This section of the FEDERAL REGISTER

contains regulatory documents having general

applicability and legal effect, most of which

are keyed to and codified in the Code of

Federal Regulations, which is published under

50 titles pursuant to 44 U.S.C. 1510.

The Code of Federal Regulations is sold by

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new books are listed in the first FEDERAL

REGISTER issue of each week.

Rules and Regulations Federal Register

77895 

Vol. 76, No. 241 

Thursday, December 15, 2011 

1http://www.accessdata.fda.gov/ 

drugsatfda_docs/nda/2011/ 

022345Orig1s000TOC.cfm; as of July 21, 2011. 

DEPARTMENT OF JUSTICE 

Drug Enforcement Administration 

21 CFR Part 1308 

[Docket No. DEA–354] 

Schedules of Controlled Substances: 

Placement of Ezogabine Into 

Schedule V 

AGENCY: Drug Enforcement 

Administration, Department of Justice. 

ACTION: Final rule. 

SUMMARY: With the issuance of this final 

rule, the Administrator of the Drug 

Enforcement Administration (DEA) 

places the substance ezogabine, 

including its salts, isomers, and salts of 

isomers whenever the existence of such 

salts, isomers, and salts of isomers is 

possible, into Schedule V of the 

Controlled Substances Act (CSA). This 

action is pursuant to the CSA which 

requires that such actions be made on 

the record after opportunity for a 

hearing through formal rulemaking. 

DATES: Effective date: December 15, 

2011. 

FOR FURTHER INFORMATION CONTACT: 

Rhea D. Moore, Office of Diversion 

Control, Drug Enforcement 

Administration, 8701 Morrissette Drive, 

Springfield, Virginia 22152; Telephone 

(202) 307–7165. 

SUPPLEMENTARY INFORMATION: 

Legal Authority 

The DEA implements and enforces 

Titles II and III of the Comprehensive 

Drug Abuse Prevention and Control Act 

of 1970, often referred to as the 

Controlled Substances Act and the 

Controlled Substances Import and 

Export Act (21 U.S.C. 801–971), as 

amended (hereinafter, ‘‘CSA’’). The 

implementing regulations for these 

statutes are found in Title 21 of the 

Code of Federal Regulations (CFR), parts 

1300 to 1321. Under the CSA, controlled 

substances are classified in one of five 

schedules based upon their potential for 

abuse, their currently accepted medical 

use, and the degree of dependence the 

substance may cause, 21 U.S.C. 812. The 

initial schedules of controlled 

substances by statute are found at 21 

U.S.C. 812(c) and the current list of 

scheduled substances is published at 21 

CFR Part 1308. 

Pursuant to 21 U.S.C. 811(a)(1), the 

Attorney General may, by rule, ‘‘add to 

such a schedule or transfer between 

such schedules any drug or other 

substance if he (A) Finds that such drug 

or other substance has a potential for 

abuse, and (B) makes 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 

* * *’’ Pursuant to 28 CFR 0.100(b), the 

Attorney General has delegated this 

scheduling authority to the 

Administrator of DEA. 

The CSA provides that 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 HHS, or (3) on the petition 

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

This action is based on a 

recommendation from the Assistant 

Secretary for Health of the Department 

of Health and Human Services (HHS) 

and on an evaluation of all other 

relevant data by DEA. This action 

imposes the regulatory controls and 

criminal sanctions of Schedule V on the 

manufacture, distribution, dispensing, 

importation, and exportation of 

ezogabine and products containing 

ezogabine. 

Pursuant to 21 CFR 1308.44(e), the 

Administrator of DEA may issue her 

final order ‘‘[I]f all interested persons 

waive or are deemed to waive their 

opportunity for the hearing or to 

participate in the hearing.’’ As no 

requests for a hearing were filed on this 

proposed scheduling action, all 

interested persons are deemed to have 

waived their opportunity for a hearing 

pursuant to 21 CFR 1308.44(d), and the 

Administrator may issue her final order 

without a hearing. 

