[Federal Register Volume 60, Number 68 (Monday, April 10, 1995)]
[Rules and Regulations]
[Pages 17992-18005]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-8628]
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CONSUMER PRODUCT SAFETY COMMISSION
16 CFR Part 1700
Requirements for Child-Resistant Packaging; Requirements for
Products Containing Lidocaine or Dibucaine
AGENCY: Consumer Product Safety Commission.
ACTION: Final rule.
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SUMMARY: Under the Poison Prevention Packaging Act of 1970, the
Commission issues a rule requiring child-resistant packaging for
products containing more than 5.0 milligrams (mg) of lidocaine in a
single package or more than 0.5 mg of dibucaine in a single package.
These requirements are issued because the Commission has determined
that child-resistant packaging is required to protect children under 5
years of age from serious personal injury and serious illness resulting
from ingesting such substances. Lidocaine and dibucaine are used in
prescription drugs and over-the-counter drug products that are applied
to the skin or mucous membranes to provide an anesthetic effect.
DATE: The rule shall be effective on April 10, 1996 and shall apply to
subject products that are packaged on or after that date.1
\1\The Commission approved unanimously (3-0) the motion of
Chairman Ann Brown to require special packaging for all products
containing more than .5 mg of dibucaine in a single package. The
Commission voted 2-1 to require special packaging for all products
containing more than 5 mg of lidocaine in a single package (Chairman
Brown and Commissioner Jacqueline Jones-Smith voting for and
Commissioner Mary Sheila Gall voting against).
The Commission then voted unanimously (1) that the regulation on
lidocaine and dibucaine not be considered a final regulation until
it is published in the Federal Register; (2) that the final
regulation be published in the Federal Register on April 8, 1995, or
as soon thereafter as practicable; and (3) to approve the most
recent draft Federal Register notice that had been forwarded to the
Commission.
Each Commissioner filed a separate statement concerning this
matter. Copies of the Commissioners' statements can be obtained from
the Commission's Office of the Secretary. [[Page 17993]]
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FOR FURTHER INFORMATION CONTACT: Michael Bogumill, Division of
Regulatory Management, Office of Compliance and Enforcement, Consumer
Product Safety Commission, Washington, DC 20207; telephone (301)504-
0621 ext. 1368.
SUPPLEMENTARY INFORMATION:
A. Background
Relevant statutes and regulations. The Poison Prevention Packaging
Act of 1970 (the ``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 packaging,'' is defined as packaging that is (1) designed or
constructed to be significantly difficult for children under 5 years of
age to open or obtain a toxic or harmful amount of the substance
contained therein within a reasonable time and (2) not difficult for
normal adults to use properly. It does not mean, however, packaging
which all such children cannot open, or obtain a toxic or harmful
amount from, within a reasonable time.
Under the PPPA, effectiveness standards have been established for
special packaging (16 CFR 1700.15), as has a procedure for evaluating
its effectiveness (Sec. 1700.20). Regulations were issued requiring
special packaging for a number of household products (Sec. 1700.14).
The findings that the Commission must make in order to issue a standard
requiring child-resistant (``CR'') packaging for a product are
discussed below in Section E of this notice. For the purposes of the
PPPA, the amount of a substance ``in a single package'' that requires
the product to be in CR packaging refers to the total amount in a
single retail unit of the substance.
One of the categories of products for which CR packaging is
required is prescription drugs intended for oral administration to
humans, with specified exemptions. 16 CFR 1700.14(a)(10). Drugs that
are applied topically (for example, ointments, creams, sprays,
suppositories, mouthwash, etc.) are not covered by the oral
prescription drug standard. Where prescription drugs are subject to a
special packaging standard, section 4(b) of the PPPA allows such
products to be sold in non-CR packaging only when (1) directed by the
prescribing medical practitioner or (2) requested by the purchaser. 15
U.S.C. 1473(b).
For nonprescription (over-the-counter, or ``OTC'') products subject
to special packaging standards, section 4(a) of the PPPA allows the
manufacturer or packer to package a single size of the product in non-
CR packaging only if (1) the manufacturer (or packer) also supplies the
substance in CR packages and (2) the non-CR packages bear conspicuous
labeling stating: ``This package for households without young
children.'' 15 U.S.C. 1473(a). If the package is too small to
accommodate this label statement, the package may bear a label stating:
``Package not child-resistant.'' 16 CFR 1700.5(b). The right of the
manufacturer or packer to market a single size of the product in
noncomplying packaging under these conditions is termed the ``single-
size exemption.''
The Commission may restrict the right to market a single size in
noncomplying packaging if the Commission finds that the substance is
not also being supplied in popular size packages that comply with the
standard. 15 U.S.C. 1473(c). In this case, the Commission may, after
giving the manufacturer or packer an opportunity to comply with the
purposes of the PPPA and an opportunity for a hearing, order that the
substance be packaged exclusively in CR packaging. To issue such an
order, the Commission must find that the exclusive use of special
packaging is necessary to accomplish the purposes of the PPPA.
Previous Commission activities. [9]2 In 1985, the Commission's
staff reviewed ingestion data for topical prescription drugs to assess
the need for CR packaging. Lidocaine, a local anesthetic, was
identified as a topical drug that presented a potential ingestion
hazard to young children. Local anesthetics are used to produce
temporary loss of feeling to a limited area of the body by decreasing
the transmission of nerve impulses in that area.
\2\Numbers in brackets indicate the number of a relevant
document as listed in Appendix 1 to this notice. When a reference
document that is cited in a document listed in Appendix 1 is
referred to, both the number of the Appendix 1 document and the
designation of the reference document as given in the Appendix 1
document are given, e.g., [1, Ref. A].
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In 1985, many manufacturers of 2-percent viscous prescription
lidocaine drugs were voluntarily using CR packaging on products
intended to be dispensed directly to the consumer. The Commission
directed the staff to pursue voluntary action to address the ingestion
hazard presented by lidocaine-containing drugs and to continue to
monitor data on topical prescription drugs. In 1986, the staff sent
letters to the known manufacturers of 2-percent viscous prescription
lidocaine products requesting that the manufacturers (1) use CR
packaging on all consumer-ready packages of 2-percent viscous lidocaine
products, and (2) label 2-percent viscous lidocaine products intended
to be repackaged by the pharmacist to advise the pharmacist to dispense
the drug in CR packaging.
In 1990, the staff updated its review of the toxicity of lidocaine.
The scope of the review was expanded to include other topical local
anesthetics marketed for consumer use, and to include OTC products as
well as prescription products. The review showed that two local
anesthetics, lidocaine and dibucaine, have caused serious adverse
effects, including death, following accidental ingestion by young
children.
After considering the available information, the Commission, on
August 4, 1992, proposed a CR packaging requirement for products
containing (1) more than 5.0 milligrams (mg) of lidocaine in a single
package or (2) more than 0.5 mg dibucaine in a single package. 57 Fed.
Reg. 34274.
B. Lidocaine
Product forms, dosage and packaging. Lidocaine is an ingredient in
a wide variety of preparations used as anesthetics, general
antiseptics, and burn remedies, and for skin care. It is used also in
preparations meeting the provisions of the Food and Drug
Administration's (FDA's) OTC monograph for male genital desensitizing
products (57 Fed. Reg. 27654; June 19, 1992; 21 CFR 348). Lidocaine
preparations are available as creams, ointments, gels, jellies, viscous
[[Page 17994]] solutions, liquids, sprays, aerosols, and injectables.
Tube packaging, used for creams, ointments, and some gels, protects its
contents from contamination and moisture and enables the administration
of a controlled volume of medication to smaller areas. Aerosol, spray,
and squeeze bottles permit liquids to be applied to cover larger areas.
OTC liquid lidocaine preparations contain 1.5 to 2.5 percent
lidocaine hydrochloride. The liquid preparations typically are packaged
in squeeze or pump bottles or aerosol sprays and are labeled for
external use only. Creams and ointments contain 0.5 to 2.5 percent
lidocaine and typically are packaged in tubes. These products are
recommended for children 2 years of age and older.
Approximately 12.1 million units of lidocaine-containing products
were sold to consumer outlets in 1992. More than half (6.2 million) of
these products were cream and ointment formulations available in tubes.
In addition, the Commission's staff estimates that less than 0.4
million bottles of consumer-ready prescription viscous lidocaine were
sold in 1992.
Prescription preparations intended for consumer use include a 2-
percent viscous solution and at least two combination lidocaine creams.
The prescription 2-percent lidocaine viscous liquids, in 100 ml bottles
(3\1/2\ fluid oz), are available from 15 suppliers at estimated
wholesale costs to pharmacies ranging from $2.28 to $4.40. One supplier
also markets a 450 ml bottle of 2-percent viscous lidocaine that,
according to a company spokesperson, is for pharmacy repackaging into
smaller containers and dispensing as prescribed by physicians.
One combination cream, a lidocaine/hydrocortisone formulation, is
marketed in a 1-oz tube; its estimated wholesale cost to pharmacies is
$32.33. The other combination is a lidocaine/prilocaine-based cream,
marketed in unit dose and 30-gm (slightly over 1 oz) tubes (cost
unknown). The unit-dose, when used by the consumer, is intended to have
its entire contents applied at home about 1 hour before a medical
procedure that will be performed in a professional setting. The
preparation is used also in professional settings.
The prescription 2-percent viscous solution of lidocaine is used
for anesthesia of irritated or inflamed mucous membranes of the mouth
and throat. Care must be taken following the oral use of viscous
lidocaine because swallowing may be impaired. It is recommended that
food not be ingested for 1 hour following oral use because of the
potential for aspiration. For adults, it is recommended for mouth pain
that one 15 ml tablespoon be swished around the mouth and spit out; for
throat pain, the same amount can be gargled and either spit out or
swallowed. The maximum recommended single adult dose is 4.5 milligrams/
kilogram (mg/kg), not to exceed 300 mg. (A kilogram equals
approximately 2.2 lb.) Although this form of lidocaine is applied to
the mouth, or even swallowed, it is not considered to be a ``drug for
human use that is in a dosage form intended for oral administration''
that already is required to be in CR packaging by 16 CFR
1700.14(a)(10). This is because its action is caused by topical
application to the affected area and not by systemic action following
ingestion.
For children under 3 years of age, it is recommended that \1/4\
teaspoonful be applied to the affected area with a cotton-tipped
applicator. For children 3 years old and older, the dose is prescribed
based on the weight and age of the child. The dose interval for
children should be at least 3 hours, so as not to exceed 4 doses in a
12-hour period.
Previously, the Commission was aware of 7 marketers of trade name
OTC pharmaceuticals containing lidocaine; 16 marketers are now known.
Some marketers represent recently introduced preparations. Also, some
preparations have been recently withdrawn from the market. Creams,
ointments and some gel preparations are available in small (\1/2\- and/
or 1-oz) tubes at estimated wholesale costs of $2.02 to $5.74. One
supplier markets a preparation in a 35-gm tube (1.25 oz) at an
estimated wholesale cost of $10.19. Liquid (and some gel) lidocaine
preparations are available in aerosol, spray pump, and spray and
squeeze bottle containers. Estimated wholesale costs for \1/4\-16 oz
liquids and gels range from $1.74 to $5.46. One new marketer supplies a
preparation for burn injuries in a foil packet containing \1/8\ oz of
gel. The preparation is currently promoted for use in the workplace
rather than in the home; the company plans to introduce this product
into the consumer market in the future.
Some lidocaine preparations, although dispensed through pharmacies,
are intended for use in a professional setting such as a doctor's or
dentist's office. According to pharmaceutical company spokespersons,
these preparations include prescription lidocaine fluids such as 2
percent, 4 percent, and 5 percent liquid solutions; 2 percent jellies;
5 percent ointments; 4 percent viscous liquids; 10 percent oral sprays;
5 percent ophthalmologic solutions and drops; and prefilled syringes
containing lidocaine solutions. Products that are not customarily
consumed, used, or stored by individuals in or about the household are
not required to comply with PPPA regulations.
Table 1 shows estimated 1992 total market sales of prescription and
OTC consumer-use preparations containing lidocaine for each of five
therapeutic categories in which lidocaine products are sold. Total
sales of lidocaine preparations in 1992 are estimated at $36.6 million,
about 12 percent of sales of all preparations in the five categories
reviewed.
Based on IMS America data, the Commission's staff estimates 1992
unit sales of consumer-ready prescription 2-percent viscous lidocaine
bottles at under 0.4 million bottles, a decrease of about 50 percent
from the 1989 estimate of 0.8 million bottles. About 98 percent of
prescription 2-percent viscous lidocaine preparations were marketed in
consumer-ready 100 ml bottles in 1989 and in 1992. Many marketers and
pharmacists are voluntarily providing CR packaging for these
preparations.
Market shares of lidocaine-containing preparations (Table 2) show
slight increases since 1989 in three categories: OTC Topical
Anesthetics (up 1 percent); General Antiseptics (up 3 percent); and
Burn Remedies (up 2 percent). The 9 percent increase in the market
share of lidocaine preparations in the Topical Anti-infectives category
is most likely due to new product introductions of combination
antibiotic/anesthetic ointments and creams. The 1992 market share of
prescription cortisone/lidocaine preparations remains unchanged from
1989.
Table 1.--Estimated Sales: Total Market\1\ Lidocaine Preparations--
Topical Dosage Forms
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1992
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Lidocaine
All preps preps
Sales ($ Sales ($
millions) millions)
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Topical Anesthetics:
(OTC)............................................. 97.7 2.0
(Prescription)\2\................................. 3.3 3.3
General Antiseptics (OTC Only).................... 33.0 8.9
Burn Remedies (OTC Only).......................... 25.1 9.2
Topical Anti-infectives (OTC Only)................ 135.4 13.1
Hydrocortisone Combinations (Prescription Only)... 7.2 .1
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[[Page 17995]]
Total....................................... 301.7 36.6
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Source: IMS America, Ltd. and CPSC Directorate for Economic Analysis.
\1\Extrapolated from IMS America, Ltd. data to estimate total sales to
drug stores, food stores, and mass merchandise outlets. Includes data
provided by pharmaceutical company spokespersons.
\2\Includes only prescription 2-percent Viscous Lidocaine; all other
prescription preparations in the category are for professional use.
Table 2.--Estimated Market Shares by Category; Lidocaine Preparations
1992 and 1989
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1992 (% 1989 (%
Share) Share)
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Topical Anesthetics (OTC)............................. 2 1
General Antiseptics (OTC Only)........................ 27 24
Burn Remedies (OTC Only).............................. 37 35
Topical Anti-infectives (OTC Only).................... 10 1
Hydrocortisone Combinations (prescription Only)....... 2 2
------------------------------------------------------------------------
Source: IMS America and CPSC Directorate for Economic Analysis.
Toxicity. [1] The toxicity of lidocaine has been demonstrated in
animals and humans. Adverse effects have been observed in humans
following both therapeutic usage and accidental overdosage. Lidocaine
is readily absorbed through mucous membranes and abraded skin. The OTC
preparations warn against using large quantities over raw or blistered
areas or puncture wounds. The first-aid spray preparations warn against
use near the mouth, eyes, ears, or other sensitive areas.
Absorption of lidocaine results in systemic side effects occurring
most commonly in the cardiovascular and central nervous systems.
Adverse effects range from minor effects, such as disorientation,
dizziness, numbness, and drowsiness, to major effects, including
convulsions, coma, and respiratory arrest. The blood level of lidocaine
that is associated with toxic effects is a concentration of over 6
micrograms/milliliter (g/ml). Major adverse effects occur with
blood levels over 10 g/ml.
Animal toxicity studies have been carried out with lidocaine using
several different species and routes of exposure. Oral LD50 values
for the rat and mouse are 317 mg/kg and 220 mg/kg, respectively. [1,
Ref. Y] The median convulsive dose was calculated to be 75 percent of
the lethal dose in one study. Id. The intravenous LD50 values were
calculated to be 20-34 mg/kg in various mice studies and 25 mg/kg in
the rat. Id. Although these animal data clearly demonstrate the high
toxicity associated with lidocaine, the human experience data described
below are more relevant for extrapolation to toxicity in children.
The staff is aware of nine deaths attributed to the accidental or
intentional overdose of lidocaine:
The CPSC Death Certificate file contains a report of a three-year-
old child who died in 1980 after the accidental ingestion of lidocaine.
[4a] The causes of death were listed as cardiac arrhythmia and
degenerative brain effects.
A second death certificate reports the 1981 death of a 2-year-old
child after accidental overdose of a combination of two drugs,
lidocaine and meperidine (a narcotic analgesic). Additional information
is not available on this case. [4a]
The CPSC Reported Incident File contains the report of the death of
an 11-month-old child, in 1984, from accidental ingestion of lidocaine.
In this case, the child removed the CR closure from the product. [4b]
The FDA Adverse Reaction Reporting System reports an accidental
death, in 1979, of a 13-month-old girl who ingested a Canadian viscous
lidocaine product. The blood lidocaine concentration was 20 g/
ml. [4c]
A case reported in the literature describes the death, in 1986, of
a 13-month-old boy. The boy had blood lidocaine levels of 19.5
g/ml, remained unconscious, and was mechanically ventilated
for 54 days. The child had suffered respiratory arrest at home prior to
hospitalization. [1, Ref. Z]
A case investigated by CPSC staff involved the death in 1990 of a
14-month-old girl who ingested an unknown amount of 2-percent viscous
lidocaine. Prior to the ingestion, the lidocaine had been applied to a
diaper rash. The child's mother had placed the bottle in the crib while
changing the child's diaper. The bottle had a CR closure, but it may
not have been properly resecured. The mother did not believe the drug
was hazardous, because she had been told by the pediatrician to rub
lidocaine on the child's gums to ease teething pain. The toxicology
report revealed high levels of lidocaine in the blood (12 g/
ml) and liver. [16, Ref. 1]
Another death in 1990 involved a 15-year-old girl who drank up to
480 ml of an OTC first-aid liquid containing 2.5 percent lidocaine. The
cause of death was aspiration of gastric contents secondary to
lidocaine intoxication. The serum lidocaine level was 18 g/ml.
[16, Ref. 2]
Two adult deaths due to intentional overdose of lidocaine are also
reported in the literature. In these two cases, the blood lidocaine
levels were 40 g/ml and 53 g/ml, respectively. [1,
Ref. S]
The following cases reported in the literature describe non-fatal
adverse effects observed in young children following therapeutic
administration or accidental ingestion of lidocaine:
A 22-month-old child, weighing 10 kg, ingested 20 to 25 ml
(approximately 50 mg/kg) of 2-percent viscous lidocaine. The child
arrived at the hospital convulsing and not breathing. The child was
successfully resuscitated, and the seizures were controlled. The child
was discharged after 2 days with no long-term effects. [1, Ref. AA]
A 3\1/2\-year-old child was given one tablespoon of 2-percent
viscous lidocaine (approximately 21 mg/kg) for a sore throat. The dose
was repeated 4 hours later. The child developed seizures and had a
lidocaine blood level of 10.6 g/ml. The child was transferred
to Pediatric Intensive Care in respiratory distress. The child was
alert approximately 10 hours following the initial seizure and was
discharged the following day. [1, Ref. BB]
A 15-month-old boy developed seizures following the prescribed use
of lidocaine. The child's lidocaine blood level was 4.9 g/ml.
[1, Ref. BB]
A mother used a finger to apply 2-percent viscous lidocaine to an
11-month-old child's gums for teething pain, five or six times a day
for a week. The child developed seizures and had a blood lidocaine
level of 10 g/ml. The child was treated in the intensive care
unit and recovered after 4 days. [1, Ref. CC] Many articles in the
medical literature warn physicians about the hazards of prescribing
lidocaine for teething pain and related symptoms in young children.
A 5-month-old boy weighing 6.5 kg suffered seizures and required 48
hours of hospitalization after 1 day of treatment with oral viscous
lidocaine. [24, p. 3 & n. 2] The 3.8 g/ml serum lidocaine
level, measured 4 hours after arrival at the emergency room, was in the
high therapeutic range. The infant [[Page 17996]] required intubation
to maintain respiration.
