Federal Register / Vol. 60, No. 238 / Tuesday, December 12, 1995 / Rules and Regulations 63619

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 (e) of this AD 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.

Note 2: This AD references certain Learjet

service bulletins for applicability

information, and inspection and replacement

procedures. This AD requires performing

certain follow-on actions repetitively,

although the service bulletins specify

accomplishing these actions just once. Where

there are differences between the AD and the

service bulletins, the AD prevails.

To prevent imbalance of the fuel loads in

the wings of the airplane, which can

significantly reduce lateral control of the

airplane, accomplish the following:

(a) Within 50 hours time-in-service after

the effective date of this AD or prior to the

accumulation of 600 hours time-in-service

since installation of the flapper valve,

whichever occurs later: Perform an

inspection to detect deterioration (such as

cracks, cuts, breaks, splits, or warpage) of

both flapper valves of the tip tank in each

wing, in accordance with either Learjet

Service Bulletin SB 23/24/25–28–2, dated

October 6, 1995 (for Model 23, 24, and 25

airplanes), or Learjet Service Bulletin SB 35/

36–28–10, dated October 6, 1995 (for Model

35 and 36 airplanes); as applicable. Repeat

this inspection thereafter at intervals not to

exceed 600 hours time-in-service.

(1) If no deterioration of the flapper valve

is detected, prior to further flight, inspect the

flapper valve to ensure proper positioning,

inspect the condition of the screws that

retain the flapper valve to the plate assembly

to ensure that the flapper valve is secure,

inspect to ensure that the flapper valve

completely covers the opening of the tube

and is seated against the tube, and inspect

the flapper valve to verify that it moves

freely; and accomplish the follow-on

corrective actions, if any discrepancy is

found. These actions shall be accomplished

in accordance with the applicable service

bulletin.

(2) If any flapper valve is found to be

deteriorated, prior to further flight, replace it

with a new flapper valve in accordance with

the applicable service bulletin.

(b) Except as provided in paragraph (c) of

this AD, at the later of the times specified in

paragraphs (b)(1) and (b)(2) of this AD:

Replace both flapper valves of the tip tank in

each wing with new flapper valves in

accordance with either Learjet Service

Bulletin SB 23/24/25–28–2, dated October 6,

1995 (for Model 23, 24, and 25 airplanes), or

Learjet Service Bulletin SB 35/36–28–10,

dated October 6, 1995 (for Model 35 and 36

airplanes); as applicable.

(1) Within 5 years since date of installation

of the flapper valve, or prior to the

accumulation of 2,400 total hours time-inservice on the flapper valve, whichever

occurs earlier.

(2) Within 50 hours time-in-service after

the effective date of this AD.

(c) For airplanes on which the age and

time-in-service of the flapper valve cannot be

determined: Within 50 hours time-in-service

after the effective date of this AD, replace

both flapper valves of the tip tank in each

wing in accordance with either Learjet

Service Bulletin SB 23/24/25–28–2, dated

October 6, 1995 (for Model 23, 24, and 25

airplanes), or Learjet Service Bulletin SB 35/

36–28–10, dated October 6, 1995 (for Model

35 and 36 airplanes); as applicable.

(d) Within 600 hours time-in-service

following replacement of any flapper valve in

accordance with the requirements of this AD,

and thereafter at intervals not to exceed 600

hours time-in-service: Accomplish the

requirements of paragraph (a) of this AD.

(e) 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, Wichita

Aircraft Certification Office (ACO), FAA,

Small Airplane Directorate. Operators shall

submit their requests through an appropriate

FAA Principal Maintenance Inspector, who

may add comments and then send it to the

Manager, Wichita ACO.

Note 3: Information concerning the

existence of approved alternative methods of

compliance with this AD, if any, may be

obtained from the Wichita ACO.

(f) 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.

