[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this action because the irradiation regulation is out of date and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
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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
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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
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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.
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From:
To:
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Other Annualized Monetized .......... .......... .......... 2018 7 10
$millions/year. .......... .......... .......... 2018 3 10
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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]
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