In another case, a 2-year-old drank from a bottle of viscous
lidocaine, choked, and began convulsing within 10 to 15 seconds. [24,
p. 3 & n. 3] Aspiration of lidocaine resulted in its rapid absorption.
Serum lidocaine levels were 0.5 g/ml 4 hours after the
ingestion. The child remained hospitalized for 14 days with intubation
and respiratory support.
FDA's Adverse Reaction Reporting System contains reports of two
children (5 months old and 1 year old) who developed seizures after
being administered viscous lidocaine. [5]
For the period 1978 through April 1990, the CPSC's Children and
Poisoning (``CAP'') data base shows four ingestions of prescription
viscous lidocaine and three ingestions of OTC lidocaine products by
children under age 5. [6] All seven children were treated in National
Electronic Injury Surveillance System (``NEISS'') hospital emergency
rooms and released. Information on the amount of product ingested or
adverse effects suffered by the children is not available.
Data collected by the FDA National Clearinghouse for Poison Control
Centers from 1980 through 1984 [7] show 176 accidental ingestions of
OTC lidocaine products, 18 of which exhibited toxic symptoms. These
data also include 28 ingestions of prescription viscous lidocaine
products, with 10 showing toxic symptoms. Details of the amount of
product ingested or specific toxic symptoms are not available. This
data base was discontinued after 1984.
For the years 1989 through 1991, the American Association of Poison
Control Centers (``AAPCC'') reported 2,422 ingestions of lidocaine-
containing products, 341 of which are known to have produced symptoms
related to the exposure. Children under age 6 were involved in 1,898 of
these ingestions. [23]
In addition to the cases noted above, several cases of accidental
lidocaine poisoning in adults are reported in the literature. The
reported cases demonstrate extreme variability in the development of
toxicity of lidocaine, with children appearing to be more sensitive to
the central nervous system side effects of the drug.
Level for Regulation. The maximum level of lidocaine that does not
produce serious side effects in children is not known. The recommended
maximum single total dose of lidocaine for children is 5.0 mg/kg, which
is approximately 50 mg in a 10 kilogram (kg) child. However, as noted
above, toxic effects were reported at therapeutic dose levels. The
staff lacks sufficient information to establish that the reported cases
involving toxic effects at therapeutic doses involved oral exposures
(the route of administration most relevant to accidental ingestion) or
that the proper therapeutic dose was not exceeded. It is possible,
however, that a child who accidentally ingests a lidocaine preparation
will already have received an intentional therapeutic dose of the
preparation. In addition, the systemic toxicity of the drug is not the
only hazard it presents; there is the risk of serious injury or illness
caused by aspiration of substances that are swallowed while the mouth
and throat are anesthetized by the drug. These considerations make it
difficult to establish a package size that would not cause serious
toxic effects if the contents are ingested by a small child.
Therefore, the Commissions staff recommended that the recommended
maximum dose of lidocaine for a 10-kg child be reduced by a factor of
10 (referred to as an ``uncertainty factor'') in order to arrive at a
level that would not cause serious injury or illness in young children.
[1, 9, 24] After considering the comments on the proposal and other
available information, the Commission accepted this recommendation.
Therefore, products containing more than 5.0 mg of lidocaine in a
single package will be subject to CR packaging standards.
C. Dibucaine
Product form, dosage and packaging. Dibucaine is used for temporary
relief of painful sunburn, minor burns, scrapes, scratches,
nonpoisonous insect bites, and external hemorrhoidal pain. OTC
dibucaine preparations are marketed in 30-gm (slightly over 1 oz), 1-
oz, 1.5-oz, and 2-oz tubes. It is used also in a few prescription
preparations. It is also marketed in a 16-oz jar whose contents,
according to the supplier, are used as the basis for a pharmacist-
compounded and repackaged preparation. It is estimated that
approximately 0.9 million tubes of dibucaine were sold to consumer
outlets in 1992.
In 1994, the 13 suppliers of OTC dibucaine distributed 16 products,
each in tubes of 25 grams (nearly 1 oz) or more. This reflects a
decrease of over 50 percent in the estimated number of suppliers of
generic OTC dibucaine since 1989, when there were 28 such suppliers.
The 3 suppliers of prescription dibucaine preparations listed by
Redbook in 1989 were not listed in 1992 or 1994.
Table 3 shows CPSC staff estimates of 1992 total market sales for
OTC dibucaine preparations in the two categories in which dibucaine
preparations are sold: OTC anti-hemorrhoidal and topical anesthetics.
The market share of dibucaine-containing preparations reported in the
topical anesthetics category remains at less than 1 percent, similar to
the 1989 estimate. In the anti-hemorrhoidal category, dibucaine-
containing preparations have an estimated 3 percent market share, down
from 5 percent in 1989. Overall sales of dibucaine-containing
preparations were an estimated $4.4 million.
Table 3.--Estimated Sales: Total Market;\1\ Dibucaine Preparations--
Topical Dosage Forms
------------------------------------------------------------------------
1992
---------------------
All Dibucaine
preps preps
Sales($ Sales($
millions) millions)
------------------------------------------------------------------------
Topical Anesthetics (OTC)......................... 97.7 .1
Anti-hemorrhoidal (OTC)........................... 161.3 4.3
------------------------------------------------------------------------
Source: IMS America, Ltd. and CPSC Directorate for Economic Analysis
\1\Extrapolated from IMS America, Ltd. data to estimate total sales to
drug stores, food stores, and mass merchandise outlets. Includes data
provided by a pharmaceutical company spokesperson.
The recommended dose for adults is to not exceed 1 ounce
(equivalent to no more than 300 mg of dibucaine) in 24 hours. The
recommended dose for a child, 2 years of age or older, is not to exceed
\1/4\ ounce (equivalent to no more than 80 mg of dibucaine) in 24
hours.
Toxicity. Dibucaine is one of the most potent and toxic local
anesthetics. Dibucaine produces serious systemic effects on both the
central nervous system and the cardiovascular system. Adverse effects
can include convulsions, depression of heart muscle contractility, and
death. Dibucaine is readily absorbed through the mucous membranes and
should not be used around the eyes or mouth. Systemic absorption may
occur following the application of large amounts of dibucaine to large
areas of abraded or damaged skin, or following rectal administration.
The FDA disapproved the use of dibucaine in sore-throat and mouth
medicines because of the possibility of systemic toxicity from
dibucaine absorbed through the mucous membranes of the mouth and
throat. [1, Ref. K]
[[Page 17997]]
The toxicity of dibucaine has been demonstrated in animals and
humans. Animal studies indicate that dibucaine is lethal at three mg/kg
in dogs, and one mg/kg in monkeys. [1, Ref. J] The toxic dose of
dibucaine in humans is not known. However, the suggested maximum adult
dose is 25 mg of dibucaine. [1, Refs. H, P]
The staff is aware of eight deaths of young children resulting from
ingestion of dibucaine local anesthetics and of one death resulting
from the rectal use of a dibucaine ointment:
During the 23-year period of 1951 through 1973, one manufacturer
received reports of 11 cases of acute intoxications of young children
from dibucaine topical preparations. [1, Refs. J, L] Ten of the cases
involved accidental ingestion; one case involved the rectal use of
dibucaine ointment in a 2-month-old infant. Four of the children who
ingested the products died, as did the 2-month-old infant. Additional
details of the incidents were not provided.
The CPSC Death Certificate File contains the report of a 2-year-old
child who died in 1987 after accidentally ingesting a dibucaine cream
used primarily for treating hemorrhoids. The child was found staggering
by his mother, was lethargic, had seizures, and could not be
resuscitated from respiratory arrest. The child had a dibucaine blood
level of 1.3 g/ml. [4d]
A second death certificate reports the death in 1988 of a 21-month-
old child who accidentally ingested 22.5 grams of a dibucaine
hemorrhoid ointment. Cardiorespiratory arrest and convulsions
developed. The child could not be resuscitated after suffering cardiac
arrest. [1, Ref. N; 4e]
CPSC has obtained a medical examiner's death report of an 18-month-
old who died on July 10, 1994, after ingestion of a 1-percent dibucaine
ointment. The victim may have ingested up to \1/2\ oz of the product.
The victim's father found the child suffering seizures in the family's
kitchen. The victim was taken to a medical center and then transferred
to a major children's hospital. The child was pronounced dead
approximately 7 hours after the ingestion. [25]
Because of deaths reported from oral ingestion of dibucaine
products, a warning was added to the labels of dibucaine products,
stating:
``Should not be swallowed. Swallowing can be hazardous,
particularly to children. In the event of accidental ingestion, consult
a physician or poison control center immediately.''
For the period of 1978 through February 1990, the CPSC CAP data
base shows two ingestions of dibucaine products by children under age
5. [6] Both children were treated in NEISS hospital emergency rooms and
released. Information on the amount of product ingested or adverse
effects suffered is not available.
Data from the FDA National Clearinghouse for Poison Control Centers
from 1980 through 1984 show 113 ingestions of dibucaine products. Six
of those individuals exhibited toxic symptoms. [7] This data base was
discontinued after 1984.
The AAPCC National Data Collection System supplied to CPSC reports
general data on the ingestion of topical local anesthetics, but does
not contain specific information on the identity of the individual
compounds involved. Lidocaine and dibucaine creams and ointments
comprise only about 5 percent of the topical local anesthetics market.
For the 5-year period 1984 through 1988, 10,330 cases of accidental
ingestion of topical local anesthetics by children under age 5 were
reported through that data system. [8] Of these cases, 883 exhibited
minor-to-moderate symptoms and 10 were life-threatening or resulted in
disability. The two cases that resulted in death were attributed to
dibucaine, and are described above. Specific information on dibucaine
ingestions was available for the years 1989 through 1991. The AAPCC
received a total of 495 poison exposure cases involving dibucaine, 433
of which involved children under age 6. [23]
A review of the literature revealed one case in which a 12-month-
old infant ingested a combination of three gm of boric acid and 300 mg
of dibucaine. The child developed seizures, and also vomited due to the
effects of the boric acid. The child was hospitalized and recovered
fully after aggressive and intensive treatment. [1, Ref. M]
Level for Regulation. The high potency and toxicity of dibucaine
are well known; however, an absolute level of safety for this drug is
difficult to determine. Most cases of reported deaths contain little
information about the concentration of the drug or the amount consumed.
