a goal, but not a requirement. NMFS is promulgating this rule in accordance with the requirements of Resolution C-14-06 with additional provisions (e.g., trip limits) to be able to effectively meet the requirements of the resolution (i.e., not exceeding catch limits). ResolutionC-14-06 and this rule represent commercial catch reductions consistent with recommendations of the IATTC scientific staff (i.e., 20 to 45 percent) to aid in the rebuilding of the stock. More specifically, the catch limits in Resolution C-14-06 (i.e., an average of 300 mt per year) represent a 40 percent reduction from U.S. commercial catch limits in previous resolutions (i.e., 500 mt per year) on the conservation and management of Pacific bluefin tuna. Lastly, requiring that fishermen target and land larger fish (i.e., greater than 30 kg) could lead to discards, as well as additional harvest costs (e.g., search time for schools of larger fish).

General Comments not Within the Scope of the Rule: NMFS received several comments outside the scope of the proposed rule regarding: Future negotiations tactics by the United States on Pacific bluefin tuna conservation and management measures in the Convention Area, recommendations for additional science needs, improvement of catch monitoring by requiring daily communication between NMFS and vessel owners, requiring full retention of Pacific bluefin tuna, objections to the current catch limit as agreed to in Resolution C-14-06, and the effects of the current fishery conditions for other species targeted by the coastal purse seiners (i.e., sardines and market squid).

Response to General Comments not Within the Scope of the Rule: NMFS will take these comments and concerns into consideration when developing future positions at upcoming IATTC meetings, as well as developing scientific partnerships to address gaps in knowledge. Regarding daily communication between vessel operators and NMFS, there would be value in increased communication to more closely monitor the fishery. NMFS is considering developing a rule to require vessel operators to notify NMFS upon landing Pacific bluefin tuna. Nonetheless, NMFS will endeavor to promote better cooperation and communication with vessel operators to receive catch data at the time of landing. NMFS views the requirement to log all catches and a requirement to land all catch (i.e., full retention) as having the same goal: To account for all Pacific bluefin tuna caught by U.S. vessels. Vessel operators are currently required to log all catch, which would be counted toward the catch limit. As described in responses above, NMFS is implementing a higher than originally proposed trip limit to address concerns about discards. Regarding other target fisheries (e.g., sardines, market squid), at the time Resolution C-14-06 was adopted (October 2014), the U.S. delegation was unaware of the drastic reductions in the fishery for Pacific sardine that are being imposed because of the reduced biomass estimates. However, the United States would have nonetheless endeavored to make cuts consistent with IATTC scientific staff recommendations to aid in rebuilding of Pacific bluefin tuna.

NMFS received a number of comments expressing concern about the potential for discards resulting from the proposal to set the initial trip limit each year at 20 mt. NMFS has concluded that a higher trip limit of 25 mt is warranted to reduce the potential for discards while still meeting the management objectives (e.g., inseason management). NMFS found that the average landing by a vessel from a trip targeting PBF during 2005 to 2014 was 30.6 mt (ranging from 0.04 mt to 75.8 mt; median is 29.2); 36 percent of these trips included landings up to 25 mt, whereas only 23 percent of the trips included landings up to 20 mt. NMFS concludes that increasing the trip limit to 25 mt will tend to reduce discards while still sufficiently reducing the rate of harvest to meet the objective of providing access to, without exceeding, the full catch limit. Consequently, NMFS is implementing trip limits as recommended by the Council, but increasing the level of the initial trip limit from 20 mt to 25 mt.

The NMFS Assistant Administrator has determined that this rule is consistent with the Tuna Conventions Act and other applicable laws.

This rule was determined to be not significant for purposes of Executive Order 12866.

Although there are no new collection-of-information requirements associated with this action that are subject to the Paperwork Reduction Act, existing collection-of-information requirements associated with the Fishery Management Plan for U.S. West Coast Fisheries for Highly Migratory Species (HMS FMP) still apply. These requirements have been approved by the Office of Management and Budget under Control Number 0648-0204. Notwithstanding any other provision of the 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.

The Chief Counsel for Regulation of the Department of Commerce certified to the Chief Counsel for Advocacy of the Small Business Administration during the proposed rule stage that this action would not have a significant economic impact on a substantial number of small entities. The factual basis for the certification was published in the proposed rule and is not repeated here. This final rule contains a change in the trip limit that was published in the proposed action. As a result of public comments, the trip limit was increased from 20 mt to 25 mt. This change is anticipated to result in a minor economic benefit for impacted business entities. No comments were received regarding the certification. Therefore, the certification published with the proposed rule, that this rule is not expected to have a significant economic impact on a substantial number of small entities, is still valid. As a result, a regulatory flexibility analysis was not required and none was prepared.

The Assistant Administrator for Fisheries has determined that the need to conserve Pacific bluefin tuna and comply with our international obligations constitutes good cause, under 5 U.S.C. 553(d)(3), to waive the requirement for a 30-day delay in effectiveness. Pacific bluefin tuna have migrated in significant numbers into waters off of southern California and commercial purse seine vessels have begun fishing for Pacific bluefin tuna off of the U.S West Coast. If the trip limits implemented by this rule were subject to the 30-day delay in effectiveness, and taking into account that a single trip could catch up to 75 mt, there is potential for a derby-style fishery that would result in exceeding the 425-mt catch limit for 2015 before this rule goes into effect. Although justification exists to waive the 30-day delay in effectiveness, NMFS is implementing a 7-day delay in effectiveness to provide sufficient time for any vessels currently operating to comply with the new regulations; vessels that target Pacific bluefin tuna typically complete their fishing trips within one to two days. As soon as the rule is filed, notice will be sent to inform members of the tuna-fishing industry.

Therefore, to conserve Pacific bluefin tuna, which are overfished, and to remain in compliance with IATTC Resolution C-14-06, NMFS has determined that implementing these measures 7 days after filing with the Office of Federal Register is in the public's interest.

For the reasons set out in the preamble, 50 CFR part 300 is amended as follows: