This section of the FEDERAL REGISTER

contains regulatory documents having general

applicability and legal effect, most of which

are keyed to and codified in the Code of

Federal Regulations, which is published under

50 titles pursuant to 44 U.S.C. 1510.

The Code of Federal Regulations is sold by

the Superintendent of Documents. Prices of

new books are listed in the first FEDERAL

REGISTER issue of each week.

Rules and Regulations Federal Register

27221

Vol. 60, No. 99

Tuesday, May 23, 1995

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 436 and 442

[Docket No. 94N–0352]

Antibiotic Drugs; Cefuroxime Axetil for

Oral Suspension

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is amending the

antibiotic drug regulations to include

the accepted standards for cefuroxime

axetil for its use in a new dosage form

of cefuroxime axetil, cefuroxime axetil

for oral suspension. The manufacturer

has supplied sufficient data and

information to establish its safety and

efficacy.

DATES: Effective June 22, 1995; written

comments, notice of participation, and

requests for a hearing by June 22, 1995;

data, information, and analyses to

justify a hearing by July 24, 1995.

ADDRESSES: Submit written comments

to the Dockets Management Branch

(HFA–305), Food and Drug

Administration, rm. 1–23, 12420

Parklawn Dr., Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT:

James Timper, Center for Drug

Evaluation and Research (HFD–520),

Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20857,

301–443–6714.

SUPPLEMENTARY INFORMATION: FDA has

evaluated data submitted in accordance

with regulations promulgated under

section 507 of the Federal Food, Drug,

and Cosmetic Act (21 U.S.C. 357), as

amended, with respect to a request for

approval of a new dosage form of

cefuroxime axetil, cefuroxime axetil for

oral suspension. The agency has

concluded that the data supplied by the

manufacturer concerning this antibiotic

drug are adequate to establish its safety

and efficacy when used as directed in

the labeling and that the regulations

should be amended in parts 436 and 442

(21 CFR parts 436 and 442) to include

the accepted standards for this product.

Environmental Impact

The agency has determined under 21

CFR 25.24(c)(6) 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.

Submitting Comments and Filing

Objections

This final rule announces standards

that FDA has accepted in a request for

approval of an antibiotic drug. Because

this final rule is not controversial and

because, when effective, it provides

notice of accepted standards, FDA finds

that notice and comment procedure is

unnecessary and not in the public

interest. This final rule, therefore, is

effective June 22, 1995. However

interested persons may, on or before

June 22, 1995, submit written comments

to the Dockets Management Branch

(address above). Two copies of any

comments are to be submitted, except

that individuals may submit one copy.

Comments are to be identified with the

docket number found in brackets in the

heading of this document. Received

comments may be seen in the Dockets

Management Branch between 9 a.m. and

4 p.m., Monday through Friday.

Any person who will be adversely

affected by this final rule may file

objections to it and request a hearing.

Reasonable grounds for the hearing

must be shown. Any person who

decides to seek a hearing must file (1)

on or before June 22, 1995, a written

notice of participation and request for a

hearing, and (2) on or before July 24,

1995, the data, information, and

analyses on which the person relies to

justify a hearing, as specified in 21 CFR

314.300. A request for a hearing may not

rest upon mere allegations or denials,

but must set forth specific facts showing

that there is a genuine and substantial

issue of fact that requires a hearing. If

it conclusively appears from the face of

the data, information, and factual

analyses in the request for a hearing that

no genuine and substantial issue of fact

precludes the action taken by this order,

or if a request for a hearing is not made

in the required format or with the

required analyses, the Commissioner of

Food and Drugs will enter summary

judgment against the person(s) who

request(s) the hearing, making findings

and conclusions and denying a hearing.

All submissions must be filed in three

copies, identified with the docket

number appearing in the heading of this

document and filed with the Dockets

Management Branch.

The procedures and requirements

governing this order, a notice of

participation and request for a hearing,

a submission of data, information, and

analyses to justify a hearing, other

comments, and grant or denial of a

hearing are contained in 21 CFR

314.300.

All submissions under this order,

except for data and information

prohibited from public disclosure under

21 U.S.C. 331(j) or 18 U.S.C. 1905, may

be seen in the Dockets Management

Branch (address above) between 9 a.m.

and 4 p.m., Monday through Friday.

List of Subjects in 21 CFR Parts 436 and

442

Antibiotics.

