Poison Prevention Packaging Requirements; Proposed Exemption of Baloxavir Marboxil Tablets in Packages Containing Not More Than 80 mg of the Drug, 51640-51643 [2021-19953]

Download as PDF 51640 Federal Register / Vol. 86, No. 177 / Thursday, September 16, 2021 / Proposed Rules interposed between the upholstery cover fabric and any interior filling material. The 2008 NPR on upholstered furniture flammability focused on performance standards which did not prescribe requirements for filling materials or require manufacturers or importers to use FR chemical additives to achieve compliance. B. The COVID–19 Act On December 27, 2020, the ‘‘COVID– 19 Regulatory Relief and Work From Home Safety Act,’’ became law. Public Law 116–260. Section 2101(c) of the COVID–19 Act mandated that, 180 days after the date of enactment of the COVID–19 Act, the standard for upholstered furniture set forth by the Bureau of Electronic and Appliance Repair, Home Furnishings and Thermal Insulation of the Department of Consumer Affairs of the State of California in Technical Bulletin (TB) 117–2013 (TB 117–2013), entitled, ‘‘Requirements, Test Procedure and Apparatus for Testing the Smolder Resistance of Materials Used in Upholstered Furniture,’’ published June 2013, ‘‘shall be considered to be a flammability standard promulgated by the Consumer Product Safety Commission under section 4 of the Flammable Fabrics Act (15 U.S.C. 1193).’’ Thus, under the COVID–19 Act, the California standard, TB 117–2013, is a federal flammability standard promulgated under section 4 of the FFA. TB 117–2013 sets forth the requirements, test procedure, and apparatus for testing the smolder resistance of materials used in upholstered furniture from hazards associated with smoldering ignition. The standard provides methods for smolder resistance of cover fabrics, barrier materials, resilient filling materials, and decking materials for use in upholstered furniture. The COVID–19 Act and the FFA (15 U.S.C. 1191 et seq.) does not preempt or otherwise affect any State or local law, regulation, code, standard, or requirement that concerns health risks associated with upholstered furniture; and is not designed to protect against the risk of occurrence of fire, or to slow or prevent the spread of fire, with respect to upholstered furniture. In addition, sections 1374 through 1374.3 of title 4, California Code of Regulations (except for subsections (b) and (c) of section 1374 of that title), as in effect on the date of enactment of the COVID–19 Act are not preempted. Finally, the California standard may not be preempted. On April 9, 2021, the Commission published a direct final rule that VerDate Sep<11>2014 16:17 Sep 15, 2021 Jkt 253001 codified the relevant statutory text of section 2101 of the COVID–19 Act under 16 CFR part 1640. 86 FR 18440. This part establishes the regulatory text of the California standard, TB 117–2013, as the mandatory federal flammability standard for upholstered furniture under section 4 of the FFA, and sets forth the statutory requirements. Because the Commission did not consider any comment received on the direct final rule to be a significant adverse comment, the rule went into effect on June 25, 2021, and applies to all upholstered furniture manufactured, imported, or reupholstered on or after that date. However, the compliance date for the new labeling requirement will go into effect on June 25, 2022. C. Termination of the Upholstered Furniture Rulemaking The direction in the COVID–19 Act requiring that the California standard, TB 117–2013, be a federally mandated flammability standard promulgated by the CPSC under section 4 of the FFA, supersedes the upholstered furniture rulemaking proceeding initiated by the Commission under the FFA in 1994. Accordingly, on March 30, 2021, the Commission voted to terminate the rulemaking associated with upholstered furniture and directed that notification of the termination of rulemaking be issued in the Federal Register.1 Through this document, the Commission has terminated the upholstered furniture rulemaking proceeding that began with the issuance of the ANPR in 1994, and all subsequent rulemakings in that proceeding including the 2008 NPR. Alberta E. Mills, Secretary, Consumer Product Safety Commission. [FR Doc. 2021–19939 Filed 9–15–21; 8:45 am] BILLING CODE 6355–01–P CONSUMER PRODUCT SAFETY COMMISSION 16 CFR Part 1700 [Docket No. CPSC–2021–0027] Poison Prevention Packaging Requirements; Proposed Exemption of Baloxavir Marboxil Tablets in Packages Containing Not More Than 80 mg of the Drug Consumer Product Safety Commission. ACTION: Notice of proposed rulemaking. AGENCY: 1 See RCA-Upholstered-Furniture-FlammabilityStandard-TB117-2013-DFR-and-NPR.pdf (cpsc.gov). PO 00000 Frm 00016 Fmt 4702 Sfmt 4702 The Consumer Product Safety Commission (Commission or CPSC) is proposing to amend the child-resistant packaging requirements to exempt baloxavir marboxil tablets in packages containing not more than 80 mg of the drug, currently marketed as XOFLUZA,TM from the special packaging requirements. XOFLUZA is used to treat the flu, and is taken in one dose within 48 hours of experiencing flu symptoms. The proposed rule would exempt this prescription drug product on the basis that child-resistant packaging is not needed to protect young children from serious injury or illness because the product is not acutely toxic and lacks adverse human experience associated with ingestion. DATES: Comments should be submitted no later than November 30, 2021. ADDRESSES: You may submit comments, identified by Docket No. CPSC–2021– 0027, by any of the following methods: Electronic Submissions: Submit