[Federal Register: January 4, 2005 (Volume 70, Number 2)]
[Rules and Regulations]               
[Page 291-294]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr04ja05-7]                         

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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Parts 1304, 1306, and 1310

[Docket No. DEA-234F]
RIN 1117-AA71

 
Recordkeeping and Reporting Requirements for Drug Products 
Containing Gamma-Hydroxybutyric Acid (GHB)

AGENCY: Drug Enforcement Administration (DEA), Justice.

ACTION: Final rule.

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SUMMARY: DEA is amending its regulations to require additional 
recordkeeping and reporting requirements for drug products containing 
gamma-hydroxybutyric acid (GHB) for which an application has been 
approved under the Federal Food, Drug, and Cosmetic Act. DEA makes 
these changes under section 4 of the ``Hillory J. Farias and Samantha 
Reid Date-Rape Drug Prohibition Act of 2000.'' These additional 
requirements are necessary to protect against the diversion of GHB for 
illicit purposes.

EFFECTIVE DATE: February 3, 2005.

FOR FURTHER INFORMATION CONTACT: Patricia M. Good, Chief, Liaison and 
Policy Section, Office of Diversion Control, Drug Enforcement 
Administration, Washington, DC 20537. Telephone (202) 307-7297.

SUPPLEMENTARY INFORMATION:

Controlled Substances and Listed Chemicals

    Controlled substances are drugs that have a potential for abuse and 
addiction; these include opiates, stimulants, depressants, 
hallucinogens, anabolic steroids, and substances that are immediate 
precursors to these controlled substances. Controlled substances are 
listed in 21 CFR part 1308. The substances are divided into five 
schedules. Schedule I substances are drugs for which there is a high 
potential for abuse, no currently accepted medical treatment in use in 
the United States, and lack accepted safety for use under medical 
supervision. Schedule II-V substances have accepted medical uses, but 
have a potential for abuse and may lead to physical and psychological 
dependence. Such drugs are subject to varying levels of control. 
Chemicals that can be used to manufacture controlled substances are 
regulated as either List I chemicals (important to the manufacture) or 
List II chemicals (used in the manufacture) of controlled substances.

Background

    Gamma-Hydroxybutyric acid (GHB) is a central nervous system 
depressant drug. In recent years, the abuse of GHB has increased 
substantially. GHB is abused for its euphoric and purported 
hallucinogenic effects, as well as for its alleged role as an agent to 
stimulate muscle growth. GHB can produce drowsiness, dizziness, nausea, 
visual disturbances, unconsciousness, seizures, severe respiratory 
depression, coma, and death.
    GHB can be produced in clandestine laboratories using a relatively 
simple synthesis with readily available and inexpensive source 
materials. Gamma-Butyrolactone (GBL), a List I chemical, is an 
industrial chemical that is used in the illicit manufacture of GHB. GBL 
and 1,4-butanediol, another industrial chemical, are also abused for 
their GHB-like effects. Due to their structural and pharmacological 
similarities to GHB, GBL and 1,4-butanediol are considered controlled 
substance analogues as defined by 21 U.S.C. 802(32). Manufactured GHB 
usually results in a clear solution that can be disguised by adding 
food coloring, flavorings, or storing it in different kinds of bottles 
and containers.
    The listed chemical GBL has many industrial applications, and has 
not been scheduled at this time to prevent an undue regulatory burden 
to legitimate commerce in this substance. Because GBL is a controlled 
substance analogue, individuals who manufacture or distribute or 
possess with intent to manufacture or distribute this chemical 
intending it for human consumption may be prosecuted under provisions 
of the Controlled Substances Act. This is

[[Page 292]]

because a controlled substance analogue which is intended for human 
consumption is treated as a Schedule I controlled substance. When 
handled for industrial purposes, with no intent for human consumption, 
it is not treated as a Schedule I controlled substance and those 
handling it are not subject to any Schedule I controlled substances 
penalties under the Controlled Substances Act.

