51234 Federal Register / Vol. 74, No. 192 / Tuesday, October 6, 2009 / Rules and Regulations 

will no longer meet or medically equal the 

criteria of a listing in this body system. 

3. * * * If you have a recurrence or relapse 

of your malignancy, your impairment may 

meet or medically equal one of the listings 

in this body system again. 

* * * * * 

I. What do we mean by the following 

terms? 

1. Metastases: The spread of tumor cells by 

blood, lymph, or other body fluid. This term 

does not include the spread of tumor cells by 

direct extension of the tumor to other tissue 

or organs. 

2. Multimodal therapy: A combination of at 

least two types of treatment modalities given 

in close proximity as a unified whole and 

usually planned before any treatment has 

begun. There are three types of treatment 

modalities: Surgery, radiation, and systemic 

drug therapy (chemotherapy, hormonal 

therapy, and immunotherapy). Examples of 

multimodal therapy include: 

a. Surgery followed by chemotherapy or 

radiation. 

b. Chemotherapy followed by surgery. 

c. Chemotherapy and concurrent radiation. 

3. Persistent: Failure to achieve a complete 

remission. 

4. Progressive: The malignancy becomes 

more extensive despite treatment. 

5. Recurrent, relapse: A malignancy that 

was in complete remission or entirely 

removed by surgery has returned. 

* * * * * 

K. How do we evaluate specific malignant 

neoplastic diseases? 

1. Lymphoma. 

a. We provide criteria for evaluating 

aggressive lymphomas that have not 

responded to antineoplastic therapy in 

113.05. Indolent (non-aggressive) lymphomas 

are rare in children. We will evaluate 

indolent lymphomas in children under 13.05 

in part A. 

* * * * * 

2. Leukemia. 

a. Acute leukemia. * * * Recurrent disease 

must be documented by peripheral blood, 

bone marrow, or cerebrospinal fluid 

examination, or by testicular biopsy. * * * 

* * * * * 

4. Brain tumors. We use the criteria in 

113.13 to evaluate malignant brain tumors. 

We consider a brain tumor to be malignant 

if it is classified as grade II or higher under 

the World Health Organization (WHO) 

classification of tumors of the central nervous 

system (WHO Classification of Tumours of 

the Central Nervous System, 2007). We 

evaluate any complications of malignant 

brain tumors, such as resultant neurological 

or psychological impairments, under the 

criteria for the affected body system. We 

evaluate benign brain tumors under 111.05. 

* * * * * 

113.09 Thyroid gland. 

B. * * * 

OR 

C. Medullary carcinoma with metastases 

beyond the regional lymph nodes. 

* * * * * 

113.13 Brain tumors. (See 113.00K4.) 

Highly malignant tumors, such as 

medulloblastoma or other primitive 

neuroectodermal tumors (PNETs) with 

documented metastases, grades III and IV 

astrocytomas, glioblastoma multiforme, 

ependymoblastoma, diffuse intrinsic brain 

stem gliomas, or primary sarcomas. 

* * * * * 

[FR Doc. E9–23896 Filed 10–5–09; 8:45 am] 

BILLING CODE 4191–02–P 

DEPARTMENT OF JUSTICE 

Drug Enforcement Administration 

21 CFR Part 1308 

[Docket No. DEA–327F] 

Schedules of Controlled Substances; 

Placement of Fospropofol Into 

Schedule IV 

AGENCY: Drug Enforcement 

Administration, Department of Justice. 

ACTION: Final rule. 

SUMMARY: With the issuance of this final 

rule, the Deputy Administrator of the 

Drug Enforcement Administration 

(DEA) places the substance fospropofol, 

including its salts, isomers and salts of 

isomers whenever the existence of such 

salts, isomers, and salts of isomers is 

possible, into schedule IV of the 

Controlled Substances Act (CSA). As a 

result of this rule, the regulatory 

controls and criminal sanctions of 

schedule IV will be applicable to the 

manufacture, distribution, dispensing, 

importation, and exportation of 

fospropofol and products containing 

fospropofol. 

