[Federal Register Volume 62, Number 102 (Wednesday, May 28, 1997)]
[Rules and Regulations]
[Pages 28798-28801]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-13842]
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CONSUMER PRODUCT SAFETY COMMISSION
16 CFR Part 1700
Final Rule: Requirements for Child-Resistant Packaging; Packages
Containing More Than 50 mg of Ketoprofen
AGENCY: Consumer Product Safety Commission.
ACTION: Final rule.
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SUMMARY: The Commission is issuing a rule to require child-resistant
packaging for ketoprofen preparations containing more than 50 mg of
ketoprofen per retail package. Ketoprofen is a nonsteroidal anti-
inflammatory drug and is used to relieve minor aches and pains and to
reduce fever. The Commission has determined that child-resistant
packaging is necessary to protect children under five years of age from
serious personal injury and serious illness resulting from ingesting
ketoprofen. The Commission takes this action under the authority of the
Poison Prevention Packaging Act of 1970.
DATES: The rule will become effective on November 24, 1997 and applies
to
[[Page 28799]]
ketoprofen preparations packaged on or after that date.
FOR FURTHER INFORMATION CONTACT: Michael Bogumill, Division of
Regulatory Management, Consumer Product Safety Commission, Washington,
D.C. 20207; telephone (301) 504-0400 ext. 1368.
SUPPLEMENTARY INFORMATION:
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'' of any household substance if (1) the degree or
nature of the hazard to children in the availability of such substance,
by reason of its packaging, is such that special packaging is required
to protect children from serious personal injury or serious illness
resulting from handling, using, or ingesting such substance and (2) the
special packaging is technically feasible, practicable, and appropriate
for such substance.
Special packaging, also referred to as ``child-resistant (CR)
packaging,'' is packaging that (1) is designed or constructed to be
significantly difficult for children under five years of age to open or
obtain a toxic or harmful amount of the substance contained therein
within a reasonable time and (2) is not difficult for ``normal adults''
to use properly. 15 U.S.C. 1471(4). Household substances for which the
Commission may require CR packaging include (among other categories)
foods, drugs, or cosmetics as these terms are defined in the Federal
Food, Drug, and Cosmetic Act (21 U.S.C. 321). 15 U.S.C. 1471(2)(B). The
Commission has performance requirements for special packaging. 16 CFR
1700.15, 1700.20.
Section 4(a) of the PPPA, 15 U.S.C. 1473(a), allows the
manufacturer or packer to package a nonprescription product subject to
special packaging standards in one size of non-CR packaging only if the
manufacturer (or packer) also supplies the substance in CR packages of
a popular size, and the non-CR packages bear conspicuous labeling
stating: ``This package for households without young children.'' 15
U.S.C. 1473(a), 16 CFR 1700.5.
2. Ketoprofen
Ketoprofen is a nonsteroidal anti-inflammatory drug (``NSAID'').
This class of compounds also includes ibuprofen and naproxen.
Ketoprofen is used to relieve minor aches and pains such as those
associated with colds, toothaches, menstrual cramps, and muscular
aches. It is also used to reduce fever.[1, 2] 1 For the past
ten years, ketoprofen has been a prescription drug. Like most
prescription drugs, it was required to be in CR packaging by the
Commission's regulation of human oral prescription drugs, 16 CFR
1700.14(a)(10). The U.S. patent on ketoprofen expired in 1993. On
October 6, 1995, the Food and Drug Administration (``FDA'') granted
nonprescription (``over-the-counter'' or ``OTC'') status to
ketoprofen.[2]
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\1\ Numbers in brackets refer to documents listed at the end of
this notice.
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The OTC formulations, ketoprofen and ketoprofen tartrazine, contain
12.5 milligrams (mg) of ketoprofen per dose. The recommended dose is
one tablet every four to six hours. The maximum daily dose is six
tablets.[2]
3. Special Packaging
The current marketers are voluntarily placing ketoprofen in CR
packaging. However, a mandatory special packaging standard for
ketoprofen products will ensure that other companies that may market
such products in the future would use CR packaging.
