Federal Register / Vol. 79, No. 209 / Wednesday, October 29, 2014 / Proposed Rules 64349 

service information related to this AD, 

contact Costruzioni Aeronautiche Tecnam 

Airworthiness Office, Via Maiorise–81043 

Capua (CE) Italy; telephone: +39 0823 

997538; fax: +39 0823 622899; email: 

technical.support@tecnam.com; Internet: 

http://www.tecnam.com/Customer-Care/

Service-Bulletins.aspx. You may review this 

referenced service information at the FAA, 

Small Airplane Directorate, 901 Locust, 

Kansas City, Missouri 64106. For information 

on the availability of this material at the 

FAA, call (816) 329–4148. 

Issued in Kansas City, Missouri, on 

October 22, 2014. 

Earl Lawrence, 

Manager, Small Airplane Directorate, Aircraft 

Certification Service. 

[FR Doc. 2014–25740 Filed 10–28–14; 8:45 am] 

BILLING CODE 4910–13–P 

DEPARTMENT OF JUSTICE 

Drug Enforcement Admininstration 

21 CFR Part 1308 

[Docket No. DEA–400] 

Schedules of Controlled Substances: 

Removal of Naloxegol From Control 

AGENCY: Drug Enforcement 

Administration, Department of Justice. 

ACTION: Notice of proposed rulemaking. 

SUMMARY: The Drug Enforcement 

Administration (DEA) proposes to 

remove naloxegol ((5a,6 a)-17-allyl-6- 

((20-hydroxy-3,6,9,12,15,18- 

hexaoxaicos-1-yl)oxy)-4,5- 

epoxymorphinon-3,14-diol) and its salts 

from the schedules of the Controlled 

Substances Act (CSA). This scheduling 

action is pursuant to the CSA which 

requires that such actions be made on 

the record after opportunity for a 

hearing through formal rulemaking. 

Naloxegol is currently a schedule II 

controlled substance because it can be 

derived from opium alkaloids. This 

action would remove the regulatory 

controls and administrative, civil, and 

criminal sanctions applicable to 

controlled substances, including those 

specific to schedule II controlled 

substances, on persons who handle 

(manufacture, distribute, reverse 

distribute, dispense, conduct research, 

import, export, or conduct chemical 

analysis) or propose to handle 

naloxegol. 

DATES: Interested persons may file 

written comments on this proposal in 

accordance with 21 CFR 1308.43(g). 

Electronic comments must be 

submitted, and written comments must 

be postmarked, on or before November 

28, 2014. Commenters should be aware 

that the electronic Federal Docket 

Management System will not accept 

comments after 11:59 p.m. Eastern Time 

on the last day of the comment period. 

Interested persons, defined at 21 CFR 

1300.01 as those ‘‘adversely affected or 

aggrieved by any rule or proposed rule 

issuable pursuant to section 201 of the 

Act (21 U.S.C. 811)’’, may file a request 

for hearing or waiver of participation 

pursuant to 21 CFR 1308.44 and in 

accordance with 21 CFR 1316.45, 

1316.47, 1316.48, or 1316.49, as 

applicable. Requests for hearing, notices 

of appearance, and waivers of an 

opportunity for a hearing or to 

participate in a hearing must be 

received on or before November 28, 

2014. 

ADDRESSES: To ensure proper handling 

of comments, please reference ‘‘Docket 

No. DEA–400’’ on all correspondence, 

including any attachments. 

• Electronic comments: The DEA 

encourages that all comments be 

submitted through the Federal 

eRulemaking Portal, which provides the 

ability to type short comments directly 

into the comment field on the Web page 

or to attach a file for lengthier 

comments. Please go to http://

www.regulations.gov and follow the 

online instructions at that site for 

submitting comments. Upon completion 

of your submission you will receive a 

Comment Tracking Number for your 

comment. Please be aware that 

submitted comments are not 

instantaneously available for public 

view on Regulations.gov. If you have 

received a comment tracking number, 

your comment has been successfully 

submitted and there is no need to 

resubmit the same comment. 

• Paper comments: Paper comments 

that duplicate an electronic submission 

are not necessary and are discouraged. 

Should you wish to mail a comment in 

lieu of an electronic format, it should be 

sent via regular or express mail to: Drug 

Enforcement Administration, Attention: 

DEA Federal Register Representative/

ODXL, 8701 Morrissette Drive, 

Springfield, Virginia 22152. 

