Document ID: FDA-2017-N-6924-0015
Agency: fda
Document Type: Rule
Title: Regulation Requiring an Approved New Drug Application for Drugs
Sterilized by Irradiation
Posted Date: 2019-12-16T05:00Z

[Federal Register Volume 84, Number 241 (Monday, December 16, 2019)]
[Rules and Regulations]
[Pages 68331-68334]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-27046]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 310

[Docket No. FDA-2017-N-6924]
RIN 0910-AH47

Regulation Requiring an Approved New Drug Application for Drugs 
Sterilized by Irradiation

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is 
issuing a final rule repealing a regulation that requires an FDA-
approved new drug application (NDA) or abbreviated new drug application 
(ANDA) for any drug product that is sterilized by irradiation (the 
irradiation regulation). Repealing the irradiation regulation will mean 
that over-the-counter (OTC) drug products that are generally recognized 
as safe and effective, are not misbranded, and comply with all 
applicable regulatory requirements can be marketed legally without an 
NDA or ANDA, even if they are sterilized by irradiation. FDA is taking 
this action because the irradiation regulation is out of date and 
unnecessary.

DATES: This rule is effective January 15, 2020.

ADDRESSES: For access to the docket to read background documents or 
comments received, go to https://www.regulations.gov and insert the 
docket number found in brackets in the heading of this final rule into 
the ``Search'' box and follow the prompts, and/or go to the Dockets 
Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Sudha Shukla, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 5234, Silver Spring, MD 20993-0002, 301-
796-3345.

SUPPLEMENTARY INFORMATION:

Table of Contents

I. Executive Summary
II. Background
III. Legal Authority
IV. Comments on the Proposed Rule
V. Effective Date
VI. Economic Analysis of Impacts
VII. Analysis of Environmental Impact
VIII. Paperwork Reduction Act of 1995
IX. Federalism
X. Consultation and Coordination With Indian Tribal Governments
XI. Reference

I. Executive Summary

    In this final rule, FDA repeals the irradiation regulation, which 
provided that any drug sterilized by irradiation was a new drug. OTC 
drugs marketed pursuant to the OTC Drug Review that are generally 
recognized as safe and effective, are not misbranded, and comply with 
all applicable regulatory requirements now can be marketed legally 
without an FDA-approved NDA or ANDA, even if the drugs are sterilized 
by irradiation. As the Agency explained in the proposed rule published 
in the Federal Register of September 12, 2018 (83 FR 46121), FDA is 
taking this action because the Agency no longer concludes that drugs 
sterilized by irradiation are necessarily new drugs. The technology of 
controlled nuclear radiation for sterilization of drugs is now well 
understood. In addition, drugs that are marketed pursuant to the OTC 
Drug Review must be manufactured in compliance with current good 
manufacturing practices (CGMPs). Appropriate and effective 
sterilization of drugs, including by irradiation, is adequately 
addressed by the CGMP requirements. Repealing the irradiation 
regulation eliminates a requirement that is no longer necessary and 
will not diminish public health protections.
    The estimated one-time costs of this rule range from $25 to $32. 
Avoiding the unnecessary preparation and review of a premarket drug 
application will generate an estimated one-time cost savings that range 
from about $0.40 million to $2.16 million. Over 10 years with a 7 
percent discount rate, the annualized net cost savings range from $0.05 
million to $0.29 million, with a primary estimate of $0.06 million; 
with a 3 percent discount rate, the annualized net cost savings range 
from $0.05 million to $0.25 million, with a primary estimate of $0.05 
million. Over an infinite horizon, we assume that one sponsor will 
benefit from this deregulatory action every 10 years; the present value 
of the net cost savings over the infinite horizon range from $0.76 
million to $4.11 million with a 7

[[Page 68332]]

percent discount rate and from $1.52 million to $8.21 million with a 3 
percent discount rate.

