Federal Register / Vol. 75, No. 124 / Tuesday, June 29, 2010 / Rules and Regulations 37295 

signed August 27, 2009, and effective 

September 15, 2009 is amended as 

follows: 

Paragraph 6005 Class E airspace areas 

extending upward from 700 feet or more 

above the surface of the earth. 

* * * * * 

ANM WA, ES Kelso, WA [Modified] 

Southwest Washington Regional Airport, WA 

(Lat. 46°07′05′′ N., long. 122°53′54′′ W.) 

* * * * * 

That airspace extending upward from 700 

feet above the surface within a 6.4-mile 

radius of the Southwest Washington Regional 

Airport, and 2.4 miles each side of the 290° 

bearing of the airport extending 9.1 miles 

west, and 4.3 miles each side of the 337° 

bearing of the airport extending 22.2 miles 

northwest, and 5.8 miles west and 3 miles 

east of the 012° bearing of the airport 

extending 18.2 miles north of the airport. 

Issued in Seattle, Washington, on June 14, 

2010. 

Kevin Nolan, 

Acting Manager, Operations Support Group, 

Western Service Center. 

[FR Doc. 2010–15436 Filed 6–28–10; 8:45 am] 

BILLING CODE 4910–13–M 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Parts 312 and 314 

[Docket No. FDA–2010–N–0010] 

Change of Address; Abbreviated New 

Drug Applications; Technical 

Amendment 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final rule; technical 

amendment. 

SUMMARY: The Food and Drug 

Administration (FDA) is amending its 

regulations to update the address for 

applicants to submit abbreviated new 

drug applications (ANDAs) and ANDA 

amendments, supplements, and 

resubmissions. FDA is also updating the 

address for ANDA applicants to submit 

investigational new drug applications 

(INDs) for in vivo bioavailability and 

bioequivalence studies in humans that 

are intended to support ANDAs. This 

action is being taken to ensure accuracy 

and clarity in the agency’s regulations. 

DATES: This rule is effective August 1, 

2010. 

FOR FURTHER INFORMATION CONTACT: 

Martin Shimer, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 7500 Standish Pl., 

MPN II, Rockville, MD 20855, 240–276– 

8675. 

SUPPLEMENTARY INFORMATION: FDA is 

amending 21 CFR 314.440(a)(2) to 

update the address for applicants to 

submit ANDAs and ANDA 

amendments, supplements, and 

resubmissions. FDA is also amending 21 

CFR 312.140(a)(1) to update the address 

for ANDA applicants to submit INDs for 

in vivo bioavailability and 

bioequivalence studies that are intended 

to support ANDAs. The new address for 

all these submissions is Office of 

Generic Drugs (HFD–600), Center for 

Drug Evaluation and Research, Food 

and Drug Administration, Metro Park 

North VII, 7620 Standish Pl., Rockville, 

MD 20855. This action is being taken to 

ensure accuracy and clarity in the 

agency’s regulations. 

Publication of this document 

constitutes final action on these changes 

under the Administrative Procedure Act 

(5 U.S.C. 553). FDA has determined that 

notice and public comment are 

unnecessary because this amendment to 

the regulations provides only technical 

changes to update an address for the 

submission of ANDAs; ANDA 

amendments, supplements, and 

resubmissions; and INDs related to 

ANDAs. 

List of Subjects 

21 CFR Part 312 

Drugs, Exports, Imports, 

Investigations, Labeling, Medical 

research, Reporting and recordkeeping 

requirements, Safety. 

21 CFR Part 314 

Administrative practice and 

procedure, Confidential business 

information, Drugs, Reporting and 

recordkeeping requirements. 

■ Therefore, under the Federal Food, 

Drug, and Cosmetic Act and under 

authority delegated to the Commissioner 

of Food and Drugs, 21 CFR parts 312 

and 314 are amended as follows: 

PART 312—INVESTIGATIONAL NEW 

DRUG APPLICATION 

■ 1. The authority citation for 21 CFR 

part 312 continues to read as follows: 

Authority: 21 U.S.C. 321, 331, 351, 352, 

353, 355, 360bbb, 371; 42 U.S.C. 262. 

§ 312.140 [Amended] 

■ 2. Section 312.140 is amended in 

paragraph (a)(1) by removing ‘‘II, 7500’’ 

and adding in its place ‘‘VII, 7620’’. 