electronic comments to the Federal eRulemaking Portal at: https:// www.regulations.gov. Follow the instructions for submitting comments. The CPSC does not accept comments submitted by electronic mail (email), except through https:// www.regulations.gov. The CPSC encourages you to submit electronic comments by using the Federal eRulemaking Portal, as described above. Mail/Hand Delivery/Courier Written Submissions: Submit comments by mail/hand delivery/courier to: Division of the Secretariat, Consumer Product Safety Commission, 4330 East West Highway, Bethesda, MD 20814; telephone (301) 504–7479. Instructions: All submissions received must include the agency name and docket number for this notice. All comments received may be posted without change, including any personal identifiers, contact information, or other personal information provided, to: https://www.regulations.gov. Do not submit electronically confidential business information, trade secret information, or other sensitive or protected information that you do not want to be available to the public. If you wish to submit such information please submit it according to the instructions for written submissions. Docket: For access to the docket to read background documents or comments received, go to: https:// www.regulations.gov, and insert the docket number, CPSC–2021–0027, into the ‘‘Search’’ box, and follow the prompts. FOR FURTHER INFORMATION CONTACT: Cheryl A. Scorpio, Ph.D., Division of SUMMARY: E:\FR\FM\16SEP1.SGM 16SEP1 Federal Register / Vol. 86, No. 177 / Thursday, September 16, 2021 / Proposed Rules Pharmacology and Physiology Assessment, Directorate for Health Sciences, Consumer Product Safety Commission, 5 Research Place, Rockville, MD 20850; telephone (301) 987–2572; cscorpio@cpsc.gov. SUPPLEMENTARY INFORMATION: A. Background 1. The Poison Prevention Packaging Act of 1970 and Implementing Regulations The Poison Prevention Packaging Act of 1970 (PPPA), 15 U.S.C. 1471–1476, gives the Commission authority to establish standards for the ‘‘special packaging’’ of household substances, such as drugs, when child-resistant (CR) packaging is necessary to protect children from serious personal injury or illness due to the substance, and the special packaging is technically feasible, practicable, and appropriate for such substance. 15 U.S.C. 1472(a). Special packaging requirements under the PPPA have been codified at 16 CFR parts 1700 and 1702. Specifically, CPSC regulations require special packaging for oral prescription drugs. 16 CFR 1700.14(a)(10). CPSC regulations allow companies to petition the Commission for an exemption from CR requirements. 16 CFR part 1702. Two ‘‘reasonable grounds’’ 1 for granting an exemption from the special packaging requirements are: (1) That the degree or nature of the hazard to children in the availability of the substance, by reason of its packaging, is such that special packaging is not required to protect children from serious personal injury or serious illness resulting from handling, using or ingesting the substance; or (2) special packing is not technically feasible, practicable, or appropriate for the subject substance. 16 CFR 1702.17(a) and (b). If the Commission determines that reasonable grounds for an exemption are presented by a petition, CPSC regulations require publication in the Federal Register of a proposed amendment to the listing of substances that require special packaging, stating that the substance at issue is exempt. 16 CFR 1702.17. 2. The Product for Which an Exemption Is Sought On March 30, 2020, Genentech, Inc. (Genentech), petitioned the Commission to exempt two specified sized tablets of baloxavir marboxil, which it markets as XOFLUZA from the special packaging 1A third reasonable ground for an exemption is that special packaging is incompatible with the particular substance. 16 CFR 1702.17(c). The petitioner has not requested an exemption on this basis so it is not relevant here. VerDate Sep<11>2014 16:17 Sep 15, 2021 Jkt 253001 requirements for oral prescription drugs. XOFLUZA was approved by the U.S. Food and Drug Administration (FDA) in October 2018, with a two-tablet dose for the acute uncomplicated flu in patients older than 12 years old showing symptoms for less than 48 hours. Single tablet doses have recently been approved by the FDA in March 2021. XOFLUZA has been marketed in tablet form and is currently dispensed in CR packaging. The petitioner asserted that an exemption from special packaging is justified because of the lack of toxicity and lack of adverse human experience with the drug. The petitioner also claimed that special packaging is not technically feasible, practicable, or appropriate for XOFLUZA. Staff’s briefing memorandum provides a detailed assessment of the petitioner’s claims regarding a request for an exemption from the special packing requirements for XOFLUZA. https:// cpsc-d8-mediaprod.s3.amazonaws.com/s3fs-public/ Petition-to-Exempt-Baloxavir-MarboxilXOFLUZA-in-40-mg-and-80-mg-TabletDoses-from-Special-PackagingRequirements-of-the-PPPA-Cleared.pdf? VersionId=sLAhJ4THOBCtVM jgA4kxiFmI2.3LzqIj. B. Toxicity and Injury Data for XOFLUZA Toxicity CPSC staff reviewed the toxicity of XOFLUZA. XOFLUZA has been studied in pediatric patients (Hirotsu, 2019; Heo, 2018; NCT03653364, CAPSTONE 2; Hayden, 2018; Dziewiatkowski et al., 2019). Overall, clinically relevant doses of XOFLUZA (40 or 80 mg total dose) in humans are well tolerated (Dziewiatkowski et al., 2019; Taieb et al., 2019; Ng, 2019; Hayden, 2018). The analysis of total adverse events (AE) included 10 studies with six treatments and 5628 patients. AE did not differ significantly between placebo and XOFLUZA. For drug-related vomiting, 3297 patients from five studies were included. XOFLUZA did not differ from placebo in these studies. (Taieb et al., 2019). The percentage of patients experiencing any adverse event 2 of 610 patients (12 to 64 years old) in the CAPSTONE 1 clinical trial was 1.0% grade 3 or grade 4, which can be categorized as not serious. Five deaths have been reported by the AER System; 3 however, these deaths have 2 The adverse events are: Diarrhea, bronchitis, nasopharyngitis, nausea, sinusitis, increase in the level of AST, headache, vomiting, dizziness, leukopenia and constipation. 