Two other NSAIDs that previously became available OTC are ibuprofen
and naproxen. After ibuprofen was introduced OTC, there was an
increased incidence of accidental ingestions of the drug by children
under five.[2]
In part to avoid a similar experience with naproxen, in 1995, the
Commission then issued a rule requiring CR packaging for naproxen
preparations containing 250 mg or more per retail package. 60 FR 38671.
The rule became effective February 6, 1996. Similar reasoning applies
to ketoprofen.
A mandatory standard for ketoprofen will also enable the Commission
to ensure that its packaging meets the performance requirements of the
PPPA test protocol set forth at 16 CFR 1700.15, 1700.20.
4. The Proposed Rule
On November 20, 1996, the Commission issued a notice of proposed
rulemaking (``NPR'') that would require CR packaging for OTC drugs
containing more than 50 mg of ketoprofen. 61 FR 59043. The Commission
received only one comment, from the American Society of Health-System
Pharmacists, in response to the proposed rule.[6] That comment
expressed support for the proposed rule, stating that the toxicity data
demonstrate that ketoprofen can cause serious illness and injury to
children and that the proposed rule was consistent with packaging rules
for other NSAIDs.
B. Toxicity of Ketoprofen
As explained in the NPR, the Commission's Directorate for
Epidemiology and Health Sciences reviewed the toxicity of ketoprofen.
Side effects commonly associated with ketoprofen, as with other
NSAID's, are gastrointestinal (GI) complications, such as nausea,
vomiting, diarrhea, constipation, heartburn, and abdominal pain. Other
common adverse effects include headache, dizziness, visual
disturbances, rash, and hypersensitivity reactions.[2]
Ketoprofen may also cause more severe adverse GI effects, such as
gastric or duodenal ulcers with bleeding or perforation; intestinal
ulcers; ulcerative stomatitis or colitis; gingival ulcers; perforation
and hemorrhage of the esophagus, stomach, small or large intestine;
hematemesis; and rectal bleeding. Renal injuries also may result from
chronic use of ketoprofen.[2]
The staff reviewed the relevant medical literature which cites
several cases of severe adverse reactions to ketoprofen administration
and ketoprofen overdoses.[2] The NPR provides details of some of these
cases. 61 FR 59044-45.
The FDA maintains a data base known as the Adverse Events Reporting
System (``AERS'') for reports of adverse reactions detected after
marketing a drug or biological product. Drug manufacturers are required
to report to the FDA any known adverse effects associated with their
products.
Of the 903 ketoprofen-associated cases reported to the FDA between
1986 and October 1995, the most common adverse reactions were abdominal
pain (122), diarrhea (87), nausea (82), GI hemorrhage (70), rash (55),
indigestion (39), labored breathing (34), allergic reaction (30),
dizziness (30), and hives (30). Among the ketoprofen cases in the AERS
database are 51 more serious reactions, i.e., hospitalizations,
reactions resulting in permanent disability, or deaths. Five of these
involved children under 16 years of age.[2]
The staff reviewed accidental ingestion data for children under age
five. The American Association of Poison Control Center (``AAPCC'')
collects incident data through its Toxic Exposure Surveillance System
(``TESS''). Poisoning incidents involving ketoprofen from 1985 to 1994
were not recorded separately from other NSAIDs unless they were fatal.
No deaths involving ketoprofen were reported during this period.[2] In
1995, CPSC
[[Page 28800]]
staff requested a separate report on ketoprofen. This report showed 250
accidental ingestions of ketoprofen involving children under five years
old in 1995. Twelve of these incidents resulted in minor outcomes.[8]
CPSC's data base, the National Electronic Injury Surveillance
System (``NEISS'') monitors emergency room visits to selected hospitals
throughout the United States. As stated in the NPR, review of NEISS
data from 1988 to June 1996 showed three cases involving ketoprofen and
children under five years old. All three incidents occurred in 1996.
