17992 Federal Register / Vol. 60, No. 68 / Monday, April 10, 1995 / Rules and Regulations

1The Commission approved unanimously (3–0)

the motion of Chairman Ann Brown to require

AD, that it will take approximately 1

work hour per airplane, per inspection

to accomplish the required actions, and

that the average labor rate is $60 per

work hour. Based on these figures, the

total cost impact of the AD on U.S.

operators is estimated to be $1,860, or

$60 per airplane, per inspection.

The total cost impact figure discussed

above is based on assumptions that no

operator has yet accomplished any of

the requirements of this AD action, and

that no operator would accomplish

those actions in the future if this AD

were not adopted.

The regulations adopted herein will

not have substantial direct effects on the

States, on the relationship between the

national government and the States, or

on the distribution of power and

responsibilities among the various

levels of government. Therefore, in

accordance with Executive Order 12612,

it is determined that this final rule does

not have sufficient federalism

implications to warrant the preparation

of a Federalism Assessment.

For the reasons discussed above, I

certify that this action (1) Is not a

‘‘significant regulatory action’’ under

Executive Order 12866; (2) is not a

‘‘significant rule’’ under DOT

Regulatory Policies and Procedures (44

FR 11034, February 26, 1979); and (3)

will not have a significant economic

impact, positive or negative, on a

substantial number of small entities

under the criteria of the Regulatory

Flexibility Act. A final evaluation has

been prepared for this action and it is

contained in the Rules Docket. A copy

of it may be obtained from the Rules

Docket at the location provided under

the caption ADDRESSES.

List of Subjects in 14 CFR Part 39

Air transportation, Aircraft, Aviation

safety, Incorporation by reference,

Safety.

Adoption of the Amendment

Accordingly, pursuant to the

authority delegated to me by the

Administrator, the Federal Aviation

Administration amends part 39 of the

Federal Aviation Regulations (14 CFR

part 39) as follows:

PART 39—AIRWORTHINESS

DIRECTIVES

1. The authority citation for part 39

continues to read as follows:

Authority: 49 U.S.C. App. 1354(a), 1421

and 1423; 49 U.S.C. 106(g); and 14 CFR

11.89.

39.13 [Amended]

2. Section 39.13 is amended by

adding the following new airworthiness

directive:

95–07–06 British Aerospace Airbus Limited

(Formerly British Aerospace

Commercial Aircraft Limited, British

Aerospace Aircraft Group): Amendment

39–9188. Docket 94–NM–165–AD.

Applicability: All Model BAC 1–11–200

and –400 series airplanes, certificated in any

category.

Note 1: This AD applies to each airplane

identified in the preceding applicability

provision, regardless of whether it has been

modified, altered, or repaired in the area

subject to the requirements of this AD. For

airplanes that have been modified, altered, or

repaired so that the performance of the

requirements of this AD is affected, the

owner/operator must use the authority

provided in paragraph (b) to request approval

from the FAA. This approval may address

either no action, if the current configuration

eliminates the unsafe condition; or different

actions necessary to address the unsafe

condition described in this AD. Such a

request should include an assessment of the

effect of the changed configuration on the

unsafe condition addressed by this AD. In no

case does the presence of any modification,

alteration, or repair remove any airplane from

the applicability of this AD.

Compliance: Required as indicated, unless

accomplished previously.

To ensure the pilot’s ability to initiate roll

control during critical phases of the flight,

accomplish the following:

(a) Within 5 years from the date of

installation of the aileron control bearings or

within 6 months after the effective date of

this AD, whichever occurs later, perform a

detailed visual and physical inspection to

detect missing or damaged sealing rings,

corrosion, or restricted movement of the

bearings of the aileron control system, in

accordance with the Accomplishment

Instructions of British Aerospace Alert

Service Bulletin 27–A–PM6023, Issue No. 2,

dated November 23, 1992.

(1) If no discrepancies are found, repeat the

inspection requirements thereafter at

intervals not to exceed 14 months.

(2) If any discrepancy is found, prior to

further flight, replace the bearing with a new

bearing in accordance with the service

bulletin. Repeat the inspection required by

this paragraph within 5 years after

replacement of the bearings, and thereafter at

intervals not to exceed 14 months.

(b) An alternative method of compliance or

adjustment of the compliance time that

provides an acceptable level of safety may be

used if approved by the Manager,

Standardization Branch, FAA, Transport

Airplane Directorate, ANM–113. Operators

shall submit their requests through an

appropriate FAA Principal Maintenance

Inspector, who may add comments and then

send it to the Manager, Standardization

Branch, ANM–113.

Note 2: Information concerning the

existence of approved alternative methods of

compliance with this AD, if any, may be

obtained from the Standardization Branch,

ANM–113.

(c) Special flight permits may be issued in

accordance with sections 21.197 and 21.199

of the Federal Aviation Regulations (14 CFR

21.197 and 21.199) to operate the airplane to

a location where the requirements of this AD

can be accomplished.

(d) The inspections and replacement shall

be done in accordance with British

Aerospace Alert Service Bulletin 27–A–

PM6023, Issue No. 2, dated November 23,

1992. This incorporation by reference was

approved by the Director of the Federal

Register in accordance with 5 U.S.C. 552(a)

and 1 CFR part 51. Copies may be obtained

from British Aerospace, Airbus Limited, P.O.