3 The Adverse Event Reporting System (AERS) is a computerized information database designed to PO 00000 Frm 00017 Fmt 4702 Sfmt 4702 51641 been determined to not be related to XOFLUZA. The most common AE of the correct dose of XOFLUZA was diarrhea (Heo, 2018; Shionogi prescribing info). The XOFLUZA Product Information, 2021 reported that diarrhea (3%), bronchitis (3%), nausea (2%), headache (1%) were the most significant adverse events found. Treatment of an overdose of XOFLUZA should consist of general supportive measures, including monitoring of vital signs and observations of the clinical status of the patient. There is no specific antidote for overdose with XOFLUZA and it is unlikely to be significantly removed by dialysis because it is highly protein bound (Prescribing Information for XOFLUZA, 2021; Poisindex, 2021). Overall, treatment with XOFLUZA is well tolerated. If accidentally ingested, the greatest potential for injury is diarrhea, nausea, and headache. For these reasons, CPSC staff determined that XOFLUZA will not cause serious injury or death upon acute exposure by a child under 5 years old. Injury Data CPSC staff searched the Consumer Product Safety Risk Management System (CPSRMS), the National Electronic Injury Surveillance System (NEISS) databases, and reviewed reports from FDA related to adverse events associated with XOFLUZA. CPSC staff found no incidents related to XOFLUZA in CPSRMS or NEISS from January 2015 through December 2020. CPSC staff also reviewed 12 reports received from FDA related to adverse events associated with XOFLUZA. Of the 12 reports, five involved XOFLUZA use only. Of these five incidents, two reported adverse effects. One patient experienced hallucination, fever, and sore throat, and the other patient suffered cardiac failure. Both were unrelated to XOFLUZA. Six incidents involved use of multiple drugs and were considered out of scope, and one was a duplicate. C. Action on the Petition After considering the information provided by the petitioner and other available toxicity and human experience data, the Commission concluded preliminarily that the ‘‘lack of toxicity and lack of adverse human experience for the substance’’ presented by the availability of 40 mg and 80 mg tablets support the FDA’s post-marketing safety surveillance program for all approved drug and therapeutic biologic products. The FDA uses AERS to monitor for new adverse events and medication errors that might occur with these marketed products. E:\FR\FM\16SEP1.SGM 16SEP1 51642 Federal Register / Vol. 86, No. 177 / Thursday, September 16, 2021 / Proposed Rules of baloxavir marboxil (currently marketed as XOFLUZA) is such that special packaging is not required to protect children from serious injury or serious illness from handling, using, or ingesting XOFLUZA. 16 CFR 1702.17(a). Additionally, the Commission found that the petitioner’s request for an exemption from special packaging, on the basis that it is not technically feasible, practicable, or appropriate for XOFLUZA, was not warranted based upon the information provided by the petitioner. Therefore, the Commission determined that reasonable grounds for an exemption were presented based on toxicity and voted to grant the petition and begin a rulemaking proceeding to exempt baloxavir marboxil tablets in packages containing not more than 80 mg of the drug from the special packaging requirements for oral prescription drugs. Once the Commission determines that reasonable grounds for an exemption are presented by the petition, CPSC regulations require publication in the Federal Register of a proposed amendment to the listing of substances that require special packaging, stating that the substance at issue is exempt. 16 CFR 1702.17. This document proposes to amend the listing of substances in 16 CFR part 1700 that require special packing to state that baloxavir marboxil tablets in packages containing not more than 80 mg of the drug do not require special packing. D. Description of the Proposed Rule The proposed rule would amend 16 CFR part 1700 to include a new exemption from the special packaging requirements for baloxavir marboxil tablets in packages containing not more than 80 mg of the drug in proposed § 1700.14(a)(10)(xxiv). The proposed exemption is intended to cover baloxavir marboxil tablets for any dosage from 80 mg or below. The proposed rule would make no other changes to part 1700. E. Regulatory Flexibility Act Under the Regulatory Flexibility Act (RFA; 5 U.S.C. 601 et seq.), an agency that engages in rulemaking generally must prepare initial and final regulatory flexibility analyses describing the impact of the rule on small businesses and other small entities. Section 605 of the Act provides that an agency is not required to prepare a regulatory flexibility analysis if the head of an agency certifies that the rule will not have a significant economic impact on a substantial number of small entities. CPSC staff prepared a preliminary assessment of the impact of the VerDate Sep<11>2014 16:17 Sep 15, 2021 Jkt 253001 