[Federal Register Volume 83, Number 177 (Wednesday, September 12, 2018)]
[Proposed Rules]
[Pages 46121-46126]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-19845]


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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


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

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is 
proposing to repeal 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 would mean that over-
the-counter (OTC) drug products that are generally recognized as safe 
and effective, that are not misbranded, and that comply with all 
applicable regulatory requirements can be marketed legally without an 
NDA or ANDA, even if they are sterilized by irradiation. FDA is 
proposing to take this action because the irradiation regulation is out 
of date and unnecessary. The technology of controlled nuclear radiation 
for sterilization of drugs is now well understood, and our regulations 
require that OTC drugs 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. This action is part of FDA's 
implementation of Executive Orders (EOs) 13771 and 13777. Under these 
EOs, FDA is comprehensively reviewing existing regulations to identify 
opportunities for repeal, replacement, or modification that will result 
in meaningful burden reduction while allowing the Agency to achieve our 
public health mission and fulfill statutory obligations.

DATES: Submit either electronic or written comments on the proposed 
rule by November 13, 2018.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before November 13, 2018. The https://www.regulations.gov electronic filing system will accept comments until 
midnight Eastern Time at the end of November 13, 2018. Comments 
received by mail/hand delivery/courier (for written/paper submissions) 
will be considered timely if they are postmarked or the delivery 
service acceptance receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to

[[Page 46122]]

the docket unchanged. Because your comment will be made public, you are 
solely responsible for ensuring that your comment does not include any 
confidential information that you or a third party may not wish to be 
posted, such as medical information, your or anyone else's Social 
Security number, or confidential business information, such as a 
manufacturing process. Please note that if you include your name, 
contact information, or other information that identifies you in the 
body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2017-N-6924 for ``Repeal of Regulation Requiring an Approved New 
Drug Application for Drugs Sterilized by Irradiation.'' Received 
comments, those filed in a timely manner (see ADDRESSES), will be 
placed in the docket and, except for those submitted as ``Confidential 
Submissions,'' publicly viewable at https://www.regulations.gov or at 
the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through 
Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, 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. 5198, Silver Spring, MD 20993-0002, 301-
796-3345.

SUPPLEMENTARY INFORMATION:

Table of Contents

I. Executive Summary
II. Background and Discussion
    A. The History of the Irradiation Regulation
    B. Sterilization by Irradiation
    C. The OTC Drug Monograph System and Current Good Manufacturing 
Practices
    D. Conclusion
III. Legal Authority
IV. Proposed Effective Date
V. Economic Analysis of Impacts
VI. Analysis of Environmental Impact
VII. Paperwork Reduction Act of 1995
VIII. Federalism
IX. Consultation and Coordination With Indian Tribal Governments
X. References

I. Executive Summary

    This proposed rule would repeal the irradiation regulation, which 
provides that any drug sterilized by irradiation is a new drug. This 
action, if finalized, would mean that OTC drugs marketed pursuant to 
the OTC Drug Review that are generally recognized as safe and 
effective, that are not misbranded, and that comply with all applicable 
regulatory requirements can be marketed legally without an FDA-approved 
NDA or ANDA, even if the drugs are sterilized by irradiation. 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 CGMPs. Appropriate 
and effective sterilization of drugs, including by irradiation, is 
adequately addressed by the CGMP requirements. Repealing the 
irradiation regulation would eliminate a requirement that is no longer 
necessary, and will not diminish public health protections.
    The estimated one-time costs of this rule range from $120 to $150. 
Avoiding the unnecessary preparation and review of a premarket drug 
application will generate an estimated one-time cost savings that range 
from about $395,000 to $2,076,000. Over 10 years with a 7 percent 
discount rate, the annualized net cost savings range from $0.05 million 
to $0.28 million, with a primary estimate of $0.06 million; with a 3 
percent discount rate, the annualized net cost savings range from $0.04 
million to $0.24 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 $0.83 million to 
$4.37 million with a 7 percent discount rate and from $1.58 million to 
$8.30 million with a 3 percent discount rate.

