[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