proposed rule to exempt baloxavir marboxil in 40 mg and 80 mg tablet form, currently marketed as XOFLUZA, from special packaging requirements. Genentech, Inc., is a subsidiary of, and owned in its entirety by the multinational corporation, Roche Group, the company that markets XOFLUZA. Roche Group employs 97,735 workers worldwide, of which 26,176 are located in North America. As of February 2020, Genentech employed 13,638 people. Roche Group’s operating businesses are organized into two divisions: Pharmaceuticals and Diagnostics. Genentech, as the former third segment, has been integrated into Roche Pharmaceuticals. Sales in the Pharmaceuticals Division were $48.1 billion in 2019. There are two main economic reasons for why granting the petition would not result in the exemption having a significant economic impact on a substantial number of small entities. First, the exemption for this drug is not likely to impact a large number of firms, therefore it is unlikely that granting the petition would impact a substantial number of small entities. Second, CR packaging for XOFLUZA tablets is unlikely to be a significant amount of any firm’s business, therefore granting the petition would not have a significant economic impact on any small entity. However, if the petitioner relocates packaging to another country, it could potentially result in some minor negative impacts for small domestic firms. Based on this assessment, we preliminarily conclude that the proposed amendment exempting baloxavir marboxil tablets in packages containing not more than 80 mg of the drug would not have a significant impact on a substantial number of small businesses or other small entities. We seek public comment on any small business impacts that might result from the exemption in the proposed rule. F. Effective Date The Administrative Procedure Act (APA) generally requires that a substantive rule must be published not less than 30 days before its effective date. 5 U.S.C. 553(d)(1). The NPR proposes an effective date of 30 days after publication of the final rule in the Federal Register, because the proposed rule would provide an exemption from the requirement to use special packaging for baloxavir marboxil tablets in packages containing not more than 80 mg of the drug. G. Environmental Considerations The Commission’s regulations provide a categorical exclusion for the PO 00000 Frm 00018 Fmt 4702 Sfmt 4702 Commission’s rules from any requirement to prepare an environmental assessment or an environmental impact statement where they ‘‘have little or no potential for affecting the human environment.’’ 16 CFR 1021.5(c)(3). Rules exempting products from poison prevention packaging rules fall within the categorical exclusion, so no environmental assessment or environmental impact statement is required. H. Preemption The PPPA provides that, generally, when a special packaging standard issued under the PPPA is in effect, ‘‘no State or political subdivision thereof shall have any authority either to establish or continue in effect, with respect to such household substance, any standard for special packaging (and any exemption therefrom and requirement related thereto) which is not identical to the [PPPA] standard.’’ 15 U.S.C. 1476(a). A state or local standard may be excepted from this preemptive effect if: (1) The state or local standard provides a higher degree of protection from the risk of injury or illness than the PPPA standard; and (2) the state or political subdivision applies to the Commission for an exemption from the PPPA’s preemption clause and the Commission grants the exemption through a process specified at 16 CFR part 1061. 15 U.S.C. 1476(c)(1). In addition, the federal government, or a state or local government, may establish and continue in effect a nonidentical special packaging requirement that provides a higher degree of protection than the PPPA requirement for a household substance for the federal, state, or local government’s own use. 15 U.S.C. 1476(b). Thus, with the exceptions noted above, the proposed rule exempting baloxavir marboxil tablets in packages containing not more than 80 mg of the drug from special packaging requirements, if finalized, would preempt nonidentical state or local special packaging standards for the substance. List of Subjects in 16 CFR Part 1700 Consumer protection, Drugs, Infants and children, Packaging and containers, Poison prevention, Toxic substances. For the reasons given above, the Commission proposes to amend 16 CFR part 1700 as follows: PART 1700—[AMENDED] 1. The authority citation for part 1700 continues to read as follows: ■ E:\FR\FM\16SEP1.SGM 16SEP1 Federal Register / Vol. 86, No. 177 / Thursday, September 16, 2021 / Proposed Rules Authority: 15 U.S.C. 1471—76. Secs. 1700.1 and 1700.14 also issued under 15 U.S.C. 2079(a). 