Therefore, under the Federal Food,

Drug, and Cosmetic Act and under

authority delegated to the Commissioner

of Food and Drugs, 21 CFR parts 436

and 442 are amended as follows:

PART 436—TESTS AND METHODS OF

ASSAY OF ANTIBIOTIC AND

ANTIBIOTIC-CONTAINING DRUGS

1. The authority citation for 21 CFR

part 436 continues to read as follows:

Authority: Sec. 507 of the Federal Food,

Drug, and Cosmetic Act (21 U.S.C. 357).

2. Section 436.215 is amended by

alphabetically adding a new entry to the

table in paragraph (b) and by revising

paragraph (c)(9) to read as follows:

§ 436.215 Dissolution test.

* * * * *

(b) * * *
27222 Federal Register / Vol. 60, No. 99 / Tuesday, May 23, 1995 / Rules and Regulations

Dosage form Dissolution medium Rotation rate 1 Sampling time(s) Apparatus

* * * * * * *

Cefuroxime axetil for oral suspension.900 mL Sorenson’s Modified Phosphate Buffer,

pH 7.0.

50 ..................................... 30 min .............................. 2

* * * * * * *

1 Rotation rate of basket or paddle stirring element (revolutions per minute).

(c) * * *

(9) Cefuroxime axetil tablets and

powder for oral suspension—(i)

Preparation of working standard

solution—(a) Cefuroxime axetil tablets.

Accurately weigh approximately 60

milligrams of cefuroxime axetil working

standard into a suitable-sized

volumetric flask. Dissolve in 5

milliliters of methanol and dilute to

volume with 0.07N hydrochloric acid to

obtain a known concentration

equivalent to 0.01 to 0.02 milligram of

cefuroxime activity per milliliter.

(b) Cefuroxime axetil for oral

suspension. Accurately weigh

approximately 15 milligrams of

cefuroxime axetil working standard into

a 100-milliliter volumetric flask.

Dissolve in 5 milliliters of methanol and

dilute to volume with Sorenson’s

Modified Phosphate Buffer, pH 7.0 (4.2

grams of sodium dihydrogen

orthophosphate dihydrate and 14.3

grams of hydrogen disodium

orthophosphate dodecahydrate per liter

of water).

(ii) Preparation of sample solution—

(a) Cefuroxime axetil tablets. Filter

through a 0.45-micron filter and dilute

an accurately measured portion of the

filtrate with sufficient 0.07N

hydrochloric acid to obtain a

concentration equivalent to 0.01 to 0.02

milligram of cefuroxime activity per

milliliter (estimated).

(b) Cefuroxime axetil for oral

suspension. Filter the sample through

an 8-micron filter. A coarse prefilter

may be used to prevent clogging. Use

the filtrate solution without further

dilution.

(iii) Procedure—(a) Cefuroxime axetil

tablets. Using a suitable

spectrophotometer and 0.07N

hydrochloric acid as the blank,

determine the absorbance of each

standard and sample solution at the

absorbance peak at approximately 280

nanometers. Determine the exact

position of the absorption peak for the

particular instrument used.

(b) Cefuroxime axetil for oral

suspension. Using a suitable

spectrophotometer and Sorenson’s

Modified Phosphate Buffer, pH 7.0 (4.2

grams of sodium dihydrogen

orthophosphate dihydrate and 14.3

grams of hydrogen disodium

orthophosphate dodecahydrate per liter

of water) as the blank, determine the

absorbance of each standard and sample

solution at the absorbance peak at

approximately 280 nanometers.

Determine the exact position of the

absorption peak for the particular

instrument used.

(iv) Calculations. Determine the total

amount of cefuroxime activity dissolved

as follows:

T A d

A

U C

s

= × × × 900

where:

T = Total milligrams of cefuroxime activity

dissolved;

AU = Absorbance of sample;

c = Cefuroxime activity of working standard

solution in milligrams per milliliter;

d = Dilution factor of sample filtrate; and

As = Absorbance of standard.

* * * * *

PART 442—CEPHA ANTIBIOTIC

DRUGS

3. The authority citation for 21 CFR

part 442 continues to read as follows:

Authority: Sec. 507 of the Federal Food,

Drug, and Cosmetic Act (21 U.S.C. 357).

§ 442.119a [Redesignated from § 442.119]

4. Section 442.119 is redesignated as

§ 442.119a and new §§ 442.119 and

442.119b are added to subpart B to read

as follows:

§ 442.119 Cefuroxime axetil oral dosage

forms.