PART 314—APPLICATIONS FOR FDA 

APPROVAL TO MARKET A NEW DRUG 

■ 3. The authority citation for 21 CFR 

part 314 continues to read as follows: 

Authority: 21 U.S.C. 321, 331, 351, 352, 

353, 355, 356, 356a, 356b, 356c, 371, 374, 

379e. 

§ 314.440 [Amended] 

■ 4. Section 314.440 is amended in the 

first sentence of paragraph (a)(2) by 

removing ‘‘II, 7500 Standish Place., rm. 

150’’ and adding in its place ‘‘VII, 7620 

Standish Pl.’’. 

Dated: June 23, 2010. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2010–15711 Filed 6–28–10; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF JUSTICE 

Drug Enforcement Administration 

21 CFR Part 1308 

[Docket No. DEA–305F] 

RIN 1117–AB16 

Control of Immediate Precursor Used 

in the Illicit Manufacture of Fentanyl as 

a Schedule II Controlled Substance 

AGENCY: Drug Enforcement 

Administration (DEA), Department of 

Justice. 

ACTION: Final Rule. 

SUMMARY: The Drug Enforcement 

Administration (DEA) is designating the 

precursor chemical, 4-anilino-Nphenethyl-4-piperidine (ANPP) as an 

immediate precursor for the schedule II 

controlled substance fentanyl under the 

definition set forth in 21 U.S.C. 802(23). 

Furthermore, DEA is finalizing the 

control of ANPP as a schedule II 

substance under the Controlled 

Substances Act (CSA), pursuant to the 

authority in 21 U.S.C. 811(e), which 

states that an immediate precursor may 

be placed in the same schedule as the 

controlled substance it produces, 

without regard to the procedures 

required by 21 U.S.C. 811(a) and (b) and 

without regard to the findings required 

by 21 U.S.C. 811(a) and 812(b). 

ANPP is the immediate chemical 

intermediary in the synthesis process 

currently used by clandestine laboratory 

operators for the illicit manufacture of 

the schedule II controlled substance 

fentanyl. In 2005 and 2006, the 

distribution of illicitly manufactured 

fentanyl caused an unprecedented 

outbreak of hundreds of fentanyl-related 


wwoods2 on DSK1DXX6B1PROD with RULES
37296 Federal Register / Vol. 75, No. 124 / Tuesday, June 29, 2010 / Rules and Regulations 

1The Chemical Abstracts Service Registry 

Number (CASRN) is created by the Chemical 

Abstracts Service (CAS) Division of the American 

Chemical Society and is part of an automated 

information system housing data and information 

on specific, definable chemical substances. The 

CASRN provides consistent and unambiguous 

identification of chemicals and facilitates sharing of 

chemical information. 

overdoses in the United States. DEA 

believes that the control of ANPP as a 

schedule II controlled substance is 

necessary to prevent its diversion as an 

immediate chemical intermediary for 

the illicit production of fentanyl. 

DATES: This rulemaking becomes 

effective August 30, 2010. 

FOR FURTHER INFORMATION CONTACT: 

Christine A. Sannerud, Ph.D., Chief, 

Drug and Chemical Evaluation Section, 

Office of Diversion Control, Drug 

Enforcement Administration, 8701 

Morrissette Drive, Springfield, VA 

22152 at (202) 307–7183. 

SUPPLEMENTARY INFORMATION: The DEA 

is extremely concerned with the recent 

increase in the illicit manufacture and 

distribution of fentanyl, which has 

resulted in hundreds of fentanyl-related 

overdoses and fentanyl-related deaths in 

several areas of the country. Therefore, 

on April 9, 2008, DEA published a 

Notice of Proposed Rulemaking (NPRM) 

[73 FR 19175] to designate the precursor 

chemical, 4-anilino-N-phenethyl-4- 

piperidine (ANPP) as an immediate 

precursor for the schedule II controlled 

substance fentanyl under the definition 

set forth in 21 U.S.C. 802(23). This 

rulemaking finalizes that NPRM. 

Under the immediate precursor 

provision in 21 U.S.C. 811(e), DEA may 

schedule an immediate precursor 

‘‘without regard to the findings required 

by’’ section 811(a) or section 812(b) and 

‘‘without regard to the procedures’’ 

prescribed by section 811(a) and (b). 