2. Section 1700.14 is amended by adding paragraph (a)(10)(xxiv) to read as follows: ■ § 1700.14 Substances requiring special packaging. (a) * * * (10) * * * (xxiv) Baloxavir marboxil tablets in packages containing not more than 80 mg of the drug. * * * * * Alberta E. Mills, Secretary, U.S. Consumer Product Safety Commission. [FR Doc. 2021–19953 Filed 9–15–21; 8:45 am] II. Background BILLING CODE 6355–01–P Executive Order (E.O.) 14012 describes a policy of the Administration to restore faith in our legal immigration system and to strengthen integration and inclusion efforts for new Americans. As a first step to advance this policy, section 3 of the E.O. tasked the Secretary of State, the Attorney General, and the Secretary of Homeland Security with identifying: DEPARTMENT OF STATE 22 CFR Parts 40, 41, and 42 [Public Notice: 11459] RIN 1400–AF30 Visas: Immigrant Visas Department of State. Request for public input. AGENCY: ACTION: The Department of State (‘‘Department’’) seeks public comments identifying barriers that impede access to, and fair, efficient adjudication of, immigration benefits, and recommendations on how to remove those barriers, and identifying any Department actions that fail to promote access to the legal immigration system. DATES: Written comments must be received on or before October 18, 2021. ADDRESSES: You may submit comments, identified by RIN 1400–AF30, by either of the following methods: • Internet (preferred): At www.regulations.gov, you can search for the document using Docket Number DOS–2021–0017 or using the notice RIN 1400–AF30. • Email: Claire Kelly, Office of Visa Services, Bureau of Consular Affairs, U.S. Department of State, VisaRegs@ state.gov. Please include the RIN or Docket Number in the Subject Line. FOR FURTHER INFORMATION CONTACT: Claire Kelly, Office of Visa Services, Bureau of Consular Affairs, Department of State, 600 19th St. NW, Washington, DC 20006, (202) 485–7586. SUPPLEMENTARY INFORMATION: SUMMARY: I. Public Participation All interested parties are invited to respond to this Request for Public Input VerDate Sep<11>2014 16:17 Sep 15, 2021 by submitting written views and comments on all aspects of the Department of State’s implementation and execution of its authorities relating to the immigrant visa function, including existing regulations, orders, guidance documents, policies, and any other similar agency actions. Comments must be submitted in English or commenters must submit an English translation. Comments that will provide the most assistance to the Department in considering recommendations will reference a specific existing regulation, order, guidance, policy, or any other similar agency action, explain the reason for any recommended change, and include information that supports the recommended change. Jkt 253001 • Barriers that impede access to immigration benefits and fair, efficient adjudications of these benefits and make recommendations on how to remove these barriers, as appropriate and consistent with applicable law; and • any agency actions that fail to promote access to the legal immigration system . . . and recommend steps, as appropriate and consistent with applicable law, to revise or rescind those agency actions.1 The Department of State’s role in facilitating access to the U.S. immigration system includes the issuance of immigrant visas to eligible individuals outside of the United States. The Department welcomes comments on: (1) Any existing barriers that impede access to, and fair, efficient adjudication of, immigrant visas, and (2) recommendations on actions the Department could take to improve access to adjudication of immigrant visas; however the Department is not soliciting comments on administrative processing or communication surrounding administrative processing as the Department at this time is unable to alter or improve communication surrounding administrative processing. Additionally, as the Department is already undertaking efforts to address the Immigrant Visa (including Diversity Visa) backlog caused by Presidential 1 E.O. PO 00000 14012, 86 FR 8277 (February 5, 2021). Frm 00019 Fmt 4702 Sfmt 4702 51643 Proclamation 10014 2 and the global pandemic’s effect on visa operations, comments on this area are less useful than comments on perceived systemic barriers pre-pandemic. This Request for Public Input is not soliciting comments on areas outside the Department’s responsibility, including the functions, roles and responsibilities vested in the Department of Homeland Security, the Department of Labor, or Department of Justice, though the Department is interested in learning whether there are areas of overlap between any of the policies of these agencies and the Department of State that create such barriers, inefficiencies, or that impede access to, fair and efficient adjudication of immigrant visas. The Department is not obligated to respond in any way to comments received in response to this Request for Public Input; however, the Department intends to consider all comments in developing the report to the President required under section 3(c) of E.O. 14012, describing its progress towards implementing a plan to advance the policy set forth in section 1 of E.O. 14012. This Request for Public Input does not create any right for members of the public who submit comments or any obligations for the Department of State. III. Request for Input A. Maximizing the Value of Public Feedback This notice contains a list of questions, the answers to which may assist the Department in identifying aspects of immigrant visa-related processes that may benefit from the Department’s review with the goals of eliminating any undue burdens on the public, saving costs for both the public and the Department, increasing navigability, saving time, reducing perceived confusion, promoting simplification, improving efficiency, and/or removing barriers that unnecessarily impede access to immigrant visas. The Department encourages public comment on these questions and seeks any other information or data commenters believe are relevant to this notice. The type of feedback that is most useful to the Department will identify specific regulations and/or processes and include actionable information and/or data and/or provide viable alternatives, that meet statutory obligations and regulatory objectives and requirements. Public feedback that simply states that a stakeholder feels strongly that the 2 Proclamation No. 10014, 85 FR 23441 (April 27, 2020). E:\FR\FM\16SEP1.SGM 16SEP1

