[Federal Register Volume 63, Number 230 (Tuesday, December 1, 1998)]
[Rules and Regulations]
[Pages 66001-66003]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-31998]


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CONSUMER PRODUCT SAFETY COMMISSION

16 CFR Part 1700


Poison Prevention Packaging Requirements; Exemption of Sucraid

AGENCY: Consumer Product Safety Commission.

ACTION: Final rule.

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SUMMARY: The Commission is issuing a rule to exempt from its child-
resistant packaging requirements the oral prescription drug Sucraid. 
Sucraid is a new liquid formulation of sacrosidase, a yeast derived 
form of the sucrase enzyme, used for the treatment of congenital 
sucrase-isomaltase deficiency. It was approved by the Food & Drug 
Administration on April 10, 1998. The Commission has determined that 
this product is exempt because human experience has shown no evidence 
of serious toxicity. The Commission takes this action under the 
authority of the Poison Prevention Packaging Act of 1970.

DATES: The rule will become effective on December 1, 1998.

FOR FURTHER INFORMATION CONTACT: Laura Washburn, Office of Compliance, 
Consumer Product Safety Commission, Washington, D.C. 20207; telephone 
(301) 504-0400 ext. 1452.

SUPPLEMENTARY INFORMATION:

[[Page 66002]]

A. Background

1. Relevant Statutory and Regulatory Provisions

    The Poison Prevention Packaging Act of 1970 (``PPPA''), 15 U.S.C. 
1471-1476, authorizes the Commission to establish standards for the 
``special packaging'' (also referred to as child-resistant (CR) 
packaging) of household substances, such as drugs, when CR packaging is 
necessary to protect children from serious personal injury or illness 
due to (1) handling, using, or ingesting such substance and (2) the 
special packaging is technically feasible, practicable, and appropriate 
for the substance. Accordingly, the Commission requires that oral 
prescription drugs be in CR packaging. 16 CFR 1700.14(a)(10).
    The Commission's regulations allow companies to petition the 
Commission for exemption from CR requirements. 16 CFR Part 1702. On 
July 10, 1997, Orphan Medical, Inc. (``Orphan Medical'') petitioned the 
Commission to exempt its product, Sucraid, from the special packaging 
requirements for oral prescription drugs. The petitioner stated that 
the exemption is justified because of lack of toxicity and lack of 
adverse human experience with the drug. The petitioner also stated that 
CR packaging is not technically feasible, practicable and appropriate 
for Sucraid. Because, as explained below, the Commission concluded that 
Sucraid lacks sufficient toxicity to justify special packaging, the 
Commission did not consider the technical feasibility, practicability, 
and appropriateness of special packaging for Sucraid.

2. The Proposed Rule

    On June 12, 1998, the Commission issued a notice of proposed 
rulemaking (NPR) to exempt Sucraid from CR packaging requirements. 63 
FR 32159. The Commission did not receive any comments on the proposed 
exemption.

3. Sucraid

    Sucraid is a liquid formulation of sacrosidase, a yeast derived 
form of the sucrase enzyme. It is used to treat patients with 
congenital sucrase-isomaltase deficiency (``CSID''). The petitioner 
estimated that there are approximately 3,000 to 10,000 cases of CSID in 
the United States. CSID is a condition characterized by absent or low 
levels of sucrase and isomaltase, two enzymes in the small intestine. 
Sucrase breaks down sucrose (table sugar) so that it can be absorbed. 
Persons with CSID have such symptoms as diarrhea, abdominal pain, 
bloating, and gas. Patients with severe CSID may require 
hospitalization for diarrhea, dehydration, malnutrition, weakness and 
muscle wasting. Sacrosidase is an enzyme replacement therapy that 
reduces the symptoms of CSID.