DATES: Effective Date: November 5, 

2009. 

FOR FURTHER INFORMATION CONTACT: 

Christine A. Sannerud, PhD, Chief, Drug 

and Chemical Evaluation Section, Office 

of Diversion Control, Drug Enforcement 

Administration, 8701 Morrissette Drive, 

Springfield, Virginia 22152, Telephone: 

(202) 307–7183. 

SUPPLEMENTARY INFORMATION: 

Background 

On December 12, 2008, the Food and 

Drug Administration (FDA) approved 

fospropofol for marketing under the 

trade name Lusedra® in the United 

States as a drug product indicated for 

monitored anesthesia care (MAC) 

sedation in adult patients undergoing 

diagnostic or therapeutic procedures. 

Fospropofol, 2,6- 

diisopropopylphenoxymethyl 

phosphate disodium, is a water soluble, 

phosphono-O-methyl prodrug of 

propofol. It is metabolized in the body 

to propofol, the active metabolite. 

Propofol has been available for medical 

use in the United States since 1989 and 

is not currently a controlled substance. 

The pharmacological effects of 

fospropofol are attributed to the 

pharmacological actions of propofol. 

Propofol binds to g-aminobutyric acid 

(GABAA) receptor and acts as a 

modulator by potentiating the activity of 

GABA at this receptor. 

Since propofol is the active metabolite 

of fospropofol, the abuse potential of 

fospropofol is comparable to that of 

propofol. Animal self-administration 

studies demonstrated that the 

reinforcing effects of propofol are 

relatively low and comparable to 

midazolam and other schedule IV 

benzodiazepines. Fospropofol elicits 

behavioral effects similar to 

methohexital and midazolam, schedule 

IV sedative-hypnotics. 

Since fospropofol is a new molecular 

entity, there has been no evidence of 

diversion, abuse, or law enforcement 

encounters involving the drug. 

On February 27, 2009, the Acting 

Assistant Secretary for Health, 

Department of Health and Human 

Services (DHHS), sent the Deputy 

Administrator of DEA a scientific and 

medical evaluation and a letter 

recommending that fospropofol be 

placed into schedule IV of the CSA. 

Enclosed with the February 27, 2009, 

letter was a document prepared by the 

FDA entitled, ‘‘Basis for the 

Recommendation for Control of 

Fospropofol and Its Salts in Schedule IV 

of the Controlled Substances Act 

(CSA).’’ The document contained a 

review of the factors which the CSA 

requires the Secretary to consider 

(21 U.S.C. 811(b)). 

After a review of the available data, 

including the scientific and medical 

evaluation and the scheduling 

recommendation from DHHS, the 

Deputy Administrator of the DEA 

published a Notice of Proposed 

Rulemaking entitled ‘‘Schedules of 

Controlled Substances: Placement of 

Fospropofol into Schedule IV’’ on July 

23, 2009 (74 FR 36424), which proposed 

placement of fospropofol into schedule 

IV of the CSA. The proposed rule 

provided an opportunity for all 

interested persons to submit their 

written comments on or before August 

24, 2009. 

Comments Received 

The DEA received two comments in 

response to the Notice of Proposed 

Rulemaking. One comment received 

from a concerned citizen did not relate 

to fospropofol, the substance that is 

being controlled. Thus DEA did not 

consider this comment. 


CPrice-Sewell on DSKGBLS3C1PROD with RULES
Federal Register / Vol. 74, No. 192 / Tuesday, October 6, 2009 / Rules and Regulations 51235 

Another comment received from a 

professional organization of 

anesthesiologists is in agreement with 

the findings of scientific and medical 

evaluation that formed the basis for the 

present rule controlling fospropofol as a 

schedule IV substance and it fully 

supported this control action. 