Agencies

[Federal Register Volume 86, Number 177 (Thursday, September 16, 2021)]
[Proposed Rules]
[Pages 51640-51643]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-19953]


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CONSUMER PRODUCT SAFETY COMMISSION

16 CFR Part 1700

[Docket No. CPSC-2021-0027]


Poison Prevention Packaging Requirements; Proposed Exemption of 
Baloxavir Marboxil Tablets in Packages Containing Not More Than 80 mg 
of the Drug

AGENCY: Consumer Product Safety Commission.

ACTION: Notice of proposed rulemaking.

-----------------------------------------------------------------------

SUMMARY: The Consumer Product Safety Commission (Commission or CPSC) is 
proposing to amend the child-resistant packaging requirements to exempt 
baloxavir marboxil tablets in packages containing not more than 80 mg 
of the drug, currently marketed as XOFLUZA,TM from the 
special packaging requirements. XOFLUZA is used to treat the flu, and 
is taken in one dose within 48 hours of experiencing flu symptoms. The 
proposed rule would exempt this prescription drug product on the basis 
that child-resistant packaging is not needed to protect young children 
from serious injury or illness because the product is not acutely toxic 
and lacks adverse human experience associated with ingestion.

DATES: Comments should be submitted no later than November 30, 2021.

ADDRESSES: You may submit comments, identified by Docket No. CPSC-2021-
0027, by any of the following methods:
    Electronic Submissions: Submit electronic comments to the Federal 
eRulemaking Portal at: https://www.regulations.gov. Follow the 
instructions for submitting comments. The CPSC does not accept comments 
submitted by electronic mail (email), except through https://www.regulations.gov. The CPSC encourages you to submit electronic 
comments by using the Federal eRulemaking Portal, as described above.
    Mail/Hand Delivery/Courier Written Submissions: Submit comments by 
mail/hand delivery/courier to: Division of the Secretariat, Consumer 
Product Safety Commission, 4330 East West Highway, Bethesda, MD 20814; 
telephone (301) 504-7479.
    Instructions: All submissions received must include the agency name 
and docket number for this notice. All comments received may be posted 
without change, including any personal identifiers, contact 
information, or other personal information provided, to: https://www.regulations.gov. Do not submit electronically confidential business 
information, trade secret information, or other sensitive or protected 
information that you do not want to be available to the public. If you 
wish to submit such information please submit it according to the 
instructions for written submissions.
    Docket: For access to the docket to read background documents or 
comments received, go to: https://www.regulations.gov, and insert the 
docket number, CPSC-2021-0027, into the ``Search'' box, and follow the 
prompts.

FOR FURTHER INFORMATION CONTACT: Cheryl A. Scorpio, Ph.D., Division of

[[Page 51641]]

Pharmacology and Physiology Assessment, Directorate for Health 
Sciences, Consumer Product Safety Commission, 5 Research Place, 
Rockville, MD 20850; telephone (301) 987-2572; [email protected].

SUPPLEMENTARY INFORMATION:

A. Background

1. The Poison Prevention Packaging Act of 1970 and Implementing 
Regulations

    The Poison Prevention Packaging Act of 1970 (PPPA), 15 U.S.C. 1471-
1476, gives the Commission authority to establish standards for the 
``special packaging'' of household substances, such as drugs, when 
child-resistant (CR) packaging is necessary to protect children from 
serious personal injury or illness due to the substance, and the 
special packaging is technically feasible, practicable, and appropriate 
for such substance. 15 U.S.C. 1472(a). Special packaging requirements 
under the PPPA have been codified at 16 CFR parts 1700 and 1702. 
Specifically, CPSC regulations require special packaging for oral 
prescription drugs. 16 CFR 1700.14(a)(10). CPSC regulations allow 
companies to petition the Commission for an exemption from CR 
requirements. 16 CFR part 1702. Two ``reasonable grounds'' \1\ for 
granting an exemption from the special packaging requirements are: (1) 
That the degree or nature of the hazard to children in the availability 
of the substance, by reason of its packaging, is such that special 
packaging is not required to protect children from serious personal 
injury or serious illness resulting from handling, using or ingesting 
the substance; or (2) special packing is not technically feasible, 
practicable, or appropriate for the subject substance. 16 CFR 
1702.17(a) and (b).
---------------------------------------------------------------------------

    \1\ A third reasonable ground for an exemption is that special 
packaging is incompatible with the particular substance. 16 CFR 
1702.17(c). The petitioner has not requested an exemption on this 
basis so it is not relevant here.
---------------------------------------------------------------------------

    If the Commission determines that reasonable grounds for an 
exemption are presented by a petition, CPSC regulations require 
publication in the Federal Register of a proposed amendment to the 
listing of substances that require special packaging, stating that the 
substance at issue is exempt. 16 CFR 1702.17.

2. The Product for Which an Exemption Is Sought

    On March 30, 2020, Genentech, Inc. (Genentech), petitioned the 
Commission to exempt two specified sized tablets of baloxavir marboxil, 
which it markets as XOFLUZA from the special packaging requirements for 
oral prescription drugs. XOFLUZA was approved by the U.S. Food and Drug 
Administration (FDA) in October 2018, with a two-tablet dose for the 
acute uncomplicated flu in patients older than 12 years old showing 
symptoms for less than 48 hours. Single tablet doses have recently been 
approved by the FDA in March 2021. XOFLUZA has been marketed in tablet 
form and is currently dispensed in CR packaging. The petitioner 
asserted that an exemption from special packaging is justified because 
of the lack of toxicity and lack of adverse human experience with the 
drug. The petitioner also claimed that special packaging is not 
technically feasible, practicable, or appropriate for XOFLUZA. Staff's 
briefing memorandum provides a detailed assessment of the petitioner's 
claims regarding a request for an exemption from the special packing 
requirements for XOFLUZA. https://cpsc-d8-media-prod.s3.amazonaws.com/s3fs-public/Petition-to-Exempt-Baloxavir-Marboxil-XOFLUZA-in-40-mg-and-80-mg-Tablet-Doses-from-Special-Packaging-Requirements-of-the-PPPA-Cleared.pdf?VersionId=sLAhJ4THOBCtVMjgA4kxiFmI2.3LzqIj.

