Requirements for Child-Resistant Packaging; Requirements for Products Containing Lidocaine or Dibucaine

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.

-----------------------------------------------------------------------

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]]

---------------------------------------------------------------------------

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].

---------------------------------------------------------------------------

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

------------------------------------------------------------------------

1992

---------------------

Lidocaine

All preps preps

Sales ($ Sales ($

millions) millions)

------------------------------------------------------------------------

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

---------------------

[[Page 17995]]

Total....................................... 301.7 36.6

------------------------------------------------------------------------

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

------------------------------------------------------------------------

1992 (% 1989 (%

Share) Share)

------------------------------------------------------------------------

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]

---------------------------------------------------------------------------

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.

---------------------------------------------------------------------------

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