§ 442.119b Cefuroxime axetil for oral

suspension.

(a) Requirements for certification—(1)

Standards of identity, strength, quality,

and purity. Cefuroxime axetil for oral

suspension is cefuroxime axetil with

one or more suitable and harmless

diluents, suspending and sweetening

agents, and flavorings. When

reconstituted as directed in the labeling,

it contains cefuroxime axetil equivalent

to 25 milligrams of cefuroxime per

millimeter. Its potency is satisfactory if

it is not less than 90 percent and not

more than 115 percent of the number of

milligrams of cefuroxime that it is

represented to contain. It passes the

dissolution test. Its moisture content is

not more than 0.2 percent. When

reconstituted as directed in the labeling,

its pH is not less than 3.5 and not more

than 5.5. It passes the identity test. The

cefuroxime axetil used conforms to the

standards prescribed by § 442.19(a)(1).

(2) Labeling. It shall be labeled in

accordance with the requirements of

§ 432.5 of this chapter.

(3) Requests for certification; samples.

In addition to complying with the

requirements of § 431.1 of this chapter,

each such request shall contain:

(i) Results of tests and assays on:

(A) The cefuroxime axetil used in

making the batch for potency, isomer A

ratio, moisture, crystallinity, and

identity.

(B) The batch for cefuroxime potency,

dissolution, moisture, pH of constituted

suspension, and identity.

(ii) Samples, if required by the

Director, Center for Drug Evaluation and

Research:

(A) The cefuroxime axetil used in

making the batch: 10 packages, each

containing approximately 500

milligrams.

(B) The batch: A minimum of 12

immediate containers.

(b) Tests and methods of assay—(1)

Potency. Proceed as directed in

§ 442.19(b)(1). Working standard and

sample solutions and calculations are as

follows:

(i) Preparation of working standard

solution. Dissolve approximately 15

milligrams of the cefuroxime axetil

working standard, accurately weighed,

in 20.0 milliliters of methanol in a 50-

milliliter volumetric flask. Dilute to

volume with deionized water, and swirl

to mix. Store for no more than 8 hours

under refrigeration and protected from

light.

(ii) Preparation of sample solution.

Reconstitute the sample as directed in
Federal Register / Vol. 60, No. 99 / Tuesday, May 23, 1995 / Rules and Regulations 27223

the labeling. Transfer an accurately

measured representative portion of the

suspension equivalent to one dose into

a 200-milliliter volumetric flask. Add 10

milliliters of methanol and disperse the

sample. Dilute to volume with

methanol. Dilute 20.0 milliliters of this

solution to volume in a 50-milliliter

volumetric flask with deionized water,

swirl to mix, and allow to stand for 10

minutes. (Note: A white turbidity is

formed.) Filter this solution via a

suitable disposable filter unit,

discarding the first 5 milliliters. Store

for no more than 8 hours under

refrigeration and protect from light.

(iii) Calculations. Calculate the

milligrams of cefuroxime per dose (5

milliliters) as follows:

Milligrams of

cefuroxime per

5 milliliters

of sample

= × ×

×

A P d

A

U S

S 1 000 ,

where:

AU = Sum of the areas of the cefuroxime

axetil sample isomer A and isomer B

peaks;

AS = Sum of the peak areas of the cefuroxime

axetil working standard isomer A and

isomer B peaks;

PS = Cefuroxime activity in the cefuroxime

axetil working standard solution in

micrograms per milliliter; and

d = Dilution factor of the sample.

(2) Dissolution. Proceed as directed in

§ 436.215 of this chapter. The quantity

Q (the amount of cefuroxime activity

dissolved) is 60 percent at 30 minutes.

(3) Moisture. Proceed as directed in

§ 436.201 of this chapter.

(4) pH. Reconstitute as directed in the

labeling and proceed as directed in

§ 436.202 of this chapter.

(5) Identity. The high-performance

liquid chromatogram of the sample

determined as directed in paragraph

(b)(1) of this section compares

qualitatively to that of the cefuroxime

axetil working standard.

Dated: May 9, 1995.

Murray M. Lumpkin,

Deputy Director, Center for Drug Evaluation

and Research.

[FR Doc. 95–12604 Filed 5–22–95; 8:45 am]

BILLING CODE 4160–01–F

21 CFR Part 522

[Docket No. 95N–0096]

Implantation or Injectable Dosage

Form New Animal Drugs; Guaifenesin

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is amending the

animal drug regulations to reflect the

change of the animal drug name from

glyceryl guaiacolate to guaifenesin. This

amendment is an administrative change

to redesignate glyceryl guaiacolate

products as guaifenesin products.