B. Toxicity and Injury Data for XOFLUZA

Toxicity

    CPSC staff reviewed the toxicity of XOFLUZA. XOFLUZA has been 
studied in pediatric patients (Hirotsu, 2019; Heo, 2018; NCT03653364, 
CAPSTONE 2; Hayden, 2018; Dziewiatkowski et al., 2019). Overall, 
clinically relevant doses of XOFLUZA (40 or 80 mg total dose) in humans 
are well tolerated (Dziewiatkowski et al., 2019; Taieb et al., 2019; 
Ng, 2019; Hayden, 2018).
    The analysis of total adverse events (AE) included 10 studies with 
six treatments and 5628 patients. AE did not differ significantly 
between placebo and XOFLUZA. For drug-related vomiting, 3297 patients 
from five studies were included. XOFLUZA did not differ from placebo in 
these studies. (Taieb et al., 2019). The percentage of patients 
experiencing any adverse event \2\ of 610 patients (12 to 64 years old) 
in the CAPSTONE 1 clinical trial was 1.0% grade 3 or grade 4, which can 
be categorized as not serious. Five deaths have been reported by the 
AER System; \3\ however, these deaths have been determined to not be 
related to XOFLUZA.
---------------------------------------------------------------------------

    \2\ The adverse events are: Diarrhea, bronchitis, 
nasopharyngitis, nausea, sinusitis, increase in the level of AST, 
headache, vomiting, dizziness, leukopenia and constipation.
    \3\ The Adverse Event Reporting System (AERS) is a computerized 
information database designed to support the FDA's post-marketing 
safety surveillance program for all approved drug and therapeutic 
biologic products. The FDA uses AERS to monitor for new adverse 
events and medication errors that might occur with these marketed 
products.
---------------------------------------------------------------------------

    The most common AE of the correct dose of XOFLUZA was diarrhea 
(Heo, 2018; Shionogi prescribing info). The XOFLUZA Product 
Information, 2021 reported that diarrhea (3%), bronchitis (3%), nausea 
(2%), headache (1%) were the most significant adverse events found.
    Treatment of an overdose of XOFLUZA should consist of general 
supportive measures, including monitoring of vital signs and 
observations of the clinical status of the patient. There is no 
specific antidote for overdose with XOFLUZA and it is unlikely to be 
significantly removed by dialysis because it is highly protein bound 
(Prescribing Information for XOFLUZA, 2021; Poisindex, 2021).
    Overall, treatment with XOFLUZA is well tolerated. If accidentally 
ingested, the greatest potential for injury is diarrhea, nausea, and 
headache. For these reasons, CPSC staff determined that XOFLUZA will 
not cause serious injury or death upon acute exposure by a child under 
5 years old.

Injury Data

    CPSC staff searched the Consumer Product Safety Risk Management 
System (CPSRMS), the National Electronic Injury Surveillance System 
(NEISS) databases, and reviewed reports from FDA related to adverse 
events associated with XOFLUZA. CPSC staff found no incidents related 
to XOFLUZA in CPSRMS or NEISS from January 2015 through December 2020. 
CPSC staff also reviewed 12 reports received from FDA related to 
adverse events associated with XOFLUZA. Of the 12 reports, five 
involved XOFLUZA use only. Of these five incidents, two reported 
adverse effects. One patient experienced hallucination, fever, and sore 
throat, and the other patient suffered cardiac failure. Both were 
unrelated to XOFLUZA. Six incidents involved use of multiple drugs and 
were considered out of scope, and one was a duplicate.

C. Action on the Petition

    After considering the information provided by the petitioner and 
other available toxicity and human experience data, the Commission 
concluded preliminarily that the ``lack of toxicity and lack of adverse 
human experience for the substance'' presented by the availability of 
40 mg and 80 mg tablets

[[Page 51642]]

of baloxavir marboxil (currently marketed as XOFLUZA) is such that 
special packaging is not required to protect children from serious 
injury or serious illness from handling, using, or ingesting XOFLUZA. 
16 CFR 1702.17(a). Additionally, the Commission found that the 
petitioner's request for an exemption from special packaging, on the 
basis that it is not technically feasible, practicable, or appropriate 
for XOFLUZA, was not warranted based upon the information provided by 
the petitioner. Therefore, the Commission determined that reasonable 
grounds for an exemption were presented based on toxicity and voted to 
grant the petition and begin a rulemaking proceeding to exempt 
baloxavir marboxil tablets in packages containing not more than 80 mg 
of the drug from the special packaging requirements for oral 
prescription drugs.
    Once the Commission determines that reasonable grounds for an 
exemption are presented by the petition, CPSC regulations require 
publication in the Federal Register of a proposed amendment to the 
listing of substances that require special packaging, stating that the 
substance at issue is exempt. 16 CFR 1702.17. This document proposes to 
amend the listing of substances in 16 CFR part 1700 that require 
special packing to state that baloxavir marboxil tablets in packages 
containing not more than 80 mg of the drug do not require special 
packing.

D. Description of the Proposed Rule

    The proposed rule would amend 16 CFR part 1700 to include a new 
exemption from the special packaging requirements for baloxavir 
marboxil tablets in packages containing not more than 80 mg of the drug 
in proposed Sec.  1700.14(a)(10)(xxiv). The proposed exemption is 
intended to cover baloxavir marboxil tablets for any dosage from 80 mg 
or below. The proposed rule would make no other changes to part 1700.