• Hearing requests: All requests for 

hearing and waivers of participation 

must be sent to: Drug Enforcement 

Administration, Attn: Hearing Clerk/LJ, 

8701 Morrissette Drive, Springfield, 

Virginia 22152. 

FOR FURTHER INFORMATION CONTACT: 

Imelda L. Paredes, Office of Diversion 

Control, Drug Enforcement 

Administration; Mailing Address: 

8701Morrissette Drive, Springfield, 

Virginia 22152; Telephone: (202) 598– 

6812. 

SUPPLEMENTARY INFORMATION: 

Posting of Public Comments 

Please note that all comments 

received in response to this docket are 

considered part of the public record. 

They will, unless reasonable cause is 

given, be made available by the DEA for 

public inspection online at http://

www.regulations.gov. Such information 

includes personal identifying 

information (such as your name, 

address, etc.) voluntarily submitted by 

the commenter. The Freedom of 

Information Act (FOIA) applies to all 

comments received. If you want to 

submit personal identifying information 

(such as your name, address, etc.) as 

part of your comment, but do not want 

it to be made publicly available, you 

must include the phrase ‘‘PERSONAL 

IDENTIFYING INFORMATION’’ in the 

first paragraph of your comment. You 

must also place the personal identifying 

information you do not want made 

publicly available in the first paragraph 

of your comment and identify what 

information you want redacted. 

If you want to submit confidential 

business information as part of your 

comment, but do not want it to be made 

publicly available, you must include the 

phrase ‘‘CONFIDENTIAL BUSINESS 

INFORMATION’’ in the first paragraph 

of your comment. You must also 

prominently identify confidential 

business information to be redacted 

within the comment. 

Comments containing personal 

identifying information and confidential 

business information identified as 

directed above will generally be made 

publicly available in redacted form. If a 

comment has so much confidential 

business information or personal 

identifying information that it cannot be 

effectively redacted, all or part of that 

comment may not be made publicly 

available. Comments posted to http://

www.regulations.gov may include any 

personal identifying information (such 

as name, address, and phone number) 

included in the text of your electronic 

submission that is not identified as 

directed above as confidential. 

An electronic copy of this document 

and supplemental information to this 

proposed rule are available at http://

www.regulations.gov for easy reference. 

The DEA specifically solicits written 

comments regarding the DEA’s 

economic analysis of the impact of these 

proposed changes. The DEA requests 

that commenters provide detailed 

descriptions in their comments of any 

expected economic impacts, especially 

to small entities. Commenters should 

provide empirical data to illustrate the 

nature and scope of such impact. 


rmajette on DSK2TPTVN1PROD with PROPOSALS
64350 Federal Register / Vol. 79, No. 209 / Wednesday, October 29, 2014 / Proposed Rules 

1As discussed in a memorandum of 

understanding entered into by the Food and Drug 

Administration (FDA) and the National Institute on 

Drug Abuse (NIDA), the FDA acts as the lead agency 

within the HHS in carrying out the Secretary’s 

scheduling responsibilities under the CSA, with the 

concurrence of NIDA. 50 FR 9518, Mar. 8, 1985. 

The Secretary of the HHS has delegated to the 

Assistant Secretary for Health of the HHS the 

authority to make domestic drug scheduling 

recommendations. 58 FR 35460, July 1, 1993. 

2http://www.accessdata.fda.gov/scripts/cder/

drugsatfda/index.cfm?fuseaction=Search 

.DrugDetails (last accessed Sept. 26, 2014). 

Request for Hearing, Notice of 

Appearance at or Waiver of 

Participation in Hearing 

Pursuant to 21 U.S.C. 811(a), this 

action is a formal rulemaking ‘‘on the 

record after opportunity for a hearing.’’ 

Such proceedings are conducted 

pursuant to the provisions of the 

Administrative Procedure Act (APA) (5 

U.S.C. 551–559). 21 CFR 1308.41– 

1308.45, and 21 CFR part 1316 subpart 

D. In accordance with 21 CFR 1308.44 

(a)–(c), requests for hearing, notices of 

appearance, and waivers of an 

opportunity for a hearing or to 

participate in a hearing may be 

submitted only by interested persons, 

defined as those ‘‘adversely affected or 

aggrieved by any rule or proposed rule 

issuable pursuant to section 201 of the 

Act (21 U.S.C. 811).’’ 21 CFR 1300.01. 

