[Federal Register Volume 59, Number 52 (Thursday, March 17, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-6224]


[[Page Unknown]]

[Federal Register: March 17, 1994]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

21 CFR Part 442

[Docket No. 93N-0431]

 

Antibiotic Drugs; Cefmetazole and Cefmetazole Sodium Injection

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending the 
antibiotic drug regulations to provide for the inclusion of accepted 
standards for a new bulk form of cefmetazole and for its use in a new 
dosage form of cefmetazole sodium, cefmetazole sodium injection. The 
manufacturer has supplied sufficient data and information to establish 
its safety and efficacy.

DATES: Effective April 18, 1994; written comments, notice of 
participation, and requests for a hearing by April 18, 1994; data, 
information, and analyses to justify a hearing by May 16, 1994.

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: Peter A. Dionne, Center for Drug 
Evaluation and Research (HFD-520), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-443-0335.

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 (1) a new bulk form of 
cefmetazole, and (2) for its use in a new dosage form of cefmetazole 
sodium, cefmetazole sodium injection. 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 21 CFR part 
442 to provide for the inclusion of 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 April 18, 1994. However, interested persons may, on or 
before April 18, 1994, 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 April 18, 1994, a written notice of participation 
and request for a hearing, and (2) on or before May 16, 1994, 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 Part 442

    Antibiotics.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
442 is amended as follows:

PART 442--CEPHA ANTIBIOTIC DRUGS

    1. 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).

    2. Section 442.69 is added to subpart A to read as follows:


Sec. 442.69  Cefmetazole.

    (a) Requirements for certification--(1) Standards of identity, 
strength, quality, and purity. Cefmetazole is (6R,7S)-7-[2-
[(cyanomethyl)thio]acetamido]-7-methoxy-3-[[(1-methyl-1H-tetrazol-5-
yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic 
acid. It is so purified and dried that:
    (i) Its potency is not less than 970 micrograms of cefmetazole 
activity per milligram.
    (ii) Its moisture content is not more than 0.5 percent.
    (iii) It gives a positive identity test for cefmetazole.
    (2) Labeling. It shall be labeled in accordance with the 
requirements of Sec. 432.5 of this chapter.
    (3) Requests for certification; samples. In addition to complying 
with the requirements of Sec. 431.1 of this chapter, each such request 
shall contain:
    (i) Results of tests and assays on the batch for potency, moisture, 
and identity.
    (ii) Samples, if required by the Director, Center for Drug 
Evaluation and Research: 10 packages each containing approximately 500 
milligrams.
    (b) Tests and methods of assay--(1) Potency. Proceed as directed in 
Sec. 442.70a(b)(1).
    (2) Moisture. Proceed as directed in Sec. 436.201 of this chapter.
    (3) Identity. Proceed as directed in Sec. 436.211 of this chapter 
using a mineral oil mull prepared as described in paragraph (b)(2) of 
that section.
    3. New Sec. 442.270 is added to subpart C to read as follows:


Sec. 442.270  Cefmetazole injectable dosage forms.

    4. New Sec. 442.270b is added to subpart C to read as follows:


Sec. 442.270b  Cefmetazole sodium injection.

    (a) Requirements for certification--(1) Standards of identity, 
strength, quality, and purity. Cefmetazole sodium injection is a 
frozen, aqueous, iso-osmotic solution of cefmetazole and sodium 
citrate. It contains one or more suitable and harmless buffer 
substances and a tonicity adjusting agent. Each milliliter contains 
cefmetazole sodium equivalent to 20 milligrams or 40 milligrams of 
cefmetazole per milliliter. Its cefmetazole content is satisfactory if 
it is not less than 90 percent and not more than 120 percent of the 
number of milligrams of cefmetazole that it is represented to contain. 
It is sterile. It contains not more than 0.2 endotoxin units per 
milligram. Its pH is not less than 4.2 and not more than 6.2. It passes 
the identity test. The cefmetazole used conforms to the standards 
prescribed by Sec. 442.69(a)(1).
    (2) Labeling. It shall be labeled in accordance with the 
requirements of Sec. 432.5 of this chapter.
    (3) Requests for certification; samples. In addition to complying 
with the requirements of Sec. 431.1 of this chapter, each such request 
shall contain:
    (i) Results of tests and assays on:
    (A) The cefmetazole used in making the batch for potency, moisture, 
and identity.
    (B) The batch for potency, sterility, bacterial endotoxins, pH, and 
identity.
    (ii) Samples, if required by the Director, Center for Drug 
Evaluation and Research:
    (A) The cefmetazole used in making the batch: 10 packages, each 
containing approximately 500 milligrams.
    (B) The batch:
    (1) For all tests except sterility: A minimum of 12 immediate 
containers.
    (2) For sterility testing: 20 immediate containers, collected at 
regular intervals throughout each filling operation.
    (b) Tests and methods of assay. Thaw the sample as directed in the 
labeling. The sample solution used for testing must be at room 
temperature.
    (1) Cefmetazole potency. Proceed as directed in Sec. 442.70a(b)(1), 
except prepare the sample solution and calculate the cefmetazole 
content as follows:
    (i) Preparation of sample solution. Using a suitable hypodermic 
needle and syringe, remove an accurately measured portion from each 
container immediately after thawing and reaching room temperature and 
dilute with mobile phase to obtain a solution containing 500 micrograms 
of cefmetazole per milliliter (estimated). Prepare the sample solution 
just prior to its introduction into the chromatograph.
    (ii) Calculation. Calculate the milligrams of cefmetazole per 
milliliter of sample as follows:

                                                                        
                                                            AU X PS X d 
      Milligrams of cefmetazole per milliliter         = ---------------
                                                            AS X 1,000  
                                                                        

where:

AU = Area of the cefmetazole peak in the chromatogram of the - 
sample (at a retention time equal to that observed for the 
standard);
AS = Area of the cefmetazole peak in the chromatogram of the 
cefmetazole working standard;
PS = Cefmetazole activity in the cefmetazole working standard 
solution in micrograms per milliliter; and
d = Dilution factor of the sample.
    (2) Sterility. Proceed as directed in Sec. 436.20 of this chapter, 
using the method described in paragraph (e)(1) of that section.
    (3) Bacterial endotoxins. Proceed as directed in the United States 
Pharmacopeia bacterial endotoxins test.
    (4) pH. Proceed as directed in Sec. 436.202 of this chapter, using 
the undiluted solution.
    (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 cefmetazole working standard.

    Dated: March 9, 1994.
Raymond E. Hamilton,
Acting Director, Office of Compliance, Center for Drug Evaulation and 
Research.
[FR Doc. 94-6224 Filed 3-16-94; 8:45 am]
BILLING CODE 4160-01-F