Ingestion of dibucaine, however, results in the same types of toxicity
as does ingestion of lidocaine. The differences between the two
compounds are in the potency and duration of action. Dibucaine is
approximately 10 times more potent than lidocaine. Therefore, a
correction factor of 10 was applied to the level for regulation derived
for lidocaine to arrive at 0.5 mg as the level for regulation. [24]
This level of regulation for dibucaine is also supported by a case
reported in the medical literature in which a 3-year-old child ingested
8 lozenges containing 1 mg of dibucaine each. The child died 8 hours
later. The total dosage was approximately 0.5-0.8 mg/kg. [22] The
author states that the child may have been sensitive to dibucaine.
D. Other Economic Considerations
[27] The total combined market for lidocaine and dibucaine
(including OTC products and prescription viscous lidocaine) in 1992
totaled an estimated 13.4 million packages available to the consumer.
This market declined 18 percent from the estimated 16.3 million
packages reported in 1989. Decreases were reported in all formulations,
most notably an estimated decline of 50 percent in the number of
packages of consumer-ready viscous lidocaine.
Most lidocaine and dibucaine preparations are OTC products sold in
packages that are not CR. The prescription creams/ointments in tubes
are also in non-CR packaging.
Table 4 shows 1992 estimated total consumer-use units and market
share by packaging type for the six categories in which IMS reports
sales of lidocaine or dibucaine. Within the six categories, lidocaine
or dibucaine preparations may not be marketed in specific package
types. For example, there are no dibucaine preparations in spray
packages. Additionally, there are no suppositories, pads, or wipes
containing lidocaine or dibucaine. Units of prescription bottles used
for 2-percent viscous lidocaine, discussed earlier, are excluded from
this table. Lidocaine-containing preparations in all package forms
amount to about 9 percent of topical anesthetic units. Nevertheless,
lidocaine in spray packages dominates the market for spray topical
anesthetic preparations (83 percent), and lidocaine in aerosol packages
represents more than half (56 percent) of the topical anesthetics
aerosol market. Lidocaine formulations packaged in tubes (creams,
ointments, and gels) and bottles (liquids and gels) comprise 7 and 8
percent of units in their respective topical anesthetic package
categories. Dibucaine-containing preparations, packaged only in tubes,
represent about 1 percent of all tubes.
[[Page 17998]]
Table 4.--Estimated 1992 Units;\1\ Consumer-Use Topical Anesthetics
Containing Lidocaine, Dibucaine, Other By Package Type
------------------------------------------------------------------------
1992
----------------------
Package type Market
Units share
(millions) (percent)
------------------------------------------------------------------------
Spray/Lidocaine.................................. 2.5 83
Spray/Dibucaine.................................. .......... .........
Spray/Other...................................... .5 17
Aerosol/Lidocaine................................ 1.9 56
Aerosol/Dibucaine................................ .......... .........
Aerosol/Other.................................... 1.5 44
Tube/Lidocaine................................... 6.2 7
Tube/Dibucaine................................... .9 1
Tube/Other....................................... 82.9 92
Bottle/Lidocaine................................. 1.5 8
Bottle/Dibucaine................................. .......... .........
Bottle/Other..................................... 16.9 92
Suppository/Lidocaine............................ .......... .........
Suppository/Dibucaine............................ .......... .........
Suppository/Other................................ 18.4 100
Pad or Wipe/Lidocaine............................ .......... .........
Pad or Wipe/Dibucaine............................ .......... .........
Pad or Wipe/Other................................ .8 100
Unknown/Other.................................... 2.3 .........
----------------------
Total Lidocaine............................ 12.1 9
Total Dibucaine............................ .9 1
Total Other................................ 123.3 90
------------------------------------------------------------------------
Source: IMS America, Ltd. and CPSC Directorate for Economic Analysis
\1\Extrapolated from IMS America, Ltd. data to estimate total sales to
drug stores, food stores, and mass merchandise outlets for the six IMS
categories in which lidocaine and dibucaine preparations are reported.
Includes data provided by pharmaceutical company spokespersons.
Table 5.--Estimated Units by Package Type;\1\ Lidocaine/Dibucaine
Preparations 1992 and 1989
------------------------------------------------------------------------
1992 1989 Units
Package type Units(millions) (millions)
------------------------------------------------------------------------
Tubes...................................... 7.1 7.6
Prescription bottles....................... .4 .8
Aerosols................................... 1.9 3.2
Spray/Bottles.............................. 4.0 4.7
Total................................ 13.4 16.3
------------------------------------------------------------------------
Source: IMS America, Ltd. and CPSC Directorate for Economic Analysis.
\1\Extrapolated from IMS America, Ltd. data to estimate total unit sales
to drug stores, food stores, and mass merchandise outlets.
The following discussion of the economic impact of this rule is
organized by the type of packaging. As noted above, lidocaine creams,
ointments, gels, viscous solutions, and liquids are packaged in tubes,
bottles and various spray containers. Dibucaine formulations are
available only in creams and ointments and are packaged only in tubes.
Prescription viscous lidocaine packaged in prescription bottles.
Most, if not all, suppliers of prescription 2-percent viscous lidocaine
formulations dispensed in bottles are voluntarily using CR packaging in
response to the Commission's 1986 request. CR packages for prescription
bottles are readily available at low incremental cost. Therefore, the
rule is not expected to have an adverse economic impact on businesses
of any size that market viscous lidocaine in prescription bottles.
Lidocaine or dibucaine creams, ointments, and gels packaged in
tubes. In 1992, an estimated 51 percent of lidocaine preparations (6.2
million units) and 100 percent of dibucaine preparations (0.9 million
units) were packaged in tubes containing 2 oz or less. There are
currently no commercially available CR packages to substitute for the
small pharmaceutical tubes used to package creams, ointments, and some
gels. Therefore, the PPPA requirement for topical anesthetics
containing lidocaine or dibucaine will affect all marketers of the
preparations packaged in tubes.
The Commission's staff identified nine marketers of OTC lidocaine
preparations packaged in tubes. Four marketers that are considered
``small businesses'' account for about 11 percent of the lidocaine/tube
preparation market. Dibucaine, available only in tubes, is marketed by
16 suppliers. Fifteen of these suppliers market generic and/or private-
label products as part of extensive product lines. Specific sales data
for the individual small marketers were not reported. However, a
pharmaceutical company spokesperson reports the aggregate market share
of small marketers is quite small. [27]
Under this rule, each marketer of lidocaine/dibucaine preparations
packaged in tubes will have to consider one of three possible marketing
options: development of acceptable CR packaging; reformulation to
eliminate lidocaine or dibucaine as an ingredient; or withdrawal from
the tube segment of the topical anesthetic market. Each marketer will
probably choose the least costly alternative. These options are
discussed below.
Reformulation: Marketers can reformulate to non-lidocaine/
dibucaine preparations and supply them in tube sizes comparable to
those they are now using. Since many marketers have tube filling
operations, this would enable the use of existing filling equipment.
However, reformulation may result in the loss of a market ``niche''
held by a specific preparation. There also are potential costs
associated with reformulation. For example, there may be research and
development costs, costs to obtain FDA approval (if required), and
additional marketing costs to regain market share. With this option,
consumers would forego the use of the original preparations.
Develop CR packaging: Marketers can work with package manufacturers
to develop CR multi-dose tubes compatible with specific lidocaine or
dibucaine formulations. The Commission concludes that the development
of CR packaging for these tubes is technically feasible, practicable
and appropriate based on existing technology. [26] A pharmaceutical
trade association contacted several major developers and suppliers of
CR closures and provided the Commission with cost and time estimates to
develop a CR tube package. The information supplied by the trade
association stated that the development cost estimates ranged from
$145,000 to $585,000 and that development would take 27-36 months.
Additional time would be needed for stability testing of the
preparation in the new package. Increased costs of up to $4.40 per tube
are estimated if development is done on an individual company basis.
Since marketers sell most lidocaine and dibucaine creams and ointments
to pharmacies at prices ranging from less than $1.00 to about $6.00,
the potential incremental cost of the tube might outweigh the cost of
certain preparations provided by small marketers. [24]
Discontinue marketing: Some marketers may be unable to absorb the
costs associated with the development of CR packaging for tubes while
maintaining a competitive price for their products. The alternative
option, reformulation, may lead to the loss of a market ``niche.'' As a
result, some firms may decide to withdraw the lidocaine/dibucaine tubes
from the market. Based on 1992 estimated total sales of all lidocaine
and dibucaine preparations ($41 million), with tubes accounting for
about 53 percent of units sold, the potential loss of sales may be
about $22 million if all such products were withdrawn. For small firms
that have extensive product lines, abandoning lidocaine or dibucaine
preparations may not be very disruptive, particularly if unit sales are
low. For a few small companies with limited product lines or a niche
preparation, withdrawal could result in disruption and financial loss.
One small firm estimated lidocaine preparations represent 30 percent of
sales, of which one-third is attributed to a preparation packaged in a
tube. The other two small firms marketing [[Page 17999]] lidocaine in
tubes would have less than 1 percent and less than 3 percent of their
respective markets affected if these products are withdrawn. Thus
lidocaine in tubes represents between less than 1 percent to 10 percent
of these companies' total sales. As in the reformulation option,
consumers would experience a loss of utility if manufacturers adopt
this option. However, preparations with similar therapeutic qualities
to any preparations withdrawn are available in the marketplace.
OTC Lidocaine liquids and gels packaged in bottles, pump sprays,
metered sprays, and aerosol sprays. OTC lidocaine preparations in
bottles and spray packages represented about 45 percent (5.9 million
units) of lidocaine shipments in 1992. Ten marketers of these
preparations have been identified. The preliminary economic assessment
discussed the availability and incremental costs of CR packaging for
these preparations. The lack of comments regarding the economic effects
of the proposal for bottle and spray packages confirms the Commission's
initial finding that costs to provide special packaging are
comparatively low and likely not to have a substantial effect on
marketers.