Such requests or notices must conform 

to the requirements of 21 CFR 1308.44 

(a) or (b), and 1316.47 or 1316.48, as 

applicable, and include a statement of 

the interest of the person in the 

proceeding and the objections or issues, 

if any, concerning which the person 

desires to be heard. Any waiver must 

conform to the requirements of 21 CFR 

1308.44(c) and 1316.49, including a 

written statement regarding the 

interested person’s position on the 

matters of fact and law involved in any 

hearing. 

Please note that pursuant to 21 U.S.C. 

811(a), the purpose and subject matter 

of a hearing is restricted to ‘‘(A) 

find[ing] that such drug or other 

substance has a potential for abuse, and 

(B) mak[ing] with respect to such drug 

or other substance the findings 

prescribed by subsection (b) of section 

812 of this title for the schedule in 

which such drug is to be placed * * *.’’ 

All requests for hearing and waivers of 

participation must be sent to the DEA 

using the address information above, on 

or before the date specified above. 

Legal Authority 

The Drug Enforcement 

Administration (DEA) implements and 

enforces titles II and III of the 

Comprehensive Drug Abuse Prevention 

and Control Act of 1970, as amended. 21 

U.S.C. 801–971. Titles II and III are 

referred to as the ‘‘Controlled 

Substances Act’’ and the ‘‘Controlled 

Substances Import and Export Act,’’ 

respectively, but they are collectively 

referred to as the ‘‘Controlled 

Substances Act’’ or the ‘‘CSA’’ for the 

purposes of this action. The DEA 

publishes the implementing regulations 

for these statutes in title 21 of the Code 

of Federal Regulations (CFR), parts 1300 

to 1321. The CSA and its implementing 

regulations are designed to prevent, 

detect, and eliminate the diversion of 

controlled substances and listed 

chemicals into the illicit market while 

providing for the legitimate medical, 

scientific, research, and industrial needs 

of the United States. Controlled 

substances have the potential for abuse 

and dependence and are controlled to 

protect the public health and safety. 

Under the CSA, each controlled 

substance is classified into one of five 

schedules based upon its potential for 

abuse, its currently accepted medical 

use in treatment in the United States, 

and the degree of dependence the drug 

or other substance may cause. 21 U.S.C. 

812. The initial schedules of controlled 

substances established by Congress are 

found at 21 U.S.C. 812(c) and the 

current list of scheduled substances is 

published at 21 CFR part 1308. 21 

U.S.C. 812(a). 

Pursuant to 21 U.S.C. 811(a)(2), the 

Attorney General may, by rule, ‘‘remove 

any drug or other substance from the 

schedules if he finds that the drug or 

other substance does not meet the 

requirements for inclusion in any 

schedule.’’ The Attorney General has 

delegated scheduling authority under 21 

U.S.C. 811 to the Administrator of the 

DEA, 28 CFR 0.100, who in turn has 

redelegated that authority to the Deputy 

Administrator of the DEA, 28 CFR part 

0, appendix to subpart R. 

The CSA provides that proceedings 

for the issuance, amendment, or repeal 

of the scheduling of any drug or other 

substance may be initiated by the 

Attorney General (1) on his own motion, 

(2) at the request of the Secretary of the 

Department of Health and Human 

Services (HHS),1 or (3) on the petition 

of any interested party. 21 U.S.C. 811(a). 

This action was initiated by a petition 

to remove naloxegol from the list of 

scheduled controlled substances of the 

CSA, and is supported by, inter alia, a 

recommendation from the Assistant 

Secretary of the HHS and an evaluation 

of all relevant data by the DEA. This 

action would remove the regulatory 

controls and administrative, civil, and 

criminal sanctions applicable to 

controlled substances, including those 

specific to schedule II controlled 

substances, on persons who handle or 

propose to handle naloxegol. 

Background 

Naloxegol, or PEG-naloxol, is a new 

molecular entity and is a polyethylene 

glycolyated (PEGylated) derivative of 

naloxone. Its chemical names are (5a,6 

a)-17-allyl-6-((20-hydroxy3,6,9,12,15,18-hexaoxaicos-1-yl)oxy)- 

4,5-epoxymorphinon-3,14-diol or alpha6mPEG7–O-naloxol. Naloxegol is an 

antagonist predominantly of peripheral 

mu opioid receptors. The Food and 

Drug Administration (FDA) approved 

naloxegol for marketing on September 

16, 2014, under the brand name 

MovantikTM.2 It is indicated for the 

treatment of opioid-induced 

constipation (OIC) in adults with 

chronic non-cancer pain. 

