21 USC 379 - Definitions

Collapse to view only § 379j-51. Definitions

§ 379j-51. Definitions
§ 379j-52. Authority to assess and use biosimilar biological product fees
§ 379j-53. Reauthorization; reporting requirements

§ 379j–51. DefinitionsFor purposes of this subpart:

(1) The term “adjustment factor” applicable to a fiscal year is the Consumer Price Index for urban consumers (Washington-Arlington-Alexandria, DC–VA–MD–WV; Not Seasonally Adjusted; All items) for September of the preceding fiscal year divided by such Index for September 2011.

(2) The term “affiliate” means a business entity that has a relationship with a second business entity if, directly or indirectly—

(A) one business entity controls, or has the power to control, the other business entity; or

(B) a third party controls, or has power to control, both of the business entities.

(3) The term “biosimilar biological product” means a specific strength of a biological product in final dosage form for which a biosimilar biological product application has been approved.

(4)

(A) Subject to subparagraph (B), the term “biosimilar biological product application” means an application for licensure of a biological product under section 262(k) of title 42.

(B) Such term does not include—

(i) a supplement to such an application;

(ii) an application filed under section 262(k) of title 42 that cites as the reference product a bovine blood product for topical application licensed before September 1, 1992, or a large volume parenteral drug product approved before such date;

(iii) an application filed under section 262(k) of title 42 with respect to—(I) whole blood or a blood component for transfusion;(II) an in vitro diagnostic biological product; or(III) a biological product for further manufacturing use only; or

(iv) an application for licensure under section 262(k) of title 42 that is submitted by a State or Federal Government entity for a product that is not distributed commercially.

(5) The term “biosimilar biological product development meeting” means any meeting, other than a biosimilar initial advisory meeting, regarding the span of a development program, including a proposed design for, or data from, a study intended to support a biosimilar biological product application.

(6) The term “biosimilar biological product development program” means the program under this subpart for expediting the process for the review of submissions in connection with biosimilar biological product development.

(7)

(A) The term “biosimilar biological product establishment” means a foreign or domestic place of business—

(i) that is at one general physical location consisting of one or more buildings, all of which are within 5 miles of each other; and

(ii) at which one or more biosimilar biological products are manufactured in final dosage form.

(B) For purposes of subparagraph (A)(ii), the term “manufactured” does not include packaging.

(8) The term “biosimilar initial advisory meeting”—

(A) means a meeting, if requested, that is limited to—

(i) a general discussion regarding whether licensure under section 262(k) of title 42 may be feasible for a particular product; and

(ii) if so, general advice on the expected span of the development program; and

(B) does not include any meeting that involves substantive review of summary data or full study reports.

(9) The term “costs of resources allocated for the process for the review of biosimilar biological product applications” means the expenses in connection with the process for the review of biosimilar biological product applications for—

(A) officers and employees of the Food and Drug Administration, contractors of the Food and Drug Administration, advisory committees, and costs related to such officers employees and committees and to contracts with such contractors;

(B) management of information, and the acquisition, maintenance, and repair of computer resources;

(C) leasing, maintenance, renovation, and repair of facilities and acquisition, maintenance, and repair of fixtures, furniture, scientific equipment, and other necessary materials and supplies; and

(D) collecting fees under section 379j–52 of this title and accounting for resources allocated for the review of submissions in connection with biosimilar biological product development, biosimilar biological product applications, and supplements.

(10) The term “final dosage form” means, with respect to a biosimilar biological product, a finished dosage form which is approved for administration to a patient without substantial further manufacturing (such as lyophilized products before reconstitution).

(11) The term “financial hold”—

(A) means an order issued by the Secretary to prohibit the sponsor of a clinical investigation from continuing the investigation if the Secretary determines that the investigation is intended to support a biosimilar biological product application and the sponsor has failed to pay any fee for the product required under subparagraph (A), (B), or (D) of section 379j–52(a)(1) of this title; and

(B) does not mean that any of the bases for a “clinical hold” under section 355(i)(3) of this title have been determined by the Secretary to exist concerning the investigation.

(12) The term “person” includes an affiliate of such person.

(13) The term “process for the review of biosimilar biological product applications” means the following activities of the Secretary with respect to the review of submissions in connection with biosimilar biological product development, biosimilar biological product applications, and supplements:

(A) The activities necessary for the review of submissions in connection with biosimilar biological product development, biosimilar biological product applications, and supplements.

