[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