Scheduling of Fospropofol 

Based on the recommendation of the 

Acting Assistant Secretary for Health, 

received in accordance with section 

201(b) of the Act (21 U.S.C. 811(b)), and 

the independent review of the available 

data by DEA, the Deputy Administrator 

of DEA, pursuant to sections 201(a) and 

201(b) of the Act (21 U.S.C. 811(a) and 

811(b)), finds that: 

(1) Fospropofol has a low potential for 

abuse relative to the drugs or substances 

in schedule III. Although there is no 

direct comparison to a schedule III 

substance, this finding is based on the 

demonstration of the abuse potential of 

propofol, the active metabolite, relative 

to the schedule IV substances, 

methohexital and midazolam; 

(2) Fospropofol has a currently 

accepted medical use in treatment in the 

United States; and 

(3) Abuse of fospropofol may lead to 

limited physical dependence or 

psychological dependence relative to 

the drugs or other substances in 

schedule III. This finding is based on 

the symptoms exhibited upon 

withdrawal from propofol. 

Based on these findings, the Deputy 

Administrator of DEA concludes that 

fospropofol, 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 IV of the CSA. (21 

U.S.C. 812(b)(4)) 

Requirements for Handling Fospropofol 

Registration. Any person who 

manufactures, distributes, dispenses, 

imports, exports, engages in research or 

conducts instructional activities with 

fospropofol, or who desires to 

manufacture, distribute, dispense, 

import, export, engage in instructional 

activities or conduct research with 

fospropofol, must be registered to 

conduct such activities in accordance 

with part 1301 of Title 21 of the Code 

of Federal Regulations. Any person who 

is currently engaged in any of the above 

activities and is not registered with DEA 

must submit an application for 

registration on or before November 5, 

2009 and may continue their activities 

until DEA has approved or denied that 

application. 

Security. Fospropofol is subject to 

schedules III–V security requirements 

and must be manufactured, distributed, 

and stored in accordance with 

§§ 1301.71, 1301.72(b), (c), and (d), 

1301.73, 1301.74, 1301.75(b) and (c), 

1301.76, and 1301.77 of Title 21 of the 

Code of Federal Regulations on or after 

November 5, 2009. 

Labeling and Packaging. All labels 

and labeling for commercial containers 

of fospropofol must comply with 

requirements of §§ 1302.03–1302.07 of 

Title 21 of the Code of Federal 

Regulations on or after November 5, 

2009. 

Inventory. Every registrant required to 

keep records and who possesses any 

quantity of fospropofol must keep an 

inventory of all stocks of fospropofol on 

hand pursuant to §§ 1304.03, 1304.04 

and 1304.11 of Title 21 of the Code of 

Federal Regulations on or after 

November 5, 2009. Every registrant who 

desires registration in schedule IV for 

fospropofol 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 §§ 1304.03, 1304.04, 

1304.21, 1304.22, and 1304.23 of Title 

21 of the Code of Federal Regulations on 

or after November 5, 2009. 

Prescriptions. All prescriptions for 

fospropofol or prescriptions for 

products containing fospropofol must be 

issued pursuant to §§ 1306.03–1306.06 

and 1306.21, 1306.22–1306.27 of Title 

21 of the Code of Federal Regulations on 

or after November 5, 2009. 

Importation and Exportation. All 

importation and exportation of 

fospropofol must be in compliance with 

part 1312 of Title 21 of the Code of 

Federal Regulations on or after 

November 5, 2009. 

Criminal Liability. Any activity with 

fospropofol not authorized by, or in 

violation of, the Controlled Substances 

Act or the Controlled Substances Import 

and Export Act shall be unlawful on or 

after November 5, 2009. 

Regulatory Certifications 

Executive Order 12866 

In accordance with the provisions of 

the CSA (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 5 U.S.C. 556 and 557 

and, as such, are exempt from review by 

the Office of Management and Budget 

pursuant to Executive Order 12866, 

section 3(d)(1). 