(B) Actions related to submissions in connection with biosimilar biological product development, the issuance of action letters which approve biosimilar biological product applications or which set forth in detail the specific deficiencies in such applications, and where appropriate, the actions necessary to place such applications in condition for approval.

(C) The inspection of biosimilar biological product establishments and other facilities undertaken as part of the Secretary’s review of pending biosimilar biological product applications and supplements.

(D) Activities necessary for the release of lots of biosimilar biological products under section 262(k) of title 42.

(E) Monitoring of research conducted in connection with the review of biosimilar biological product applications.

(F) Postmarket safety activities with respect to biologics approved under biosimilar biological product applications or supplements, including the following activities:

(i) Collecting, developing, and reviewing safety information on biosimilar biological products, including adverse-event reports.

(ii) Developing and using improved adverse-event data-collection systems, including information technology systems.

(iii) Developing and using improved analytical tools to assess potential safety problems, including access to external data bases.

(iv) Implementing and enforcing section 355(o) of this title (relating to postapproval studies and clinical trials and labeling changes) and section 355(p) of this title (relating to risk evaluation and mitigation strategies).

(v) Carrying out section 355(k)(5) of this title (relating to adverse-event reports and postmarket safety activities).

(14) The term “supplement” means a request to the Secretary to approve a change in a biosimilar biological product application which has been approved, including a supplement requesting that the Secretary determine that the biosimilar biological product meets the standards for interchangeability described in section 262(k)(4) of title 42.

(June 25, 1938, ch. 675, § 744G, as added Pub. L. 112–144, title IV, § 402, July 9, 2012, 126 Stat. 1026; amended Pub. L. 115–52, title IV, § 402, Aug. 18, 2017, 131 Stat. 1028; Pub. L. 117–180, div. F, title IV, § 4002, Sept. 30, 2022, 136 Stat. 2160.)

§ 379j–52. Authority to assess and use biosimilar biological product fees

(a) Types of fees

Beginning in fiscal year 2023, the Secretary shall assess and collect fees in accordance with this section as follows:

(1) Biosimilar biological product development program fees

(A) Initial biosimilar biological product development fee

(i) In general

(ii) Meeting request

(iii) Clinical protocol for IND

(iv) Due date

The initial biosimilar biological product development fee shall be due by the earlier of the following:

(I) Not later than 7 days after the Secretary grants a request for a biosimilar biological product development meeting.(II) The date of submission of an investigational new drug application describing an investigation that the Secretary determines is intended to support a biosimilar biological product application.

(v) Transition rule

Each person that has submitted an investigational new drug application prior to July 9, 2012, shall pay the initial biosimilar biological product development fee by the earlier of the following:

(I) Not later than 60 days after July 9, 2012, if the Secretary determines that the investigational new drug application describes an investigation that is intended to support a biosimilar biological product application.(II) Not later than 7 days after the Secretary grants a request for a biosimilar biological product development meeting.

(B) Annual biosimilar biological product development fee

(i) In general

(ii) Due date

The annual biosimilar biological product development fee for each fiscal year will be due on the later of—

(I) the first business day on or after October 1 of each such year; or(II) the first business day after the enactment of an appropriations Act providing for the collection and obligation of fees for such year under this section.

(iii) Exception

The annual biosimilar biological product development fee for each fiscal year will be due on the date specified in clause (ii), unless the person has—

(I) submitted a marketing application for the biological product that was accepted for filing;(II) discontinued participation in the biosimilar biological product development program for the product under subparagraph (C); or(III) been administratively removed from the biosimilar biological product development program for the product under subparagraph (E)(v).

(iv) Refund

A person may discontinue participation in the biosimilar biological product development program for a product, effective October 1 of a fiscal year, by, not later than August 1 of the preceding fiscal year—

(i) if no investigational new drug application concerning the product has been submitted, submitting to the Secretary a written declaration that the person has no present intention of further developing the product as a biosimilar biological product; or

(ii) if an investigational new drug application concerning the product has been submitted, withdrawing the investigational new drug application in accordance with part 312 of title 21, Code of Federal Regulations (or any successor regulations).