II. Background

    On February 24, 2017, E.O. 13777, ``Enforcing the Regulatory Reform 
Agenda'' (https://www.gpo.gov/fdsys/pkg/FR-2017-03-01/pdf/2017-04107.pdf) was issued (82 FR 12285). One of the provisions in the E.O. 
requires Agencies to evaluate existing regulations and make 
recommendations to the Agency head regarding their repeal, replacement, 
or modification, consistent with applicable law. As part of this 
initiative, FDA is repealing the irradiation regulation as specified in 
this rule.
    In the November 29, 1955, issue of the Federal Register, FDA issued 
a statement of interpretation relating to the sterilization of drugs by 
irradiation (20 FR 8747 at 8748).\1\ In the statement, FDA explained 
that there was an interest in the utilization of newly developed 
sources of radiation for the sterilization of drugs. The Agency went on 
to state that it was necessary in the interest of protecting the public 
health to establish by adequate investigations that the irradiation 
treatment does not cause the drug to become unsafe or otherwise 
unsuitable for use. For this reason, all drug products sterilized by 
irradiation would be regarded as new drugs within the meaning of 
section 201(p) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) 
(21 U.S.C. 321(p)), which would mean that an effective new drug 
application would be required for such products.
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    \1\ Available at: https://www.loc.gov/item/fr020231/. A month 
later, this provision was included in Sec.  3.45 in the 
republication of chapter 21 of the Code of Federal Regulations (CFR) 
in the Federal Register. See 20 FR 9525 at 9554 (December 20, 1955), 
available at: http://cdn.loc.gov/service/ll/fedreg/fr020/fr020246/fr020246.pdf. In 1975, FDA republished and recodified the rule in 21 
CFR 200.30. See 40 FR 13996 at 13997 (March 27, 1975), available at: 
https://www.loc.gov/item/fr040060/.
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    In 1996, FDA proposed to revise the statement and consolidate it 
with similar provisions into a single list of drugs that have been 
determined by previous rulemaking procedures to be new drugs within the 
meaning of section 201(p) of the FD&C Act (61 FR 29502 at 29503 to 
29504 (June 11, 1996)). The Agency proposed to remove from the 
regulatory text any existing background information describing the 
Agency's basis for its determination of new drug status.
    In 1997, FDA finalized these provisions, now located in Sec.  
310.502 (21 CFR 310.502), entitled ``Certain drugs accorded new drug 
status through rulemaking procedures'' (62 FR 12083 at 12084 (March 14, 
1997)). Section 310.502(a) sets forth a list of drugs that have been 
determined by rulemaking procedures to be ``new drugs'' within the 
meaning of section 201(p) of the FD&C Act. Included on the list was 
``[s]terilization of drugs by irradiation'' (Sec.  310.502(a)(11)). 
Because this regulation reflected an FDA determination that the drugs 
on the list are ``new drugs,'' an NDA or ANDA had to be submitted and 
approved by FDA before those drugs could be marketed legally.
    When the paragraph now reflected in Sec.  310.502(a)(11) was 
published in 1955, the technology of controlled nuclear radiation for 
sterilization of drugs was not well understood. In addition, neither 
the OTC drug monograph system nor the CGMP requirements existed. The 
authorizing legislation that the CGMP regulations implement, section 
501(a)(2)(B) of the FD&C Act (21 U.S.C. 351(a)(2)(B)), was enacted in 
1962 (``Drug Amendments of 1962,'' October 10, 1962, Public Law 87-781, 
Title I, sec. 101), and the first CGMP regulations followed in 1963 
(``Part 133--Drugs; Current Good Manufacturing Practice in Manufacture, 
Processing, Packing, or Holding,'' 28 FR 6385 (June 20, 1963) available 
at: https://www.loc.gov/item/fr028120/). The regulations creating 
procedures for establishing OTC drug monographs were issued in 1972 (37 
FR 9464 (May 11, 1972)) available at: https://www.loc.gov/item/fr037092/).
    Today, as the proposed rule explained (83 FR 46121 at 46123 to 
46124), the technology of controlled nuclear radiation for 
sterilization of drugs is well understood, and all drug products 
marketed under the OTC Drug Review are subject to the requirement set 
forth in 21 CFR 330.1(a) that they be manufactured in compliance with 
current good manufacturing practices, as established by parts 210 and 
211 (21 CFR parts 210 and 211). The CGMP requirements in parts 210 and 
211 encompass sterilization, including by irradiation. As a result, as 
discussed in the proposed rule (83 FR 46121 at 46124), Sec.  
310.502(a)(11) can be repealed and manufacturers will still be 
obligated to ensure that, if they use radiation: (1) The drug products 
that they purport to be sterile are in fact sterile and (2) their use 
of radiation does not have a detrimental effect on their drug products' 
identity, strength, quality, purity, or stability.