Ezogabine is a new drug with a novel 

mechanism of action for the treatment of 

partial onset seizures. Because 

ezogabine is a new drug with possible 

immediate medical application to a lifethreatening illness not always treatable 

with medications currently available 

and because it may not be prescribed in 

the United States until this final 

rulemaking action is in effect and the 

subsequent requirements that result 

from this final action are satisfied, the 

Administrator hereby finds that it is in 

the interest of public health to forego 

the 30 day period prior to this final rule 

taking effect. This will impose no 

hardship on any interested party and is 

responsive to comments intended to 

facilitate the availability of ezogabine as 

soon as possible for that population of 

people suffering from seizures that may 

benefit from treatment with ezogabine. 

Therefore, in accordance with this 

finding of conditions of public health 

and of good cause to waive the 30 day 

period and pursuant to 21 CFR 1308.45 

and 5 U.S.C. 553(d)(3), this final rule is 

effective upon publication. 

Background 

Ezogabine, known chemically as N-[2- 

amino-4-(4-fluorobenzylamino)-phenyl]- 

carbamic acid ethyl ester, is a new 

chemical substance with central 

nervous system depressant properties 

and is classified as a sedative-hypnotic. 

Pharmacological studies indicate that 

ezogabine primarily acts as a ligand at 

ion-gated channels in the brain to 

enhance potassium currents mediated 

by neuronal KCNQ (Kv7) channels. 

Additionally, ezogabine indirectly 

enhances the gamma-aminobutyric acid 

(GABA) mediated neurotransmission. 

On June 10, 2011, the Food and Drug 

Administration (FDA) approved a New 

Drug Application (NDA) for ezogabine 

as an adjunct treatment of partial onset 

seizures, to be marketed under the trade 

name Potiga®.1

Determination To Schedule Ezogabine 

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

proceedings to add a drug or substance 

to those controlled under the CSA may 

be initiated by request of the Secretary 

of HHS. On January 12, 2011, HHS 

provided DEA with a scientific and 

medical evaluation document prepared 

by FDA entitled ‘‘Basis for the 

Recommendation for Control of 

Ezogabine in Schedule V of the 

Controlled Substances Act.’’ Pursuant to 

21 U.S.C. 811(b), this document 


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2Comprehensive Drug Abuse Prevention and 

Control Act of 1970, H.R. Rep. No. 91–1444, 91st 

Cong., Sess. 1 (1970); 1970 U.S.C.C.A.N. 4566, 4601. 

contained an eight-factor analysis of the 

abuse potential of ezogabine as a new 

drug, along with HHS’ recommendation 

to control ezogabine under Schedule V 

of the CSA. In response, DEA conducted 

an eight-factor analysis of ezogabine’s 

abuse potential pursuant to 21 U.S.C. 

811(c). 

Following analysis, the Administrator 

of DEA published a Notice of Proposed 

Rulemaking entitled ‘‘Schedules of 

Controlled Substances: Placement of 

Ezogabine into Schedule V’’ on October 

21, 2011 (76 FR 65424), which proposed 

placement of ezogabine into Schedule V 

of the CSA. The proposed rule provided 

an opportunity for all interested persons 

to request a hearing or to submit 

comments on or before November 21, 

2011. 

Included below is a brief summary of 

each factor as analyzed by HHS and 

DEA, and as considered by DEA in the 

scheduling decision. Please note that 

both the DEA and HHS analyses are 

available under ‘‘Supporting and 

Related Material’’ of the public docket 

for this rule at www.regulations.gov 

under docket number DEA–354. 

1. The Drug’s Actual or Relative 

Potential for Abuse: Ezogabine is a new 

chemical substance that has not been 

marketed in the U.S. As such, there is 

no information available which details 

actual abuse of ezogabine. However, the 

legislative history of the CSA offers 

another methodology for assessing a 

drug or substance’s potential for abuse: 

The drug or drugs containing such a 

substance are new drugs so related in their 

action to a drug or drugs already listed as 

having a potential for abuse to make it likely 

that the drug will have the same potentiality 

for abuse as such drugs, thus making it 

reasonable to assume that there may be 

significant diversions from legitimate 

channels, significant use contrary to or 

without medical advice, or that it has a 

substantial capability of creating hazards to 

the health of the user or to the safety of the 

community.2

Ezogabine acts as a ligand at ion-gated 

channels in the brain, similar to the 

Schedule V substances pregabalin and 

lacosamide, and, like those drugs, 

ezogabine is indicated for the treatment 

of epileptic conditions in humans. 