E. Regulatory Flexibility Act

    Under the Regulatory Flexibility Act (RFA; 5 U.S.C. 601 et seq.), 
an agency that engages in rulemaking generally must prepare initial and 
final regulatory flexibility analyses describing the impact of the rule 
on small businesses and other small entities. Section 605 of the Act 
provides that an agency is not required to prepare a regulatory 
flexibility analysis if the head of an agency certifies that the rule 
will not have a significant economic impact on a substantial number of 
small entities.
    CPSC staff prepared a preliminary assessment of the impact of the 
proposed rule to exempt baloxavir marboxil in 40 mg and 80 mg tablet 
form, currently marketed as XOFLUZA, from special packaging 
requirements. Genentech, Inc., is a subsidiary of, and owned in its 
entirety by the multinational corporation, Roche Group, the company 
that markets XOFLUZA. Roche Group employs 97,735 workers worldwide, of 
which 26,176 are located in North America. As of February 2020, 
Genentech employed 13,638 people. Roche Group's operating businesses 
are organized into two divisions: Pharmaceuticals and Diagnostics. 
Genentech, as the former third segment, has been integrated into Roche 
Pharmaceuticals. Sales in the Pharmaceuticals Division were $48.1 
billion in 2019.
    There are two main economic reasons for why granting the petition 
would not result in the exemption having a significant economic impact 
on a substantial number of small entities. First, the exemption for 
this drug is not likely to impact a large number of firms, therefore it 
is unlikely that granting the petition would impact a substantial 
number of small entities. Second, CR packaging for XOFLUZA tablets is 
unlikely to be a significant amount of any firm's business, therefore 
granting the petition would not have a significant economic impact on 
any small entity. However, if the petitioner relocates packaging to 
another country, it could potentially result in some minor negative 
impacts for small domestic firms. Based on this assessment, we 
preliminarily conclude that the proposed amendment exempting baloxavir 
marboxil tablets in packages containing not more than 80 mg of the drug 
would not have a significant impact on a substantial number of small 
businesses or other small entities. We seek public comment on any small 
business impacts that might result from the exemption in the proposed 
rule.

F. Effective Date

    The Administrative Procedure Act (APA) generally requires that a 
substantive rule must be published not less than 30 days before its 
effective date. 5 U.S.C. 553(d)(1). The NPR proposes an effective date 
of 30 days after publication of the final rule in the Federal Register, 
because the proposed rule would provide an exemption from the 
requirement to use special packaging for baloxavir marboxil tablets in 
packages containing not more than 80 mg of the drug.

G. Environmental Considerations

    The Commission's regulations provide a categorical exclusion for 
the Commission's rules from any requirement to prepare an environmental 
assessment or an environmental impact statement where they ``have 
little or no potential for affecting the human environment.'' 16 CFR 
1021.5(c)(3). Rules exempting products from poison prevention packaging 
rules fall within the categorical exclusion, so no environmental 
assessment or environmental impact statement is required.

H. Preemption

    The PPPA provides that, generally, when a special packaging 
standard issued under the PPPA is in effect, ``no State or political 
subdivision thereof shall have any authority either to establish or 
continue in effect, with respect to such household substance, any 
standard for special packaging (and any exemption therefrom and 
requirement related thereto) which is not identical to the [PPPA] 
standard.'' 15 U.S.C. 1476(a). A state or local standard may be 
excepted from this preemptive effect if: (1) The state or local 
standard provides a higher degree of protection from the risk of injury 
or illness than the PPPA standard; and (2) the state or political 
subdivision applies to the Commission for an exemption from the PPPA's 
preemption clause and the Commission grants the exemption through a 
process specified at 16 CFR part 1061. 15 U.S.C. 1476(c)(1). In 
addition, the federal government, or a state or local government, may 
establish and continue in effect a nonidentical special packaging 
requirement that provides a higher degree of protection than the PPPA 
requirement for a household substance for the federal, state, or local 
government's own use. 15 U.S.C. 1476(b).
    Thus, with the exceptions noted above, the proposed rule exempting 
baloxavir marboxil tablets in packages containing not more than 80 mg 
of the drug from special packaging requirements, if finalized, would 
preempt nonidentical state or local special packaging standards for the 
substance.

List of Subjects in 16 CFR Part 1700

    Consumer protection, Drugs, Infants and children, Packaging and 
containers, Poison prevention, Toxic substances.

    For the reasons given above, the Commission proposes to amend 16 
CFR part 1700 as follows:

PART 1700--[AMENDED]

0
1. The authority citation for part 1700 continues to read as follows:


[[Page 51643]]


    Authority:  15 U.S.C. 1471--76. Secs. 1700.1 and 1700.14 also 
issued under 15 U.S.C. 2079(a).

0
2. Section 1700.14 is amended by adding paragraph (a)(10)(xxiv) to read 
as follows:


Sec.  1700.14   Substances requiring special packaging.

    (a) * * *
    (10) * * *
    (xxiv) Baloxavir marboxil tablets in packages containing not more 
than 80 mg of the drug.
* * * * *

Alberta E. Mills,
Secretary, U.S. Consumer Product Safety Commission.
[FR Doc. 2021-19953 Filed 9-15-21; 8:45 am]
BILLING CODE 6355-01-P
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