(D) Reactivation fee

(i) In general

A person that has discontinued participation in the biosimilar biological product development program for a product under subparagraph (C), or who has been administratively removed from such program for a product under subparagraph (E)(v), shall, if the person seeks to resume participation in such program, pay all annual biosimilar biological product development fees previously assessed for such product and still owed and a fee (referred to in this section as “reactivation fee”) by the earlier of the following:

(I) Not later than 7 days after the Secretary grants a request by such person for a biosimilar biological product development meeting for the product (after the date on which such participation was discontinued or the date of administrative removal, as applicable).(II) Upon the date of submission (after the date on which such participation was discontinued or the date of administrative removal, as applicable) by such person of an investigational new drug application describing an investigation that the Secretary determines is intended to support a biosimilar biological product application for that product.

(ii) Application of annual fee

(E) Effect of failure to pay fees

(i) No biosimilar biological product development meetings

(ii) No receipt of investigational new drug applications

Except in extraordinary circumstances, the Secretary shall not consider an investigational new drug application to have been received under section 355(i)(2) of this title if—

(I) the Secretary determines that the investigation is intended to support a biosimilar biological product application; and(II) the sponsor has failed to pay an initial or annual biosimilar biological product development fee for the product as required under subparagraph (A) or (B), or a reactivation fee as required under subparagraph (D).

(iii) Financial hold

Notwithstanding section 355(i)(2) of this title, except in extraordinary circumstances, the Secretary shall prohibit the sponsor of a clinical investigation from continuing the investigation if—

(iv) No acceptance of biosimilar biological product applications or supplements

(v) Administrative removal from the biosimilar biological product development program

(F) Limits regarding fees

(i) Refunds

(ii) No waivers, exemptions, or reductions

(2) Biosimilar biological product application fee

(A) In general

Each person that submits, on or after October 1, 2017, a biosimilar biological product application shall be subject to the following fees:

(i) A fee established under subsection (c)(5) for a biosimilar biological product application for which clinical data (other than comparative bioavailability studies) with respect to safety or effectiveness are required for approval.

(ii) A fee established under subsection (c)(5) for a biosimilar biological product application for which clinical data (other than comparative bioavailability studies) with respect to safety or effectiveness are not required for approval. Such fee shall be equal to half of the amount of the fee described in clause (i).

(B) Rule of applicability; treatment of certain previously paid fees

Any person who pays a fee under subparagraph (A), (B), or (D) of paragraph (1) for a product before October 1, 2017, but submits a biosimilar biological product application for that product after such date, shall—

(i) be subject to any biosimilar biological product application fees that may be assessed at the time when such biosimilar biological product application is submitted; and

(ii) be entitled to no reduction of such application fees based on the amount of fees paid for that product before October 1, 2017, under such subparagraph (A), (B), or (D).

(D) Exception for previously filed application

(E) Refund of application fee if application refused for filing or withdrawn before filing

(F) Fees for applications previously refused for filing or withdrawn before filing

(3) Biosimilar biological product program fee

(A) In general

Each person who is named as the applicant in a biosimilar biological product application shall pay the annual biosimilar biological product program fee established for a fiscal year under subsection (c)(5) for each biosimilar biological product that—

(i) is identified in such a biosimilar biological product application approved as of October 1 of such fiscal year;

(ii) may be dispensed only under prescription pursuant to section 353(b) of this title; and

(iii) as of October 1 of such fiscal year, does not appear on a list, developed and maintained by the Secretary, of discontinued biosimilar biological products.

(B) Due date

The biosimilar biological product program fee for a fiscal year shall be due on the later of—

(i) the first business day on or after October 1 of each such year; or

(ii) the first business day after the enactment of an appropriations Act providing for the collection and obligation of fees for such year under this section.

(D) Limitation

(E) Movement to discontinued list

(i) Date of inclusion

If a written request to place a product on the list referenced in subparagraph (A) of discontinued biosimilar biological products is submitted to the Secretary on behalf of an applicant, and the request identifies the date the product is, or will be, withdrawn from sale, then for purposes of assessing the biosimilar biological product program fee, the Secretary shall consider such product to have been included on such list on the later of—

(I) the date such request was received; or(II) if the product will be withdrawn from sale on a future date, such future date when the product is withdrawn from sale.