Gastrointestinal adverse events (AEs) 

effects are commonly experienced by 

chronic users of opioid analgesics. 

Opioids delay gastric emptying and 

intestinal transport, which over time 

leads to debilitating constipation. OIC is 

caused by activation of the mu opioid 

receptor in the GI tract. 

Proposed Determination To Decontrol 

Naloxegol 

Pursuant to 21 U.S.C. 811(a), 

proceedings to issue, amend, or repeal 

scheduling actions may be initiated on 

the petition of any interested party. In 

accordance with 21 CFR 1308.43, the 

DEA received a petition from the drug 

sponsor dated March 22, 2012, 

requesting that the DEA amend 21 CFR 

1308.12(b)(1) to exclude naloxegol as a 

schedule II controlled substance. The 

petitioner stated that naloxegol is a mu 

opioid receptor antagonist without mu 

opioid agonist or partial agonist 

properties. In accordance with 21 CFR 

1308.43(c), the DEA accepted the 

petition for filing on October 1, 2012. 

Pursuant to 21 U.S.C. 811(b), the DEA 

gathered the necessary data on 

naloxegol and on February 7, 2013, 

forwarded to the HHS the data with the 

sponsor’s petition along with a request 

for a scientific and medical evaluation 

and the HHS’s recommendation as to 

whether or not naloxegol should be 

removed from the list of controlled 

substances. According to the HHS, the 

sponsor submitted a New Drug 

Application (NDA) for naloxegol on 

September 16, 2013. Based on the NDA, 

the HHS summarized that naloxegol is 

an antagonist of peripheral opioid 

receptors for the treatment of OIC. 


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Federal Register / Vol. 79, No. 209 / Wednesday, October 29, 2014 / Proposed Rules 64351 

3U.S. Food and Drug Administration, Department 

of Health and Human Services, Basis for the 

Recommendation to Decontrol Naloxegol and Its 

Salts from Schedule II of the Controlled Substances 

Act (2014), p. 6. 

4The National Forensic Laboratory Information 

System (NFLIS) is a program of the DEA, Office of 

Diversion Control. NFLIS systematically collects 

drug identification results and associated 

information from drug cases submitted to and 

analyzed by State and local forensic laboratories. 

NFLIS represents an important resource in 

monitoring illicit drug abuse and trafficking, 

including the diversion of legally manufactured 

pharmaceuticals into illegal markets. NFLIS is a 

comprehensive information system that includes 

data from forensic laboratories that handle 

approximately 90% of an estimated 1.0 million 

distinct annual State and local drug analysis cases. 

NFLIS includes drug chemistry results from 

completed analyses only. While NFLIS data is not 

direct evidence of abuse, it can lead to an inference 

that a drug has been diverted and abused. See 76 

FR 77330, 77332, Dec. 12, 2011. 

5The System to Retrieve Information from Drug 

Evidence (STRIDE) is a database of drug exhibits 

sent to DEA laboratories for analysis. Exhibits from 

the database are from the DEA, other federal 

agencies, and local law enforcement agencies. 

On August 8, 2014, the HHS provided 

to the DEA a scientific and medical 

evaluation document prepared by the 

FDA entitled ‘‘Basis for the 

Recommendation to Decontrol 

Naloxegol and its Salts from Schedule II 

of the Controlled Substances Act.’’ 

Pursuant to 21 U.S.C. 811(b), this 

document contained an eight-factor 

analysis of naloxegol as a new drug, 

along with the HHS’s recommendation 

to remove naloxegol from the schedules 

of the CSA. 

In response, the DEA reviewed the 

scientific and medical evaluation and 

scheduling recommendation provided 

by the HHS, and all other relevant data, 

and completed its own eight-factor 

review document on naloxegol pursuant 

to 21 U.S.C. 811(c). Included below is a 

brief summary of each factor as 

analyzed by the HHS and DEA, and as 

considered by the DEA in this proposal 

to remove naloxegol from the schedules 

of the CSA. Please note that both the 

DEA and HHS analyses are available in 

their entirety under ‘‘Supporting and 

Related Material’’ of the public docket 

for this rule at http://

www.regulations.gov under docket 

number DEA–400. 

