[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