None were fatal or required hospitalization.[2] Since publication of
the NPR, seven new cases of children ingesting ketoprofen were reported
through NEISS.[8]
C. Level for Regulation
This rule requires special packaging for OTC ketoprofen products
containing more than 50 mg ketoprofen per retail package, the same
level as proposed in the NPR. This level is based on established
guidelines for medical treatment following pediatric ingestion of
NSAIDs.[5] These guidelines suggest medical treatment for young
children who ingest five times the maximum single therapeutic dose. For
ketoprofen, the maximum single therapeutic dose is 75 mg or 1.08 mg/kg
assuming an average adult weight of 70 kg. The dose of ketoprofen
requiring medical intervention would be five times 1.08 mg/kg, which in
a 10-kg child would be more than 50 mg of ketoprofen, or four OTC
tablets.[2]
D. Statutory Considerations
1. Hazard to Children
As noted above and in the NPR, the toxicity data concerning
children's ingestion of ketoprofen demonstrate that this compound can
cause serious illness and injury to children. Moreover, the
preparations are readily available to children. The Commission
concludes that a regulation is needed to ensure that products subject
to the regulation will be placed in CR packaging. The regulation will
enable the Commission to enforce the CR packaging requirement and
ensure that effective CR packaging is used.
Pursuant to section 3(a) of the PPPA, 15 U.S.C. 1472(a), the
Commission finds that the degree and nature of the hazard to children
from ingesting ketoprofen is such that special packaging is required to
protect children from serious illness. The Commission bases this
finding on the toxic nature of these products, described above, and
their accessibility to children in the home.
2. Technical Feasibility, Practicability, and Appropriateness
In issuing a standard for special packaging under the PPPA, the
Commission is required to find that the special packaging is
``technically feasible, practicable, and appropriate.'' 15 U.S.C.
1472(a)(2). Technical feasibility may be found when technology exists
or can be readily developed and implemented by the effective date to
produce packaging that conforms to the standards. Practicability means
that special packaging complying with the standards can utilize modern
mass production and assembly line techniques. Packaging is appropriate
when it will adequately protect the integrity of the substance and not
interfere with the substance's intended storage or use.[4, 10]
The current marketers of OTC ketoprofen voluntarily use CR
packaging. Similar designs have been shown to meet the revised testing
protocol for senior adult use effectiveness. Therefore, the Commission
concludes that CR packaging for ketoprofen is technically feasible,
practicable, and appropriate.[3, 4, 10]
3. Other Considerations
In establishing a special packaging standard under the PPPA, the
Commission must consider the following:
a. The reasonableness of the standard;
b. Available scientific, medical, and engineering data concerning
special packaging and concerning childhood accidental ingestions,
illness, and injury caused by household substances;
c. The manufacturing practices of industries affected by the PPPA;
and
d. The nature and use of the household substance. 15 U.S.C.
1472(b).
The Commission has considered these factors with respect to the
various determinations made in this notice, and finds no reason to
conclude that the rule is unreasonable or otherwise inappropriate.
E. Effective Date
The PPPA provides that no regulation shall take effect sooner than
180 days or later than one year from the date such final regulation is
issued, except that, for good cause, the Commission may establish an
earlier effective date if it determines an earlier date to be in the
public interest. 15 U.S.C. 1471n.
The Commission does not believe that a shorter effective date is
necessary to protect the public interest. The companies that are
currently marketing ketoprofen are voluntarily using CR packaging. The
Commission does not have any indication that quantities of ketoprofen
will be marketed in non-CR packaging before a 180-day effective date,
other than in a single size non-CR package, as allowed under the PPPA.
Thus, the Commission finds that a 180-day effective date is consistent
with the public interest. Accordingly, this rule will take effect 180
days after its publication in the Federal Register and will apply to
products that are packaged on or after the effective date.
F. Regulatory Flexibility Act Certification
When an agency undertakes a rulemaking proceeding, the Regulatory
Flexibility Act, 5 U.S.C. 601 et seq., generally requires the agency to
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.
When the Commission issued its proposed rule, the Commission's
Directorate for Economic Analysis prepared a preliminary assessment of
the impact of a rule to require special packaging for ketoprofen
preparations with more than 50 mg ketoprofen in a single package.[3]
Based on this assessment, the Commission concluded that such a
requirement would not have a significant impact on a substantial number
of small businesses or other small entities because the current
marketers of ketoprofen are using CR packaging and the relatively low
costs of CR packaging should not be an entry burden for future
marketers. The Commission received no comments on this determination
and is aware of no information that would alter its determination.[9]
Therefore, the Commission certifies that this rule would not have a
significant impact on a substantial number of small businesses or other
small entities.