Regulatory History

    On February 18, 2000, the ``Hillory J. Farias and Samantha Reid 
Date-Rape Drug Prohibition Act of 2000'' was enacted (Pub. L. 106-172, 
114 Stat. 7). Public Law 106-172 declared GHB an imminent hazard to 
public safety that required immediate regulatory action under the 
Controlled Substances Act. Public Law 106-172 required the Attorney 
General to list GHB as a Schedule I controlled substance and designated 
GBL as a List I chemical. As a result of the Hillory J. Farias and 
Samantha Reid Date-Rape Drug Prohibition Act, DEA issued two final 
rules: Schedules of Controlled Substances: Addition of Gamma-
Hydroxybutyric Acid to Schedule I (65 FR 13235, March 13, 2000) 
(corrected at 65 FR 17440, April 3, 2000) and Placement of Gamma-
Butyrolactone in List I of the Controlled Substances Act (21 U.S.C. 
802(34)) (65 FR 21645, April 24, 2000).
    Under the March 13, 2000 final rule, GHB and its salts, isomers, 
and salts of isomers were placed in Schedule I, and GHB became subject 
to the regulatory controls and administrative, civil, and criminal 
sanctions applicable to the manufacture, distribution, dispensing, 
importing, and exporting of a Schedule I controlled substance. As 
required by the Hillory J. Farias and Samantha Reid Date-Rape Drug 
Prohibition Act, the March 13, 2000 final rule created an exception for 
drug products containing GHB, including its salts, isomers, and salts 
of isomers, for which an application is approved under section 505 of 
the Federal Food, Drug, and Cosmetic Act (FDCA) (21 U.S.C. 355). The 
exception placed any such drug products--there were none approved at 
the time the legislation was passed--in Schedule III. Therefore, 
registered manufacturers and distributors of FDA-approved drug products 
containing GHB are subject to Schedule III regulatory requirements. 
However, criminal penalties for unlawful distributions of these drug 
products are those for Schedule I controlled substances.
    On July 17, 2002, the Food and Drug Administration (FDA) approved 
Xyrem, a drug product containing gamma-hydroxybutyric acid, as a drug 
for the treatment of cataplexy associated with narcolepsy.