Box 77, Bristol BS99 7AR, England. Copies

may be inspected at the FAA, Transport

Airplane Directorate, 1601 Lind Avenue,

SW., Renton, Washington; or at the Office of

the Federal Register, 800 North Capitol

Street, NW., suite 700, Washington, DC.

(e) This amendment becomes effective on

May 10, 1995.

Issued in Renton, Washington, on March

29, 1995.

Darrell M. Pederson,

Acting Manager, Transport Airplane

Directorate, Aircraft Certification Service.

[FR Doc. 95–8172 Filed 4–7–95; 8:45 am]

BILLING CODE 4910–13–U

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 childresistant 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-thecounter 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
Federal Register / Vol. 60, No. 68 / Monday, April 10, 1995 / Rules and Regulations 17993

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.

2Numbers 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].

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 (§ 1700.20). Regulations

were issued requiring special packaging

for a number of household products

(§ 1700.14). The findings that the

Commission must make in order to

issue a standard requiring childresistant (‘‘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-thecounter, 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 childresistant.’’ 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.

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 lidocainecontaining 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
17994 Federal Register / Vol. 60, No. 68 / Monday, April 10, 1995 / Rules and Regulations

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 consumerready 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 (31⁄2 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/prilocainebased 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

All

preps

Sales

($ millions)

Lidocaine

preps

Sales

($ 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
Federal Register / Vol. 60, No. 68 / Monday, April 10, 1995 / Rules and Regulations 17995

TABLE 1.—ESTIMATED SALES: TOTAL

MARKET 1 LIDOCAINE PREPARATIONS—TOPICAL DOSAGE FORMS—

Continued

1992

All

preps

Sales

($ millions)

Lidocaine

preps

Sales

($ millions)

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

Source: IMS America, Ltd. and CPSC Directorate for Economic Analysis. 1Extrapolated 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

(%

Share)

1989

(%

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 (μg/ml). Major

adverse effects occur with blood levels

over 10 μg/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 μg/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 μg/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 μg/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 μg/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 μg/ml

and 53 μg/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 31⁄2-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 μg/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 μg/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 μg/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 μg/ml serum

lidocaine level, measured 4 hours after

arrival at the emergency room, was in

the high therapeutic range. The infant
17996 Federal Register / Vol. 60, No. 68 / Monday, April 10, 1995 / Rules and Regulations

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 μg/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 antihemorrhoidal and topical anesthetics.

The market share of dibucainecontaining 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

preps

Sales

($ millions)

Dibucaine

preps

Sales

($ millions)

Topical Anesthetics (OTC) 97.7 .1

Anti-hemorrhoidal (OTC) .. 161.3 4.3

Source: IMS America, Ltd. and CPSC Directorate for Economic Analysis 1Extrapolated 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]
Federal Register / Vol. 60, No. 68 / Monday, April 10, 1995 / Rules and Regulations 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 μg/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-monthold 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-yearold 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. Lidocainecontaining 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.
17998 Federal Register / Vol. 60, No. 68 / Monday, April 10, 1995 / Rules and Regulations

TABLE 4.—ESTIMATED 1992 UNITS;1

CONSUMER-USE TOPICAL ANESTHETICS CONTAINING LIDOCAINE, DIBUCAINE, OTHER BY PACKAGE TYPE

Package type

1992

Units

(millions)

Market

share

(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 1Extrapolated 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

Package type

1992

Units

(millions)

1989

Units

(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. 1Extrapolated 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
Federal Register / Vol. 60, No. 68 / Monday, April 10, 1995 / Rules and Regulations 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 meteredspray 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
18000 Federal Register / Vol. 60, No. 68 / Monday, April 10, 1995 / Rules and Regulations

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 lidocainecontaining 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 dibucainecontaining 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]
Federal Register / Vol. 60, No. 68 / Monday, April 10, 1995 / Rules and Regulations 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 dibucainecontaining products. Since lidocaineand 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 lidocainecontaining 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.
18002 Federal Register / Vol. 60, No. 68 / Monday, April 10, 1995 / Rules and Regulations

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 continuousthreaded 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]

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 continuousthreaded 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

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 childresistant 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 consumerready 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 continuousthreaded special packaging designs that

can replace the non-CR continuousthreaded 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,
Federal Register / Vol. 60, No. 68 / Monday, April 10, 1995 / Rules and Regulations 18003

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.

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.

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
18004 Federal Register / Vol. 60, No. 68 / Monday, April 10, 1995 / Rules and Regulations

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:

§ 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:

* * * * *
Federal Register / Vol. 60, No. 68 / Monday, April 10, 1995 / Rules and Regulations 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 § 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 § 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

DEPARTMENT OF DEFENSE

Office of the Secretary

32 CFR Part 290

Defense Contract Audit Agency

(DCAA) Freedom of Information Act

Program

AGENCY: Office of the Secretary of

Defense, DoD.

ACTION: Final rule.

SUMMARY: This administrative

amendment is published to inform

potential FOIA requestors of the

geographical coverage of Wyoming from

the Western region to the Central region

as part of its reorganization. This part

also authorizes the ‘‘DCAA Label 4’’

(For official use only coversheet).

EFFECTIVE DATE: (April 10, 1950).

FOR FURTHER INFORMATION CONTACT:

Mr. Dave Henshall, Attn: CMR, Defense

Contract Audit Agency, Cameron

Station, Alexandria, VA 22304–6168,

telephone 703–274-4400.

List of Subjects in 32 CFR Part 290

Freedom of information.

Accordingly, 32 CFR Part 290 is

amended as follows: