[Federal Register Volume 59, Number 35 (Tuesday, February 22, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-3815]
[[Page Unknown]]
[Federal Register: February 22, 1994]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
21 CFR Part 455
[Docket No. 93N-0365]
Antibiotic Drugs; Vancomycin Hydrochloride 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 dosage form of vancomycin hydrochloride, vancomycin
hydrochloride injection. The manufacturer has supplied sufficient data
and information to establish its safety and efficacy.
DATES: Effective March 24, 1994; written comments, notice of
participation, and request for a hearing by March 24, 1994; data,
information, and analyses to justify a hearing by April 25, 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 a new dosage form of vancomycin
hydrochloride, vancomycin hydrochloride 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 455 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 March 24, 1994. However, interested persons may, on or
before March 24, 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 March 24, 1994, a written notice of participation
and request for a hearing, and (2) on or before April 25, 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 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 455
Antibiotics.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
455 is amended as follows:
PART 455--CERTAIN OTHER ANTIBIOTIC DRUGS
1. The authority citation for 21 CFR part 455 continues to read as
follows:
Authority: Sec. 507 of the Federal Food, Drug, and Cosmetic Act
(21 U.S.C. 357).
2. Section 455.86 is added to subpart A to read as follows:
Sec. 455.86 Vancomycin.
(a) Requirements for certification--(1) Standards of identity,
strength, quality, and purity. Vancomycin is a tricyclic glycopeptide.
It is a free flowing white to off-white colored powder. It is so
purified and dried that:
(i) It contains not less than 925 micrograms of vancomycin per
milligram, calculated on the anhydrous basis.
(ii) It contains not less than 92 percent vancomycin factor B and
not more than 3 percent of any individual vancomycin related factor.
(iii) Its moisture content is not more than 20 percent.
(iv) Its heavy metals content is not more than 30 parts per
million.
(v) It gives a positive identity test for vancomycin.
(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,
chromatographic purity, moisture, heavy metals, and identity.
(ii) Samples required: 12 packages, each containing approximately
500 milligrams.
(b) Tests and methods of assay--(1) Potency. Proceed as directed in
Sec. 436.105 of this chapter, preparing the sample for assay as
follows: Place an accurately weighed sample of approximately 100
milligrams in a 100-milliliter volumetric flask and dissolve in
approximately 50 milliliters of distilled water and 1.0 milliliter of
0.1N hydrochloric acid. Swirl or sonicate to dissolve the sample and
bring to volume with distilled water. Further dilute an aliquot of this
solution with 0.1M potassium phosphate buffer, pH 4.5 (solution 4), to
the reference concentration of 10 micrograms of vancomycin per
milliliter (estimated).
(2) Chromatographic purity. Proceed as directed in Sec. 436.366 of
this chapter. The relative amount of vancomycin B is not less than 92
percent, and the relative amount of any related substance is not more
than 3 percent.
(3) Moisture. Proceed as directed in Sec. 436.201 of this chapter.
(4) Heavy metals. Proceed as directed in Sec. 436.208 of this
chapter.
(5) Identity. Proceed as directed in Sec. 436.211 of this chapter,
using the 0.5 percent potassium bromide disc preparation as described
in Sec. 436.211(b)(1).
3. Section 455.285c is added to subpart C to read as follows:
Sec. 455.285c Vancomycin hydrochloride injection.
(a) Requirements for certification--(1) Standards of identity,
strength, quality, and purity. Vancomycin hydrochloride injection is a
frozen, aqueous, iso-osmotic solution of vancomycin hydrochloride and a
tonicity adjusting agent. Each milliliter contains vancomycin
hydrochloride equivalent to 5 milligrams of vancomycin. Its vancomycin
content is satisfactory if it is not less than 90 percent and not more
than 115 percent of the number of milligrams of vancomycin that it is
represented to contain. It contains not less than 88 percent vancomycin
factor B. It contains not more than 4 percent of any individual
vancomycin related factor. It is sterile. It contains not more than
0.33 U.S.P. Endotoxin Unit per milligram of vancomycin hydrochloride.
Its pH is not less than 3.0 and not more than 5.0. The vancomycin used
conforms to the standards prescribed by Sec. 455.86.
(2) Labeling. It shall be labeled in accordance with the
requirements of Sec. 432.5 of this chapter. In addition, this drug
shall be labeled ``vancomycin hydrochloride injection.''
(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 vancomycin used in making the batch for vancomycin potency,
chromatographic purity, moisture, heavy metals, and identity.
(B) The batch for vancomycin content, chromatographic purity,
sterility, bacterial endotoxins, pH, and identity.
(ii) Samples, if required by the Director, Center for Drug
Evaluation and Research:
(A) The vancomycin used in making the batch: 10 packages, each
containing approximately 300 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) Vancomycin content. Proceed as directed in Sec. 436.105 of this
chapter, preparing the sample solution as follows: Using a suitable
hypodermic needle and syringe, remove an accurately measured
representative portion from each container immediately after thawing
and reaching room temperature. Dilute with 0.1M potassium phosphate
buffer, pH 4.5 (solution 4), to the reference concentration of 10
micrograms of vancomycin per milliliter (estimated).
(2) Chromatographic purity. Proceed as directed in Sec. 436.366 of
this chapter. The relative amount of vancomycin B is not less than 88
percent and the relative amount of any related substance is not more
than 4 percent.
(3) Sterility. Proceed as directed in Sec. 436.20 of this chapter,
using the method described in Sec. 436.20(e)(1), except use sterile
distilled water in lieu of diluting fluid A.
(4) Bacterial endotoxins. Proceed as directed in the U.S.P.
bacterial endotoxins test. The specimen under test contains not more
than 0.33 U.S.P. Endotoxin Unit per milligram of vancomycin
hydrochloride.
(5) pH. Proceed as directed in Sec. 436.202 of this chapter, using
the undiluted solution.
(6) Identity. The high-performance liquid chromatogram of the
sample determined as directed in paragraph (b)(2) of this section
compares qualitatively to that of the vancomycin working standard.
Dated: February 9, 1994.
Stephanie R. Gray,
Acting Director, Office of Compliance, Center for Drug Evaluation and
Research.
[FR Doc. 94-3815 Filed 2-18-94; 8:45 am]
BILLING CODE 4160-01-F