Because of the authority in section 

811(e), DEA need not address the 

‘‘factors determinative of control’’ in 

section 811 or the findings required for 

placement in schedule II in section 

812(b)(2). 

This rulemaking finalizes two actions. 

It (1) designates the precursor chemical 

ANPP as an immediate precursor for the 

schedule II controlled substance 

fentanyl under the definition set forth in 

21 U.S.C. 802(23); and (2) controls 

ANPP as a schedule II substance 

pursuant to the authority in 21 U.S.C. 

811(e). 

Background 

Fentanyl is a schedule II controlled 

substance. Fentanyl and analogues of 

fentanyl are the most potent opioids 

available for human and veterinary use. 

Fentanyl produces opioid effects that 

are indistinguishable from morphine or 

heroin, but fentanyl has a greater 

potency and a shorter duration of 

action. Fentanyl is approximately 50 to 

100 times more potent than morphine 

and 30 to 50 times more potent than 

heroin, depending on the physiological 

or behavioral measure, the route of 

administration, and other factors. 

The legitimate medical use of fentanyl 

is for anesthesia and analgesia, but 

fentanyl’s euphoric effects are highly 

sought after by narcotic addicts. 

Fentanyl can serve as a direct 

pharmacological substitute for heroin in 

opioid-dependent individuals. Fentanyl 

is a very dangerous substitute for 

heroin, however, because the amount 

that produces a euphoric effect also 

induces respiratory depression. 

Furthermore, due to fentanyl’s greater 

potency, illicit drug dealers have trouble 

adjusting (‘‘cutting’’) pure fentanyl into 

non-lethal dosage concentrations. 

Heroin users similarly have difficulty 

determining how much to take to get 

their ‘‘high’’ and sometimes mistakenly 

take a lethal quantity of the fentanyl. 

Unfortunately, only a slight excess of 

fentanyl can be, and is often, lethal 

because the resulting level of respiratory 

depression is sufficient to cause the user 

to stop breathing. 

Illicit Fentanyl-Related Deaths 

In 2005 and 2006, DEA saw a sharp 

increase in the seizures of illicit 

fentanyl. The distribution of illicit 

fentanyl or illicit fentanyl combined 

with heroin or with cocaine (i.e., a 

‘‘speedball’’) resulted in an outbreak of 

hundreds of confirmed and suspected 

fentanyl-related overdose deaths in the 

United States since April 2005, 

according to the Centers for Disease 

Control and Prevention and medical 

examiners representing numerous cities 

and counties across the United States. 

DEA terms fentanyl-related deaths 

‘‘suspected’’ until confirmed through the 

completion of an autopsy, a positive 

toxicological testing result for fentanyl 

in the blood and the reporting of the 

death to the DEA. 

To address this emergency health 

situation, DEA published an Interim 

Final Rule, ‘‘Control of a Chemical 

Precursor Used in the Illicit 

Manufacture of Fentanyl as a List I 

Chemical’’ (72 FR 20039, April 23, 

2007), followed by a Final Rule (73 FR 

43355, July 25, 2008), to control Nphenethyl-4-piperidone (NPP), the 

chemical precursor to ANPP, as a List I 

chemical. As DEA discussed extensively 

in that Interim Final Rule, at least 972 

confirmed fentanyl-related deaths, and 

162 suspected fentanyl-related deaths, 

mostly in Delaware, Illinois, Maryland, 

Michigan, Missouri, New Jersey, and 

Pennsylvania were initially reported to 

the DEA. The number of fentanylrelated deaths significantly decreased 

after October 2006 and continued at 

lower levels following control of the 

precursor NPP in 2007. 

From the information and data 

collected, there is a strong indication 

that the fentanyl in these confirmed and 

suspected fentanyl-related deaths is the 

result of illicitly manufactured fentanyl, 

rather than from fentanyl diverted from 

legal pharmaceutical manufacturers. 

Forensic testing of seized fentanyl drug 

exhibits can identify manufacture 

procedure markers such as 

benzylfentanyl and ANPP. The forensic 

data suggests that most of these 

fentanyl-related deaths are from 

fentanyl illicitly manufactured by the 

procedure called the Siegfried method, 

discussed in DEA’s Interim Final Rule, 

which uses NPP/ANPP. 