1. The Drug’s Actual or Relative 

Potential for Abuse 

Naloxegol is a new molecular entity 

that has not been marketed in the 

United States or in any other country. 

As such, there is no information 

available regarding actual abuse of 

naloxegol. However, scientific studies 

show that naloxegol does not 

demonstrate a potential for abuse. 

Naloxegol is a conjugation of 

polyethylene glycol (PEG) to naloxone. 

Naloxegol binds to mu, delta, and kappa 

opioid receptors and acts as an 

antagonist at these receptors. 

PEGylation of naloxone decreases the 

capacity of the substance to cross the 

blood-brain barrier, limiting the 

availability of naloxegol to peripheral 

opioid receptors (Diego et al., 2011; 

HHS review). Due to naloxegol being an 

antagonist at the three opioid receptors, 

mu, delta, and kappa, the HHS asserts 

that naloxegol does not have opioid 

agonist properties. Further, in abuse 

liability studies in animals, naloxegol 

did not produce responses seen with 

morphine administration. In clinical 

studies, the reports show that naloxegol 

does not produce euphoria or abuse 

potential related AEs. For example, the 

HHS stated that ‘‘[n]aloxegol (30 to 

1,000 mg/kg) produced less than 20% 

morphine-appropriate responding at any 

dose, which meets criteria for a ‘nodrug’ interoceptive cue.’’ 3 Therefore, 

naloxegol does not demonstrate a 

potential for abuse. 

2. Scientific Evidence of the Drug’s 

Pharmacological Effects, if Known 

Binding studies showed that 

naloxegol does not bind significantly 

(>50% inhibition) to other molecular 

central nervous system (CNS) receptors, 

including dopamine, serotonin, 

glutamate, a-aminobutyric acid (GABA), 

sigma, acetylcholine, norepinephrine, 

cannabinoid, histamine, and 

monoamine transporters. Toxicological 

studies in rats and dogs did not produce 

behavioral signs of abuse potential, e.g. 

increased or decreased motor behavior, 

decreased body weight, or food intake. 

In two analgesia models in rodents, 

naloxegol did not produce any analgesic 

effects, demonstrating the lack of mu 

opioid receptor activation. Naloxegol 

was also tested in both analgesia models 

for its potency in reversing morphineinduced (subcutaneous or intravenous, 

1–32 mg/kg) analgesia. Naloxegol did 

not fully reverse the analgesia produced 

by morphine, demonstrating that 

antagonistic actions of naloxegol were 

predominantly at the peripheral opioid 

receptor and not at the opioid receptors 

in the CNS. According to the HHS, oral 

naloxegol (12.5 and 25 mg/day) did 

precipitate opioid withdrawal in 

patients receiving opioids for pain 

management in the Phase 2/3 clinical 

trials. The incidence of withdrawal was 

low, the symptoms of opioid 

withdrawals occurred in patients taking 

naloxegol (2%) compared to placebo 

(<1%). It occurred with a higher 

incidence in patients receiving 

naloxegol (3%) at the higher dose (25 

mg/day) than those receiving the 12.5 

mg/day dose (1%). The HHS asserts that 

the withdrawal symptoms reported did 

not always meet the criteria of a 

clinically meaningful opioid withdrawal 

syndrome. 

3. The State of Current Scientific 

Knowledge Regarding the Drug or Other 

Substance 

Naloxegol is known as (5a,6a)-17- 

allyl-6-((20-hydroxy-3,6,9,12,15,18- 

hexaoxaicos-1-yl)oxy)-4,5- 

epoxymorphinon-3,14-diol and also as 

alpha-6mPEG7–O-naloxol. The CAS 

number is 854601–70–0. The molecular 

formula of naloxegol is C34H53NO11 

and the molecular weight is 651.8 g/

mol. It is a white to off-white powder 

and is soluble in aqueous solvents over 

a pH range of 1 to 7.5. Naloxegol is 

synthesized in a five-step process from 

naloxone hydrochloride, an opioid 

antagonist derived from thebaine. 

Naloxegol (25 mg/day) is rapidly 

absorbed following oral administration 

in healthy volunteers. Maximum plasma 

concentrations were reached in 1.5 to 2 

hours. The plasma half-life (t 1⁄2) is 7 to 

9 hours, with a maximal plasma 

concentration (Cmax) of 45 ng/ml. In a 

drug distribution study in humans with 

radiolabeled naloxegol, the highest 

levels of radioactivity were in the liver 

and kidneys. The elimination t 1⁄2 of 

naloxegol is rapid, with majority being 

eliminated within 24-hours post-dose. 