B. Toxicity Data

    Sacrosidase is derived from bakers yeast. It is Generally 
Recognized as Safe (``GRAS'') for use in food by the Food and Drug 
Administration (``FDA''). 21 CFR 170.30. Sucraid contains about 1.5 
milligrams per milliliter of the enzyme in a 50:50 solution of glycerol 
and water.
    One bottle of Sucraid contains 150 mg of protein, 59 ml of water 
and 59 ml of glycerol. Similar to dietary proteins, the protein 
component of Sucraid is digested to amino acids that are used to make 
new protein and are not expected to cause toxicity. Glycerol is a sweet 
liquid used as a solvent, preservative, and moisturizer. FDA recognizes 
glycerol as GRAS for use as a food. 21 CFR 182.1320. It is also used as 
a drug, for example, to reduce intraocular and intracranial pressure. 
It also can be used as a laxative.
    Possible adverse effects associated with glycerol include nausea, 
vomiting, headache, and dehydration. Less commonly reported effects 
include diarrhea, thirst, dizziness, and mental confusion. Some more 
serious effects have been reported with intravenous administration of 
glycerol and with certain high risk patients. However, the Hazardous 
Chemicals Desk Reference indicates that glycerol is only mildly toxic 
by ingestion. In addition, the Handbook of Common Poisonings in 
Children characterizes glycerol as a laxative, stating that ``acute 
exposure to most laxatives produces nausea, vomiting, and diarrhea, 
which are usually mild and self-limiting.''
    The CPSC staff found three cases in the National Electronic Injury 
Surveillance System (``NEISS'') of children under five years old 
ingesting products containing glycerol. The products involved were a 
glycerol suppository, a baby enema preparation, and an ear solution. In 
all three cases the child was treated and released or examined and 
released without treatment.
    Thus, based on the information discussed above, the glycerol 
component of Sucraid is not likely to cause significant toxicity to 
children.

C. Human Experience Data

    Investigators conducting clinical trials of Sucraid did not rate 
any of the adverse effects encountered as probably or definitely 
related to the drug. Some effects were considered to be possibly 
related to the drug.
    The investigators considered most of the adverse effects to be 
unrelated to Sucraid and due to illnesses common to children (e.g., 
flu, ear infection and strep throat). Unrelated effects included sore 
throat, fever, cough, runny nose, diarrhea, cramping and abdominal 
pain.
    The clinical investigator rated some adverse events as possibly 
related to Sucraid. These symptoms included abdominal pain, diarrhea, 
nausea, vomiting, constipation, dehydration, cramps, headache, 
insomnia, nervousness, and wheezing. The petitioner noted that many of 
these were gastrointestinal symptoms typical of CSID. Thus, the dose of 
Sucraid given may not have been adequate to alleviate all symptoms of 
the disease. An asthmatic child had an acute hypersensitivity reaction 
(wheezing) to Sucraid that resolved without sequelae. This patient was 
withdrawn from the trial.

D. Action on the Petition

    After considering the information provided by the petitioner and 
other available toxicity and human experience data, the Commission 
concludes that the degree and nature of the hazard to children 
presented by the availability of Sucraid do not require special 
packaging to protect children from serious personal injury or serious 
illness resulting from handling, using, or ingesting the substance. For 
these reasons, the Commission has decided to issue the proposed 
exemption on a final basis.

E. Effective Date

    Because the rule issued below provides an exemption, the provisions 
of 5 U.S.C. 553(c) requiring a delay in the effective date is not 
applicable. Accordingly, the exemption issued below shall become 
effective on December 1, 1998.

F. Regulatory Flexibility Act Certification

    Under the Regulatory Flexibility Act, 5 U.S.C. 601 et seq., an 
agency that engages in rulemaking generally must prepare proposed and 
final regulatory flexibility analyses describing the impact of the rule 
on small businesses and other small entities. Section 605 of the Act 
provides that an agency is not required to prepare a regulatory 
flexibility analysis if the head of an agency certifies that the rule 
will not have a significant economic impact on a substantial number of 
small entities.
    In the proposed rule, the Commission's Directorate for Economic 
Analysis prepared a preliminary assessment of the impact of a rule to

[[Page 66003]]

exempt Sucraid from special packaging requirements. The staff reports 
that because of the small number of cases of CSID (3,000 to 10,000 in 
the U.S.), the market for Sucraid is expected to be small. The 
petitioner, Orphan Medical, is a small manufacturer based on its 
employment and sales. Orphan Medical has marketing exclusivity for 
Sucraid for seven years. The exemption from special packaging 
requirements will allow the company to avoid costs associated with 
providing CR packaging.
    Based on this assessment, the Commission concludes that this 
regulation exempting Sucraid from special packaging requirements would 
not have a significant impact on a substantial number of small 
businesses or other small entities.

G. Environmental Considerations

    The Commission's regulations governing environmental review 
procedures state that exemption of products from requirements for CR 
packaging under the PPPA normally has little or no potential for 
affecting the environment. (See 16 CFR 1021.5(c)(3).) The Commission 
does not foresee any special or unusual circumstances surrounding the 
exemption issued below. For this reason, the Commission concludes that 
neither an environmental assessment nor an environmental impact 
statement is required in this proceeding.