EFFECTIVE DATE: May 23, 1995.

FOR FURTHER INFORMATION CONTACT:

Mohammad I. Sharar, Center for

Veterinary Medicine (HFV–216), Food

and Drug Administration, 7500 Standish

Pl., Rockville, MD 20855, 301–594–

1722.

SUPPLEMENTARY INFORMATION: In the

Federal Register of June 30, 1972 (37 FR

12936) and November 5, 1976 (41 FR

48732), FDA published final rules

which reflected approval of injectable

glyceryl guaiacolate products. In the

Federal Register of December 10, 1984

(49 FR 48038), FDA published a final

rule which reflected approval of a

guaifenesin powder for injection.

Guaifenesin is the newer chemical name

for glyceryl guaiacolate. At the time of

the December 10, 1984, approval, the

prior approvals were not amended to

reflect the newer chemical name. FDA

is amending the regulations in part 522

(21 CFR part 522) to reflect the newer

chemical name by removing

§§ 522.1060, 522.1060a, and 522.1060b;

by adding a new sponsor to § 522.1085;

and by adding new § 522.1086

Guaifenesin injection.

FDA has determined under 21 CFR

25.24(a)(9) 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.

List of Subjects in 21 CFR Part 522

Animal drugs.

Therefore, under the Federal Food,

Drug, and Cosmetic Act and under

authority delegated to the Commissioner

of Food and Drugs and redelegated to

the Center for Veterinary Medicine, 21

CFR part 522 is amended as follows:

PART 522—IMPLANTATION OR

INJECTABLE DOSAGE FORM NEW

ANIMAL DRUGS

1. The authority citation for 21 CFR

part 522 continues to read as follows:

Authority: Sec. 512 of the Federal Food,

Drug, and Cosmetic Act (21 U.S.C. 360b).

§ 522.1060 [Removed]

2. Section 522.1060 Glyceryl

guaiacolate implantation or injectable

dosage forms is removed.

§ 522.1060a [Removed]

3. Section 522.1060a Glyceryl

guaiacolate sterile powder is removed.

§ 522.1060b [Removed]

4. Section 522.1060b Glyceryl

guaiacolate injection is removed.

§ 522.1085 [Amended]

5. Section 522.1085 Guaifenesin

sterile powder is amended in paragraph

(b) by removing ‘‘000031’’ and adding in

its place the phrase ‘‘000031 and

037990’’.

6. New § 522.1086 is added to read as

follows:

§ 522.1086 Guaifenesin injection.

(a) Specifications. Each milliliter of

sterile aqueous solution contains 50

milligrams of guaifenesin and 50

milligrams of dextrose.

(b) Sponsor. See No. 037990 in

§ 510.600(c) of this chapter.

(c) Conditions of use. (1) The drug is

used intravenously in horses as a

skeletal muscle relaxant.

(2) Administer rapidly at a dosage of

1 milliliter per pound of body weight.

(3) No to be used in horses intended

for food.

(4) Federal law restricts this drug to

use by or on the order of a licensed

veterinarian.

Dated: May 5, 1995.

Stephen F. Sundlof,

Director, Center for Veterinary Medicine.

[FR Doc. 95–12506 Filed 5–22–95; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF EDUCATION

34 CFR Parts 78, 208, 215, 230, 232,

233, 234, 236, 238, 241, 245, 246, 247,

250, 251, 252, 253, 254, 255, 256, 257,

258, 282, 298, 346, 347, 354, 362, 372,

374, 405, 407, 408, 409, 414, 416, 417,

418, 419, 422, 423, 424, 445, 462, 463,

471, 473, 474, 475, 476, 500, 501, 520,

524, 525, 526, 537, 538, 548, 555, 561,

573, 574, 581, 629, 665, 671, 673, 691,

698, 700, 706, 707, 708, 722, 750, 755,

757, 758, 760, 761, 762, 763, 768, 773,

778, 779, and 790

Removal of Regulations

AGENCY: Department of Education.

ACTION: Final regulations.

SUMMARY: The Secretary amends the

Code of Federal Regulations (CFR) to

remove unnecessary and obsolete

regulations. As a result of new

legislation, absence of funding, and

review in accordance with the

President’s regulatory reinvention

initiative, the Secretary has determined