Synthesis of Fentanyl 

DEA has determined from the forensic 

testing of seized illicit fentanyl that two 

primary synthesis routes (i.e., the 

Janssen synthesis route and the 

Siegfried method) are being used to 

produce fentanyl clandestinely. In 1965, 

Janssen Pharmaceutical patented the 

original synthesis procedure for 

fentanyl. The Janssen synthesis route is 

difficult to perform and is beyond the 

rudimentary skills of most clandestine 

laboratory operators. Only individuals 

who have acquired advanced chemistry 

knowledge and skills have successfully 

used this synthesis route. Forensic 

laboratories can determine whether 

fentanyl was manufactured illicitly by 

the Janssen route by detecting the 

impurity benzylfentanyl in the tested 

fentanyl drug exhibit. 

In the early 1980s, an alternate route 

for fentanyl synthesis was published in 

the scientific literature; it uses Nphenethyl-4-piperidone (NPP) as the 

starting material. The NPP synthesis 

route is described on the Internet and is 

referred to as the Siegfried method. The 

chemical intermediary ANPP is 

produced during the synthesis and is 

the immediate precursor used in the 

illicit manufacture of fentanyl in the last 

stage of the Siegfried method. The 

Chemical Abstracts Service Registry 

Number 1 (CASRN) for ANPP is 21409– 

26–7. The detection of the impurity 4- 

anilino-N-phenethyl-4-piperidine 

(ANPP) without the presence of 

benzylfentanyl in the fentanyl drug 

exhibit suggests that the fentanyl was 

manufactured by the Siegfried method 

(or a modified version) that produces 


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Federal Register / Vol. 75, No. 124 / Tuesday, June 29, 2010 / Rules and Regulations 37297 

2Under administrative scheduling of a substance 

pursuant to 21 U.S.C. 811(c), DEA must consider 

the ‘‘factors determinative of control.’’ The DEA 

must consider the following factors with respect to 

each drug or other substance proposed to be 

controlled in a schedule: 

(1) Its actual or relative potential for abuse; 

(2) Scientific evidence of its pharmacological 

effect, if known; 

(3) The state of current scientific knowledge 

regarding the drug or other substance; 

(4) Its history and current pattern of abuse; 

Continued 

the precursor ANPP and then converts 

ANPP directly to fentanyl. (A small 

amount of ANPP is not consumed in the 

last reaction in the synthesis, and thus 

a trace amount of ANPP remains in the 

fentanyl.) 

The increase in street-level fentanyl 

may be the result of the relative ease 

with which fentanyl can be produced 

via the Siegfried method and the 

widespread distribution of the Siegfried 

method on the Internet. Preliminary 

data indicate that the majority of the 

deaths in the 2005–2006 fentanyl 

outbreak have resulted from the 

distribution of illicit fentanyl made by 

the Siegfried method and marked by 

traces of ANPP rather than 

benzylfentanyl. 

Role of ANPP in Synthesis of Fentanyl 

Since 2000, four of the five domestic 

fentanyl clandestine laboratories seized 

by law enforcement agents have used 

the Siegfried method or a modified 

version of the Siegfried method in 

manufacturing fentanyl. The amount of 

illicit fentanyl and precursor chemicals 

found at these four laboratories could 

have generated a total of 5,800 grams of 

illicit fentanyl. Since fentanyl is potent 

in sub-milligram quantities, the 

subsequent ‘‘cutting’’ of 5,800 grams of 

illicit fentanyl would be sufficient to 

make about 46 million fentanyl doses. 

The precursor chemical NPP is the 

starting material utilized in the Siegfried 

method of synthesizing fentanyl, both in 

industry and in illicit drug laboratories. 

Under a separate rulemaking first 

published as an interim rule on April 

23, 2007 (72 FR 20039), followed by a 

final rule on July 25, 2008 (73 FR 

43355), DEA has controlled the 

precursor NPP as a List I chemical 

under the regulatory control provisions 

of the CSA (21 CFR part 1300). 

During the production process, the 

starting material, NPP, is subjected to a 

series of chemical reactions in order to 

produce the intermediary chemical 

ANPP. The ANPP is then subjected to a 

simple chemical reaction resulting in 

the synthesis of fentanyl. DEA has not 

identified any industrial uses for ANPP 

and believes that ANPP is only 

produced as a chemical intermediary in 

the production of fentanyl, either in the 

legitimate production of pharmaceutical 

fentanyl or the illicit production of 

fentanyl in clandestine laboratories. 