H. Executive Orders

    According to Executive Order 12988 (February 5, 1996), agencies 
must state in clear language the preemptive effect, if any, of new 
regulations.
    The PPPA provides generally that when a special packaging standard 
issued under the PPPA is in effect, ``no State or political subdivision 
thereof shall have any authority either to establish or continue in 
effect, with respect to such household substance, any standard for 
special packaging (and any exemption therefrom and requirement related 
thereto) which is not identical to the [PPPA] standard.'' 15 U.S.C. 
1476(a). Upon application to the Commission, a State or local standard 
may be excepted from this preemptive effect if the State or local 
standard (1) provides a higher degree of protection from the risk of 
injury or illness than the PPPA standard and (2) does not unduly burden 
interstate commerce. In addition, the Federal government, or a State or 
local government, may establish and continue in effect a non-identical 
special packaging requirement that provides a higher degree of 
protection than the PPPA requirement for a household substance for the 
Federal, State or local government's own use. 15 U.S.C. 1476(b).
    Thus, with the exceptions noted above, the final rule exempting 
Sucraid from special packaging requirements preempts non-identical 
state or local special packaging standards for the substance.
    In accordance with Executive Order 12612 (October 26, 1987), the 
Commission certifies that this regulation does not have sufficient 
implications for federalism to warrant a Federalism Assessment.

List of Subjects in 16 CFR Part 1700

    Consumer protection, Drugs, Infants and children, Packaging and 
containers, Poison prevention, Toxic substances.

    For the reasons given above, 16 CFR part 1700 is amended to read as 
follows:

PART 1700--[AMENDED]

    1. The authority citation for part 1700 continues to read as 
follows:

    Authority: Pub. L. 91-601, secs. 1-9, 84 Stat. 1670-74, 15 
U.S.C. 1471-76. Secs. 1700.1 and 1700.14 also issued under Pub. L. 
92-573, sec. 30(a), 88 Stat. 1231, 15 U.S.C. 2079(a).

    2. Section 1700.14 is amended by republishing paragraph (a) 
introductory text and paragraph (a)(10) introductory text, and by 
adding new paragraph (a)(10)(xx) to read as follows:


Sec. 1700.14  Substances requiring special packaging.

    (a) Substances. The Commission has determined that the degree or 
nature of the hazard to children in the availability of the following 
substances, by reason of their packaging, is such that special 
packaging meeting the requirements of Sec. 1700.20(a) is required to 
protect children from serious personal injury or serious illness 
resulting from handling, using, or ingesting such substances, and the 
special packaging herein required is technically feasible, practicable, 
and appropriate for these substances:
* * * * *
    (10) Prescription drugs. Any drug for human use that is in a dosage 
form intended for oral administration and that is required by Federal 
law to be dispensed only by or upon an oral or written prescription of 
a practitioner licensed by law to administer such drug shall be 
packaged in accordance with the provisions of Sec. 1700.15 (a), (b), 
and (c), except for the following:
* * * * *
    (xx) Sacrosidase (sucrase) preparations in a solution of glycerol 
and water.

    Dated: November 24, 1998.
Sadye E. Dunn,
Secretary, Consumer Product Safety Commission.

List of Relevant Documents

(Note. This list of relevant documents will not be printed in the 
Code of Federal Regulations.)

    1. Briefing memorandum from Jacqueline Ferrante, Ph.D., EH, to the 
Commission, ``Petition (PP 97-1) to Exempt Sucraid from the Special 
Packaging Requirements for Oral Prescription Drugs,'' May 20, 1998.
    2. Memorandum from Jacqueline Ferrante, Ph.D., EH, to Mary Ann 
Danello, Ph.D., Associate Executive Director, EH, ``Sucraid Review,'' 
April 1, 1998.
    3. Memorandum from Marcia P. Robins, EC, to Jacqueline Ferrante, 
Ph.D., EH, ``Economic Considerations: Petition for exemption from PPPA 
Requirements for Oral Prescription Drug Sucraid,'' April 2, 1998.
    4. Briefing memorandum from J. Ferrante to the Commission, ``Final 
rule to Exempt Sucraid from CRP requirements, November 12, 1998.''
    5. Memorandum from Marcie Robins to J. Ferrante, ``Exemption from 
CRP requirements for Preparations containing sacrosidase (sucrase): 
Small Business Effects,'' September 15, 1998.

[FR Doc. 98-31998 Filed 11-30-98; 8:45 am]
BILLING CODE 6355-01-P