(g) The actions shall be done in accordance

with either Learjet Service Bulletin SB 23/24/

25–28–2, dated October 6, 1995; or Learjet

Service Bulletin SB 35/36–28–10, dated

October 6, 1995; as applicable. 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 Learjet,

Inc., One Learjet Way, Wichita, Kansas

67209–2942. Copies may be inspected at the

FAA, Transport Airplane Directorate, 1601

Lind Avenue, SW., Renton, Washington; or at

the FAA, Wichita Aircraft Certification

Office, Small Airplane Directorate, 1801

Airport Road, Room 100, Mid-Continent

Airport, Wichita, Kansas; or at the Office of

the Federal Register, 800 North Capitol

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

(h) This amendment becomes effective on

December 27, 1995.

Issued in Renton, Washington, on

November 27, 1995.

Darrell M. Pederson,

Acting Manager, Transport Airplane

Directorate, Aircraft Certification Service.

[FR Doc. 95–29300 Filed 12–11–95; 8:45 am]

BILLING CODE 4910–13–U

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 184

[Docket No. 88G–0318]

Glyceryl Palmitostearate; Affirmation

of GRAS Status of Direct Food

Substance

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is amending its

regulations to affirm that glyceryl

palmitostearate is generally recognized

as safe (GRAS) for use as a formulation

aid in excipient mixtures used in

tablets. This action is in response to a

petition filed on behalf of Gattefosse ́,

S.A.

EFFECTIVE DATE: December 12, 1995.

FOR FURTHER INFORMATION CONTACT:

Dennis M. Keefe, Center for Food Safety

and Applied Nutrition (HFS–206), Food

and Drug Administration, 200 C St. SW.,

Washington, DC 20204, 202–418–3090.

SUPPLEMENTARY INFORMATION:

I. Background

A. Regulatory History

In accordance with the procedures

described in 21 CFR 170.35, a petition

was submitted (GRASP 8G0344) on

behalf of Gattefosse ́, S.A., 36 Chemin de

Genas, Saint Priest, France, requesting

that glyceryl palmitostearate be affirmed

as GRAS for use as an excipient in

tablets.

FDA published a notice of filing of

this petition in the Federal Register of

October 20, 1988 (53 FR 41241), and

gave interested parties an opportunity to

submit comments to the Dockets

Management Branch (HFA–305), Food

and Drug Administration, rm.1–23,

12420 Parklawn Dr., Rockville, MD

20857. FDA received no comments in

response to that notice.

B. Standards for GRAS Affirmation

Under § 170.30 (21 CFR 170.30),

general recognition of safety may be

based only on the views of experts

qualified by scientific training and
63620 Federal Register / Vol. 60, No. 238 / Tuesday, December 12, 1995 / Rules and Regulations

experience to evaluate the safety of food

substances. The basis of such views may

be either scientific procedures, or in the

case of a substance used in food before

January 1, 1958, through experience

based on common use in food. General

recognition of safety based upon

scientific procedures shall require the

same quantity and quality of scientific

evidence as is required to obtain

approval of a food additive regulation,

and ordinarily is to be based upon

published studies, which may be

corroborated by unpublished studies

and other data and information

(§ 170.30(b)).

The subject petition relies on

scientific procedures evidence to

support GRAS affirmation of glyceryl

palmitostearate as an excipient in

tablets.

C. Manufacturing Process and Identity

According to information contained

in the petition, glyceryl palmitostearate

is manufactured by heating a mixture of

glycerin (glycerol) and a mixture of fatty

acids of vegetable origin composed of

roughly equal amounts (48 to 50

percent) of palmitic and stearic acid,

and 4 percent myristic acid.

Glyceryl palmitostearate prepared in

this way is a mixture of mono-, di-, and

triglycerides of palmitic and stearic

acids. It contains primarily di- and

triglycerides (>78.5 percent), a small

amount of monoglycerides (8 to 17

percent), and trace amounts of free

glycerin (<1.0 percent) and free palmitic

and stearic acid moieties (<3.0 percent).