There is strong evidence, described 

below, that ezogabine produces 

behavioral effects in humans and in 

animals that are similar to those 

produced by pregabalin and lacosamide. 

Phase 1 clinical studies indicate that 

the rate of euphoria-related adverse 

events (AEs) resulting from 

administration of ezogabine was 6–9%. 

This is similar to the AE rates for 

administration of pregabalin (10%) and 

lacosamide (>7%), while Phase 2⁄3

clinical studies indicated similar AE 

rates between ezogabine (<1%) and 

lacosamide (<2%). Animal studies 

involving administration of ezogabine to 

animals produced a sedative behavioral 

profile similar to that produced from 

administration of pregabalin and 

lacosamide, including decreased 

locomotion, decreased muscle tone, and 

an increase in ataxia. Further, in abuse 

potential studies conducted with 

sedative-hypnotic abusers, ezogabine, 

pregabalin, and lacosamide, when 

compared to placebos, are similar in 

their ability to produce statistically 

significant increases in subjective 

responses including ‘‘Drug Liking,’’ 

‘‘Euphoria,’’ ‘‘Overall Drug Liking,’’ 

‘‘Good Drug Effects,’’ and ‘‘High.’’ 

Because of the similarities between 

ezogabine, pregabalin, and lacosamide, 

it is very likely that ezogabine will have 

an abuse potential similar to those 

Schedule V substances. Currently there 

is a lack of evidence regarding the 

diversion, illicit manufacturing or 

deliberate misuse of ezogabine due to its 

commercial unavailability in any 

country, but since ezogabine is not 

readily synthesized from available 

substances, any diversion would be 

from legitimate channels. The above 

referenced studies, which include 

demonstration of the significant 

euphoric effects produced by ezogabine 

in humans, predict that there will be 

significant use of ezogabine contrary to 

or without medical advice. 

2. Scientific Evidence of the Drug’s 

Pharmacological Effects, If Known: 

Ezogabine acts to enhance potassium 

currents mediated by neuronal KCNQ 

(Kv7) channels with a secondary action 

through the augmentation of GABAmediated neurotransmission without 

direct GABA receptor stimulation. In 

individuals with histories of 

recreational sedative-hypnotic abuse, 

ezogabine (300 and 600 mg orally) 

produced increased ratings on the 

primary positive subjective scales [VASDrug-liking, VAS-Overall Drug Liking, 

ARCI-MBG (Euphoria), VAS-Take Drug 

Again] for peak responses (Emax for the 

first eight hours after drug 

administration) that were significantly 

different from the placebo. This effect is 

similar to that produced by alprazolam 

(1.5 and 3.0 mg orally; Schedule IV). On 

secondary positive subjective scales 

[VAS-High, VAS-Good Effects, ARCIAmphetamine (Activation)] for peak 

responses, both ezogabine and 

alprazolam produced significant 

increases compared to the placebo, 

while there were no differences between 

ezogabine and alprazolam on those 

measures. 

In human abuse potential studies, 

ezogabine (300 and 600 mg), upon oral 

administration, increased ratings on 

negative and sedating subjective 

measures [VAS-Bad Effects, ARCI-LSD 

(dysphoria) and ARCI-PCAG (sedation)] 

compared to the placebo, but these 

increases were lower than those 

produced by 1.5 and 3.0 mg alprazolam. 

These data for ezogabine are similar to 

those produced by lacosamide. A 900 

mg dose of ezogabine produced VASDrug Liking and VAS-Good Effects that 

were higher than those produced by the 

two lower doses of ezogabine and either 

dose of alprazolam. However, the 

changes in VAS-Bad Effects and ARCILSD (dysphoria) following 900 mg 

ezogabine were less than or similar to 

those produced by lower doses of 

ezogabine and either dose of 

alprazolam. The adverse events 

following 900 mg ezogabine are similar 

to those described in the NDA file for 

the human abuse potential study 

conducted with lacosamide. These 

included euphoria, somnolence, visual 

disturbances, and altered auditory 

perception. 

In human abuse potential studies, 

ezogabine, similar to pregabalin and 

lacosamide, also produced ratings on 

each of the positive subjective responses 

that were statistically similar to those 

produced by Schedule IV 

benzodiazepines (alprazolam or 

diazepam). Although this appears to 

suggest that these drugs have an abuse 

potential similar to that of Schedule IV 

substances, the other data from human 

abuse potential studies, the adverse 

effect profile data from safety and 

efficacy studies, and the data from the 

preclinical animal behavioral studies 

demonstrate that ezogabine has abuse 

potential less than that of Schedule IV 

drugs but similar to that of Schedule V 

drugs. 

