[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