D. Use and Exposure

The proposed use of the substance is

as a lubricating agent in excipient

mixtures for preparation of tablets

(vitamin and related products). The

technical properties of the substance in

excipient formulations are similar to

those of other fatty acid glycerides. The

petitioner asserts that the normal use

level of the substance will be 6 to 40

percent of the total tablet weight and

that the 40 percent level is typical for

long-duration timed-release

formulations. The petitioner also

estimates that although the typical

dosage is approximately two tablets per

day, some individuals may take as many

as six tablets per day.

Based on a typical dose of two 600-

milligram (mg) tablets per person per

day, FDA estimates that the typical

intake of glyceryl palmitostearate would

be from 72 to 480 mg per person per day

(Ref. 2). The petitioner estimates that on

the basis of 2,000 to 2,700 calories per

person per day total food intake and 35

percent fat in the diet (one-third of all

ingested fat being fully saturated), the

intake of saturated fat per person per

day is between 20 and 30 grams. This

estimate is consistent with dietary data

compiled by the United States

Department of Agriculture (1985). Based

on this information, FDA concludes that

the proposed use of glyceryl

palmitostearate will increase the dietary

intake of saturated fat by 2.4 percent per

person per day (Ref. 2).

II. Safety

The notice of filing in this proceeding

used the name ‘‘glyceryl

palmitostearate’’ to represent the

substance that is the subject of the

petition. The agency considers this

name to be appropriate, although the

substance is actually not a single

chemical entity, but rather a mixture of

di- and triglycerides with a small

amount of monoglycerides.

Triglycerides (triacylglycerols) are the

most abundant form of fat in the human

diet (Ref. 1). Their component fatty

acids are the major energy reserve of

plant and animal cells (Ref. 1). When

ingested, triglycerides are initially

digested into free fatty acids and

diglycerides. Diglycerides are further

digested into a mixture of

monoglycerides, glycerol, and free fatty

acids. Monoglycerides, glycerol, and

free fatty acids are the chemical forms

in which dietary fats are absorbed into

the body (Ref. 1). Thus, all of the

components of glyceryl palmitostearate

are present as components of fats found

in foods or are generated in large

amounts in the human digestive tract

during the digestion of fat (Ref. 1). As

previously stated, the proposed use of

glyceryl palmitostearate will not result

in a material increase in exposure to

these substances (Ref. 2).

The agency has previously examined

the safety of the components of glyceryl

palmitostearate. Glycerin is listed as a

multipurpose GRAS substance in 21

CFR 182.1320. Mono- and diglycerides

prepared from fats, oils, or fat-forming

acids derived from edible sources,

including palmitic and stearic acids, are

affirmed as GRAS in 21 CFR 184.1505.

Stearic and palmitic acid are approved

as multipurpose food additives in 21

CFR 172.860. Glyceryl tristearate, a

component of glyceryl palmitostearate,

is approved as a multipurpose food

additive in 21 CFR 172.811. Glyceryl

monostearate is affirmed as GRAS (21

CFR 184.1324).

The Select Committee on GRAS

Substances (SCOGS) reviewed all

available toxicological studies on monoand diglycerides and concluded:

There is no evidence in the available

information on mono- and diglycerides of fatforming fatty acids that demonstrates or

suggests reasonable grounds to suspect a

hazard to the public when they are used at

levels that are now current or that might

reasonably be expected in the future.

(Ref. 4, p. 23.)

The Joint Expert Committee on Food

Additives (JECFA) of the Food and

Agriculture Organization and the World

Health Organization (FAO/WHO) has

also reviewed the safety of mono- and

diglycerides. Based on its review, JECFA

has concluded that no limit on the

acceptable daily intake of mono- and

diglycerides need be established (Ref.

5).