(ii) Treatment as withdrawn from sale

(iii) Special rule for products removed from discontinued list

(b) Fee revenue amounts

(1) In general

For each of the fiscal years 2023 through 2027, fees under subsection (a) shall, except as provided in subsection (c), be established to generate a total revenue amount equal to the sum of—

(A) the annual base revenue for the fiscal year (as determined under paragraph (3));

(B) the dollar amount equal to the inflation adjustment for the fiscal year (as determined under subsection (c)(1));

(D) the dollar amount equal to the capacity planning adjustment for the fiscal year (as determined under subsection (c)(3));

(E) the dollar amount equal to the operating reserve adjustment for the fiscal year, if applicable (as determined under subsection (c)(4));

(F) for fiscal year 2023 an additional amount of $4,428,886; and

(G) for fiscal year 2024 an additional amount of $320,569.

(2) Allocation of revenue amount among fees

(A) Allocation

The Secretary shall determine the percentage of the total revenue amount for a fiscal year to be derived from, respectively—

(i) initial and annual biosimilar biological product development fees and reactivation fees under subsection (a)(1);

(ii) biosimilar biological product application fees under subsection (a)(2); and

(iii) biosimilar biological product program fees under subsection (a)(3).

(B) Biosimilar biological product development fees

(3) Annual base revenue

For purposes of paragraph (1), the dollar amount of the annual base revenue for a fiscal year shall be—

(A) for fiscal year 2023, $43,376,922; and

(B) for fiscal years 2024 through 2027, the dollar amount of the total revenue amount established under paragraph (1) for the previous fiscal year, excluding any adjustments to such revenue amount under subsection (c)(4).

(1) Inflation adjustment

(A) In general

For purposes of subsection (b)(1)(B), the dollar amount of the inflation adjustment to the annual base revenue for each fiscal year shall be equal to the product of—

(i) such annual base revenue for the fiscal year under subsection (b)(1)(A); and

(ii) the inflation adjustment percentage under subparagraph (B).

(B) Inflation adjustment percentage

The inflation adjustment percentage under this subparagraph for a fiscal year is equal to the sum of—

(i) the average annual percent change in the cost, per full-time equivalent position of the Food and Drug Administration, of all personnel compensation and benefits paid with respect to such positions for the first 3 years of the preceding 4 fiscal years, multiplied by the proportion of personnel compensation and benefits costs to total costs of the process for the review of biosimilar biological product applications (as defined in section 379j–51(13) of this title) for the first 3 years of the preceding 4 fiscal years; and

(ii) the average annual percent change that occurred in the Consumer Price Index for urban consumers (Washington-Arlington-Alexandria, DC–VA–MD–WV; Not Seasonally Adjusted; All items; Annual Index) for the first 3 years of the preceding 4 years of available data multiplied by the proportion of all costs other than personnel compensation and benefits costs to total costs of the process for the review of biosimilar biological product applications (as defined in section 379j–51(13) of this title) for the first 3 years of the preceding 4 fiscal years.

(2) Strategic hiring and retention adjustment

(3) Capacity planning adjustment

(A) In general

(B) Methodology

(D) Publication in Federal Register

(4) Operating reserve adjustment

(A) Increase

(B) Decrease

(i) Fiscal year 2023

(ii) Fiscal year 2024

(iii) Fiscal year 2025 and subsequent fiscal years

(5) Annual fee setting

For fiscal year 2023 and each subsequent fiscal year, the Secretary shall, not later than 60 days before the start of each such fiscal year—

(A) establish, for the fiscal year, initial and annual biosimilar biological product development fees and reactivation fees under subsection (a)(1), biosimilar biological product application fees under subsection (a)(2), and biosimilar biological product program fees under subsection (a)(3), based on the revenue amounts established under subsection (b) and the adjustments provided under this subsection; and

(B) publish such fee revenue and fees in the Federal Register.