3. The State of Current Scientific 

Knowledge Regarding the Drug or Other 

Substance: The chemical name of 

ezogabine is N-[2-amino-4-(4- 

fluorobenzylamino)-phenyl]-carbamic 

acid ethyl ester. It is an achiral molecule 

with a molecular formula of 

C16H18FN3O2 and a molecular weight of 

303.3 g/mol. Ezogabine is a nonhygroscopic white to slightly colored 

powder with a melting point of 

140–143 °C. It is soluble in 0.9% saline, 

methanol, chloroform, but only 

sparingly soluble in ethanol and 0.1N 

HCL. 

Ezogabine in humans has a Tmax (time 

required for ezogabine to reach 

maximum plasma concentration) 

ranging from 1–4 hours following both 


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acute and multiple dosing, and, without 

the involvement of cytochrome P450, 

undergoes an extensive and almost 

exclusively phase 2 metabolic 

biotransformation. Ezogabine is 

predominantly metabolized by Nglucuronidation, resulting in the 

formation of two distinct Nglucuronides of the unchanged parent 

drug and to a lesser extent by Nacetylation to form N-acetyl-retigabine, 

the major bioactive metabolite of 

ezogabine. The half-life of both 

ezogabine and N-acetyl-retigabine is 

approximately eight hours and the Cmax

(maximum plasma concentration) of 

both components is dose proportional 

after both acute and multiple dosing, 

suggesting a lack of accumulation with 

repeated administration. 

4. Its History and Current Pattern of 

Abuse: As stated in the summary of 

Factor 1, information on ezogabine’s 

history and current pattern of abuse is 

unavailable as it has not been marketed 

in any country. As such, evaluation of 

abuse potential for ezogabine derives 

from positive indicators in clinical 

studies which are believed to be 

predictive of drug abuse and which are 

discussed in Factors 1 and 2 above. 

5. The Scope, Duration, and 

Significance of Abuse: Because 

ezogabine has not yet been marketed, 

information on the scope, duration, and 

significance of abuse of ezogabine is 

unavailable. However, epidemiological 

data on pregabalin, a Schedule V drug 

with an abuse potential similar to that 

of ezogabine, is available from the Drug 

Abuse Warning Network (DAWN) 

database. 

The ‘‘abuse frequency ratio,’’ 

calculated as the ratio of nonmedical 

use related annual emergency 

department visits (as reported in 

DAWN) to the total number of annual 

prescriptions for pregabalin is less than 

that for the Schedule IV drug, 

alprazolam. Further, because ezogabine 

has abuse-related human and animal 

data in its NDA file similar to data 

generated for pregabalin, ezogabine is 

likely to have an abuse potential similar 

to pregabalin. The ‘‘abuse frequency 

ratios’’ for pregabalin range from 29 to 

47, while those for alprazolam are 

approximately three to six times higher, 

ranging from 160 to 235. Thus, 

pregabalin was placed into Schedule V 

based both on abuse-related human and 

animal data submitted in its NDA and 

by epidemiological data which justified 

placement relative to drugs in Schedule 

IV. Given that ezogabine has abuserelated human and animal data in its 

NDA file similar to the data generated 

by pregabalin, it is likely that ezogabine 

will have an abuse potential similar to 

this Schedule V drug. 

6. What, if any, Risk There is to the 

Public Health: The data indicates that 

ezogabine may present a serious safety 

risk to the public health, and the 

predicted level of risk is similar to that 

observed with pregabalin and 

lacosamide but less than that produced 

by Schedule IV benzodiazepines. In 

Phase 1 clinical safety studies, the 

overall adverse event profile following 

ezogabine administration was similar to 

those from pregabalin and lacosamide 

and includes not only euphoria, but also 

somnolence, and feeling or thinking 

abnormally. Further, the human abuse 

potential study showed that the majority 

of subjects receiving the 900 mg dose of 

ezogabine experienced multiple adverse 

events such as euphoria, somnolence, 

visual disturbance, amnesia, hypoaesthesia, paranoia, fear, confusion and 

hallucination. Although the 900 mg 

dose is three times greater than the 

recommended therapeutic dose, 

individuals who abuse drugs typically 

do so at supra-therapeutic doses. 