III. Legal Authority

    We are issuing this final rule under the drugs and general 
administrative provisions of the FD&C Act (sections 201, 301, 501, 502, 
503, 505, 510, 701, 702, and 704 (21 U.S.C. 321, 331, 351, 352, 353, 
355, 360, 371, 372, and 374)) and under section 361 of the Public 
Health Service Act (PHS Act) (42 U.S.C. 264). The FD&C Act gives us the 
authority to issue and enforce regulations designed to help ensure that 
drug products are safe, effective, and manufactured according to 
current good manufacturing practices, while section 361 of the PHS Act 
gives us the authority to issue and enforce regulations designed to 
prevent the introduction, transmission, or spread of communicable 
diseases.

IV. Comments on the Proposed Rule

    We received five comment letters on the proposed rule by the close 
of the comment period, all from individuals. Each of the five comment 
letters contained general remarks supporting the proposed rule.

V. Effective Date

    This final rule is effective January 15, 2020.

VI. Economic Analysis of Impacts

    We have examined the impacts of the final rule under E.O. 12866, 
E.O. 13563, E.O. 13771, the Regulatory Flexibility Act (5 U.S.C. 601-
612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 104-4). 
E.O.s 12866 and 13563 direct us to assess all costs and benefits of 
available regulatory alternatives and, when regulation is necessary, to 
select regulatory approaches that maximize net benefits (including 
potential economic, environmental, public health and safety, and other 
advantages; distributive impacts; and equity). E.O. 13771 requires that 
the costs associated with significant new regulations ``shall, to the 
extent permitted by law, be offset by the elimination of existing costs 
associated with at least two prior regulations.'' We believe that this 
final rule is not a significant regulatory action as defined by E.O. 
12866.
    The Regulatory Flexibility Act requires us to analyze regulatory 
options that would minimize any significant impact of a rule on small 
entities. Because few entities will be affected and the net effect will 
be cost savings to affected firms, we certify that the final rule will 
not have a significant economic impact on a substantial number of small 
entities.
    The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires 
us to prepare a written statement, which includes an assessment of 
anticipated costs and benefits, before issuing ``any rule that includes 
any Federal mandate that may result in the expenditure by

[[Page 68333]]

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 $154 million, using the most current (2018) Implicit 
Price Deflator for the Gross Domestic Product. This final rule would 
not result in an expenditure in any year that meets or exceeds this 
amount.
    Table 1 summarizes our estimate of the annualized costs and 
benefits of the final rule.

                                       Table 1--Summary of Benefits, Costs, and Distributional Effects of the Rule
                                                                       [$ million]
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                                                                                           Units
                                                                           ------------------------------------
               Category                   Primary       Low        High                               Period                      Notes
                                         estimate    estimate    estimate      Year      Discount     covered
                                                                              dollars    rate (%)     (years)
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Benefits:
    Annualized Monetized $millions/          $0.06       $0.05       $0.29        2018           7          10  Benefits are cost savings.
     year.                                    0.05        0.05        0.25        2018           3          10  Benefits are cost savings.
    Annualized Quantified.............  ..........  ..........  ..........        2018           7          10
                                        ..........  ..........  ..........        2018           3          10
                                       ------------------------------------------------------------------------
    Qualitative.......................
 
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Costs:
    Annualized Monetized $millions/           0.00        0.00        0.00        2018           7          10  Less than $100.
     year.                                    0.00        0.00        0.00        2018           3          10  Less than $100.
    Annualized Quantified.............  ..........  ..........  ..........        2018           7          10
                                        ..........  ..........  ..........        2018           3          10
                                       ------------------------------------------------------------------------
    Qualitative.......................
 
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Transfers:
    Federal Annualized Monetized              0.16        0.16        0.16        2018           7          10  User Fee.
     $millions/year.                          0.14        0.14        0.14        2018           3          10  User Fee.
                                       ------------------------------------------------------------------------
                                        From:
                                        To:
                                       -----------------------------------------------------------------------------------------------------------------
    Other Annualized Monetized          ..........  ..........  ..........        2018           7          10
     $millions/year.                    ..........  ..........  ..........        2018           3          10
                                       ------------------------------------------------------------------------
                                        From:
                                        To:
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Effects:
    State, Local, or Tribal Government: None.
    Small Business: None.
    Wages: None.
    Growth: None.
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    In line with Executive Order 13771, in table 2 we estimate present 
and annualized values of costs and cost savings over an infinite time 
horizon. With a 7 percent discount rate, the estimated annualized net 
cost-savings equal $0.06 million in 2016 dollars over an infinite 
horizon. Based on these cost savings, this final rule would be 
considered a deregulatory action under E.O. 13771.