Notice of Proposed Rulemaking

    The March 13, 2000 final rule did not address the recordkeeping and 
reporting requirements recommended by the Hillory J. Farias and 
Samantha Reid Date-Rape Drug Prohibition Act for drug products 
containing GHB for which an application is approved under section 505 
of the FDCA. On November 25, 2003 DEA issued a notice of proposed 
rulemaking (68 FR 66048) to establish requirements to prevent the 
diversion of Schedule III GHB drug products for illicit purposes as was 
intended by Congress as part of the regulatory scheme for these 
products. DEA received no comments in response to the November 25, 2003 
notice of proposed rulemaking and is adopting the rule language as 
proposed.
    In response to section 4 of the Hillory J. Farias and Samantha Reid 
Date-Rape Drug Prohibition Act, this rule establishes recordkeeping 
requirements for practitioners dispensing Schedule III GHB drug 
products and reporting requirements for manufacturers and distributors 
of Schedule III GHB drug products. Under existing 21 CFR 1304.22(c), 
dispensers of any controlled substance, including GHB, are required to 
maintain the name and address of the person to whom the controlled 
substance was dispensed, the date of dispensing, the number of units or 
volume dispensed, and the written or typewritten name or initials of 
the individual who dispensed or administered the substance on behalf of 
the dispenser. This final rule adds 21 CFR 1304.26, which requires 
pharmacies and practitioners dispensing GHB to maintain and make 
available for inspection the name of the prescribing practitioner, the 
prescribing practitioner's Federal and State registration numbers with 
expiration dates, verification that the prescribing practitioner 
possesses appropriate registration, and the patient's insurance 
provider, if available. Section 4 of the Hillory J. Farias and Samantha 
Reid Date-Rape Drug Prohibition Act also recommended that DEA establish 
a recordkeeping requirement for ``documentation by a medical 
practitioner licensed and registered to prescribe the drug of the 
patient's medical need for the drug.'' Part of this recommendation is 
satisfied by existing DEA requirements in 21 CFR 1306.04 which state 
that prescriptions ``must be issued for a legitimate medical purpose.'' 
To further satisfy this statutory requirement, DEA has amended 21 CFR 
1306.05 to require that the medical need be written on the 
prescription.
    This final rule also amends 21 CFR 1304.33 to include Schedule III 
GHB drug products as controlled substances that must be reported under 
the Automation of Reports and Consolidated Orders System (ARCOS). ARCOS 
is an automated, comprehensive drug reporting system that monitors the 
flow of DEA controlled substances from their point of manufacture 
through commercial distribution channels to point of sale or 
distribution at the dispensing/retail level, e.g., hospitals, retail 
pharmacies, practitioners, mid-level practitioners, and teaching 
institutions. Included in the list of controlled substance transactions 
tracked by ARCOS are the following: All Schedules I and II materials 
(manufacturers and distributors); Schedule III narcotic materials 
(manufacturers and distributors); and selected Schedules III and IV 
psychotropic controlled substances (manufacturers only). This final 
rule adds Schedule III GHB drug products to this list for both 
manufacturers and distributors.
    In addition, section 4 of the Hillory J. Farias and Samantha Reid 
Date-Rape Drug Prohibition Act recommended that DEA apply the mail 
order reporting requirements of 21 U.S.C. 830(b)(3) to ``gamma 
hydroxybutyric acid to the same extent and in the same manner as such 
section applies with respect to the chemicals and drug products 
specified in subparagraph (B)(i) of such section.'' DEA has complied 
with these recommendations in this final rule by amending 21 CFR 
1310.03(c), which makes GHB subject to mail order requirements 
established under the Methamphetamine Anti-Proliferation Act of 2000 
(MAPA) (Title XXXVI of the ``Children's Health Act of 2000'' (Pub. L. 
106-310, 114 Stat. 1101)). The Methamphetamine Anti-Proliferation Act 
of 2000 imposed mail order reporting requirements for export 
transactions involving ephedrine, pseudoephedrine, or 
phenylpropanolamine. These reporting requirements do not apply to 
distributions of drug products, including GHB, under a valid 
prescription, which were excluded under MAPA (21 U.S.C. 830(b)(3)(D)). 
Regulations implementing MAPA were published October 7, 2003 (68 FR 
57799). The net effect is that all export transactions involving GHB 
must be reported to DEA. Transactions involving prescriptions of GHB 
are not required to be reported to DEA.

[[Page 293]]

Regulatory Certifications

Regulatory Flexibility Act

    The Deputy Assistant Administrator certifies that this rulemaking 
has been drafted in accordance with the Regulatory Flexibility Act (5 
U.S.C. 605(b)). The Deputy Assistant Administrator has reviewed this 
regulation, and by approving it certifies that it will not have a 
significant economic impact upon a substantial number of small 
entities. This rulemaking creates new recordkeeping and reporting 
requirements which will have an extremely limited impact on a small 
number of registrants due to the restricted use of GHB for legitimate 
medical purposes. As a condition of Xyrem's (the FDA-approved product 
containing GHB) approval, a risk management program was designed to 
limit its distribution. Under this program, Xyrem will only be 
available to physicians and patients through a single centralized 
pharmacy. As a result of this program, at this time, controlled 
substance distributors and retail pharmacies will not be handling Xyrem 
and, thus, will not be affected by these requirements. For those few 
persons affected by these regulations, the information requested by 
these added records is readily and commonly available, and due to the 
limited distribution of GHB, the impact on reporting requirements 
should be minimal.

Executive Order 12866

    The Deputy Assistant Administrator further certifies that this 
regulation has been drafted in accordance with the principles of 
Executive Order 12866, Section 1(b). This action has been determined to 
be a ``significant regulatory action'' under Executive Order 12866, and 
accordingly this rule has been reviewed by the Office of Management and 
Budget.

Executive Order 12988

    This regulation meets the applicable standards set forth in 
Sections 3(a) and 3(b)(2) of Executive Order 12988.

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 rulemaking will not result in the expenditure by State, local, 
and tribal governments in the aggregate, or by the private sector, of 
$114.5 million or more in any one year, and will not significantly or 
uniquely affect small governments. Therefore, no actions were deemed 
necessary under the provisions of the Unfunded Mandates Reform Act of 
1995.

