[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