ANPP is, therefore, an immediate 

chemical intermediary in the synthesis 

of fentanyl and is produced primarily 

for this purpose. 

DEA is controlling ANPP as a 

schedule II controlled substance in an 

effort to prevent its use in production of 

illicit fentanyl. DEA believes control is 

necessary to prevent unscrupulous 

chemists from synthesizing and 

distributing ANPP (as an unregulated 

material), and selling it through the 

Internet and other channels to 

individuals who may wish to acquire an 

unregulated precursor for fentanyl 

synthesis. DEA believes this action is 

also advisable in order to deter the theft 

of ANPP from legitimate pharmaceutical 

firms where it is generated in the course 

of fentanyl production. It has been 

determined by DEA’s Office of Forensic 

Sciences that ANPP can also be 

produced through synthetic pathways 

that do not require NPP as the starting 

material. Therefore, DEA believes that 

controlling ANPP directly is necessary 

to prevent the illicit production of 

fentanyl. 

Designation as an Immediate Precursor 

Under 21 U.S.C. 811(e), the Attorney 

General may place an immediate 

precursor into the same schedule as the 

controlled substance that the immediate 

precursor is used to make. The 

substance must meet the requirements 

of an immediate precursor under 21 

U.S.C. 802(23). The term ‘‘immediate 

precursor’’ as defined in 21 U.S.C. 

802(23) means a substance: 

(A) Which the Attorney General has found 

to be and by regulation designated as being 

the principal compound used, or produced 

primarily for use, in the manufacture of a 

controlled substance; 

(B) which is an immediate chemical 

intermediary used or likely to be used in the 

manufacture of such controlled substance; 

and 

(C) the control of which is necessary to 

prevent, curtail, or limit the manufacture of 

such controlled substance. 

DEA finds that ANPP meets the three 

criteria for the definition of an 

immediate precursor under 21 U.S.C 

802(23). First, DEA finds that ANPP is 

produced primarily for use in the 

manufacture of the schedule II 

controlled substance fentanyl. As stated 

in the preceding section, under the 

Siegfried method, ANPP is typically 

produced from the starting material NPP 

and is then subjected to a simple onestep chemical reaction to obtain the 

schedule II controlled substance 

fentanyl. DEA has not identified any 

industrial or other uses for ANPP and 

believes that it is produced primarily 

during the synthesis of fentanyl. 

Second, DEA finds that ANPP is an 

immediate chemical intermediary used 

in the manufacture of the controlled 

substance fentanyl. As stated earlier, 

ANPP is produced as an intermediary in 

the fentanyl synthetic pathway. After it 

is synthesized, the ANPP is subjected to 

a simple chemical reaction that converts 

it directly to fentanyl. 

Third, DEA finds that controlling 

ANPP is necessary to prevent, curtail, 

and limit the unlawful manufacture of 

the controlled substance fentanyl. As 

noted above, DEA believes this action is 

necessary to assist in preventing the 

possible theft of ANPP from legitimate 

pharmaceutical firms where it is a 

chemical intermediary generated for 

fentanyl production. As a schedule II 

substance, ANPP will be safeguarded to 

the same degree that pharmaceutical 

firms now safeguard the fentanyl that 

they produce. DEA believes this 

increased level of security is necessary 

to prevent diversion of ANPP. 

As noted previously, ANPP can also 

be produced through synthetic 

pathways that do not require NPP as the 

precursor material. Accordingly, DEA 

believes control is necessary to prevent 

unscrupulous chemists from 

synthesizing ANPP and selling it (as an 

unregulated material) through the 

Internet and other channels to 

individuals who may wish to acquire an 

unregulated precursor for fentanyl 

synthesis, in order to circumvent the 

regulation of NPP as a List I chemical. 

DEA believes that the control of ANPP 

is necessary to prevent its production 

and use in the illicit production of 

fentanyl. Therefore, DEA is designating 

ANPP as an immediate precursor of 

fentanyl pursuant to 21 U.S.C. 802(23) 

and 21 U.S.C. 811(e). 

