02-27745. Poison Prevention Packaging Requirements; Exemption of Hormone Replacement Therapy Products

AGENCY:

Consumer Product Safety Commission.

ACTION:

Final rule.

SUMMARY:

The Commission is amending its child-resistant packaging 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 rule would uniformly exempt from child resistant packaging requirements all HRT products that rely solely on the activity of one or more progestogen or estrogen substances.

DATES:

The rule is effective November 1, 2002, and applies to products packaged on or after that date.

FOR FURTHER INFORMATION CONTACT:

Geri Smith, Office of Compliance and Enforcement, Consumer Product Safety Commission, Washington, DC 20207; telephone [phone] ext. 1160.

SUPPLEMENTARY INFORMATION:

A. Background

The Poison Prevention Packaging Act of 1970 (“PPPA”), 15 U.S.C. 1471-1476, authorizes the Commission to issue standards for the special packaging of household substances, such as drugs, when (1) Child resistant packaging is necessary to protect children from serious personal injury or illness due to the substance and (2) the special packaging is technically feasible, practicable, and appropriate for the substance. Accordingly, a Commission rule 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 that have low acute toxicity. 16 CFR 1702.1(b) and 1702.7. Current regulations provide 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.

On February 19, 2002, the Commission published a notice of proposed rulemaking (“NPR”) proposing to exempt from the special packaging requirements HRT products containing one or more progestogen or estrogen substances. 67 FR 7319. This rule will make the exemption of HRT products more uniform by exempting all HRT products that rely solely on the activity of one or more progestogen or estrogen substances.^[1]

B. HRT Products

HRT is used to replace the estrogen and progesterone that normally decline following menopause (the cessation of menstruation). Women may experience a range of menopausal symptoms. Additionally, menopause accelerates bone depletion that commonly occurs with aging, leading to osteoporosis.

HRT has been used to relieve a number of menopausal symptoms and help to prevent osteoporosis. HRT consists of using estrogen alone or various combinations of estrogens and progestins, similar to oral contraceptives. Some are natural hormones (e.g., estradiol) and others are semi-synthetic or synthetic (e.g., norgestimate). Since available HRT products contain estrogen/progestin combinations similar to oral contraceptives, it is reasonable and consistent to exempt them similarly.

Recently, studies have raised questions about the health effects of HRT. A Women's Health Initiative study indicated that women treated for about 5 years with a combination of estrogen and progestin had an increased risk of breast cancer, heart disease, stroke and blood clots compared to placebo. While this study suggests that HRT may not be indicated for long term use, it did not examine different doses, different estrogen or progestins or alternative formulations. It is likely that physicians may consider prescribing short term hormone therapy for menopausal symptoms after evaluating the risks and benefits for individual patients. Because the acute toxicity of HRT is low and its use is likely to continue even with the questions raised about its long term use, the Commission believes that a rule uniformly exempting HRT products from CR packaging requirements is appropriate.

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.

The medical literature provides little information concerning acute overdosage of progestins or estrogens. One case mentioned in the NPR 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.

For the NPR, the staff reviewed poisoning data from the American Association of Poison Control Centers (“AAPCC”) Toxic Exposure Surveillance System (“TESS”) 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.

For this final rule, the staff reviewed available AAPCC data since the NPR was published, and found no major outcomes or deaths in any of the hormone categories in 1999 and 2000 (the most recent data available).

D. Public Comment on the NPR

The Commission received one comment in response to the NPR. It came from Berlex Laboratories, which wrote that it currently markets estrogen replacement therapy, long-acting contraception, and oral contraception products and plans to market an oral HRT product in the near future. Berlex states that the proposed exemption is “beneficial in terms of cost and efficiency” and provides “drug producers greater flexibility in meeting the needs of the HRT patient population.”

E. Effective Date

With this rule, the Commission issues an exemption from the child-resistant packaging requirements generally applicable to oral prescription drugs. Thus, the rule imposes no new requirements, but lifts requirements currently in existence for some HRT products (some HRT products are already exempt from CR packaging requirements). Under these circumstances the Commission believes it is appropriate for the rule to become effective on the date it is published in the Federal Register.

F. Impact on Small Business

As discussed in the NPR, the Commission preliminarily concluded 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. This conclusion was based on the fact that 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. Thus, the exemption is not likely to have a significant impact on a substantial number of companies, regardless of size.

G. Environmental Considerations

In the NPR, the Commission also discussed possible impact on the environment as required by the National Environmental Policy Act, and in accordance with the Council on Environmental Quality regulations and CPSC procedures for environmental review. The Commission found that, because the rule would have no adverse effect on the environment, neither an environmental assessment nor an environmental impact statement is required.

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 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).

Accordingly, with the exceptions noted above, the 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 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 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 amends 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. The introductory text of paragraphs (a) and (a)(10) is republished. Section 1700.14 is amended by adding new paragraph (a)(10)(xxi) to read as follows:

§ 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 § 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 § 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: October 28, 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, “Final Rule to Exempt Hormone Replacement Therapy Products from the Special Packaging Requirements of the Poison Prevention Packaging Act,” October 9, 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,” September 9, 2002.

Footnotes

1.  Commissioner Thomas H. Moore issued a statement, which is on file in the Commission's Office of the Secretary, Room 501, 4330 East-West Highway, Bethesda, Maryland 20814.