4. Its History and Current Pattern of 

Abuse 

According to HHS, there has been no 

evidence of abuse-related signals from 

the human clinical trials. Naloxegol is a 

mu opioid antagonist, which as a class 

does not have abuse potential. 

5. The Scope, Duration, and 

Significance of Abuse 

There have been no reports of abuse 

of naloxegol. According to the National 

Forensic Laboratory Information System 

(NFLIS) 4 and the System to Retrieve 

Information from Drug Evidence 

(STRIDE),5 there have been no reports of 

naloxegol seizures from 2010 to the 

present. 

6. What, if Any, Risk There Is to the 

Public Health 

According to the HHS, naloxegol is 

well-tolerated and safe at the 

therapeutic doses of 12.5 mg and 25 mg. 

Preclinical and clinical studies showed 

no evidence of potential for abuse of 

naloxegol and thus there is little public 

health risk from naloxegol. 


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7. Its Psychic or Physiological 

Dependence Liability 

There were no symptoms of physical 

dependence in a naloxegol physical 

dependence liability study in rats. The 

HHS also mentioned that the lack of 

naloxegol self-administration by 

animals is consistent with a lack of 

psychic dependence liability. 

8. Whether the Substance is an 

Immediate Precursor of a Substance 

Already Controlled Under the CSA 

Naloxegol is not considered an 

immediate precursor of any controlled 

substance. 

Conclusion 

Based on consideration of the 

scientific and medical evaluation and 

accompanying recommendation of the 

HHS, and based on the DEA’s 

consideration of its own eight-factor 

analysis, the DEA finds that these facts 

and all relevant data demonstrate that 

naloxegol does not possess abuse or 

dependence potential. Accordingly, the 

DEA finds that naloxegol does not meet 

the requirements for inclusion in any 

schedule, and should be removed from 

control under the CSA. 

Regulatory Analyses 

Executive Orders 12866 and 15363 

In accordance with 21 U.S.C. 811(a), 

this scheduling action is subject to 

formal rulemaking procedures done ‘‘on 

the record after opportunity for a 

hearing,’’ which are conducted pursuant 

to the provisions of 5 U.S.C. 556 and 

557. The CSA sets forth the criteria for 

scheduling a drug or other substance. 

Such actions are exempt from review by 

the Office of Management and Budget 

(OMB) pursuant to section 3(d)(1) of 

Executive Order 12866 and the 

principles reaffirmed in Executive Order 

13563. 

Executive Order 12988 

This regulation meets the applicable 

standards set forth in sections 3(a) and 

3(b)(2) of Executive Order 12988 Civil 

Justice Reform to eliminate drafting 

errors and ambiguity, minimize 

litigation, provide a clear legal standard 

for affected conduct, and promote 

simplification and burden reduction. 

Executive Order 13132 

This rulemaking does not have 

federalism implications warranting the 

application of Executive Order 13132. 

The rule does not have substantial 

direct effects on the States, on the 

relationship between the Federal 

Government and the States, or the 

distribution of power and 

responsibilities among the various 

levels of government. 

Executive Order 13175 

This rule does not have tribal 

implications warranting the application 

of Executive Order 13175. This rule 

does not 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. 

Regulatory Flexibility Act 

The Deputy Administrator, in 

accordance with the Regulatory 

Flexibility Act (5 U.S.C. 601–612) 

(RFA), has reviewed this proposed rule 

and by approving it certifies that it will 

not have a significant economic impact 

on a substantial number of small 

entities. The purpose of this rule is to 

remove naloxegol from the list of 

schedules of the CSA. This action will 

remove regulatory controls and 

administrative, civil, and criminal 

sanctions applicable to controlled 

substances for handlers and proposed 

handlers of naloxegol. Accordingly, it 

has the potential for some economic 

impact in the form of cost savings. 

Naloxegol is a new molecular entity 

and is not currently available or 

marketed in any country. According to 

publicly available information reviewed 

by the DEA, naloxegol is anticipated to 

enjoy patent protection for an extended 

period of time before generic 

equivalents may be manufactured and 

marketed in the United States. Although 

the number of manufacturers of 

naloxegol may initially be limited, there 

is potential for numerous handlers in 

various business activities, e.g., 

distributors, hospitals/clinics, 

pharmacies, practitioners, etc. 