Placement in Schedule II—Findings 

Required Under CSA Immediate 

Precursor Provisions 

Under the authority in 21 U.S.C. 

811(e), once ANPP is designated as an 

immediate precursor under 21 U.S.C. 

802(23), it may be placed directly into 

schedule II (or a schedule with a higher 

numerical designation). The immediate 

precursor provision in 21 U.S.C. 811(e) 

permits DEA to schedule an immediate 

precursor ‘‘without regard to the 

findings required by’’ section 811(a) or 

section 812(b) and ‘‘without regard to 

the procedures’’ prescribed by section 

811(a) and (b). Accordingly, DEA need 

not address the ‘‘factors determinative of 

control’’ in section 811(c) 2 or the 


wwoods2 on DSK1DXX6B1PROD with RULES
37298 Federal Register / Vol. 75, No. 124 / Tuesday, June 29, 2010 / Rules and Regulations 

(5) The scope, duration, and significance of 

abuse; 

(6) What, if any, risk there is to the public health; 

(7) Its psychic or physiological dependence 

liability; and 

(8) Whether the substance is an immediate 

precursor of a substance already controlled. 

21 U.S.C. 811(e) specifies that none of these 

factors must be considered, however, in the control 

of an ‘‘immediate precursor.’’ 

3The findings for schedule II include (A) the drug 

or other substance has a high potential for abuse; 

(B) the drug or other substance has a currently 

accepted medical use in treatment in the United 

States or a currently accepted medical use with 

severe restrictions; and (C) abuse of the drug or 

other substance may lead to severe psychological or 

physical dependence. 

findings required for placement in 

schedule II in section 812(b)(2).3

Based on the finding that ANPP is an 

‘‘immediate precursor’’ for fentanyl, DEA 

is hereby placing ANPP directly into 

schedule II. 

NPRM Comments 

As part of this NPRM, DEA solicited 

comments and requested information on 

any possible legitimate uses of ANPP 

unrelated to fentanyl (including 

industrial uses) to assess the potential 

commercial impact of scheduling ANPP. 

DEA solicited input from all potentially 

affected parties regarding: (1) The types 

of legitimate industries using ANPP; (2) 

the legitimate uses of ANPP; (3) the size 

of the domestic market for ANPP; (4) the 

number of manufacturers of ANPP; (5) 

the number of distributors of ANPP; (6) 

the level of import and export of ANPP; 

(7) the potential burden these proposed 

regulatory controls of ANPP may have 

on legitimate commercial activities; (8) 

the potential number of individuals/ 

firms that may be adversely affected by 

these proposed regulatory controls 

(particularly with respect to the impact 

on small businesses); and (9) any other 

information on the manner of 

manufacturing, distribution, 

consumption, storage, disposal, and 

uses of ANPP by industry and others. 

DEA invited all interested parties to 

provide any information on any 

legitimate uses of ANPP in industry, 

commerce, academia, research and 

development, or other applications. 

In response to the NPRM, DEA 

received only one comment. The 

commenter expressed concerns that the 

Aggregate Production Quotas for ANPP 

would need to take into account 

production losses that are inherent in 

the manufacture of fentanyl. 

Additionally, the commenter expressed 

concerns that the effective date of the 

rulemaking may adversely impact the 

timetable for production of fentanyl, 

since manufacturers would be required 

to obtain ANPP registrations and 

manufacturing quotas prior to being able 

to produce fentanyl. 

In response to this comment, DEA 

recognizes that the ANPP Aggregate 

Production Quota must be established at 

a level that allows adequate production 

losses. Additionally, DEA is aware of 

the concerns of fentanyl manufacturers 

and will use its best efforts to minimize 

the impact of the new ANPP regulations 

on the legitimate production of fentanyl 

for medical use. Any person who 

manufactures, distributes, imports, 

exports, engages in research or conducts 

instructional activities with ANPP, or 

who desires to manufacture, distribute, 

import, export, engage in instructional 

activities or conduct research with 

ANPP, must be registered to conduct 

such activities in accordance with part 

1301 of Title 21 of the Code of Federal 

Regulations. Current bulk 

manufacturers, importers, and exporters 

of ANPP must submit an application for 

registration or an application to amend 

an existing registration to include ANPP 

on or before August 30, 2010 and may 

continue their activities until DEA has 

approved or denied that application. 