7. Its Psychic or Physiological 

Dependence Liability: Ezogabine may 

produce limited psychic or 

physiological dependence liability 

following extended administration. 

Since there are no studies detailing 

abrupt discontinuation of ezogabine, 

there are minimal adequate data to 

evaluate the ability of ezogabine to 

induce withdrawal symptoms that are 

indicative of physical dependence. 

Many of the adverse events reported 

from the discontinuation of ezogabine 

were also reported prior to its 

discontinuation, including dizziness, 

somnolence, and a state of confusion. 

By comparison, abrupt or rapid 

discontinuation of pregabalin in human 

studies resulted in patient-reported 

symptoms of nausea, headache or 

diarrhea, which are suggestive of 

physical dependence, while abrupt 

termination of lacosamide produced no 

signs or symptoms of withdrawal in 

diabetic neuropathic pain patients. 

Unlike ezogabine and pregabalin, the 

withdrawal syndrome following 

discontinuation of Schedule IV 

substances such as alprazolam can range 

from mild dysphoria and insomnia to a 

major syndrome including abdominal 

pain, muscle cramps, vomiting, 

sweating, tremors and convulsions. 

These are similar in character to those 

associated with other sedativehypnotics. 

The study of ezogabine abuse 

potential in humans with histories of 

recreational abuse of sedative-hypnotics 

found that ezogabine produces euphoria 

(18–33%) in these individuals. 

Additionally, ezogabine produced 

euphoria (8.5%) in Phase 1 studies in 

healthy individuals. These euphoriarelated adverse events following 

administration of ezogabine are 

suggestive of its ability to produce 

psychic dependence, and the adverse 

events appear to be less severe and 

occur less frequently than Schedule IV 

drugs (diazepam and alprazolam) and 

are more similar to those of Schedule V 

drugs, pregabalin and lacosamide. 

8. Whether the Substance is an 

Immediate Precursor of a Substance 

Already Controlled Under the CSA: 

Ezogabine is not an immediate 

precursor of any controlled substance. 

Requests for a Hearing and Comments 

DEA received no requests for a 

hearing on this scheduling action. DEA 

received two comments on the NPRM to 

schedule ezogabine. 

Comment: The first comment 

requested that ezogabine be placed into 

Schedule IV of the CSA instead of 

Schedule V as proposed. While the 

commenter stated that ezogabine may 

help those who have not had success 

with current epilepsy treatments, the 

commenter believed that ezogabine’s 

new mechanism of action, including its 

effect on the central nervous system as 

an anticonvulsant and the potential side 

effects of the drug therein, warrant 

closer scrutiny and supervision under 

Schedule IV. 

DEA Response: DEA disagrees. That 

ezogabine has an effect on the central 

nervous system is alone not enough to 

merit its inclusion into Schedule IV of 

the CSA, nor is the possibility that 

persons to whom ezogabine is 

prescribed would need to monitor their 

medications closely. Instead, as detailed 

in the HHS and DEA analyses and the 

HHS recommendation, studies indicate 

that the abuse potential and likely 

effects of ezogabine are similar to those 

of the Schedule V drugs pregabalin and 

lacosamide, and, therefore, merit 

ezogabine’s inclusion into Schedule V 

of the CSA. 

Comment: The second comment 

stated that because epilepsy is a serious 

and potentially life-threatening illness 

that may not be adequately treated with 

currently available medicines, 

conditions of public health necessitate 

an early effective date for the final rule 

pursuant to 21 CFR 1308.45. As such, 

the commenter requested an effective 

date for the rule concurrent with its 

publication in the Federal Register. 

DEA Response: As stated under 

‘‘Legal Authority,’’ DEA agrees that this 

rule should become effective upon 

publication. Ezogabine, unlike the 

currently available anticonvulsant 


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medications, may act as an 

anticonvulsant through a novel 

mechanism of action. Because some 

patients with epilepsy do not achieve 

satisfactory seizure control from 

treatments currently in use, the 

availability of ezogabine becomes an 

important and potentially life-saving 

option for such patients. Thus, for 

public health reasons pursuant to 21 

CFR 1308.45 and based on finding good 

cause pursuant to 5 U.S.C. 553(d)(3) as 

outlined, this final rule is effective upon 

publication in the Federal Register. 