II. Background and Discussion

    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. 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 
proposing to repeal the irradiation regulation as specified in this 
rule.
    In addition, in a citizen petition dated August 14, 2014, Richard 
O. Wood of The Wood Burditt Group LLC requested that the irradiation 
regulation be revoked. FDA has responded to Mr. Wood's citizen 
petition. A copy of the response is available at: https://www.regulations.gov under Docket No. FDA-2014-P-1784.

[[Page 46123]]

A. The History of the Irradiation Regulation

    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 to 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), 
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 at Sec.  3.45 in the 
republication of chapter 21 of the Code of Federal Regulations 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 re-codified the rule at 
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 any existing 
background information describing the Agency's basis for determination 
of new drug status from the regulatory text.
    In 1997, FDA finalized these provisions, now located in 21 CFR 
310.502, entitled ``Certain drugs accorded new drug status through 
rulemaking procedures.'' (62 FR 12084 at 12084 (March 14, 1997).) 
Paragraph 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 is 
sterilization of drugs by irradiation (Sec.  310.502(a)(11) (21 CFR 
310.502(a)(11)). Because this regulation reflects an FDA determination 
that the drugs on the list are ``new drugs,'' an NDA or ANDA must be 
submitted and approved by FDA before they can be marketed legally. For 
a non-prescription drug that could otherwise be legally marketed 
without an approved NDA or ANDA in effect pursuant to the OTC Drug 
Review, the effect of Sec.  310.502(a)(11) is that, if the drug is 
sterilized by irradiation, an approved NDA or ANDA is necessary.

B. Sterilization by Irradiation

    Since the paragraph now reflected at Sec.  310.502(a)(11) was 
published in 1955, the technology of controlled nuclear radiation for 
sterilization of drugs has become well understood. Gamma ray 
irradiation has been recognized as a method of sterilizing drug 
products for half a century (Refs. 1 and 2). Electron beam and x-ray 
irradiation are also recognized methods for sterilizing drugs (Ref. 1).
    Information and data on whether a particular drug can safely and 
effectively be sterilized by irradiation are available in the 
scientific literature (Ref. 1). The United States Pharmacopeial 
Convention (USP) has provided guidance on irradiation sterilization of 
drug products since 1965 (Refs. 1 and 3). This includes chapter <1229> 
on ``Sterilization of Compendial Articles,'' which sets forth 
principles that may be applied to the sterilization of compendial and 
non-compendial drug products, and chapter <1229.10> on ``Radiation 
Sterilization,'' which sets forth guidelines on validation of 
sterilization by irradiation (Refs. 3 and 4). The American National 
Standards Institute, the Association for the Advancement of Medical 
Instrumentation, ASTM International, and the International Organization 
for Standardization (ISO) have also published standards on the 
irradiation of medical products, including drugs (Ref. 1). ISO standard 
11137, which sets forth several methods that can be used to determine 
the appropriate radiation dose for health care products, was first 
published in 1984 \2\ (Ref. 1).
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    \2\ ISO 11137-1 specifies standards for the development, 
validation, and routine control of a radiation sterilization process 
for medical devices, while ISO 11137-2 specifies dose establishment 
and dose audit methods and defines product family approaches for 
dose establishment and dose audits. Additional target sterilization 
doses are covered in ISO Technical Information Report (TIR) 13004. 
Neither ISO 11137-2 nor TIR 13004 is explicitly limited to medical 
devices. In addition, both ISO 11137-2 and ISO TIR 13004 reference 
ISO 11137-1 as ``indispensable for the application of this 
document.'' This implies that the concepts in ISO 11137-1 may be 
applied to sterilization of drug products.
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    USP chapter <1229.10> states that the methods set forth in ISO 
11137 typically guide the choice of radiation dose (Ref. 3). Relevant 
factors include a drug's pre-sterilization level of microbial 
contamination (sometimes referred to as its bioburden) and the desired 
sterility assurance level (Ref. 1). Once the dose is selected, USP 
General Chapter <1229.10> states that all materials exposed to 
radiation, especially the drug product and its primary container, 
should be evaluated for immediate and long-term effects, and 
``[p]roduct stability, safety, and functionality should be confirmed 
over the product's intended use period'' (Ref. 3). Among the advantages 
of sterilizing drug products by irradiation is that due to radiation's 
high penetrability, drug products can be irradiated after they are 
placed in their final containers (Ref. 1). Known as terminal 
sterilization, this provides a greater degree of sterilization 
assurance than aseptic processing and, where feasible, its use is 
preferable to relying solely on aseptic processing to ensure sterility 
(Ref. 5). Other advantages to irradiation sterilization of drugs 
include low chemical reactivity; the very low rise in temperature 
associated with radiation, which allows for its use on heat-sensitive 
products; that irradiation sterilization has fewer process variables 
than other methods, which translates into fewer sterility rejections; 
and that radiation does not leave behind any sterilant residuals (Refs. 
1 and 6).