Requirements for Handling Schedule II 

Substances 

This rulemaking finalizes two actions. 

It (1) designates the precursor chemical 

ANPP as an immediate precursor for the 

schedule II controlled substance 

fentanyl under the definition set forth in 

21 U.S.C. 802(23); and (2) controls 

ANPP as a schedule II substance 

pursuant to the authority in 21 U.S.C. 

811(e). 

The scheduling of ANPP as an 

immediate precursor will subject ANPP 

to all of the regulatory controls and 

administrative, civil, and criminal 

sanctions applicable to the manufacture, 

distribution, dispensing, importing, and 

exporting of a schedule II controlled 

substance. 

DEA has not identified any legitimate 

industrial use for ANPP, other than its 

role as an intermediary chemical in the 

production of fentanyl by the 

pharmaceutical industry. If ANPP is 

used only to manufacture fentanyl, the 

regulation of ANPP as an immediate 

precursor will not represent a new, 

major regulatory burden because 

fentanyl manufacturers have already 

implemented the CSA requirements for 

schedule II substances. For example, 

since fentanyl is a schedule II controlled 

substance, these firms will already be 

schedule II registrants and will already 

have adequate schedule II security. As 

a result of this rulemaking, these firms 

will need to begin storing ANPP under 

the same security controls already used 

for the final product fentanyl. The 

impact upon legitimate industry of 

controlling ANPP as a schedule II 

substance should be minimal. The 

regulatory requirements will include the 

following: 

Registration. Any person who 

manufactures, distributes, imports, 

exports, engages in research or conducts 

instructional activities with ANPP, or 

who desires to manufacture, distribute, 

import, export, engage in instructional 

activities or conduct research with 

ANPP, must be registered to conduct 

such activities in accordance with 21 

CFR part 1301. Current bulk 

manufacturers, importers and exporters 

of ANPP must submit an application for 

registration or an application to amend 

an existing registration to include ANPP 

on or before August 30, 2010 and may 

continue their activities until DEA has 

approved or denied that application. 

Security. ANPP will be subject to 

schedule II security requirements. To 

prevent diversion, ANPP will have to be 

manufactured, distributed, and stored in 

accordance with the standards for 

physical security and the operating 

procedures set forth in 21 CFR 1301.71, 

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

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

and 1301.77. 

This rule does not establish any new 

security requirements for schedule II 

controlled substances. The following 

existing security requirements are 

provided for informational purposes 

only. 

Existing DEA physical security 

regulations require that, for schedule I 

and II controlled substances, raw 

material, bulk materials awaiting further 

processing, and finished products be 

stored in either a safe or steel cabinet (if 

the quantity is small) or in a vault (21 

CFR 1301.72). DEA regulations set forth 

specific requirements regarding these 

structures. Controlled substances must 

be stored in these facilities during the 

manufacturing process except where a 

continuous manufacturing process 

should not be interrupted (21 CFR 

1301.73). Secure storage areas are 

required to have an alarm system which, 

upon attempted unauthorized entry, 

shall transmit a signal directly to a 

central protection company or to a local 

or state police agency which has a legal 

duty to respond, or a 24-hour control 

station operated by the registrant, or 

other protection as approved by DEA 

(21 CFR 1301.72(a)(1)(iii), 

1301.72(a)(3)(iv)). The controlled 

substances storage areas are required to 

be accessible only to an absolute 

minimum number of specifically 

authorized employees (21 CFR 

1301.72(d)). When it is necessary for 

other personnel or guests to be present 


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Federal Register / Vol. 75, No. 124 / Tuesday, June 29, 2010 / Rules and Regulations 37299 

in, or pass through, such secure areas, 

the registrant shall provide for adequate 

observation of the area by an employee 

(21 CFR 1301.72(d), 1301.73(c)). 

Labeling and Packaging. All labels 

and labeling for commercial containers 

of ANPP that are distributed will be 

required to comply with the 

requirements of 21 CFR 1302.03– 

1302.07. 

Quotas. Quotas for ANPP will be 

established pursuant to 21 CFR part 

1303. 

Inventory. Every registrant who 

possesses any quantity of ANPP will be 

required to keep an inventory of all 

stocks of the substance on hand 

pursuant to 21 CFR 1304.03, 1304.04 

and 1304.11. 