Scheduling Conclusion 

Based on consideration of the 

scientific and medical evaluation and 

accompanying recommendation of HHS, 

and based on DEA’s consideration of its 

own eight-factor analysis, DEA finds 

that these facts and all relevant data 

constitute substantial evidence of 

potential for abuse of ezogabine. As 

such, DEA will schedule ezogabine as a 

controlled substance under the CSA. 

Determination of Appropriate Schedule 

The CSA establishes five schedules of 

controlled substances known as 

Schedules I, II, III, IV, and V. The statute 

outlines the findings required to place a 

drug or other substance in any 

particular schedule. 21 U.S.C. 812(b). 

After consideration of the analysis and 

recommendation of the Assistant 

Secretary for Health of HHS and review 

of all available data, the Administrator 

of DEA, pursuant to 21 U.S.C. 812(b)(5), 

finds that: 

(1) Ezogabine has a low potential for 

abuse relative to the drugs or other 

substances in Schedule IV. The overall 

abuse potential of ezogabine is 

comparable to the Schedule V 

substances such as pregabalin and 

lacosamide; 

(2) Ezogabine has a currently accepted 

medical use in treatment in the United 

States. Ezogabine was approved for 

marketing by FDA as an adjunct 

treatment of partial onset seizures; and 

(3) Abuse of ezogabine may lead to 

limited physical dependence or 

psychological dependence relative to 

the drugs or other substances in 

Schedule IV. 

Based on these findings, the 

Administrator of DEA concludes that 

ezogabine, including its salts, isomers 

and salts of isomers, whenever the 

existence of such salts, isomers, and 

salts of isomers is possible, warrants 

control in Schedule V of the CSA (21 

U.S.C. 812(b)(5)). 

Requirements for Handling Ezogabine 

Upon the effective date of this final 

rule, ezogabine is subject to the CSA 

and the Controlled Substances Import 

and Export Act (CSIEA) regulatory 

controls and administrative, civil and 

criminal sanctions applicable to the 

manufacture, distribution, dispensing, 

importing and exporting of a Schedule 

V controlled substance, including the 

following: 

Registration. Any person who 

manufactures, distributes, dispenses, 

imports, exports, engages in research or 

conducts instructional activities with 

ezogabine, or who desires to 

manufacture, distribute, dispense, 

import, export, engage in research or 

conduct instructional activities with 

ezogabine, must be registered to conduct 

such activities pursuant to 21 U.S.C. 822 

and in accordance with 21 CFR Part 

1301. 

Security. Ezogabine is subject to 

Schedules III–V security requirements 

and must be manufactured, distributed, 

and stored pursuant to 21 U.S.C. 823 

and in accordance with 21 CFR 1301.71, 

1301.72(b), (c), and (d), 1301.73, 

1301.74, 1301.75(b) and (c), 1301.76, 

and 1301.77. 

Labeling and Packaging. All labels 

and labeling for commercial containers 

of ezogabine which are distributed on or 

after the effective date of this final rule 

must be in accordance with 21 CFR 

1302.03–1302.07, pursuant to 21 U.S.C. 

825. 

Inventory. Every registrant required to 

keep records and who possesses any 

quantity of ezogabine must keep an 

inventory of all stocks of ezogabine on 

hand pursuant to 21 U.S.C. 827 and in 

accordance with 21 CFR 1304.03, 

1304.04, and 1304.11. Every registrant 

who desires registration in Schedule V 

for ezogabine must conduct an 

inventory of all stocks of the substance 

on hand at the time of registration. 

Records. All registrants must keep 

records pursuant to 21 U.S.C. 827 and 

in accordance with 21 CFR 1304.03, 

1304.04, 1304.06, 1304.21, 1304.22, and 

1304.23. 

Prescriptions. Ezogabine or products 

containing ezogabine must be 

distributed or dispensed pursuant to 21 

U.S.C. 829 and in accordance with 21 

CFR 1306.03–1306.06, 1306.08, 1306.21, 

and 1306.23–1306.27. 

Importation and Exportation. All 

importation and exportation of 

ezogabine must be done in accordance 

with 21 CFR Part 1312, pursuant to 21 

U.S.C. 952, 953, 957, and 958. 