Regulatory Flexibility Act 

The Deputy Administrator, in 

accordance with the Regulatory 

Flexibility Act (5 U.S.C. 601–612), has 

reviewed this final rule and by 

approving it certifies that it will not 

have a significant economic impact on 

a substantial number of small entities. 

Fospropofol products will be used for 

monitored anesthesia care (MAC) 

sedation in adult patients undergoing 

diagnostic or therapeutic procedures. 

Handlers of fospropofol also handle 

other controlled substances used for 

sedation which are already subject to 

the regulatory requirements of the CSA. 

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. 

Executive Order 13132 

This rulemaking does not preempt or 

modify any provision of state law; nor 

does it impose enforcement 

responsibilities on any state; nor does it 

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. 

Unfunded Mandates Reform Act of 1995 

This rule will not result in the 

expenditure by state, local and tribal 

governments, in the aggregate, or by the 

private sector, of $120,000,000 or more 

(adjusted for inflation) in any one year, 

and will not significantly or uniquely 

affect small governments. Therefore, no 

actions were deemed necessary under 

provisions of the Unfunded Mandates 

Reform Act of 1995. 

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, 

Narcotics, Prescription drugs. 

■ Under the authority vested in the 

Attorney General by section 201(a) of 

the CSA (21 U.S.C. 811(a)), and 

delegated to the Administrator of DEA 

by Department of Justice regulations (28 

CFR 0.100), and redelegated to the 

Deputy Administrator pursuant to 28 


CPrice-Sewell on DSKGBLS3C1PROD with RULES
51236 Federal Register / Vol. 74, No. 192 / Tuesday, October 6, 2009 / Rules and Regulations 

CFR 0.104, the Deputy Administrator 

hereby amends 21 CFR part 1308 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 1308.14 is amended in 

paragraph (c), by redesignating 

paragraphs (c)(23) through (c)(51) as 

paragraphs (c)(24) through (c)(52) and 

adding a new paragraph (c)(23) as 

follows: 

§ 1308.14 Schedule IV. 

* * * * * 

(c) * * * 

(23) Fospropofol ................................ 2138 

* * * * * 

Dated: September 28, 2009. 

Michele M. Leonhart, 

Deputy Administrator. 

[FR Doc. E9–23971 Filed 10–5–09; 8:45 am] 

BILLING CODE 4410–09–P 

DEPARTMENT OF STATE 

22 CFR Part 41 

[Public Notice: 6779] 

Visas: Documentation of 

Nonimmigrants Under the Immigration 

and Nationality Act, as Amended; 

Requirements for Aliens in Religious 

Occupations 

AGENCY: State Department. 

ACTION: Final rule. 

SUMMARY: To comply with the 

Department of Homeland Security 

regulation requiring sponsoring 

employers to file petitions for all aliens 

for whom R–1 nonimmigrant status is 

sought. This rule establishes the 

requirement that consular officers 

ensure that R–1 visa applicants have 

obtained an approved U.S. Citizenship 

and Immigration Services Form I–129 

petition from the Department of 

Homeland Security before issuance of a 

visa. 

DATES: This rule is effective October 6, 

2009. 

FOR FURTHER INFORMATION CONTACT: 

Lauren A. Prosnik, Legislation and 

Regulations Division, Visa Services, 

Department of State, 2401 E Street, NW., 

Room L–603D, Washington, DC 20520– 

0106, (202) 663–2951. 

SUPPLEMENTARY INFORMATION: 

Why is the Department promulgating 

this rule? 

On November 26, 2008, the 

Department of Homeland Security 

(DHS) promulgated regulations 

requiring sponsoring employers to file 

petitions for all aliens for whom R–1 

nonimmigrant status is sought. 73 FR 

72276. As a result, the requirements for 

an R–1 nonimmigrant visa now include 

establishing that the applicant is the 

beneficiary of an approved petition. U.S. 