Paperwork Reduction Act

    While, technically, this rule requires new, minimal recordkeeping 
and reporting requirements for drug products containing GHB, DEA does 
not believe that these recordkeeping and reporting requirements create 
any greater hour or cost burden for respondents than what already 
exists. Records required to be maintained by dispensing practitioners 
under 21 CFR 1304.26, including the prescribing practitioner's name, 
address, state license and federal registration numbers, and the 
patient's insurance provider (if available) are all records which are 
maintained as a usual course of professional practice by a dispensing 
practitioner. The reporting requirements in 21 CFR 1304.33 are part of 
an already-approved collection of information (OMB 1117-0003: ARCOS 
Transaction Reporting--DEA Form 333). DEA believes that the additional 
reporting requirements will have no impact on the hour or cost burden 
for respondents as reports are generated and submitted electronically. 
As has been stated previously, due to the risk management plan 
established for Xyrem (the FDA-approved drug product containing GHB) 
this product has an extremely limited distribution potential. Because 
of the nature of this product's distribution, DEA anticipates that 
fewer than five persons will be impacted by the requirement to report 
handling Schedule III GHB products to ARCOS, and those persons are 
already filing reports with DEA for other controlled substances 
handled. The system modifications necessary to generate this report 
will occur as a normal part of a registrant's handling of this product. 
Therefore, DEA is not submitting any changes or amendments to its 
active information collections under the Paperwork Reduction Act of 
1995.

Small Business Regulatory Enforcement Fairness Act of 1996

    This rulemaking is not a major rule as defined by section 804 of 
the Small Business Regulatory Enforcement Fairness Act of 1996. 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 significant adverse 
effects on competition, employment, investment, productivity, 
innovation or on the ability of U.S.-based companies to compete with 
foreign-based companies in domestic and export markets.

List of Subjects

21 CFR Part 1304

    Drug traffic control, Reporting and recordkeeping requirements.

21 CFR Part 1306

    Drug traffic control, Prescription drugs.

21 CFR Part 1310

    Drug traffic control, List I and List II chemicals, Reporting and 
recordkeeping requirements.

0
For the reasons set out above, 21 CFR parts 1304, 1306, and 1310 are 
amended as follows:

PART 1304--RECORDS AND REPORTS OF REGISTRANTS

0
1. The authority citation for 21 CFR part 1304 continues to read as 
follows:

    Authority: 21 U.S.C. 821, 827, 871(b), 958, 965, unless 
otherwise noted.


0
2. Section 1304.22 is amended by revising paragraph (c) to read as 
follows:


Sec.  1304.22  Records for manufacturers, distributors, dispensers, 
researchers, importers and exporters.

* * * * *
    (c) Records for dispensers and researchers. Each person registered 
or authorized to dispense or conduct research with controlled 
substances shall maintain records with the same information required of 
manufacturers pursuant to paragraph (a)(2)(i), (ii), (iv), (vii), and 
(ix) of this section. In addition, records shall be maintained of the 
number of units or volume of such finished form dispensed, including 
the name and address of the person to whom it was dispensed, the date 
of dispensing, the number of units or volume dispensed, and the written 
or typewritten name or initials of the individual who dispensed or 
administered the substance on behalf of the dispenser. In addition to 
the requirements of this paragraph, practitioners dispensing gamma-
hydroxybutyric acid under a prescription must also comply with Sec.  
1304.26.
* * * * *

0
3. Section 1304.26 is added to read as follows:

[[Page 294]]

Sec.  1304.26  Additional recordkeeping requirements applicable to drug 
products containing gamma-hydroxybutyric acid.

    In addition to the recordkeeping requirements for dispensers and 
researchers provided in Sec.  1304.22, practitioners dispensing gamma-
hydroxybutyric acid that is manufactured or distributed in accordance 
with an application under section 505 of the Federal Food, Drug, and 
Cosmetic Act must maintain and make available for inspection and 
copying by the Attorney General, all of the following information for 
each prescription:
    (a) Name of the prescribing practitioner.
    (b) Prescribing practitioner's Federal and State registration 
numbers, with the expiration dates of these registrations.
    (c) Verification that the prescribing practitioner possesses the 
appropriate registration to prescribe this controlled substance.
    (d) Patient's name and address.
    (e) Patient's insurance provider, if available.