C. The OTC Drug Monograph System and Current Good Manufacturing 
Practices

    The OTC Drug Review was established to evaluate the safety and 
effectiveness of OTC drug products marketed in the United States before 
May 11, 1972. As set forth in 21 CFR 330.10, it is a multiphase public 
rulemaking process (each phase requiring a Federal Register 
publication) resulting in the establishment of monographs for OTC 
therapeutic drug classes. OTC drug monographs, which can be found in 
Title 21, chapter I, subchapter D of the Code of Federal Regulations, 
cover acceptable ingredients, doses, formulations, other conditions, 
and labeling for certain OTC drugs. A company can legally make and 
market an OTC product that meets each of the conditions contained in an 
applicable monograph and, in addition, each of the general conditions 
set forth in Sec.  330.1. Among the general conditions that apply to 
all drug products marketed under the OTC Drug Review is the requirement 
set forth in Sec.  330.1(a) that they be manufactured in compliance 
with current good manufacturing practices, as established by parts 210 
and 211 of this chapter. The CGMP requirements in parts 210 and 211

[[Page 46124]]

encompass sterilization, including by irradiation.\3\
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    \3\ We note that sterilization is not generally a condition 
specifically covered by OTC monographs. Currently, the monograph for 
ophthalmic drug products at 21 CFR part 349 is the only monograph 
that incorporates a sterility condition. There are, however, OTC 
products covered by a monograph or tentative final monograph that 
are not required to be sterile, but which manufacturers may choose 
to sterilize. These may include consumer and healthcare antiseptics, 
such as consumer hand washes, body washes, and hand rubs, first aid 
antiseptics, health care personnel hand washes and hand rubs, 
surgical hand scrubs and rubs, and patient preoperative skin 
preparations. In 2013, FDA asked manufacturers to voluntarily revise 
the product labels for topical antiseptics to indicate whether the 
product is manufactured as a sterile or nonsterile product (Ref. 7).
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    In 1955, when the determination with respect to drugs sterilized by 
irradiation (now reflected in Sec.  310.502(a)(11)) was made, 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, Pub. L. 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/). Because of these subsequent statutes and regulations, Sec.  
310.502(a)(11) can be revoked 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.
    CGMP regulations require manufacturers to take steps to ensure that 
sterile drug products are free of objectionable microorganisms. (See, 
e.g., 21 CFR 211.28(a), 211.42(b) and (c), 211.67(a), 211.84(c), 
211.110(a), 211.113(b), 211.165(b), 211.167(a).) The CGMP regulations 
also include provisions that ensure that irradiation or any other 
sterilization processes do not have a detrimental effect on a drug 
product's identity, strength, quality, purity, or stability. (See, 
e.g., 21 CFR 211.22, 211.25(b), 211.68, 211.100, 211.160(b), 211.165, 
211.166.)
    Numerous records relating to the manufacture of the drug product 
must be maintained and made available for inspection (21 CFR part 211, 
subpart J). FDA conducts inspections at manufacturing facilities, 
including irradiation facilities, to ensure that the CGMP regulations 
are followed. Inspection findings are reviewed and, when appropriate, 
action may be recommended against manufacturers observed to be out of 
compliance.
    Choosing the sterilization process that is suitable for a 
particular drug product is the responsibility of the manufacturer and 
is an important part of pharmaceutical development. To guide them in 
choosing an appropriate method of sterilization and otherwise complying 
with the CGMP requirements, manufacturers can turn to voluntary 
consensus standards that are widely-known by industry and recognized by 
FDA for the development, validation, and routine control of the 
sterilization of drugs by irradiation. As noted previously in this 
document, ISO publishes standards that address the different doses of 
radiation that are appropriate depending on the type and amount of 
microbiological contamination and the necessary degree of sterility 
assurance (Ref. 3). These include the following:
     ISO 11137-1:2006: Sterilization of health care products--
Radiation--Part 1: Requirements for development, validation and routine 
control of a sterilization process for medical devices;
     ISO 11137-2:2013: Sterilization of health care products--
Radiation--Part 2: Establishing the sterilization dose;
     ISO 11137-3:2006: Sterilization of health care products--
Radiation--Part 3: Guidance on dosimetric aspects; and
     ISO/TS 13004:2013: Sterilization of health care products--
Substantiation of selected sterilization dose: Method VDmaxSD.
     The USP also provides guidance on irradiation 
sterilization, including in chapter <1229.10>, which specifically 
addresses the topic (Ref. 3).