Citizenship and Immigration Services 

(USCIS) has implemented the petition 

requirement for nonimmigrant religious 

workers as a way to determine the bona 

fides of a petitioning religious 

organization located in the United 

States and to determine that a religious 

worker will be admitted to the United 

States to work for a specific religious 

organization at the request of that 

religious organization. This rule amends 

the Department regulations to ensure 

consistency with the regulations set 

forth by DHS. 

Regulatory Findings 

Administrative Procedure Act 

This regulation involves a foreign 

affairs function of the United States and, 

therefore, in accordance with 5 U.S.C. 

553(a)(1), is not subject to the rule 

making procedures set forth at 5 U.S.C. 

553. 

Regulatory Flexibility Act/Executive 

Order 13272: Small Business 

Because this final rule is exempt from 

notice and comment rulemaking under 

5 U.S.C. 553, it is exempt from the 

regulatory flexibility analysis 

requirements set forth at sections 603 

and 604 of the Regulatory Flexibility 

Act (5 U.S.C. 603 and 604). Nonetheless, 

consistent with section 605(b) of the 

Regulatory Flexibility Act (5 U.S.C. 

605(b)), the Department certifies that 

this rule will not have a significant 

economic impact on a substantial 

number of small entities. This regulates 

individual aliens who seek 

consideration for R–1 nonimmigrant 

visas and does not affect any small 

entities, as defined in 5 U.S.C. 601(6). 

The Unfunded Mandates Reform Act of 

1995 

Section 202 of the Unfunded 

Mandates Reform Act of 1995 (UFMA), 

Public Law 104–4, 109 Stat. 48, 2 U.S.C. 

1532, generally requires agencies to 

prepare a statement before proposing 

any rule that may result in an annual 

expenditure of $100 million or more by 

State, local, or tribal governments, or by 

the private sector. This rule will not 

result in any such expenditure, nor will 

it significantly or uniquely affect small 

governments. 

The Small Business Regulatory 

Enforcement Fairness Act of 1996 

This rule is not a major rule as 

defined by 5 U.S.C. 804, for purposes of 

congressional review of agency 

rulemaking under the Small Business 

Regulatory Enforcement Fairness Act of 

1996, Public Law 104–121. This rule 

will not result in an annual effect on the 

economy of $100 million or more; a 

major increase in costs or prices; or 

adverse effects on competition, 

employment, investment, productivity, 

innovation, or the ability of United 

States-based companies to compete with 

foreign based companies in domestic 

and import markets. 

Executive Order 12866 

The Department of State has reviewed 

this proposed rule to ensure its 

consistency with the regulatory 

philosophy and principles set forth in 

Executive Order 12866 and has 

determined that the benefits of this final 

regulation justify its costs. The 

Department does not consider this final 

rule to be an economically significant 

action within the scope of section 3(f)(1) 

of the Executive Order since it is not 

likely to have an annual effect on the 

economy of $100 million or more or to 

adversely affect in a material way the 

economy, a sector of the economy, 

competition, jobs, the environment, 

public health or safety, or State, local or 

tribal governments or communities. 

Executive Orders 12372 and 13132: 

Federalism 

This regulation will not have 

substantial direct effects on the States, 

on the relationship between the national 

government and the States, or the 

distribution of power and 

responsibilities among the various 

levels of government. Nor will the rule 

have federalism implications warranting 

the application of Executive Orders No. 

12372 and No. 13132. 

Executive Order 12988: Civil Justice 

Reform 

The Department has reviewed the 

regulations in light of sections 3(a) and 

3(b)(2) of Executive Order No. 12988 to 

eliminate ambiguity, minimize 

litigation, establish clear legal 

standards, and reduce burden. 

Paperwork Reduction Act 

This rule does not impose information 

collection requirements under the 

provisions of the Paperwork Reduction 

Act, 44 U.S.C., Chapter 35. 


CPrice-Sewell on DSKGBLS3C1PROD with RULES