Criminal Liability. Any activity with 

ezogabine not authorized by, or in 

violation of, Subchapter I Part D and 

Subchapter II of the CSA or the CSIEA 

occurring on or after the effective date 

of this final rule is unlawful. 

Regulatory Analyses 

Executive Orders 12866 and 13563 

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 

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 ambiguity, 

minimize litigation, establish clear legal 

standards, and reduce burden. 

Executive Order 13132 

This rulemaking does not preempt or 

modify any provision of state law or 

impose enforcement responsibilities on 

any state or diminish the power of any 

state to enforce its own laws. 

Accordingly, this rulemaking does not 

have federalism implications warranting 

the application of Executive Order 

13132. 

Executive Order 13175 

This rule will not have tribal 

implications and will not impose 

substantial direct compliance costs on 

Indian tribal governments. 

Paperwork Reduction Act of 1995 

This action does not impose a new 

collection of information under the 

Paperwork Reduction Act of 1995, 44 

U.S.C. 3501–3521. 

Congressional Review Act 

This rule is not a major rule as 

defined by § 804 of the Small Business 

Regulatory Enforcement Fairness Act of 

1996 (Congressional Review Act). This 

rule will not result in an annual effect 

on the economy of $100,000,000 or 

more, a major increase in costs or prices, 

or significant adverse effects on 

competition, employment, investment, 

productivity, innovation, or on the 

ability of United States-based 

companies to compete with foreign 

based companies in domestic and 

export markets. 

List of Subjects in 21 CFR Part 1308 

Administrative practice and 

procedure, Drug traffic control, 

Reporting and recordkeeping 

requirements. 


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For the reasons set out above, 21 CFR 

Part 1308 is amended 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. Section 1308.15 is amended by 

redesignating paragraphs (e)(1) and (2) 

as paragraphs (e)(2) and (3), and adding 

a new paragraph (e)(1) to read as 

follows: 

§ 1308.15 Schedule V. 

* * * * * 

(e) * * * 

(1) Ezogabine [N-[2-amino-4-(4- 

fluorobenzylamino)-phenyl]-carbamic acid 

ethyl ester]–2779 

* * * * * 

Dated: December 8, 2011. 

Michele M. Leonhart, 

Administrator. 

[FR Doc. 2011–32172 Filed 12–14–11; 8:45 am] 

BILLING CODE 4410–09–P 

DEPARTMENT OF TRANSPORTATION 

Federal Aviation Administration 

14 CFR Part 71 

[Docket No. FAA–2011–0893; Airspace 

Docket No. 11–ANM–18] 

Modification of Class E Airspace; The 

Dalles, OR 

AGENCY: Federal Aviation 

Administration (FAA), DOT. 

ACTION: Final rule. 

SUMMARY: This action modifies Class E 

airspace at The Dalles, OR. Controlled 

airspace is necessary to accommodate 

aircraft using Area Navigation (RNAV) 

Global Positioning System (GPS) 

standard instrument approach 

procedures at Columbia Gorge Regional/ 

The Dalles Municipal Airport. This 

action also changes the airport name. 

This improves the safety and 

management of Instrument Flight Rules 

(IFR) operations at the airport. 

DATES: Effective date, 0901 UTC, April 

5, 2012. The Director of the Federal 

Register approves this incorporation by 

reference action under 1 CFR part 51, 

subject to the annual revision of FAA 

Order 7400.9 and publication of 

conforming amendments. 

FOR FURTHER INFORMATION CONTACT: 

Eldon Taylor, Federal Aviation 

Administration, Operations Support 

Group, Western Service Center, 1601 

Lind Avenue SW., Renton, WA 98057; 

telephone (425) 203–4537. 

SUPPLEMENTARY INFORMATION: 

History 

On October 12, 2011, the FAA 

published in the Federal Register a 

notice of proposed rulemaking to 

modify controlled airspace at The 

Dalles, OR (76 FR 63235). Interested 

parties were invited to participate in 

this rulemaking effort by submitting 

written comments on the proposal to the 

FAA. No comments were received. 

Class E airspace designations are 

published in paragraph 6005, of FAA 

Order 7400.9V dated August 9, 2011, 

and effective September 15, 2011, which 

is incorporated by reference in 14 CFR 

71.1. The Class E airspace designations 

listed in this document will be 

published subsequently in that Order. 