(6) Limit

(d) Application fee waiver for small business

(1) Waiver of application fee

(2) Considerations

(3) Small business defined

(e) Effect of failure to pay fees

(f) Crediting and availability of fees

(1) In general

(2) Collections and appropriation Acts

(A) In general

(B) Use of fees and limitations

(i) In general

The fees authorized by this section shall be available—

(I) for fiscal year 2023, to defray the costs of the process for the review of biosimilar biological product applications (including such costs for an additional number of full-time equivalent positions in the Department of Health and Human Services to be engaged in such process), only if the Secretary allocates for such purpose an amount for such fiscal year (excluding amounts from fees collected under this section) no less than $20,000,000, multiplied by the adjustment factor applicable to such fiscal year; and(II) for fiscal year 2024 and each subsequent fiscal year, to defray the costs of the process for the review of biosimilar biological product applications (including such costs for an additional number of full-time equivalent positions in the Department of Health and Human Services to be engaged in such process), only if the sum of the amounts allocated by the Secretary for such costs, excluding costs paid from fees collected under this section, plus other costs for the maintenance, renovation, and repair of facilities and acquisition, maintenance, and repair of fixtures, furniture, and other necessary materials and supplies in connection with the process for the review of biosimilar biological product applications, is no less than $20,000,000, multiplied by the adjustment factor applicable to the fiscal year involved.

(ii) Leasing and necessary equipment

(D) Provision for early payments

(3) Authorization of appropriations

(g) Collection of unpaid fees

(h) Written requests for waivers and returns; disputes concerning fees

(i) Construction

(June 25, 1938, ch. 675, § 744H, as added Pub. L. 112–144, title IV, § 402, July 9, 2012, 126 Stat. 1029; amended Pub. L. 114–255, div. A, title III, § 3101(a)(2)(V), Dec. 13, 2016, 130 Stat. 1155; Pub. L. 115–52, title IV, § 403, title IX, § 905(b)(4), Aug. 18, 2017, 131 Stat. 1028, 1090; Pub. L. 116–136, div. A, title III, § 3856(b)(1), Mar. 27, 2020, 134 Stat. 458; Pub. L. 117–180, div. F, title IV, § 4003, Sept. 30, 2022, 136 Stat. 2160; Pub. L. 117–328, div. FF, title III, § 3625(b), Dec. 29, 2022, 136 Stat. 5880.)

§ 379j–53. Reauthorization; reporting requirements

(a) Performance report

(1) General requirements

(2) Additional informationThe report under this subsection shall include the progress of the Food and Drug Administration in achieving the goals, and future plans for meeting the goals, including—

(A) information on all previous cohorts for which the Secretary has not given a complete response on all biosimilar biological product applications and supplements in the cohort;

(B) the number of original biosimilar biological product applications filed per fiscal year, and the number of approvals issued by the agency for such applications; and

(C) the number of resubmitted original biosimilar biological product applications filed per fiscal year and the number of approvals 2

2 So in original.

letters issued by the agency for such applications.

(3) Real time reporting

(A) In general

(B) DataThe Secretary shall post the following data in accordance with subparagraph (A):

(i) The number and titles of draft and final guidance on topics related to the process for the review of biosimilars, and whether such guidances were required by statute or pursuant to a commitment under the letters described in section 401(b) 1 of the Biosimilar User Fee Amendments of 2022.

(ii) The number and titles of public meetings held on topics related to the process for the review of biosimilars, and whether such meetings were required by statute or pursuant to a commitment under the letters described in section 401(b) 1 of the Biosimilar User Fee Amendments of 2022.

(4) Rationale for BSUFA program changesBeginning with fiscal year 2020, the Secretary shall include in the annual report under paragraph (1)—

(A) data, analysis, and discussion of the changes in the number of individuals hired as agreed upon in the letters described in section 4001(b) of the Biosimilar User Fee Amendments of 2022 and the number of remaining vacancies, the number of full-time equivalents funded by fees collected pursuant to section 379j–52 of this title, and the number of full time equivalents funded by budget authority at the Food and Drug Administration by each division within the Center for Drug Evaluation and Research, the Center for Biologics Evaluation and Research, the Office of Regulatory Affairs, and the Office of the Commissioner;

(B) data, analysis, and discussion of the changes in the fee revenue amounts and costs for the process for the review of biosimilar biological product applications, including identifying—

(i) drivers of such changes; and

(ii) changes in the average total cost per full-time equivalent in the biosimilar biological product review program;

(C) for each of the Center for Drug Evaluation and Research, the Center for Biologics Evaluation and Research, the Office of Regulatory Affairs, and the Office of the Commissioner, the number of employees for whom time reporting is required and the number of employees for whom time reporting is not required; and

(D) data, analysis, and discussion of the changes in the average full-time equivalent hours required to complete review of each type of biosimilar biological product application.