III. Conclusion

FDA concludes that there is no

meaningful difference between the

components of glyceryl palmitostearate

and dietary fats or the products of

digestion of fats. The agency further

concludes that there will not be a

materially significant increase in

exposure to these substances from the

petitioned use of glyceryl

palmitostearate. The safety of the monoand diglyceride components of glyceryl

palmitostearate has been reviewed by

independent bodies of experts qualified

by training and experience to evaluate

the safety of food ingredients. These

experts have concluded that mono- and

diglycerides are safe. The information

that the agency used to arrive at these

conclusions is publicly available in

published form (Refs. 1, 3, 4, and 5).

FDA, therefore, concludes that the

petitioned use of glyceryl

palmitostearate fully meets the

requirements outlined in § 170.30(b) for

GRAS affirmation based on scientific

procedures. Therefore, in accordance

with 21 CFR 184.1(b)(1), the agency is

affirming that the use of glyceryl

palmitostearate as a formulation aid in

excipients for tablets is GRAS with no

limitations other than current good

manufacturing practice. The agency is

listing the specific use as a formulation

aid in excipients for tablets in the

regulation solely to reflect that the

affirmation of GRAS status is based on

the evaluation of this use.

IV. Environmental Impact

The agency has determined under 21

CFR 25.24(b)(7) that this action is of a

type that does not individually or

cumulatively have a significant effect on

the human environment. Therefore,

neither an environmental assessment

nor an environmental impact statement

is required.

V. Economic Impact

FDA has examined the impacts of this

final rule under Executive Order 12866

and the Regulatory Flexibility Act (Pub.
Federal Register / Vol. 60, No. 238 / Tuesday, December 12, 1995 / Rules and Regulations 63621

L. 96–354). Executive Order 12866

directs agencies to assess all costs and

benefits of available regulatory

alternatives and, when regulation is

necessary, to select regulatory

approaches that maximize net benefits

(including potential economic,

environmental, public health and safety,

and other advantages; distributive

impacts; and equity). The agency

believes that this final rule is consistent

with the regulatory philosophy and

principles identified in Executive Order

12866. In addition, the final rule is not

a significant regulatory action as defined

by the Executive Order and so is not

subject to review under the Executive

Order.

The Regulatory Flexibility Act

requires agencies to analyze regulatory

options that would minimize any

significant impact on small entities.

Because no current activity is prohibited

by this final rule, the compliance cost to

firms is zero. Because no increase in the

health risks faced by consumers will

result from this final rule, total costs are

also zero. Potential benefits include

wider use of this substance because of

reduced uncertainty concerning its

GRAS status, and any resources saved

by eliminating the need to prepare

further petitions to affirm the GRAS

status of this substance for this use. The

agency certifies, therefore, that the final

rule will not have a significant

economic impact on a substantial

number of small entities. Therefore,

under the Regulatory Flexibility Act, no

further analysis is required.

VI. References

The following references have been

placed on display in the Dockets

Management (address above) and may

be seen by interested persons between 9

a.m. and 4 p.m., Monday through

Friday.

1. Gurr, M. I., and A. T. James, Lipid

Biochemistry: An Introduction, John Wiley

and Sons, Inc., New York, 1975.

2. Memorandum dated September 6, 1988,

from M. Dinovi to J. Ziyad, ‘‘GRP 8G0344—

Parexel Int. Corp. (PI) for Gattefosse ́, SA.

Glyceryl Palmitostearate.’’

3. Park, Y. K., and E. A. Yetley ‘‘Trend

Changes in Use and Current Intakes of

Tropical Oils in The United States’’

American Journal of Clinical Nutrition

51:738–748, 1990.

4. Select Committee on GRAS Substances.

‘‘Evaluation of the Health Aspects of Glycerin

and Glycerides as Food Ingredients’’

(SCOGS–30) PB–254 536, 1975.

