[Federal Register Volume 59, Number 34 (Friday, February 18, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-3730]


[[Page Unknown]]

[Federal Register: February 18, 1994]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 430, 436, and 441

[Docket No. 93N-0366]

 

Antibiotic Drugs; Updates, Technical Changes, and Correction

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 by updating, making noncontroversial 
technical changes, and making a correction in accepted standards of 
antibiotic and antibiotic-containing drugs for human use. These changes 
will result in more accurate and usable regulations.

DATES: Effective February 18, 1994; written comments, notice of 
participation, and request for a hearing by March 21, 1994; data, 
information, and analyses to justify a hearing by April 19, 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 is amending the antibiotic drug 
regulations by updating, making noncontroversial technical changes, and 
making a correction in certain antibiotic drug regulations that provide 
for accepted standards of antibiotic and antibiotic containing drugs 
intended for human use.
    In Sec. 430.6(b)(89) (21 CFR 430.6(b)(89)), the amount of imipenem 
master standard that is equivalent to 1 microgram of imipenem activity 
(potency) is revised from ``1.07'' to ``1.085'' micrograms to reflect 
the total moisture content and impurities in the master standard.
    In Sec. 436.215(b) (21 CFR 436.215(b)), the rotation rate of the 
paddle in the dissolution test for cephalexin hydrochloride monohydrate 
tablets of ``100'' revolutions per minute (rpm) is corrected to read 
``150'' rpm. In the Federal Register of November 28, 1989 (54 FR 
48859), the rotation rate of the apparatus in the dissolution test for 
cephalexin hydrochloride tablets was incorrectly given as ``100'' rpm. 
The only manufacturer of this product brought this error to the 
agency's attention and requested that the rotation rate be revised to 
read ``150'' rpm. The manufacturer has presented data that show that a 
rotation rate of ``100'' rpm causes wide variation in the dissolution 
results for the 500-milligram tablets. This variation causes an 
increase in the relative standard deviation of the data to the point 
that a significant number of lots would be rejected. The manufacturer 
has also submitted data that show that these rejected lots are fully 
bioavailable. FDA agrees that the 100 rpm rate was an error and that a 
150 rpm rotation rate should be used.
    In Sec. 441.20a(a)(1)(i) (21 CFR 441.20a(a)(1)(i)), the potency 
specification for sterile imipenem monohydrate is revised from ``not 
less than 849 micrograms and not more than 990 micrograms'' to ``not 
less than 900 micrograms and not more than 1,050 micrograms'' of 
imipenem per milligram on an anhydrous basis. The former potency 
specification incorrectly reflects the monohydrate form rather than the 
anhydrous form of the bulk material.

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

    These amendments institute changes that are corrective, editorial, 
or of a minor technical nature. Because the amendments are not 
controversial, and because when effective they provide notice of 
accepted standards, FDA finds that notice, public procedure, and 
delayed effective date are unnecessary and not in the public interest. 
This final rule, therefore, becomes effective February 18, 1994. 
However, interested persons may, on or before March 21, 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 21, 1994, a written notice of 
participation and request for a hearing, and (2) on or before April 19, 
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

21 CFR Part 430

    Administrative practice and procedure, Antibiotics.

21 CFR Parts 436 and 441

    Antibiotics.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR parts 
430, 436, and 441 are amended as follows:

PART 430--ANTIBIOTIC DRUGS; GENERAL

    1. The authority citation for 21 CFR part 430 continues to read as 
follows:

    Authority: Secs. 201, 501, 502, 503, 505, 507, 701 of the 
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 351, 352, 353, 
355, 357, 371); secs. 215, 301, 351 of the Public Health Service Act 
(42 U.S.C. 216, 241, 262).

    2. Section 430.6 is amended by revising paragraph (b)(89) to read 
as follows:


Sec. 430.6  Definitions of the terms ``unit'' and ``microgram'' as 
applied to antibiotic substances.

* * * * *
    (b) * * *
    (89) Imipenem. The term ``microgram'' applied to imipenem 
monohydrate means the imipenem activity (potency) contained in 1.085 
micrograms of the imipenem master standard.
* * * * *

PART 436--TESTS AND METHODS OF ASSAY OF ANTIBIOTIC AND ANTIBIOTIC-
CONTAINING DRUGS

    3. 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).

    4. Section 436.215 is amended in the table in paragraph (b) by 
revising the entry for ``Cephalexin hydrochloride monohydrate tablets'' 
to read as follows:


Sec. 436.215  Dissolution test.

* * * * *
    (b) * * *

--------------------------------------------------------------------------------------------------------------------------------------------------------
                     Dosage form                         Dissolution medium         Rotation rate1          Sampling time(s)            Apparatus       
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                        * ******                                                                        
Cephalexin hydrochloride monohydrate tablets           900 mL distilled water                      150                   45 min                        1
                                                                        * ******                                                                        
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\Rotation rate of basket or paddle stirring element (revolutions per minute).                                                                         

PART 441--PENEM ANTIBIOTIC DRUGS

    5. The authority citation for 21 CFR part 441 continues to read as 
follows:

    Authority: Sec. 507 of the Federal Food, Drug, and Cosmetic Act 
(21 U.S.C. 357).

    6. Section 441.20a is amended by revising paragraph (a)(1)(i) to 
read as follows:


Sec. 441.20a  Sterile imipenem monohydrate.

    (a) * * *
    (1) * * *
    (i) Its potency is not less than 900 micrograms and not more than 
1,050 micrograms of imipenem per milligram on an anhydrous basis.
* * * * *

    Dated: February 9, 1994.
 Stephanie R. Gray,
 Office of Compliance, Center for Biologics Evaluation and Research.
[FR Doc. 94-3730 Filed 2-17-94; 8:45 am]
BILLING CODE 4160-01-F