Federal Register / Vol. 83, No. 177 / Wednesday, September 12, 2018 / Proposed Rules 46121 

be kept within the amount authorized in 

the Order. 

A review of historical information and 

preliminary information pertaining to 

the upcoming fiscal year indicates that 

the average grower price for the 2018– 

2019 season should be approximately 

$296 per ton of pears for processing. 

Therefore, the estimated assessment 

revenue for the 2018–2019 fiscal period 

as a percentage of total grower revenue 

would be about 2.4 percent ($7.15 per 

ton assessment divided by $296 per ton 

grower price). 

This proposed action would decrease 

the assessment obligation imposed on 

handlers for the 2018–2019 and 

subsequent fiscal periods. Assessments 

are applied uniformly on all handlers, 

and some of the costs may be passed on 

to producers. However, decreasing the 

assessment rate would reduce the 

burden on handlers, and may reduce the 

burden on producers. 

The Committee’s meetings were 

widely publicized throughout the 

Oregon and Washington processed pear 

industry. All interested persons were 

invited to attend the meetings and 

participate in Committee deliberations 

on all issues. Like all Committee 

meetings, the May 30, 2018, meeting 

was a public meeting and all entities, 

both large and small, were able to 

express views on this issue. Finally, 

interested persons are invited to submit 

comments on this proposed rule, 

including the regulatory and 

information collection impacts of this 

action on small businesses. 

In accordance with the Paperwork 

Reduction Act of 1995 (44 U.S.C. 

chapter 35), the Order’s information 

collection requirements have been 

previously approved by OMB and 

assigned OMB No. 0581–0189. No 

changes in those requirements would be 

necessary because of this action. Should 

any changes become necessary, they 

would be submitted to OMB for 

approval. 

This proposed rule would not impose 

any additional reporting or 

recordkeeping requirements on either 

small or large Oregon and Washington 

processed pear handlers. As with all 

Federal marketing order programs, 

reports and forms are periodically 

reviewed to reduce information 

requirements and duplication by 

industry and public sector agencies. 

AMS is committed to complying with 

the E-Government Act, to promote the 

use of the internet and other 

information technologies to provide 

increased opportunities for citizen 

access to Government information and 

services, and for other purposes. 

USDA has not identified any relevant 

Federal rules that duplicate, overlap, or 

conflict with this proposed rule. 

A small business guide on complying 

with fruit, vegetable, and specialty crop 

marketing agreements and orders may 

be viewed at: http://www.ams.usda.gov/ 

rules-regulations/moa/small-businesses. 

Any questions about the compliance 

guide should be sent to Richard Lower 

at the previously mentioned address in 

the FOR FURTHER INFORMATION CONTACT

section. 

List of Subjects in 7 CFR Part 927 

Marketing agreements, Pears, 

Reporting and recordkeeping 

requirements. 

For the reasons set forth in the 

preamble, 7 CFR part 927 is proposed to 

be amended as follows: 

PART 927—PEARS GROWN IN 

OREGON AND WASHINGTON 

■ 1. The authority citation for 7 CFR 

part 927 continues to read as follows: 

Authority: 7 U.S.C. 601–674. 

■ 2. In § 927.237 revise the intro 

paragraph text and paragraph (a) to read 

as follows: 

§ 927.237 Assessment rate. 

On and after July 1, 2018, the 

following base rates of assessment for 

pears for processing are established for 

the Processed Pear Committee: 

(a) $7.15 per ton for any or all 

varieties or subvarieties of pears for 

canning classified as ‘‘summer/fall’’ 

excluding pears for other methods of 

processing; 

* * * * * 

Dated: September 6, 2018. 

Bruce Summers, 

Administrator, Agricultural Marketing 

Service. 

[FR Doc. 2018–19683 Filed 9–11–18; 8:45 am] 

BILLING CODE 3410–02–P 

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. 

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 


daltland on DSKBBV9HB2PROD with PROPOSALS
46122 Federal Register / Vol. 83, No. 177 / Wednesday, September 12, 2018 / Proposed Rules 

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 FDAapproved 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. 