0
4. Section 1304.33 is amended by revising paragraph (c) and the 
introductory text of paragraph (d)(1) to read as follows:


Sec.  1304.33  Reports to ARCOS.

* * * * *
    (c) Persons reporting. For controlled substances in Schedules I, 
II, narcotic controlled substances in Schedule III, and gamma-
hydroxybutyric acid drug product controlled substances in Schedule III, 
each person who is registered to manufacture in bulk or dosage form, or 
to package, repackage, label or relabel, and each person who is 
registered to distribute, including each person who is registered to 
reverse distribute, shall report acquisition/distribution transactions. 
In addition to reporting acquisition/distribution transactions, each 
person who is registered to manufacture controlled substances in bulk 
or dosage form shall report manufacturing transactions on controlled 
substances in Schedules I and II, each narcotic controlled substance 
listed in Schedules III, IV, and V, gamma-hydroxybutyric acid drug 
product controlled substances in Schedule III, and on each psychotropic 
controlled substance listed in Schedules III and IV as identified in 
paragraph (d) of this section.
    (d) Substances covered. (1) Manufacturing and acquisition/
distribution transaction reports shall include data on each controlled 
substance listed in Schedules I and II, on each narcotic controlled 
substance listed in Schedule III (but not on any material, compound, 
mixture or preparation containing a quantity of a substance having a 
stimulant effect on the central nervous system, which material, 
compound, mixture or preparation is listed in Schedule III or on any 
narcotic controlled substance listed in Schedule V), and on gamma-
hydroxybutyric acid drug products listed in Schedule III. Additionally, 
reports on manufacturing transactions shall include the following 
psychotropic controlled substances listed in Schedules III and IV:
* * * * *

PART 1306--PRESCRIPTIONS

0
5. The authority citation for part 1306 continues to read as follows:

    Authority: 21 U.S.C. 821, 829, 871(b) unless otherwise noted.


0
6. Section 1306.05 is amended by revising paragraph (a) to read as 
follows:


Sec.  1306.05  Manner of issuance of prescriptions.

    (a) All prescriptions for controlled substances shall be dated as 
of, and signed on, the day when issued and shall bear the full name and 
address of the patient, the drug name, strength, dosage form, quantity 
prescribed, directions for use and the name, address and registration 
number of the practitioner. Where a prescription is for gamma-
hydroxybutyric acid, the practitioner shall note on the face of the 
prescription the medical need of the patient for the prescription. A 
practitioner may sign a prescription in the same manner as he would 
sign a check or legal document (e.g., J.H. Smith or John H. Smith). 
Where an oral order is not permitted, prescriptions shall be written 
with ink or indelible pencil or typewriter and shall be manually signed 
by the practitioner. The prescriptions may be prepared by the secretary 
or agent for the signature of a practitioner, but the prescribing 
practitioner is responsible in case the prescription does not conform 
in all essential respects to the law and regulations. A corresponding 
liability rests upon the pharmacist, including a pharmacist employed by 
a central fill pharmacy, who fills a prescription not prepared in the 
form prescribed by DEA regulations.
* * * * *

PART 1310--RECORDS AND REPORTS OF LISTED CHEMICALS AND CERTAIN 
MACHINES

0
7. The authority citation for part 1310 is revised to read as follows:

    Authority: 21 U.S.C. 802, 827(h), 830, 871(b) 890.


0
8. Section 1310.03 is amended by revising paragraph (c) to read as 
follows:


Sec.  1310.03  Persons required to keep records and file reports.

* * * * *
    (c) Each regulated person who engages in a transaction with a 
nonregulated person or who engages in an export transaction that 
involves ephedrine, pseudoephedrine, phenylpropanolamine, or gamma-
hydroxybutyric acid, including drug products containing these 
chemicals, and uses or attempts to use the Postal Service or any 
private or commercial carrier must file monthly reports of each such 
transaction as specified in Sec.  1310.05 of this part.

    Dated: December 22, 2004.
William J. Walker,
Deputy Assistant Administrator, Office of Diversion Control.
[FR Doc. 05-56 Filed 1-3-05; 8:45 am]

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