D. Conclusion

    We propose the repeal of Sec.  310.502(a)(11) 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 and sterilization is a 
manufacturing process that is adequately addressed by the regulations 
governing the OTC drug monograph system and CGMPs.

III. Legal Authority

    FDA is issuing this proposed 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. Proposed Effective Date

    Any final rule that results from this proposed rule will be 
effective 30 days after the date of the final rule's publication in the 
Federal Register.

V. Economic Analysis of Impacts

    We have examined the impacts of the proposed 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). EOs 
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 
proposed 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 propose to certify that the 
proposed rule, if finalized, 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 proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after

[[Page 46125]]

adjustment for inflation is $150 million, using the most current (2017) 
Implicit Price Deflator for the Gross Domestic Product. This proposed 
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 proposed 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       $0.28        2016           7          10  Benefits are cost savings.
     year.
                                               0.05        0.04        0.24        2016           3          10  Benefits are cost savings.
    Annualized Quantified..............  ..........  ..........  ..........        2016           7          10
                                         ..........  ..........  ..........        2016           3          10  .......................................
                                        ----------------------------------------------------------------------------------------------------------------
Qualitative
--------------------------------------------------------------------------------------------------------------------------------------------------------
Costs:
    Annualized Monetized $millions/year        0.00        0.00        0.00        2016           7          10  Costs total less than $100.
                                               0.00        0.00        0.00        2016           3          10  Costs total less than $100.
    Annualized Quantified..............  ..........  ..........  ..........        2016           7          10
                                         ..........  ..........  ..........        2016           3          10
--------------------------------------------------------------------------------------------------------------------------------------------------------
Qualitative
--------------------------------------------------------------------------------------------------------------------------------------------------------
Transfers:
    Federal Annualized Monetized               0.14        0.14        0.14        2016           7          10  User Fee.
     $millions/year.
                                               0.12        0.12        0.12        2016           3          10  User Fee.
                                        ----------------------------------------------------------------------------------------------------------------
                                         From:
                                         To:
                                        ----------------------------------------------------------------------------------------------------------------
    Other Annualized Monetized           ..........  ..........  ..........        2016           7          10
     $millions/year.
                                         ..........  ..........  ..........        2016           3          10
                                        ----------------------------------------------------------------------------------------------------------------
                                         From:
                                         To:
--------------------------------------------------------------------------------------------------------------------------------------------------------
Effects:
--------------------------------------------------------------------------------------------------------------------------------------------------------
    State, Local or Tribal Government: None.............................................................................................................
    Small Business: None................................................................................................................................
    Wages: None.........................................................................................................................................
    Growth: None........................................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------

    Because the proposed rule will repeal an outdated regulation and 
generate net cost savings, we consider this action a deregulatory 
action under E.O. 13771. Table 2 presents a summary of the E.O. 13771 
impacts of the proposed rule over an infinite horizon. For this 
estimate, we assume that one sponsor will benefit from this 
deregulatory action every 10 years.