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Federal Register / Vol. 83, No. 177 / Wednesday, September 12, 2018 / Proposed Rules 46123 

1Available at: https://www.loc.gov/item/ 

fr020231/. A month later, this provision was 

included at § 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/. 

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. 

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. 

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 

(§ 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 

§ 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 

§ 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). 

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 presterilization 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 § 330.1. 

Among the general conditions that 

apply to all drug products marketed 

under the OTC Drug Review is the 

requirement set forth in § 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 


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46124 Federal Register / Vol. 83, No. 177 / Wednesday, September 12, 2018 / Proposed Rules 

3We 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). 

encompass sterilization, including by 

irradiation.3

In 1955, when the determination with 

respect to drugs sterilized by irradiation 

(now reflected in § 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, § 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 

§ 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 


daltland on DSKBBV9HB2PROD with PROPOSALS
Federal Register / Vol. 83, No. 177 / Wednesday, September 12, 2018 / Proposed Rules 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] 

Category Primary 

estimate 

Low 

estimate 

High 

estimate 

Units 

Notes Year 

dollars 

Discount 

rate 

(%) 

Period 

covered 

(years) 

Benefits: 

Annualized, Monetized $millions/year .................. $0.06 $0.05 $0.28 2016 7 10 Benefits are cost savings. 

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 $millions/year ...... 0.14 0.14 0.14 2016 7 10 User Fee. 

0.12 0.12 0.12 2016 3 10 User Fee. 

From: To: 

Other Annualized Monetized $millions/year ......... .................. .................. .................. 2016 7 10 

.................. .................. .................. 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] 

Primary 

(7%) 

Lower bound 

(7%) 

Upper bound 

(7%) 

Primary 

(3%) 

Lower bound 

(3%) 

Upper bound 

(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 


daltland on DSKBBV9HB2PROD with PROPOSALS
46126 Federal Register / Vol. 83, No. 177 / Wednesday, September 12, 2018 / Proposed Rules 

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/guidance

complianceregulatoryinformation/ 

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 

■ 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. 

■ 2. In § 310.502, revise paragraph (a) 

introductory text and remove and 

reserve paragraph (a)(11) to read as 

follows: 

§ 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 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 261 

[EPA–R10–RCRA–2018–0538; SW–FRL– 

9982–05—Region 10] 

Hazardous Waste Management 

System; Proposed Exclusion for 

Identifying and Listing Hazardous 

Waste 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Proposed rule and request for 

comment. 

SUMMARY: The Environmental Protection 

Agency (also, ‘‘the Agency’’ or ‘‘we’’ in 

this preamble) is proposing to grant a 

petition submitted by Sandvik Special 

Metals (Sandvik), in Kennewick, 

Washington to exclude (or ‘‘delist’’) up 

to 1,500 cubic yards of F006 wastewater 

treatment sludge per year from the list 

of federal hazardous wastes. 

The Agency is proposing to grant the 

petition based on an evaluation of 

waste-specific information provided by 

Sandvik. This proposed decision, if 

finalized, conditionally excludes the 

petitioned waste from the requirements 

of hazardous waste regulations under 

the Resource Conservation and 

Recovery Act. 

We conclude that Sandvik’s 

petitioned waste is nonhazardous with 

respect to the original federal listing 

criteria and that there are no other 

factors (including additional 

constituents) other than those for which 

the waste was listed that would warrant 

retaining the waste as a hazardous 

waste. Subject to state-only 

requirements within the state of 

Washington, or federally-authorized or 

state-only requirements in other states 

where the subject wastes may be 

disposed of, Sandvik’s petitioned waste 

may be disposed of in a Subtitle D 

landfill which is permitted, licensed, or 

registered by a State to manage 

industrial solid waste. 

DATES: Comments must be received on 

or before October 12, 2018. Requests for 

an informal hearing must reach the EPA 

by September 27, 2018. 

ADDRESSES: Submit your comments, 

identified by Docket ID No. EPA–R10– 

RCRA–2018–0538 by one of the 

following methods: 


daltland on DSKBBV9HB2PROD with PROPOSALS