                                                         Table 2--Executive Order 13771 Summary
                                                 [In $ millions 2016 dollars, over an infinite horizon]
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                                                                            Lower bound     Upper bound                     Lower bound     Upper bound
                                                           Primary (7%)        (7%)            (7%)        Primary (3%)        (3%)            (3%)
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Present Value of Costs..................................           $0.00           $0.00           $0.00           $0.00           $0.00           $0.00
Present Value of Cost Savings...........................            0.88            0.75            4.01            1.75            1.50            8.01
Present Value of Net Costs..............................          (0.88)          (0.75)          (4.01)          (1.75)          (1.50)          (8.01)
Annualized Costs........................................            0.00            0.00            0.00            0.00            0.00            0.00
Annualized Cost Savings.................................            0.06            0.05            0.28            0.05            0.05            0.24
Annualized Net Costs....................................          (0.06)          (0.05)          (0.28)          (0.05)          (0.05)          (0.24)
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Note: Net costs are calculated as costs minus cost savings. Values in parentheses denote net negative costs (i.e., cost-savings).

    We have developed a comprehensive Economic Analysis of Impacts that 
assesses the impacts of the final rule. The full analysis of economic 
impacts is available in the docket for this final rule (Ref. 1) and at: 
https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.

VII. Analysis of Environmental Impact

    We have determined under 21 CFR 25.30(h) and 25.31(a) that this 
action is of a type that does not individually or cumulatively have a 
significant effect on the human environment. Therefore, neither an 
environmental assessment nor an environmental impact statement is 
required.

VIII. Paperwork Reduction Act of 1995

    This final rule contains no collections of information. Therefore, 
clearance by the Office of Management and Budget

[[Page 68334]]

under the Paperwork Reduction Act of 1995 is not required.

IX. Federalism

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

X. Consultation and Coordination With Indian Tribal Governments

    We have analyzed this rule in accordance with the principles set 
forth in E.O. 13175. We have determined that the rule does not contain 
policies that have substantial direct effects on one or more Indian 
Tribes, on the relationship between the Federal Government and Indian 
Tribes, or on the distribution of power and responsibilities between 
the Federal Government and Indian Tribes. Accordingly, we conclude that 
the rule does not contain policies that have tribal implications as 
defined in the E.O. and, consequently, a tribal summary impact 
statement is not required.

XI. Reference

    The following reference is on display in the Dockets Management 
Staff (see ADDRESSES), and is available for viewing by interested 
persons between 9 a.m. and 4 p.m. Monday through Friday; it is also 
available electronically at https://www.regulations.gov. FDA has 
verified the website addresses, as of the date this document publishes 
in the Federal Register, but websites are subject to change over time.
    1. FDA Final Regulatory Impact Analysis, ``Regulation Requiring an 
Approved New Drug Application for Drugs Sterilized by Irradiation,'' 
available at https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.

List of Subjects in 21 CFR Part 310

    Administrative practice and procedure, Drugs, Labeling, Medical 
devices, Reporting and recordkeeping requirements.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and the 
Public Health Service Act and under authority delegated to the 
Commissioner of Food and Drugs, 21 CFR part 310 is amended as follows:

PART 310--NEW DRUGS

0
1. The authority citation for part 310 continues to read as follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360b-360f, 
360j, 360hh-360ss, 361(a), 371, 374, 375, 379e, 379k-1; 42 U.S.C. 
216, 241, 242(a), 262.

0
2. In Sec.  310.502, revise paragraph (a) introductory text and remove 
and reserve paragraph (a)(11) to read as follows:

Sec.  310.502   Certain drugs accorded new drug status through 
rulemaking procedures.

    (a) The drugs listed in this paragraph (a) have been determined by 
rulemaking procedures to be new drugs within the meaning of section 
201(p) of the Federal Food, Drug, and Cosmetic Act. An approved new 
drug application under section 505 of the Federal Food, Drug, and 
Cosmetic Act and part 314 of this chapter is required for marketing the 
following drugs:
* * * * *

    Dated: December 9, 2019.
Brett P. Giroir,
Acting Commissioner of Food and Drugs.
[FR Doc. 2019-27046 Filed 12-13-19; 8:45 am]
BILLING CODE 4164-01-P