[Federal Register Volume 67, Number 33 (Tuesday, February 19, 2002)]
[Proposed Rules]
[Pages 7319-7321]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-3999]


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CONSUMER PRODUCT SAFETY COMMISSION

16 CFR Part 1700


Poison Prevention Packaging Requirements; Proposed Exemption of 
Hormone Replacement Therapy Products

AGENCY: Consumer Product Safety Commission.

ACTION: Proposed rule.

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SUMMARY: The Commission is proposing to amend its child-resistant 
packaging

[[Page 7320]]

requirements to exempt hormone replacement therapy (``HRT'') products 
containing one or more progestogen or estrogen substances. Current 
exemptions cover some HRT products, but not others. This proposal would 
uniformly exempt all HRT products that rely solely on the activity of 
one or more progestogen or estrogen substances from child resistant 
packaging requirements.

DATES: Comments on the proposal should be submitted no later than May 
6, 2002.

ADDRESSES: Comments should be mailed to the Office of the Secretary, 
Consumer Product Safety Commission, Washington, DC 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]. Comments should be 
captioned ``Proposed HRT exemption.''

FOR FURTHER INFORMATION CONTACT: Jacqueline Ferrante, Ph.D., Division 
of Health Sciences, Directorate for Epidemiology and Health Sciences, 
Consumer Product Safety Commission, Washington, DC 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 exemptions from this requirement 
for substances with low acute toxicity. Currently, there are four PPPA 
exemptions for sex hormones: (1) Oral contraceptives in mnemonic 
packages containing one or more progestogen or estrogen substances; (2) 
conjugated estrogen tablets in mnemonic packages; (3) norethindrone 
acetate tablets in mnemonic packaging; and (4) medroxyprogesterone 
acetate tablets. 16 CFR 1700.14(a)(10)(iv), (xvii), (xviii) and (xix). 
Some HRT products fall within these exemptions, but because of the way 
these exemptions are written, other HRT products currently require CR 
packaging. The proposed exemption would cover all HRT products that 
rely solely on the activity of one or more progestogen or estrogen 
substances.

B. HRT Products

    HRT is used to replace the estrogen and progesterone that normally 
decline following menopause (the cessation of menstruation). Generally, 
women experience a range of symptoms with some reporting minimal 
discomfort, while others have more severe effects. Hot flashes are the 
most frequent symptom and often begin several years before other 
menopausal symptoms. Additionally, menopause accelerates bone depletion 
that commonly occurs with aging, leading to osteoporosis.
    HRT relieves a number of menopausal symptoms (e.g., hot flashes and 
vaginitis) and helps to prevent osteoporosis. HRT consists of using 
estrogen alone or various combinations of estrogens and progestins. The 
latter regimen is similar to that for oral contraceptive products 
except the goal of therapy is to replace declining hormone levels 
rather than to prevent pregnancy.
    Because the life expectancy of women in the United States is 
increasing, it is estimated that 40 million women will go through 
menopause in the next 20 years. Therefore, the pharmaceutical industry 
is developing new prescription products specifically designed and 
marketed for HRT post-menopausal women. Some of these products may not 
be covered under current PPPA regulations although their toxicity is as 
low as those products currently exempt.
    Sex hormone products contain various estrogens and progestins. Some 
are natural hormones (e.g., estradiol) and others are semi-synthetic or 
synthetic (e.g., norgestimate). Synthetic hormones are usually 
developed to alter bioavailability (e.g., enhance oral absorption) or 
to reduce side effects. Since available HRT products contain similar 
estrogen/progestin combinations, it is reasonable and consistent to 
exempt them like oral contraceptives.

C. Toxicity Data

    Human toxic doses for estrogens or progestins have not been 
defined. Exposure summaries in the Poisindex for estrogens, 
progestins, and oral contraceptives state that acute toxicity is 
unlikely following overdosage. Gastrointestinal effects (e.g., nausea, 
vomiting, abdominal cramps) may occur after an acute overdose, but 
typically no treatment is necessary.
    There is little information in the medical literature concerning 
acute overdosage of progestins or estrogens. One case showed that a 
single dose of 160 mg estradiol valerate (80 tablets/2 mg each), 
ingested by a 19-year-old woman in a suicide attempt, produced little 
toxicity. The woman slept easily during the night of the ingestion and 
the next evening presented in the emergency clinic in generally good 
condition with nausea and a headache.
    Poisoning data from the American Association of Poison Control 
Centers (``AAPCC'') Toxic Exposure Surveillance System (``TESS''), 
corroborate the lack of acute toxicity associated with sex hormones. 
The staff reviewed data showing acute exposures in children less than 
five years old to estrogens, progestins, and oral contraceptives from 
1993 to 1998. There were no deaths and most of the exposures were non-
toxic. There was one major outcome out of 37,645 exposures to oral 
contraceptives, but no details are readily available relating to this 
case. It is possible that this oral contraceptive formulation contained 
iron or that the child was exposed to a second substance or product.

D. Impact on Small Business

    The Commission's Directorate for Economic Analysis prepared a 
preliminary assessment of the impact of a rule to exempt HRT products 
from special packaging requirements. The staff reports that it does not 
know the universe of companies that would be affected by the proposed 
exemption or how many companies would be small businesses. However, the 
exemption is not likely to have a significant impact on a substantial 
number of companies, regardless of size. The exemption would actually 
increase the packaging options for manufacturers because it would allow 
them to package the affected HRT products in non-CR packages. Although 
the cost to manufacturers of CR packaging is small--usually only a few 
cents per package--the exemption would allow manufacturers to use 
slightly cheaper packages and thus reduce the final cost of the HRT 
products.
    Based on this assessment, the Commission preliminarily concludes 
that the proposed amendment exempting HRT products from special 
packaging requirements would not have a significant impact on a 
substantial number of small businesses or other small entities.

E. Environmental Considerations

    Pursuant to the National Environmental Policy Act, and in

[[Page 7321]]

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 nor an environmental impact statement is 
required.

F. 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 
HRT products from special packaging requirements would preempt non-
identical state or local special packaging standards for those 
products.
    The Commission has also evaluated the proposed rule in light of the 
principles stated in Executive Order 13132 concerning federalism, even 
though that Order does not apply to independent regulatory agencies 
such as CPSC. The Commission does not expect that the proposed rule 
will have any substantial direct effects on the States, the 
relationship between the national government and the States, or the 
distribution of power and responsibilities among various levels of 
government.

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 adding new paragraph (a)(10)(xxi) 
to read as follows (although unchanged, the introductory texts of 
paragraph (a) and paragraph (10) are included below for context):


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:
* * * * *
    (xxi) Hormone Replacement Therapy Products that rely solely upon 
the activity of one or more progestogen or estrogen substances.
* * * * *

    Dated: February 12, 2002.
Todd Stevenson,
Secretary, Consumer Product Safety Commission.

List of Relevant Documents

    1. Briefing memorandum from Jacqueline Ferrante, Ph.D., 
Directorate for Health Sciences, to the Commission, ``Proposed Rule 
to Exempt HRT Products from the Special Packaging Requirements of 
the PPPA,'' January 14, 2002.
    2. Memorandum from Robert Franklin, Directorate for Economic 
Analysis, to Jacqueline Ferrante, Ph.D., Project Manager, ``Small 
Business and Environmental Considerations Related to Exempting HRT 
Products from PPPA Requirements,'' December 20, 2001.

[FR Doc. 02-3999 Filed 2-15-02; 8:45 am]
BILLING CODE 6355-01-P