If finalized, the proposed rule will 

affect all persons who would handle, or 

propose to handle, naloxegol. Due to the 

wide variety of unidentifiable and 

unquantifiable variables that potentially 

could influence the distribution and 

dispensing rates of new molecular 

entities, the DEA is unable to determine 

the number of entities and small entities 

which might handle naloxegol. 

However, the DEA estimates that all 

persons who would handle, or propose 

to handle naloxegol, are currently 

registered with the DEA to handle 

schedule II controlled substances. 

Therefore, the 1.5 million (1,469,418 as 

of September 2014) controlled substance 

registrations, representing 

approximately 426,714 entities, would 

be the maximum number of entities 

affected by this rule. The DEA estimates 

that 417,302 (97.8%) of 426,714 affected 

entities are ‘‘small entities’’ in 

accordance with the RFA and Small 

Business Administration size standards. 

The DEA estimates all controlled 

substances registrants handle both 

controlled and non-controlled 

substances and these registrants are 

expected to continue to handle 

naloxegol if the proposed rule were 

finalized. Additionally, since 

prospective naloxegol handlers are 

likely to handle other schedule II 

controlled substances, the cost savings 

they would receive as a result of the decontrol of naloxegol would be nominal. 

As naloxegol handlers continue to 

handle other scheduled II controlled 

substances, they will need to maintain 

their DEA registration and keep the 

same security and recordkeeping 

processes, equipment, and facilities in 

place and would experience only a 

nominal reduction in security, 

inventory, recordkeeping, and labeling 

costs. 

While the DEA does not have a basis 

to estimate the number of affected 

entities, the DEA estimates that the 

maximum number of affected entities is 

426,714 of which 417,302 are estimated 

to be small entities. Since the affected 

entities are expected to handle other 

schedule II controlled substances and 

maintain security and recordkeeping 

facilities and processes consistent with 

schedule II controlled substances 

handling requirements, the DEA 

estimates any economic impact (cost 

savings) will be nominal. Because of 

these facts, this rule will not result in a 

significant economic impact on a 

substantial number of small entities. 

Unfunded Mandates Reform Act of 1995 

On the basis of information contained 

in the ‘‘Regulatory Flexibility Act’’ 

section above, the DEA has determined 

and certifies pursuant to the Unfunded 

Mandates Reform Act of 1995 (UMRA), 

2 U.S.C. 1501 et seq., that this action 

would not result in 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 for 

inflation) in any one year * * *.’’ 

Therefore, neither a Small Government 

Agency Plan nor any other action is 

required under provisions of UMRA. 

Paperwork Reduction Act 

This action does not impose a new 

collection of information requirement 

under the Paperwork Reduction Act, 44 

U.S.C. 3501–3521. This action would 

not impose recordkeeping or reporting 

requirements on State or local 

governments, individuals, businesses, or 


rmajette on DSK2TPTVN1PROD with PROPOSALS
Federal Register / Vol. 79, No. 209 / Wednesday, October 29, 2014 / Proposed Rules 64353 

organizations. An agency may not 

conduct or sponsor, and a person is not 

required to respond to, a collection of 

information unless it displays a 

currently valid OMB control number. 

List of Subjects in 21 CFR Part 1308 

Administrative practice and 

procedure, Drug traffic control, 

Reporting and recordkeeping 

requirements. 

For the reasons set out above, 21 CFR 

part 1308 is proposed to be amended to 

read as follows: 

PART 1308—SCHEDULES OF 

CONTROLLED SUBSTANCES 

■ 1. The authority citation for 21 CFR 

part 1308 continues to read as follows: 

Authority: 21 U.S.C. 811, 812, 871(b), 

unless otherwise noted. 

■ 2. In § 1308.12, amend the 

introductory text of paragraph (b)(1) by 

adding the word ‘‘naloxegol,’’ between 

‘‘nalmefene,’’ and ‘‘naloxone,’’ to read 

as follows: 

§ 1308.12 Schedule II. 

(a) * * * 

(b) * * * 

(1) Opium and opiate, and any salt, 

compound, derivative, or preparation of 

opium or opiate excluding 

apomorphine, thebaine-derived 

butorphanol, dextrorphan, nalbuphine, 

nalmefene, naloxegol, naloxone, and 

naltrexone, and their respective salts, 

but including the following: 

* * * * * 

Dated: October 23, 2014. 