                                                               Table 2--E.O. 13771 Summary
                                                 [In $ millions 2016 dollars, over an infinite horizon]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                            Lower bound     Upper bound                     Lower bound     Upper bound
                                                           Primary (7%)        (7%)            (7%)        Primary (3%)        (3%)            (3%)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Present Value of Costs..................................           $0.00           $0.00           $0.00           $0.00           $0.00           $0.00
Present Value of Cost Savings...........................            0.97            0.83            4.37            1.84            1.58            8.30
Present Value of Net Costs..............................          (0.97)          (0.83)          (4.37)          (1.84)          (1.58)          (8.30)
Annualized Costs........................................           $0.00           $0.00           $0.00           $0.00           $0.00           $0.00
Annualized Cost Savings.................................           $0.07           $0.06           $0.31           $0.06           $0.05           $0.25
Annualized Net Costs....................................          (0.07)          (0.06)          (0.31)          (0.06)          (0.05)          (0.25)
--------------------------------------------------------------------------------------------------------------------------------------------------------

    We have developed a comprehensive Economic Analysis of Impacts that 
assesses the impacts of the proposed rule. The full analysis of 
economic impacts is available in the docket for this proposed rule 
(Ref. 8) and at: https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.

VI. 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.

VII. Paperwork Reduction Act of 1995

    This proposed rule refers to previously approved collections of 
information that are subject to review by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3520). The collections of information resulting from compliance with 
CGMPs have been

[[Page 46126]]

approved under OMB control number 0910-0139.

VIII. Federalism

    We have analyzed this proposed rule in accordance with the 
principles set forth in E.O. 13132. We have determined that this 
proposed 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.

IX. Consultation and Coordination With Indian Tribal Governments

    We have analyzed this proposed rule in accordance with the 
principles set forth in E.O. 13175. We have tentatively determined that 
the rule does not contain policies that would have a substantial direct 
effect on one or more Indian Tribes, on the relationship between the 
Federal Government and Indian Tribes, or on the distribution of power 
and responsibilities between the Federal Government and Indian Tribes. 
The Agency solicits comments from tribal officials on any potential 
impact on Indian Tribes from this proposed action.

X. References

    The following references are on display in the Dockets Management 
Staff (see ADDRESSES) and are available for viewing by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday; they are 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. Jacobs, G., ``Validation of the Radiation Sterilization of 
Pharmaceuticals.'' In: J. Agalloco and F. J. Carleton (eds.), 
Validation of Pharmaceutical Processes (3rd Ed.) Informa USA, New 
York, 2007.
2. Microbiology Sub-Committee, Radiation Sterilization Task Force, 
Parenteral Drug Association, Technical Report No. 11, 
``Sterilization of Parenterals by Gamma Radiation,'' Journal of 
Parenteral Science and Technology, 42 (3S), 1988, available at: 
https://store.pda.org/ProductCatalog/Product.aspx?ID=1170.
3. United States Pharmacopeial Convention (USP 40), Radiation 
Sterilization <1229.10>, 2017.
4. United States Pharmacopeial Convention (USP 40), Sterilization of 
Compendial Articles <1229>, 2017.
5. FDA Guidance for Industry on ``Sterile Drug Products Produced by 
Aseptic Processing--Current Good Manufacturing Practice,'' September 
2004; available at https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm070342.pdf.
6. United States Pharmacopeial Convention (USP 40), Sterilization 
and Sterility Assurance of Compendial Articles <1211>, 2017.
7. FDA Drug Safety Communication, ``FDA Requests Label Changes and 
Single-Use Packaging for Some Over-the-Counter Topical Antiseptic 
Products to Decrease Risk of Infection,'' November 13, 2013; 
available at https://www.fda.gov/Drugs/DrugSafety/ucm374711.htm.
8. FDA Preliminary Regulatory Impact Analysis, Repeal of Regulation 
Requiring an Approved New Drug Application for Drugs Sterilized by 
Irradiation; 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, it is proposed that 21 CFR part 310 be 
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 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:
* * * * *
    (11) [Reserved]
* * * * *

    Dated: September 7, 2018.
Scott Gottlieb,
Commissioner of Food and Drugs.
[FR Doc. 2018-19845 Filed 9-11-18; 8:45 am]
 BILLING CODE 4164-01-P