E. Comments on the Proposal
Ten comments were received on the proposal. The comments focused on
several areas, including the level of drug for regulation, contentions
that there is a lack of information to include all products with
lidocaine and dibucaine, and the lack of a CR tube for creams and
ointments. One commenter supported the rule. The Commission's responses
to the comments are explained below.
Scope of the proposed regulation. Comment: Several commenters
indicated that the Commission had insufficient information to require
CR packaging of all products containing lidocaine and dibucaine. The
Nonprescription Drug Manufacturers Association (NDMA) stated that the
Commission had not demonstrated that a significant number of children
have been harmed by the accidental ingestion of OTC lidocaine and
dibucaine. The NDMA contracted with Pegus Research to analyze poison
exposures to OTC products containing topical anesthetics. The study
examined poisoning incidents associated with OTC products containing
lidocaine, dibucaine, and benzocaine.
Response: The staff's review of the toxicity of lidocaine and
dibucaine was included in the February 27, 1992, briefing package for
the proposed rule and updated in a supplemental package dated May 27,
1992. The documents described nine deaths attributed to the accidental
or intentional overdose of lidocaine and several medical case reports
of adverse effects following therapeutic administration or accidental
ingestion of lidocaine. Six of these deaths were children under 5 years
of age. The majority of the cases where the formulation is known
involved 2-percent viscous lidocaine (a prescription drug). One death
followed an intentional ingestion by a 15-year-old of an OTC product
containing 2.5 percent lidocaine. The staff toxicity review described
the deaths of six children (two known to be under 5 years of age)
following the ingestion of dibucaine. An additional death of an 18-
month-old girl following the ingestion of dibucaine ointment was
reported recently.
While the data do not indicate whether any of the accidental deaths
of children associated with lidocaine involved OTC formulations, these
products contain amounts of lidocaine similar to the prescription
viscous formulation. Young children are being exposed to OTC topical
anesthetic products containing lidocaine or dibucaine. This is verified
by the NDMA-sponsored study. The CPSC staff's analysis indicates that
the proportion of children under 6 exposed to lidocaine or dibucaine is
significantly larger than the proportion of children in this age group
exposed to other substances.
The Commission concurs with the conclusion of the NDMA-sponsored
analysis that the lidocaine and dibucaine poisonings generally do not
have severe outcomes. However, four deaths from these compounds were
documented from 1987 to the present, attesting to the toxicity of these
substances.
Cream and ointment products are included in the rule because
details from the three most recent deaths following ingestion of
dibucaine (1987, 1988, 1994) specified that dibucaine was in a cream or
ointment formulation. These deaths demonstrate the toxicity of
dibucaine and the potential for toxicity from cream and ointment
formulations in general.
Comment: A manufacturer of a male genital desensitizing agent
containing lidocaine indicated that the Commission had not considered
this product class and therefore it should not be covered in the rule.
Response: At the time of the proposal, the staff was unaware of the
FDA's monograph for male genital desensitizing agents. Because the
ingestion cases do not specify the formulation of the OTC lidocaine
products, the staff cannot determine if any poisoning exposures are
attributed to this class of products. However, the rule should not
exempt these products, since the potential for injury and death from
these lidocaine-containing products is equivalent to other OTC
lidocaine spray products. The amount of lidocaine in one metered spray
of this product exceeds the 5 mg regulated amount. Tests of a similar
metered-spray package have shown that 48 of the 50 children in the test
for child resistance actuated the spray and that, on average, each of
the 48 actuated the spray over 90 times each during the 10-minute test.
[30]
Inhalation and aspiration of aerosol and spray products can result
in absorption from the lungs. The local anesthetic drugs are also
readily absorbed through mucous membranes of the mouth and throat,
therefore, an ``ingestion'' does not have to occur to result in
toxicity. Aerosol and spray product formulations are included in the
proposed rule because a child can access a potentially harmful dose.
There is a documented case of a child spraying himself with another
topical anesthetic (benzocaine 20 percent). The child experienced
cardiac arrest resulting in death.
Comment: One commenter indicated that the rule should be clarified
to exempt formulations of lidocaine intended for administration by
injection. The commenter contended that lidocaine for injection
purposes does not fit the definition of a household substance as
described in the PPPA regulations.
Response: The Commission disagrees with the commenter's contention
that the PPPA does not apply to injectable prescription pharmaceutical
products. The definition of ``household substance'' in section 2(2) of
the PPPA includes drugs and other hazardous substances that are
``customarily produced or distributed for sale for consumption or use,
or customarily stored, by individuals in or about the household.'' 15
U.S.C. 1471(2). However, the PPPA does not extend to products used
exclusively in hospitals, in nursing homes, or by medical
professionals, because such items are not customarily consumed, used,
or stored by individuals in or about the household. If the injectable
lidocaine preparations truly are for professional use only and are not
available to the consumer for use or storage at home, it is not
necessary to separately state an exemption of these products.
However, if lidocaine injectable formulations were customarily
available [[Page 18000]] for home consumer use (as is the case with
insulin), the products would not be exempted. Injectable lidocaine is a
liquid formulation that could be accessed by children if available in
the home. The commenter provided no rationale for excluding these
products in that case.
The staff is aware of other lidocaine-containing prescription
products that may be used exclusively by physicians, dentists, and in
hospital settings. A company supplied the staff with information about
the usage of these products during a meeting on October 15, 1992. The
products include creams, jellies, and liquids. The liquids are
available in prefilled syringes, ampules, sprays, and bottles. As
discussed above, if these products are for professional use only and
are not obtained by consumers for use or storage at home, the
requirements of the PPPA do not apply.
Regulated levels of lidocaine and dibucaine. Comment: Several
comments were received regarding the proposed amount (level) of the two
drug products that should be regulated. One commenter questioned the
use of a 10-fold uncertainty factor for lidocaine. Another commenter
questioned the use of an additional 10-fold factor for dibucaine.
Response: The level for regulation of lidocaine- and dibucaine-
containing products is based on the maximum recommended single
therapeutic dose of lidocaine (5 mg/kg or 50 mg for a 10 kg child). A
10-fold uncertainty factor was used to arrive at the 5 mg level of
lidocaine.
It is true that a 10-fold uncertainty factor applied to a
recommended therapeutic dose provides a more stringent level for
regulation than that normally used by CPSC staff. Applying the
uncertainty factor to the therapeutic dose is justified for lidocaine
and dibucaine, however, for the following reasons: (1) Toxicity can
occur at therapeutic doses of lidocaine and dibucaine; (2) children are
particularly susceptible to the toxic effects of repeated therapeutic
doses of these drugs; (3) since these drugs are used on children as
well as adults, an accidental exposure could occur following a previous
therapeutic dose of the drugs; (4) the metabolites of lidocaine and
dibucaine are potentially toxic, especially to young children; and (5)
risks of aspirating food or liquids are associated with oral exposure
to these drugs, even at nonlethal and therapeutic doses. These reasons
support the level chosen for regulating lidocaine.
The level for regulation of dibucaine was derived from the level
for lidocaine, based on the relative difference in potency of the two
drugs. Dibucaine is approximately 10 times more potent than lidocaine;
therefore, the staff applied an additional 10-fold factor to the 5 mg
level for lidocaine to arrive at a 0.5 mg level for dibucaine. While
the commenter questioned the use of the additional 10-fold correction
factor for dibucaine, the commenter agreed that dibucaine is
approximately 10 times more potent than lidocaine.
The commenter suggested an alternative level derived from ingestion
cases reported to the company. The commenter considers the cases to be
confidential information, so they are not discussed here in detail.
However, in addition to the cases discussed by the commenter, there was
a death of a 3-year-old child following the ingestion of 8 lozenges,
containing 1 mg of dibucaine each, that was reported in the medical
literature in 1955. The child died 8 hours later from respiratory
failure. The total dosage was approximately 0.5-0.8 mg/kg. The authors
speculated that the child may have been sensitive to this drug product;
however, dibucaine is very potent and readily absorbed from mucous
membranes. The FDA later disapproved the use of dibucaine as an active
ingredient in oral health-care products. The level of regulation being
adopted for dibucaine (0.5 mg) is supported by this reported literature
case. The Commission believes that these are appropriate levels for
regulating lidocaine and dibucaine.
Comment: One commenter indicated that a 10-fold correction factor
was not necessary for metered spray products because a child cannot
spray enough to obtain a toxic blood level. The commenter indicated
that the male genital desensitizing agent packages ``already are child
resistant in that the drug product is dispensed in a metered spray.''
The commenter estimates that only \1/3\ of each spray would be absorbed
by a child. The commenter states that any risk of aspiration is
unsupported.
Response: Metered sprays are tested for child-resistance as
described in 16 CFR 1700.20 for unit packaging. The commenter provided
no test results describing how many sprays a child can access during
the test period. It should be noted that each spray of the commenter's
product contains 7.68 mg of lidocaine per spray, an amount greater than
the recommended level for regulation. This product contains 150 sprays
per container. The FDA monograph for these preparations restricts the
dosage to 10 mg of lidocaine per spray. Thus each spray of a male
genital desensitizing agent can contain two times the proposed level
for regulation for lidocaine. The commenter did not supply data to
support its estimate of the access and absorption of the product.
The commenter also contended that the 10-fold uncertainty factor
for lidocaine was established because of the Commission's concern for
the aspiration hazard for sprays. This is not the case. Aspiration
following oral usage of local anesthetics is documented in the medical
literature and in CPSC injury records and is not limited to aerosol
products. [24, Refs. 3, 7]
Comment: Commenters stated that the 5-mg level for lidocaine and
the 0.5 mg level for dibucaine were below the therapeutic
concentrations recommended by the FDA for cream and ointment
preparations.