Thomas M. Harrigan, 

Deputy Administrator. 

[FR Doc. 2014–25685 Filed 10–28–14; 8:45 am] 

BILLING CODE 4410–09–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 52 

[EPA–R09–OAR–2014–0696; FRL–9918–58– 

Region 9] 

Revisions to the California State 

Implementation Plan, Ventura County 

Air Pollution Control District 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Proposed rule. 

SUMMARY: The Environmental Protection 

Agency (EPA) is proposing to approve a 

State Implementation Plan (SIP) 

revision submitted by California for the 

Ventura County Air Pollution Control 

District (VCAPCD or ‘‘the District’’) 

portion of the California SIP. The 

submitted SIP revision contains the 

District’s demonstration regarding 

Reasonably Available Control 

Technology (RACT) requirements for 

the 2008 8-hour ozone National 

Ambient Air Quality Standards 

(NAAQS). We are proposing to approve 

the submitted SIP revision under the 

Clean Air Act as amended in 1990 (CAA 

or the Act). We are taking comments on 

this proposal and plan to follow with a 

final action. 

DATES: Any comments must arrive by 

November 28, 2014. 

ADDRESSES: Submit comments, 

identified by docket number EPA–R09– 

OAR–2014–0696, by one of the 

following methods: 

1. Federal eRulemaking Portal: 

www.regulations.gov. Follow the on-line 

instructions. 

2. Email: steckel.andrew@epa.gov. 

3. Mail or deliver: Andrew Steckel 

(Air-4), U.S. Environmental Protection 

Agency Region IX, 75 Hawthorne Street, 

San Francisco, CA 94105–3901. 

Instructions: All comments will be 

included in the public docket without 

change and may be made available 

online at www.regulations.gov, 

including any personal information 

provided, unless the comment includes 

Confidential Business Information (CBI) 

or other information whose disclosure is 

restricted by statute. Information that 

you consider CBI or otherwise protected 

should be clearly identified as such and 

should not be submitted through 

www.regulations.gov or email. 

www.regulations.gov is an ‘‘anonymous 

access’’ system, and EPA will not know 

your identity or contact information 

unless you provide it in the body of 

your comment. If you send email 

directly to EPA, your email address will 

be automatically captured and included 

as part of the public comment. If EPA 

cannot read your comment due to 

technical difficulties and cannot contact 

you for clarification, EPA may not be 

able to consider your comment. 

Electronic files should avoid the use of 

special characters, any form of 

encryption, and be free of any defects or 

viruses. 

Docket: Generally, documents in the 

docket for this action are available 

electronically at www.regulations.gov 

and in hard copy at EPA Region IX, 75 

Hawthorne Street, San Francisco, 

California. While all documents in the 

docket are listed at 

www.regulations.gov, some information 

may be publicly available only at the 

hard copy location (e.g., copyrighted 

material, large maps), and some may not 

be publicly available in either location 

(e.g., CBI). To inspect the hard copy 

materials, please schedule an 

appointment during normal business 

hours with the contact listed in the FOR

FURTHER INFORMATION CONTACT section. 

FOR FURTHER INFORMATION CONTACT: 

Stanley Tong, EPA Region IX, (415) 

947–4122, tong.stanley@epa.gov. 

SUPPLEMENTARY INFORMATION: 

Throughout this document, ‘‘we,’’ ‘‘us’’ 

and ‘‘our’’ refer to EPA. 

Table of Contents 

I. The State’s Submittal 

A. What document did the State submit? 

B. Are there other versions of document? 

C. What is the purpose of the RACT SIP 

submission? 

II. EPA’s Evaluation and Proposed Action 

A. How is EPA evaluating the RACT SIP 

submission? 

B. Does the RACT SIP submission meet the 

evaluation criteria? 

C. EPA’s Recommendation To Strengthen 

the RACT SIP 

D. Proposed Action and Public Comment 

III. Statutory and Executive Order Reviews 

I. The State’s Submittal 

A. What document did the State submit? 

Table 1 lists the document addressed 

by this proposal with the date that it 

was adopted by the local air agency and 

submitted by the California Air 

Resources Board. 

TABLE 1—SUBMITTED DOCUMENT

Local agency Document Adopted Submitted 

VCAPCD ................... 2014 Reasonably Available Control Technology (RACT) State Implementation Plan 

(SIP) Revision (‘‘2014 RACT SIP’’).

6/10/14 7/18/14 


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