(5) AnalysisFor each fiscal year, the Secretary shall include in the report an analysis of the following:

(A) The difference between the aggregate number of biosimilar biological product applications and supplements filed and the aggregate number of approvals issued by the agency, accounting for—

(i) such applications filed during one fiscal year for which a decision is not scheduled to be made until the following fiscal year; and

(ii) the aggregate number of applications for each fiscal year that did not meet the goals identified by the letters described in section 401(b) 1 of the Biosimilar User Fee Amendments of 2022 for the applicable fiscal year.

(B) Relevant data to determine whether the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research have met the performance enhancement goals identified by the letters described in section 401(b) 1 of the Biosimilar User Fee Amendments of 2022 for the applicable fiscal year.

(C) The most common causes and trends for external or other circumstances affecting the ability of the Secretary to meet review time and performance enhancement goals identified by the letters described in section 401(b) 1 of the Biosimilar User Fee Amendments of 2022.

(b) Fiscal report

(c) Corrective action reportFor each fiscal year for which fees are collected under this subpart, the Secretary shall prepare and submit a corrective action report to the Committee on Energy and Commerce and Committee on Appropriations of the House of Representatives and the Committee on Health, Education, Labor, and Pensions and Committee on Appropriations of the Senate. The report shall include the following information, as applicable:

(1) Goals met

(2) Goals missedFor each of the goals identified by the letters described in section 401(b) 1 of the Biosimilar User Fee Amendments of 2022 for the applicable fiscal year that the Secretary determines to not have been met, the corrective action report shall include—

(A) a justification for such determination and a description of the types of circumstances and trends, as applicable, under which biosimilar biological product applications missed the review goal times but were approved during the first cycle review, or review goals were missed; and

(B) with respect to performance enhancement goals that were not achieved, a description of efforts the Food and Drug Administration has put in place for the fiscal year in which the report is submitted to improve the ability of such agency to meet each such goal for the such 2 fiscal year.

(d) Enhanced communication

(1) Communications with Congress

(2) Participation in congressional hearing

(e) Public availability

(f) Reauthorization

(1) ConsultationIn developing recommendations to present to the Congress with respect to the goals described in subsection (a), and plans for meeting the goals, for the process for the review of biosimilar biological product applications for the first 5 fiscal years after fiscal year 2027, and for the reauthorization of this subpart for such fiscal years, the Secretary shall consult with—

(A) the Committee on Energy and Commerce of the House of Representatives;

(B) the Committee on Health, Education, Labor, and Pensions of the Senate;

(D) health care professionals;

(E) representatives of patient and consumer advocacy groups; and

(F) the regulated industry.

(2) Prior public inputPrior to beginning negotiations with the regulated industry on the reauthorization of this subpart, the Secretary shall—

(A) publish a notice in the Federal Register requesting public input on the reauthorization;

(B) hold a public meeting at which the public may present its views on the reauthorization;

(C) provide a period of 30 days after the public meeting to obtain written comments from the public suggesting changes to this part; and

(D) publish the comments on the Food and Drug Administration’s website.

(3) Periodic consultation

(4) Updates to Congress

(5) Public review of recommendationsAfter negotiations with the regulated industry, the Secretary shall—

(A) present the recommendations developed under paragraph (1) to the congressional committees specified in such paragraph;

(B) publish such recommendations in the Federal Register;

(D) hold a meeting at which the public may present its views on such recommendations; and

(E) after consideration of such public views and comments, revise such recommendations as necessary.

(6) Transmittal of recommendations

(7) Minutes of negotiation meetings

(A) Public availability

(B) Content

(June 25, 1938, ch. 675, § 744I, as added Pub. L. 112–144, title IV, § 403, July 9, 2012, 126 Stat. 1037; amended Pub. L. 115–52, title IV, § 404, title IX, §§ 903(d), 904(d), Aug. 18, 2017, 131 Stat. 1035, 1081, 1087; Pub. L. 117–180, div. F, title IV, § 4004, Sept. 30, 2022, 136 Stat. 2166; Pub. L. 117–328, div. FF, title III, § 3626(d), Dec. 29, 2022, 136 Stat. 5886.)