Response: The level for regulation does not affect or restrict the
concentration of the product. The Commission's rule simply requires
that products containing more than the regulated level must have CR
packaging. The comment about the regulated levels being below the
therapeutic concentrations can be interpreted as a complaint that the
level is too restrictive and that all lidocaine- and dibucaine-
containing products would require CR packaging. However, this is not
the case, since the PPPA allows a manufacturer or packager to package
an OTC product in one size of non-CR packaging if the manufacturer also
supplies the products in CR packages and the non-CR package is labeled
properly. The amount of product in the noncomplying package is not
restricted.
Effectiveness of Requiring CR Packaging. Comment: One commenter
supported the rule but stated that CR packaging would have prevented
only a few of the deaths. This commenter stressed the need for enhanced
educational activity. In addition, several commenters indicated that
the viscous lidocaine responsible for two of the deaths was already in
CR packaging. Other commenters indicated that the rule would have a
limited effect, since no deaths have occurred in the past several
years.
Response: Several of the deaths described in the toxicity review
were accidental or intentional overdose cases. The purpose of
discussing these cases is to illustrate the toxicity of the products.
The results of the study of ingestion cases indicate that children are
accessing products containing lidocaine and dibucaine. There were 676
ingestions of lidocaine-containing products and 110 ingestions of
dibucaine-containing products by children under 5 years of age reported
to poison control centers in 1992. [29] [[Page 18001]] While most of
these children did not experience major effects, each of the ingestions
had the potential to result in serious injury or death. For example,
with dibucaine, a company reported four deaths of children who
accidently ingested dibucaine products from 1951 to 1973. Two more
deaths were reported in 1987 and 1988, more than 10 years after the
last reported death. The death reported in 1994 demonstrates that the
risk of injury from dibucaine continues to exist. CR packaging
requirements may prevent future deaths from products containing these
ingredients.
No information is available as to whether the ``CR'' packaging,
used voluntarily by several companies, actually meets the criteria of
the PPPA regulations. A requirement for CR packaging of these products,
instead of voluntary usage, would permit CPSC to enforce the PPPA
requirements for these products.
CR packaging has saved many lives, but CR packaging is not child
proof. The Commission agrees that education is an important part of
poison prevention. The Commission acts as the secretariat for the
Poison Prevention Week Council, which promotes the poison prevention
message.
Development of CR Tubes. Closures that can be put on the small
tubes that are in current production to make them child resistant are
not currently commercially available. The following discussion
addresses some general comments related to packaging for the cream and
ointment products.
Comment: One manufacturer supplied limited test results of a 1-inch
diameter plastic squeeze tube with a European 18-mm ASTM type IA
closure. The company reported that the package was closed at 7 inch-
torque-pounds (ITP). Twenty children were tested, and eleven children
were able to open the package during the test period. None of the
children used teeth to open the package. The commenter contended that
these test data show that CR tubes are not technically feasible.
Response: The staff indicated in the proposed rule that special
packaging for tubes could be achieved by using commercially available
22-mm closure bottle threads on a suitable laminated plastic tube. This
would allow the use of a ``senior friendly'' ASTM type IA continuous
threaded closure to be used to obtain child-resistance. The staff is
unaware of any data from protocol tests conducted on a tube with the
22-mm ASTM type IA closure.
The child-resistance function of the European closure used by this
commenter is unknown. This closure has never been tested by the
Commission on any package. It is difficult to know whether the failures
in the test were associated with the closure itself or a problem with
the combination of the closure and tube. The package tested had a small
diameter closure, and 7 ITP is a very low closing force. Both of these
factors make the package more accessible to children. The larger
closure size (22 mm) proposed by the CPSC's staff is harder for
children to remove and easier to put on at higher forces. These data do
not change the Commission's view that a plastic tube can be made CR
using a 22-mm ASTM type IA closure and existing technology. See also
Section E.2, below.
Comment: Commenters indicated that unit packaging is not
appropriate for products containing lidocaine and dibucaine because the
FDA does not define a dose for lidocaine- and dibucaine-containing
creams and ointments. Commenters indicated that people use varying
amounts of these products depending on the indication for use and the
potential for partial use exists. In addition, the NDMA stated that one
of their members attempted to package in a foil pouch and could not
achieve stability of the product.
Response: The Commission is aware of the lack of a defined dose for
lidocaine and dibucaine. The Commission agrees that nonreclosable
packaging for many of the creams and ointments may not be possible due
to this variation in the definition of single use and the potential for
residual product in the package. It is difficult to package a unit
amount for these products that will not result in potential harm to
children if it is not completely used. A package cannot be marketed
containing less than the regulated amount, because this level is below
the therapeutic level required by the FDA.
The technical finding of appropriateness includes shelf life and
stability. Neither the NDMA, its member companies, nor other commenters
supplied data to document the lack of stability in pouches. The staff
is aware of a lidocaine-containing product packaged in foil pouches.
This product is currently used in industrial settings, although the
company advertises the potential for home use. The Commission
recognizes that not all formulations are equivalent; different
ingredients have different stability properties. However, the
Commission believes that suitable pouch materials can be found for any
lidocaine- or dibucaine-containing product. Because of the problem of
hazardous residual amounts, however, the amount packaged would have to
be extremely small. Therefore, pouches or other unit-dose packages may
not be a practical way to market these products to comply with the
regulation.
Comment: Bottles and jars are unsuitable for cream and ointment
formulations of hemorrhoidal relief use products, and anesthetic first
aid products due to preservation and contamination issues.
Response: Other creams, such as cosmetic cold creams, are packaged
in jars. However, the usage of these products differs substantially
from the usages of lidocaine- or dibucaine-containing products. Since
lidocaine- and dibucaine-containing products are used in the anal area
(hemorrhoidal preparations) or on open wounds (first aid preparations),
the Commission agrees that contamination is possible if individuals
reenter the container for more product without washing their hands
thoroughly. This limits the appropriateness of jars and bottles for
these products.
Comment: Plastic or laminate tubes are not a viable alternative.
One commenter reported that it cannot achieve stability of the
lidocaine product in plastic or laminate tubes.
Response: Metal tubes currently are used for packaging many
lidocaine-containing products and all the dibucaine-containing
products. The proposed rule indicated that manufacturers may have to
change from a metal tube to a plastic tube to achieve child-resistance.
No commenter supplied data to support the claim that stability cannot
be attained in plastic or laminate tubes. One manufacturer currently
markets a lidocaine-based cream product in a plastic tube. Although the
different vehicles in different formulations have different stability
properties, development testing will determine which plastics or
laminates are compatible with any particular formulation.
Comment: Tubes cannot be made CR because children will bite through
the tube, thereby gaining access to the tube's contents. The NDMA cited
the opinion of Dr. Alexander Perritt, president of Perritt
Laboratories, a CR package testing laboratory.
Response: One NDMA member supplied limited child test data to the
Commission staff. The company tested a plastic tube with a CR closure
that allegedly meets the different European child-resistance standards
on other types of packaging. While many of the 20 children tested in
these tests opened the tube package, none did so with their teeth.
There is no reason to conclude that tubes cannot be made sufficiently
strong to withstand the teeth of children under age 5. [[Page 18002]]
Additional information on the technical feasibility of plastic
tubes is in Section E.2 of this notice.
E. Statutory Considerations
1. Hazard to children. Pursuant to section 3(a) of the PPPA, 15
U.S.C. 1472(a), the Commission finds that because of the toxic nature
of lidocaine and dibucaine preparations, described above, and the
accessibility of such preparations to children in the home, the degree
and nature of the hazard to children in the availability of such
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 these
substances.
2. Technical feasibility, practicability, and appropriateness. [26]
In issuing a standard for special packaging under the PPPA, the
Commission is required by section 3(a)(2) of the PPPA, 15 U.S.C.
1472(a)(2), to find that the special packaging is ``technically
feasible, practicable, and appropriate.'' Technical feasibility exists
when technology exists or readily can be developed and implemented by
the effective date to produce packaging conforming to the standards.
Practicability means that special packaging complying with the
standards can utilize modern mass production and assembly line
techniques. Appropriateness exists when packaging complying with the
standards will adequately protect the integrity of the substance and
not interfere with the intended storage or use.
A. Technical feasibility. Lidocaine and dibucaine prescription and
OTC products are presently packaged in tubes, spray containers,
aerosols, and prescription containers. Most of the current packaging
appears to be non-CR. The manufacturers of most viscous lidocaine-based
non-oral prescription drugs have voluntarily packaged these drugs in
consumer-ready CR prescription containers, even though they are not now
required to do so under the PPPA regulations. [2, Ref. 3] For those
manufacturers using non-CR packaging, various types and designs of non-
tube CR packaging can be obtained.
CR packaging for OTC and prescription tubes can be accomplished by
using commercially available bottle threads on plastic tubes. [2, Ref.
4] This would allow the use of readily available CR continuous-threaded
closures on the tube. The Commission is aware of tubes now on the
market that use bottle threads that could be outfitted with existing
push-and-turn continuous-threaded CR closures. However, the Commission
does not know that such CR tubes are available in all the sizes
currently used or lidocaine and dibucaine products. Therefore, it may
be necessary for the manufacturers of these products to develop and
test such packaging and incorporate it into their production lines. For
those manufacturers using metal tubes, a change to a plastic tube, with
appropriate stability testing, may be necessary.3
\3\ There are other potential designs for making metal tubes CR.
[26] Those designs are not being relied upon to make the technical
feasibility finding in this proceeding, however, because they were
not discussed in the proposal and, therefore, not made available for
public comment.
One alternative CR package design that can be adapted to the
existing metal tubes involves modifying a hinged snap cap. A
continuous-threaded cap with a hinged snap cap can be permanently
attached to the threads of the tube. The snap cap can be modified by
providing a slot to allow opening of the package with a tool. This
design, if developed, should be both CR and senior friendly.
Moreover, it can be adapted to existing metal tubes and be mass
produced without degrading the integrity of the product.
In addition, two prototype closures were made for metal tubes in
the past. While these were never developed commercially, the
prototypes illustrate different approaches that can be used to
achieve CR tube packaging.
