[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) * * *
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Dosage form Dissolution medium Rotation rate1 Sampling time(s) Apparatus
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* ******
Cephalexin hydrochloride monohydrate tablets 900 mL distilled water 150 45 min 1
* ******
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\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