G. 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 assessed the
possible environmental effects associated with the proposed PPPA
requirements for ketoprofen preparations.
The Commission's regulations state that rules requiring special
packaging
[[Page 28801]]
for consumer products normally have little or no potential for
affecting the human environment. 16 CFR 1021.5(c)(3). Therefore, as
stated in the proposed rule, because the rule would have no adverse
effect on the environment, neither an environmental assessment nor an
environmental impact statement is required.[3]
H. Preemption
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). Also, 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 rule requiring CR
packaging for ketoprofen would preempt non-identical state or local
special packaging standards for ketoprofen.
I. Other Executive Orders
The Commission certifies that the rule does not have sufficient
implications for federalism to warrant a Federalism Assessment under
Executive Order 12612 (October 26, 1987). Independent regulatory
agencies are encouraged, but not required, to comply with Executive
Order 13045 (April 23, 1997). This rulemaking is not subject to that
order because it is not a ``covered agency action'' as defined in the
order and because the rulemaking was initiated before the order was
issued. In any event, the Commission's discussion in this notice of the
issues involved in the rulemaking comply with the order's requirements
for an analysis of the rule and its environmental, health and safety
effects on children.
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 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 adding new paragraph (a)(26) 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 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:
* * * * *
(26) Ketoprofen. Ketoprofen preparations for human use and
containing more than 50 mg of ketoprofen in a single retail package
shall be packaged in accordance with the provisions of Sec. 1700.15(a),
(b) and (c).
* * * * *
Dated: May 21, 1997.
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., HSPS, to the
Commission, ``Proposed Rule to Require Child-Resistant Packaging for
Ketoprofen,'' October 15, 1996.
2. Memorandum from Susan C. Aitken, Ph.D., HSHE, to Jacqueline
Ferrante, Ph.D., HSPS, ``Toxicity of Ketoprofen,'' August 19, 1996.
3. Memorandum from Marcia P. Robins, EC, to Jacqueline Ferrante,
Ph.D., HSPS, ``Preliminary Assessment of Economic and Environmental
Effects of a Proposal to Require Child-Resistant Packaging for OTC
Pharmaceuticals Containing Ketoprofen,'' August 19, 1996.
4. Memorandum from Charles Wilbur, HSPS, to Jacqueline Ferrante,
Ph.D., HSPS, ``Technical Feasibility, Practicability, and
Appropriateness Determination for the Proposed Rule to Require
Child-Resistant Packaging for OTC Products Containing Ketoprofen,''
August 20, 1996.
5. Vale, J.S. and Meredith, T.J., Acute Poisoning Due to Non-
steroidal Anti-inflammatory Drugs: Clinical Features and Management.
Med. Toxicol. 1:12-31, 1986.
6. Letter from Gary C. Stein, Ph.D., Senior Government Affairs
Associate, American Society of Health-System Pharmacists, to Office
of the Secretary, CPSC, dated January 30, 1997.
7. Briefing memorandum from Jacqueline Ferrante, Ph.D., HSPS, to the
Commission, ``Final Rule to Require Child-Resistant Packaging for
Ketoprofen,'' May 5, 1997.
8. Memorandum from Susan C. Aitken, Ph.D., HSHE, to Jacqueline
Ferrante, Ph.D., HSPS, ``Update of Injuries to Accidental Ingestion
of Ketoprofen Products,'' March 4, 1997.
9. Memorandum from Marcia P. Robins, EC, to Jacqueline Ferrante,
Ph.D., HSPS, ``Final Rule for Child-Resistant Packaging for OTC
Packages Containing More than 50 mgs Ketoprofen: Regulatory
Flexibility Issues,'' February 18, 1997.
10. Memorandum from Charles Wilbur, HSPS, to Jacqueline Ferrante,
Ph.D., HSPS, ``Technical Feasibility, Practicability, and
Appropriateness Determination for the Final Rule to Require Child-
Resistant Packaging for OTC Products Containing Ketoprofen,''
February 27, 1997.
[FR Doc. 97-13842 Filed 5-27-97; 8:45 am]
BILLING CODE 6355-01-P