Furthermore, a company has indicated that metal tubes can be
provided with threads that can accommodate existing continuous-
threaded closures known to be child resistant on other package
types. [31, 33]
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The Commission's determination that plastic tubes for these
products are technically feasible has been confirmed by additional
information. One cap manufacturer has notified the Commission that it
has two cap designs that should be suitable. [37] One of these is
currently commercially available in stock sizes as small as 20 mm,
including the 22 mm size relied on in the proposal. This cap is child-
resistant under the Commission's current regulations and meets the
proposed senior-friendly requirements that may be adopted in the future
(see Section I of this notice). The other cap is a squeeze-and-turn
model that currently is not available in sizes below 28 mm. However,
the manufacturer indicated that a development program for smaller sizes
would require 3 months to produce prototypes, with full commercial
availability in an additional 6 months.
Another manufacturer submitted information showing steps leading to
a child-resistant plastic tube with appropriate stability
characteristics that could be distributed commercially within a 52-week
period. [35]
Technical feasibility for lidocaine prescription drug products and
OTC spray containers that are presently in non-CR packaging is
demonstrated by: (1) Many manufacturers are voluntarily using CR
packaging (ASTM type IA closures on bottles) for prescription 2-percent
viscous lidocaine consumer-ready preparations. (2) CR packaging for OTC
products that are dispensed by spraying is also commercially available.
Similar CR packaging designs have passed the proposed protocols for
``senior friendly'' packaging. (See section I below.)
CR packaging for aerosol and mechanical pump packaging is
technically feasible and commercially available. The staff has
information that this type of packaging can be made senior friendly.
Additional time to develop suitable packaging may be necessary for some
products containing lidocaine, due to the small size of the package.
For example, male genital desensitizing agents containing lidocaine are
available in metered spray packaging containing less than \1/2\ oz. An
overcap can be made for this product that would require the use of a
tool to remove. It is unknown whether this feature would be senior
friendly on this small package. If not, it may be necessary to use an
alternative type of package, such as a larger diameter aerosol with a
CR and senior-friendly overcap. Manufacturers of these products and
other products available in small mechanical pumps or aerosols may need
more than 1 year to develop senior-friendly CR packaging for these
small packages. However, as noted above, larger diameter packages can
be used, and such packages could be available within 1 year.
There are numerous continuous-threaded special packaging designs
that can replace the non-CR continuous-threaded closures presently
being used with viscous lidocaine prescription medication and OTC spray
packaging.
CR packaging for aerosols also can be obtained, and a number of
commercially available designs could be used. Therefore, the Commission
concludes that there are numerous package designs that meet the
requirements of 16 CFR 1700.15(b) that are suitable for use with the
forms of these products.
b. Practicability. Companies that are presently using CR packaging
for viscous prescription drug products containing 2-percent lidocaine
have implemented assembly line and mass production techniques in their
manufacturing processes. This shows that it is practicable to package
2-percent viscous lidocaine-containing products in special packaging.
No major problems from the manufacturing standpoint are anticipated in
the change from non-CR to CR packaging, except for the multiple-dose
tube-type packaging, [[Page 18003]] which may require the use of a
contract packager.
The manufacturers of non-tube CR packaging do not anticipate any
problems with supplying CR closures and containers. The major suppliers
of CR packaging and materials indicate that they can supply more than
the 6.2 million non-tube units estimated to be needed for lidocaine and
dibucaine products.
In most cases, manufacturers can incorporate CR packaging into
their existing packaging lines. If there were any problems in modifying
or obtaining new equipment, i.e., capping, etc., a contract packager
could be used in the interim to package lidocaine- and dibucaine-
containing products. Many existing designs suitable for use with the
products that are the subject of the regulation are currently being
used in the packaging of other products, or can be readily developed.
Special packaging for this product is therefore practicable in that it
is adaptable to modern mass production and assembly line techniques.
The Commission anticipates no major supply or procurement problems for
the packagers of these products or the manufacturers of CR closure and
capping equipment.
c. Appropriateness. Information available to the staff indicates
that the CR packaging of lidocaine- and dibucaine-containing products
is appropriate. Some companies are presently voluntarily using special
packaging for their viscous prescription drug products containing 2-
percent lidocaine. Other companies can utilize existing CR packaging
designs and materials that are not detrimental to the integrity of the
substance and do not interfere with its storage or use. Product shelf-
life and integrity would not be expected to change, as it is
anticipated that the same packaging materials could be used in contact
with the product.
In the case of the multiple-dose CR tube packaging, however, it may
be necessary, for example, to change from a metal tube to a plastic
tube in order to provide a suitable mating surface for a CR cap. A
major product manufacturer contacted by the Commission's staff
indicated that it could find an appropriate multilayer plastic tube to
replace the metal tube, but that the suitability of the new tube would
have to be confirmed by protocol and product stability testing.
The Commission concludes, therefore, that special packaging is
appropriate because it is available in forms that are not detrimental
to the integrity of the substance and that do not interfere with its
storage or use.
Accordingly, the Commission finds that special packaging is
technically feasible, practicable, and appropriate.
3. Reasonableness. In establishing a special packaging standard,
section 3(b) of the PPPA requires the Commission to consider the
available data concerning whether the standard is reasonable. 15 U.S.C.
1472(b). However, the Commission is not required to make a positive
finding that the standard is reasonable. S. Rep. No. 91-845, 91st
Cong., 2d Sess. 10 (1970).
After considering the available data, the Commission concludes that
there are no data that warrant a conclusion that the proposed rule is
not reasonable.
4. Other considerations. Section 3(b) of the PPPA also requires the
Commission, in establishing a special packaging standard, to consider:
a. Available scientific, medical, and engineering data concerning
special packaging and concerning childhood accidental ingestions,
illness, and injury caused by household substances;
b. The manufacturing practices of industries affected by the PPPA;
and
c. The nature and use of the household substance. 15 U.S.C.
1472(b).
The Commission has considered these items in making the various
determinations in this notice.
F. Effective Date
The PPPA provides that no regulation shall take effect sooner than
180 days or later than one year from the date such regulation is
final,4 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 concludes that
production of CR packaging can be fully implemented within a year from
the publication of this rule. Therefore, the final rule will become
effective April 10, 1996, as to all products subject to the rule that
are packaged on or after that date.
\4\ The Commission voted on September 28, 1994, to issue this
rule, and, at that time, the Commission directed that the rule would
become final on its date of publication in the Federal Register. The
Commission also directed that the date of publication would be April
8, 1995, or as soon thereafter as practicable.
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This 1-year effective date may not allow adequate time to modify or
replace all multiple-dose tubes, aerosols, and mechanical pumps if
unusual difficulties are encountered, if the initial design intended to
be CR is found to be unsuitable, or if data on the stability of the
package contents need to be approved by the FDA. Where necessary,
affected parties using any type of package can apply to the Commission
for a temporary exemption for the minimum period required to market
their products in CR packaging. Applications for such exemptions should
describe the efforts since the issuance of the final rule to implement
complying package designs, explain why such efforts were diligent yet
unsuccessful, and explain why additional efforts within a limited
period should result in a complying package.
G. Regulatory Flexibility Act Certification
When an agency undertakes a rulemaking proceeding, the Regulatory
Flexibility Act (Pub. L. 96-354, 5 U.S.C. 601 et seq.) generally
requires the agency to prepare initial and final regulatory flexibility
analyses describing the impact of the rule on small businesses and
other small entities. The purpose of the Regulatory Flexibility Act, as
stated in section 2(b) (5 U.S.C. 602 note), is to require agencies,
consistent with their objectives, to fit the requirements of
regulations to the scale of the businesses, organizations, and
governmental jurisdictions subject to the regulations. 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.
The initial certification indicated that the incremental costs for
CR packaging for lidocaine preparations in aerosols and squeeze and
spray bottles were comparatively low and likely to have a minimal
effect on small businesses. Since the proposal, the staff has not
received any additional information regarding adverse impacts on small
business from comments on the proposed rule or from any other source.
Therefore, the Commission concludes that the action to require CR
packaging for topical anesthetics containing lidocaine packaged in
aerosols, squeeze, and spray bottles will not have a significant
economic effect on a substantial number of small entities.
The initial certification indicated also that packaging industry
spokespersons were unaware of any appropriate types of CR packages for
the small pharmaceutical tubes now used to package lidocaine and
dibucaine creams and ointments (and some gels). The analysis concluded
that if costs associated with the use of alternate packaging were
prohibitive to small manufacturers, they may drop the product from
their lines. Since the proposal, the staff has received additional
information regarding [[Page 18004]] adverse impacts of the proposed
rule on small businesses.
Industry representatives have confirmed that there are no known CR
closures commercially available for the small pharmaceutical tubes
currently used to package creams, ointments, and some gels. Although CR
unit-dose sachets are available, specific chemical formulations used in
various preparations are reported to be incompatible with the materials
used for the sachets. Since there is no alternative packaging currently
commercially available, some small businesses advise that a PPPA
requirement for creams and ointments containing lidocaine or dibucaine
will result in the withdrawal of their products from the market. For a
few small companies, particularly those with limited product lines or a
niche preparation, withdrawal could result in disruption and financial
loss, as discussed in Section D of this notice.
The Commission concludes that the action to require CR packaging
for topical anesthetics containing lidocaine or dibucaine cream and
ointment formulations may have an adverse effect on a few small
businesses, but the number of businesses subject to such effects is not
likely to be substantial.
For the reasons given above, the Commission certifies that the rule
will not have a significant economic impact on a substantial number of
small entities.
H. 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
packaging requirements for topical drug preparations containing
lidocaine or dibucaine and presented its findings in the Preliminary
Economic Assessment (Revised April 1992). Re-assessment of the possible
environmental effects confirms the original determination that the rule
will have no significant effects on the environment. There is little
likelihood that CR unit dose tubes or sachets will replace the
currently used multi-dose tubes. But even if unit dose packaging was
available, the amount of additional packaging used would be relatively
insignificant. Since there appears to be no alternative packaging for
preparations packaged in tubes, the proposal will affect only
preparations packaged in bottles and various forms of spray containers.