The Rule 

This action amends Title 14 Code of 

Federal Regulations (14 CFR) Part 71 by 

modifying Class E airspace extending 

upward from 700 feet above the surface, 

at Columbia Gorge Regional/The Dalles 

Municipal Airport, to accommodate IFR 

aircraft executing RNAV (GPS) standard 

instrument approach procedures at the 

airport. This also notes the airport’s 

name change from The Dalles Municipal 

Airport to Columbia Gorge Regional/The 

Dalles Municipal Airport. This action is 

necessary for the safety and 

management of IFR operations. 

The FAA has determined this 

regulation only involves an established 

body of technical regulations for which 

frequent and routine amendments are 

necessary to keep them operationally 

current. Therefore, this regulation: (1) Is 

not a ‘‘significant regulatory action’’ 

under Executive Order 12866; (2) is not 

a ‘‘significant rule’’ under DOT 

Regulatory Policies and Procedures (44 

FR 11034; February 26, 1979); and (3) 

does not warrant preparation of a 

regulatory evaluation as the anticipated 

impact is so minimal. Since this is a 

routine matter that will only affect air 

traffic procedures and air navigation, it 

is certified this rule, when promulgated, 

will not have a significant economic 

impact on a substantial number of small 

entities under the criteria of the 

Regulatory Flexibility Act. The FAA’s 

authority to issue rules regarding 

aviation safety is found in Title 49 of the 

U.S. Code. Subtitle 1, Section 106 

discusses the authority of the FAA 

Administrator. Subtitle VII, Aviation 

Programs, describes in more detail the 

scope of the agency’s authority. This 

rulemaking is promulgated under the 

authority described in Subtitle VII, Part 

A, Subpart I, Section 40103. Under that 

section, the FAA is charged with 

prescribing regulations to assign the use 

of airspace necessary to ensure the 

safety of aircraft and the efficient use of 

airspace. This regulation is within the 

scope of that authority as it creates 

additional controlled airspace at 

Columbia Gorge Regional/The Dalles 

Municipal Airport, The Dalles, OR. 

List of Subjects in 14 CFR Part 71 

Airspace, Incorporation by reference, 

Navigation (air). 

Adoption of the Amendment 

In consideration of the foregoing, the 

Federal Aviation Administration 

amends 14 CFR part 71 as follows: 

PART 71—DESIGNATION OF CLASS A, 

B, C, D AND E AIRSPACE AREAS; AIR 

TRAFFIC SERVICE ROUTES; AND 

REPORTING POINTS 

■ 1. The authority citation for 14 CFR 

part 71 continues to read as follows: 

Authority: 49 U.S.C. 106(g), 40103, 40113, 

40120; E.O. 10854, 24 FR 9565, 3 CFR, 1959– 

1963 Comp., p. 389. 

§ 71.1 [Amended] 

■ 2. The incorporation by reference in 

14 CFR 71.1 of the Federal Aviation 

Administration Order 7400.9V, Airspace 

Designations and Reporting Points, 

dated August 9, 2011, and effective 

September 15, 2011 is amended as 

follows: 

Paragraph 6005 Class E airspace areas 

extending upward from 700 feet or more 

above the surface of the earth. 

* * * * * 

ANM OR E5 The Dalles, OR [Modified] 

Columbia Gorge Regional/The Dalles 

Municipal Airport, OR 

(Lat. 45°37′07′′ N., long. 121°10′02′′ W.) 

Klickitat VOR/DME 

(Lat. 45°42′49′′ N., long. 121°06′03′′ W.) 

That airspace extending upward from 700 

feet above the surface within a 12.9-mile 

radius of Columbia Gorge Regional/The 

Dalles Municipal Airport; that airspace 

extending upward from 1,200 feet above the 

surface within a 20.1-mile radius of the VOR/ 

DME extending clockwise from the 088° 

radial to the 272° radial. 

Issued in Seattle, Washington, on 

December 6, 2011. 

Johanna Forkner, 

Acting Manager, Operations Support Group, 

Western Service Center. 

[FR Doc. 2011–32043 Filed 12–14–11; 8:45 am] 

BILLING CODE 4910–13–P 


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