Records. All registrants will be 

required to keep records pursuant to 21 

CFR 1304.03, 1304.04, and 1304.21– 

1304.23. 

Reports. All registrants will be 

required to submit reports in accordance 

with 21 CFR 1304.33. 

Orders. All registrants involved in the 

distribution of ANPP will be required to 

comply with the order requirements of 

21 CFR part 1305. 

Importation and Exportation. All 

registrants involved in the importation 

and exportation of ANPP will be 

required to comply with 21 CFR part 

1312. 

Prescriptions. All prescriptions for 

ANPP or prescriptions for products 

containing ANPP will be required to be 

issued pursuant to 21 CFR 1306.03– 

1306.06 and 21 CFR §§ 1306.11– 

1306.15. 

Criminal Liability. Any activity with 

ANPP in violation of or not authorized 

under the Controlled Substances Act or 

the Controlled Substances Import and 

Export Act will be unlawful and 

potentially subject to criminal penalties 

(21 U.S.C. 841–863 and 959–964). 

Regulatory Certifications 

Regulatory Flexibility and Small 

Business Concerns 

The Regulatory Flexibility Act (5 

U.S.C. 601–612) requires agencies to 

determine whether a rule will have a 

significant economic impact on a 

substantial number of small entities. If 

an agency finds that there is a 

significant economic impact on a 

substantial number of small entities, the 

agency must consider whether 

alternative approaches could mitigate 

the impact on small entities. The size 

criteria for small entities are defined by 

the Small Business Administration in 13 

CFR 121.201. 

DEA has not identified any legitimate 

industrial use for ANPP, other than its 

role as an intermediary chemical in the 

production of fentanyl by the 

pharmaceutical industry. DEA has not 

identified any firms that import, export, 

or distribute ANPP. If ANPP is used 

only to manufacture fentanyl, the 

potential regulation of ANPP as an 

immediate precursor will not represent 

a new, major regulatory burden, because 

fentanyl manufacturers have already 

implemented the CSA requirements for 

the handling of schedule II substances. 

Consequently, DEA believes this rule 

will not have a significant economic 

impact on a substantial number of small 

entities. DEA did not receive any 

comments suggesting that this rule will 

result in a significant economic impact 

on any small entities. 

Executive Order 12866 

The Deputy Administrator certifies 

that this rulemaking has been drafted in 

accordance with the principles in 

Executive Order 12866 § 1(b). It has 

been determined that this is ‘‘a 

significant regulatory action.’’ Therefore, 

this action has been reviewed by the 

Office of Management and Budget. 

DEA is regulating ANPP as a schedule 

II substance. Any person manufacturing, 

distributing, dispensing, conducting 

research with, importing, or exporting 

ANPP will have to register each location 

where ANPP is handled, maintain 

records of transactions involving ANPP, 

and take steps to ensure that inventories 

are secure (e.g., stored in sealed 

containers in areas where access can be 

controlled or monitored). DEA has not 

identified any domestic chemical 

companies that distribute ANPP, other 

than the production as an intermediate 

during the manufacture of fentanyl. 

Such manufacturers are already 

registered with DEA for the schedule II 

drug fentanyl. 

Executive Order 12988 

This regulation meets the applicable 

standards set forth in §§ 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 are deemed necessary under the 

provisions of the Unfunded Mandates 

Reform Act of 1995. 

Congressional Review Act 

This rule is not a major rule as 

defined by Section 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 cost or prices; or significant adverse 

effects on competition, employment, 

investment, productivity, innovation, or 

on the ability of United States-based 

companies to compete with foreignbased 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. 

■ 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 part 1308 

continues to read as follows: 

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

unless otherwise noted. 

■ 2. Section 1308.12 is amended by 

adding a new paragraph (g)(3) to read as 

follows: 

§ 1308.12 Schedule II. 

* * * * * 

(g) * * * 

(3) Immediate precursor to fentanyl: 

(i) 4-anilino-N-phenethyl-4-piperidine (ANPP) ................................ 8333 

(ii) [Reserved] 

Dated: June 19, 2010. 

Michele M. Leonhart, 

Deputy Administrator. 

[FR Doc. 2010–15520 Filed 6–28–10; 8:45 am] 

BILLING CODE 4410–09–P 


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