[Federal Register Volume 63, Number 113 (Friday, June 12, 1998)]
[Proposed Rules]
[Pages 32159-32161]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-15493]


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CONSUMER PRODUCT SAFETY COMMISSION

16 CFR Part 1700


Poison Prevention Packaging Requirements; Proposed Exemption of 
Sucraid

AGENCY: Consumer Product Safety Commission.

ACTION: Proposed rule.

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SUMMARY: The Commission is proposing 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. The Commission proposes this exemption because human 
experience has shown no evidence of serious toxicity.

DATES: Comments on the proposal should be submitted no later than 
August 26, 1998.

ADDRESSES: Comments should be mailed to the Office of the Secretary, 
Consumer Product Safety Commission, Washington, D.C. 20207, or 
delivered to the Office of the Secretary, Consumer Product Safety 
Commission, Room 502, 4330 East-West Highway, Bethesda, Maryland 20814-
4408, telephone (301) 504-0800. Comments may also be filed by 
telefacsimile to (301) 504-0127 or by email to [email protected].

FOR FURTHER INFORMATION CONTACT: Jacqueline Ferrante, Ph.D., Division 
of Health Sciences, Directorate for Epidemiology and Health Sciences, 
Consumer Product Safety Commission, Washington, D.C. 20207; telephone 
(301) 504-0477 ext. 1199.

SUPPLEMENTARY INFORMATION:

A. Background

    The Poison Prevention Packaging Act of 1970 (``PPPA''), 15 U.S.C. 
1471-1476, provides the Commission with authority to establish 
standards for the ``special packaging'' of household substances, such 
as drugs, when child resistant packaging is necessary to protect 
children from serious personal injury or illness due to the substance 
and the special packaging is technically feasible, practicable, and 
appropriate for such substance. Accordingly, the Commission requires 
that oral prescription drugs be in child resistant (``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. 
Possible grounds for granting the exemption are that:

    (a) The degree or nature of the hazard to children in the 
availability of the substance, by reason of its packaging, is such 
that special packaging is not required to protect children from 
serious personal injury or serious illness resulting from handling, 
using or ingesting the substance, or
    (b) Special packaging is not technically feasible, practicable, 
or appropriate for the subject substance, or
    (c) Special packaging is incompatible with the particular 
substance.16 CFR 1702.17.

    On July 10, 1997, Orphan Medical, Inc. (``Orphan Medical'') 
petitioned the Commission to exempt its product, Sucraid, from the 
special packaging

[[Page 32160]]

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 concludes 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.
    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 
estimates that there are approximately 3000 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 which 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

    According to the petitioner, there have been three clinical trials 
of Sucraid, two of which are complete. The clinical investigators 
conducting the trials 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 did rate some adverse events in the 
second trial 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 
preliminarily 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. Therefore, the Commission voted to grant the petition and 
begin a rulemaking proceeding to exempt Sucraid from the special 
packaging requirements for oral prescription drugs.

E. 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.
    The Commission's Directorate for Economic Analysis prepared a 
preliminary assessment of the impact of a rule to 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 obtaining CR packaging.
    Based on this assessment, the Commission preliminarily concludes 
that the proposed amendment exempting Sucraid from special packaging 
requirements would not have a significant impact on a substantial 
number of small businesses or other small entities.

F. Environmental Considerations

    Pursuant to the National Environmental Policy Act, and in 
accordance with the Council on Environmental Quality regulations and 
CPSC procedures for environmental review, the Commission has assessed 
the possible environmental effects associated with the proposed PPPA 
amendment.
    The Commission's regulations state that rules requiring special 
packaging for consumer products normally have little or no potential 
for affecting the human environment. 16 CFR 1021.5(c)(3). Nothing in 
this proposed rule alters that expectation. (3) Therefore, because the 
rule would have no adverse effect on the environment, neither an 
environmental assessment

[[Page 32161]]

nor an environmental impact statement is required.

G. 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 that, generally, 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). A State or local standard may be 
excepted from this preemptive effect if (1) the State or local standard 
provides a higher degree of protection from the risk of injury or 
illness than the PPPA standard; and (2) the State or political 
subdivision applies to the Commission for an exemption from the PPPA's 
preemption clause and the Commission grants the exemption through a 
process specified at 16 CFR Part 1061. 15 U.S.C. 1476(c)(1). 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 proposed rule exempting 
Sucraid from special packaging requirements would preempt non-identical 
state or local special packaging standards for the substance.
    In accordance with Executive Order 12612 (October 26, 1987), the 
Commission certifies that the proposed rule 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, the Commission proposes to amend 16 
CFR part 1700 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: June 4, 1998.
Sadye E. Dunn,
Secretary, Consumer Product Safety Commission.

List of Relevant Documents

    1. Briefing memorandum from Jaqueline 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 Jaqueline 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.

[FR Doc. 98-15493 Filed 6-11-98; 8:45 am]
BILLING CODE 6355-01-P