5. Food and Agriculture Organization of

the United Nations, ‘‘Toxicological

Evaluation of Some Food Additives

Including Anticaking Agents, Antimicrobials,

Antioxidants, Emulsifiers and Thickening

Agents.’’ FAO Nutrition Meetings Report

Series No. 53A, Rome, 1974.

List of Subjects in 21 CFR Part 184

Food additives, Food ingredients.

Therefore, under the Federal Food,

Drug, and Cosmetic Act and under

authority delegated to the Commissioner

of Food and Drugs and redelegated to

the Director, Center for Food Safety and

Applied Nutrition, 21 CFR part 184 is

amended as follows:

PART 184—DIRECT FOOD

SUBSTANCES AFFIRMED AS

GENERALLY RECOGNIZED AS SAFE

1. The authority citation for 21 CFR

part 184 continues to read as follows:

Authority: Secs. 201, 402, 409, 701 of the

Federal Food, Drug, and Cosmetic Act (21

U.S.C. 321, 342, 348, 371).

2. New § 184.1329 is added to subpart

B to read as follows:

§ 184.1329 Glyceryl palmitostearate.

(a) Glyceryl palmitostearate is a

mixture of mono-, di-, and triglyceryl

esters of palmitic and stearic acids made

from glycerin, palmitic acid, and stearic

acid.

(b) The ingredient meets the following

specifications:

(1) The substance is a mixture of

mono-, di-, and triglycerides of palmitic

acid and stearic acid.

(2) Heavy metals (as lead): Not more

than 10 parts per million.

(c) In accordance with § 184.1(b)(1),

the ingredient is used in food with no

limitation other than current good

manufacturing practice. The affirmation

of this ingredient as generally

recognized as safe (GRAS) as a direct

human food ingredient is based upon

the following current good

manufacturing practice conditions of

use:

(1) The ingredient is used as a

formulation aid, as defined in §

170.3(o)(14) of this chapter.

(2) The ingredient is used in excipient

formulations for use in tablets at levels

not to exceed good manufacturing

practice.

Dated: November 16, 1995.

Janice F. Oliver,

Deputy Director for Systems and Support,

Center for Food Safety and Applied Nutrition.

[FR Doc. 95–30125 Filed 12–11–95; 8:45 am]

BILLING CODE 4160–01–F

21 CFR Parts 510, 520, and 522

Animal Drugs, Feeds, and Related

Products; Diphenylhydantoin Sodium

Capsules, et al.

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is amending the

animal drug regulations to remove those

portions of the regulations that reflect

approval of one new animal drug

application (NADA) held by ParkeDavis, Division of Warner-Lambert Co.,

three held by Akorn, Inc., and one held

by Veterinary Research and

Development, Inc. All of the sponsors

submitted written requests that the

agency withdraw approval of the

NADA’s. In a notice published

elsewhere in this issue of the Federal

Register, FDA is withdrawing approval

of the NADA’s.

EFFECTIVE DATE: December 22, 1995.

FOR FURTHER INFORMATION CONTACT:

Mohammad I. Sharar, Center for

Veterinary Medicine (HFV–216), Food

and Drug Administration, 7500 Standish

Pl., Rockville, MD 20855, 301–827–

0159.

SUPPLEMENTARY INFORMATION: In a notice

published elsewhere in this issue of the

Federal Register, FDA is withdrawing

approval of the following NADA’s:

NADA No. Drug name Sponsor name and address

6–032 ....................................... Diphenylhydantoin sodium capsules ............................. Parke-Davis, Division of Warner-Lambert Co., 201

Tabor Rd., Morris Plains, NJ 07950

12–444 ..................................... Sterile prednisolone suspension ................................... Akorn, Inc., 100 Akorn Dr., Abita Springs, LA 70420

94–978 ..................................... Phenylbutazone injection .............................................. Do.

110–046 ................................... Dexamethasone injection .............................................. Do.

140–904 ................................... Copper disodium edetate injection ................................ Veterinary Research and Development, Inc., P.O. Box

1299, Truckee, CA 95734