Manufacturers of affected products will have time to use up existing
closure inventories and will not need to dispose of them in bulk. The
rule will not significantly increase the number of CR packages in use
and, in any event, the manufacture, use, and potential disposal of the
CR packages present the same potential environmental effects as do the
currently used packages.
Therefore, because this rule has no adverse effect on the
environment, neither an environmental assessment nor an environmental
impact statement is required.
I. Possible Changes to the PPPA Test Protocol
For the purpose of determining whether a package is CR, the current
regulations provide that a package must be capable of resisting opening
by 85 percent of a panel of 200 children after a 5-minute test and by
80 percent of the panel after an additional 5-minute test. In order to
determine that the package can be used by adults, the package must also
be able to be opened and, if appropriate, properly closed within 5
minutes by 90 percent of a panel of 100 persons of ages from 18 to 45
years.
On October 5, 1990, the Commission proposed to amend its
requirements under the PPPA. 55 FR 40856. In its proposal, the
Commission concluded that, if CR packages were easier to use, more
people would purchase and properly use CR packaging. Accordingly, the
Commission proposed to substitute a panel of 100 older adults, of ages
from 60 to 75 years for the panel of 18- to 45-year-olds. The
Commission also solicited comment on allowing a 5-minute
familiarization period in the adult test, during which the subject must
open the package, before the 1-minute test. 56 FR 9181 (March 5, 1991).
Other amendments, intended to simplify the current child test
procedures, add a procedure for determining whether the package was
adequately resecured by the adults, and to ensure that the tests
produced more consistent results, were also proposed.
The Commission received a number of comments on the proposed rule,
and contracted for additional testing to obtain information to address
the comments on the proposed 5-minute/1-minute test. On March 21, 1994,
the Commission published a Federal Register notice outlining the new
information obtained, describing possible changes to the proposed test
procedure, and requesting comment on these matters. 59 Fed. Reg. 13264.
The possible changes to the test procedure included:
1. Dividing the 60-75-year-olds into 3 age groups and distributing
the participants in the groups to reduce variability.
2. Modifying the sequential testing scheme for older adults to
provide more certainty about passing or failing ``borderline''
packages. This involves testing sequential panels of 100 seniors, up to
400 subjects, until a statistically valid determination is made.
3. Adopting the 5-minute/1-minute older adult test on which comment
was sought previously.
The additional data also resulted in other minor changes to the
proposal and provided information that the Commission can use to
address other comments that did not warrant any changes.
The Commission may vote later this year on whether to issue these
revisions to the PPPA protocol. Manufacturers of lidocaine- and
dibucaine-containing products are urged to consider changing to CR
packaging that not only meets the current PPPA requirements but will
meet the new procedures that may be adopted. This would eliminate any
need to change packaging twice in a relatively short period of time.
List of Subjects in 16 CFR Part 1700
Consumer protection, Drugs, Infants and children, Packaging and
containers, Poison prevention, Toxic substances.
J. Conclusion
For the reasons given above, the Commission amends 16 CFR 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 paragraphs (a)(23) and
(a)(24) and the introductory text of paragraph (a) is republished 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:
* * * * * [[Page 18005]]
(23) Lidocaine. Products containing more than 5.0 mg of lidocaine
in a single package (i.e., retail unit) shall be packaged in accordance
with the provisions of Sec. 1700.15(a) and (b).
(24) Dibucaine. Products containing more than 0.5 mg of dibucaine
in a single package (i.e., retail unit) shall be packaged in accordance
with the provisions of Sec. 1700.15(a) and (b).
Dated: April 3, 1995.
Sadye E. Dunn,
Secretary, Consumer Product Safety Commission.
Appendix 1--List of References
(This Appendix will not be printed in the Code of Federal Regulations.)
1. Memorandum from CPSC's Directorate for Health Sciences, dated
June 21, 1990 (toxicity).
2. Memorandum from CPSC's Directorate for Health Sciences, dated
July 24, 1989 (technical feasibility, practicability, and
appropriateness).
3. Memorandum from CPSC's Directorate for Economic Analysis,
dated December 10, 1991 (a. economic information; b. regulatory
flexibility analysis; and c. environmental assessment).
4. Death and injury data:
a. CPSC Death Certificate File, 1981, lidocaine.
b. CPSC Injury or Potential Injury Incident File, 1984,
lidocaine.
c. FDA Drugs and Biologics Adverse Reaction Reporting System
Data Base, 1979, lidocaine.
d. CPSC Death Certificate File, 1987, dibucaine.
e. CPSC Death Certificate File, 1988, dibucaine.
5. FDA Drugs and Biologics Adverse Reaction Reporting System
Data Base.
6. CPSC National Electronic Injury Surveillance System Data
Base--1978 through April 1990.
7. National Clearinghouse for Poison Control Centers Data Base
1980-1984.
8. AAPCC National Data Collection System 1984-1988.
9. Briefing package, OS #3309, ``Draft Proposed Rules--Special
Packaging Standards For Topical Anesthetics,'' February 27, 1992.
10. Briefing package, ``Supplemental Information--Special
Packaging Standards For Topical Anesthetics,'' May 27, 1992.
11. Log of Meeting with Ciba Consumer Pharmaceuticals, April 8,
1992.
12. Memorandum from CPSC's Directorate for Economic Analysis,
``Market Sketch: Topical Preparations Containing Lidocaine and
Dibucaine,'' Oct. 2, 1990 (revised April 23, 1992).
13. Memorandum from CPSC's Directorate for Economic Analysis,
``Supplemental Information on Lidocaine and Dibucaine,'' April 23,
1992.
14. Memorandum from CPSC's Directorate for Health Sciences,
``The Amount of Lidocaine and Dibucaine in Marketed Products,''
April 27, 1992.
15. Memorandum from CPSC's Directorate for Economic Analysis,
``Amended Economic Data: Proposal to Require Child-Resistant
Packaging for Topical Preparations Containing Lidocaine or
Dibucaine,'' dated April 27, 1992 (with revised preliminary economic
assessment).
16. Memorandum from CPSC's Directorate for Health Sciences,
``Additional Human Experience Data for Lidocaine and Dibucaine,''
April 27, 1992.
17. Memorandum from CPSC's Directorate for Health Sciences,
``Supplemental Information on Lidocaine and Dibucaine,'' May 28,
1992.
18. Log of Meeting with NDMA Lidocaine/Dibucaine Task Force,
October 15, 1992.
19. Comments on proposed rule (10). On file in the Office of the
Secretary.
20. Log of meeting with Ciba Consumer Pharmaceuticals, January
11, 1994.
21. Log of Meeting with NDMA Lidocaine/Dibucaine Task Force, May
25, 1994.
22. McClenahan, W., Fatal Poisoning with Dibucaine Hydrochloride
(Nuporal) Lozenges, Journal of American Medical Association, 158(7),
565, 1955.
23. Memorandum from Terry L. Kissinger, EPHA, ``Response to
Comments and analysis of Available Data Regarding Child-resistant
Packaging for Topical Anesthetics Containing Lidocaine or
Dibucaine,'' April 29, 1994.
24. Memorandum from Susan C. Aitken, Ph.D., HSPS, ``Health
Sciences Staff Responses to Comments on Proposed Packaging Standards
for Lidocaine and Dibucaine,'' July 19, 1994.
25. Memorandum from Terry L. Kissinger, EPHA, ``Recent Death
Involving Ingestion of a Dibucaine-Containing Product,'' July 27,
1994.
26. Memorandum from Charles J. Wilbur, HSPS, ``PPPA Final Rule
Lidocaine and Dibucaine Technical Feasibility, Practicability, and
Appropriateness,'' July, 1994.
27. Memorandum from Marcia P. Robins, ECSS, ``Final Economic
Assessments: Proposal to Require Child-resistant Packaging for
Topical Anesthetics Containing Lidocaine or Dibucaine,'' June 15,
1994, (and telephone conversation 10/1/93).
28. Letter from Vincent De Stefano (Ciba Consumer
Pharmaceuticals) to Ann Brown, June 10, 1994.
29. Poison Control Centers Toxic Exposure Surveillance System,
1992.
30. Wilbur, Charles J., Laboratory Report, form 221, Non-CR
Finger Mechanical Pump Spray with Overcap, 2 fl. oz., S-400-0802,
CPSC, August 2, 1994 (Confidential).
31. Memorandum to file, Mike Gidding, CEAL, ``Memorandum of
visit to Teledyne Corporation,'' August 4, 1994.
32. Letter from Andrew S. Krulwich and Julie Jacobs, counsel to
Combe, Inc., to Eric A. Rubel, General Counsel, in support of
exemption for OTC topical lidocaine preparations, September 8, 1994.
33. Memorandum from Suzanne Barone, HS, to the Commission,
``Supplemental Information on Lidocaine and Dibucaine,'' September
9, 1994.
34. Vote sheet from the Office of the General Counsel to the
Commission, with revised Federal Register notice, September 9, 1994.
35. Log of meeting and attached material submitted by a
manufacturer--FOR OFFICIAL USE ONLY.
36. Letter from John B. Dubeck, Keller and Heckman, on behalf of
Pound International, Inc., September 12, 1994.
37. Letter from Jeffrey C. Minnette, Sunbeam Plastics, September
16, 1994.
38. Memorandum from Marcia Robins, ECSS, to Suzanne Barone,
Ph.D., Project Manager, HS, ``Lidocaine/Dibucaine'' (about share of
revenue for lidocaine in tubes for three small companies), September
19, 1994.
39. Letter from Andrew S. Krulwich and Julie Jacobs, Wiley, Rein
& Fielding, on behalf of Combe, Inc., September 20, 1994.
40. Tape recordings of Commission briefing on September 21, 1994
(portion containing discussion of confidential data is for official
use only).
41. Letter from John Dubeck, Keller and Heckman, representing
Pound International, September 26, 1994 (non-confidential version).
42. Additional data from AAPCC, September 27, 1994.
43. Revised draft Federal Register notice, September 27, 1994.
44. Tape recording of Commission meeting on September 28, 1994.
45. Separate statements of the Commissioners.
[FR Doc. 95-8628 Filed 4-7-95; 8:45 am]
BILLING CODE 6335-01-P