[Federal Register Volume 63, Number 91 (Tuesday, May 12, 1998)]
[Rules and Regulations]
[Pages 26066-26069]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-12543]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 430, 431, 432, 433, 436, 440, 441, 442, 443, 444, 446, 
448, 449, 450, 452, 453, 455, and 460

[Docket No. 98N-0211]


Removal of Regulations Regarding Certification of Antibiotic 
Drugs

AGENCY: Food and Drug Administration, HHS.

ACTION: Direct final rule.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is repealing its 
regulations governing certification of antibiotic drugs. The agency is 
taking this action in accordance with provisions of the Food and Drug 
Administration Modernization Act of 1997 (FDAMA). FDAMA repealed the 
statutory provision in the Federal Food, Drug, and Cosmetic Act (the 
act) under which the agency certified antibiotic drugs. FDAMA also made 
conforming amendments to the act.

DATES: The direct final rule is effective September 24, 1998. Submit 
written comments on or before July 27, 1998. If no timely significant 
adverse comments are received, the agency will publish a document in 
the Federal Register before August 25, 1998, confirming the effective 
date of the direct final rule. If timely significant adverse comments 
are received, the agency will publish a document of significant adverse 
comment in the Federal Register withdrawing this direct final rule 
before August 25, 1998.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23, 
Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT: Wayne H. Mitchell or Christine F. 
Rogers, Center for Drug Evaluation and Research (HFD-7), Food and Drug 
Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-594-2041.

SUPPLEMENTARY INFORMATION:

I. FDAMA

    On November 21, 1997, the President signed FDAMA (Pub. L. 105-115). 
Section 125(b) of FDAMA repealed section 507 of the act (21 U.S.C. 
357). Section 507 of the act was the section under which the agency 
certified antibiotic drugs. Section 125(b) of FDAMA also made 
conforming amendments to the act.
    FDA has determined that it will be most efficient to make changes 
in its regulations to reflect the repeal of section 507 of the act in 
phases. In this first phase, this direct final rule removes parts 430 
through 460 (21 CFR parts 430 through 460). These regulations provide 
the procedures and standards used to certify antibiotic drugs, 
including FDA's antibiotic drug monographs. FDA plans to initiate a 
second phase direct final rulemaking procedure to make various, 
noncontroversial conforming amendments to the balance of Title 21 of 
the Code of Federal Regulations (CFR), such as removing citations to 
section 507 of the act and references to the certification of 
antibiotics. The agency recognizes that as it implements the transition 
from regulating the premarket review and approval of antibiotic drugs 
under section 507 of the act to section 505 of the act (21 U.S.C. 355), 
other issues may arise that could require additional rulemaking. These 
issues will be addressed in the third phase of implementation.

II. Direct Final Rulemaking

    FDA has determined that the subject of this rulemaking is suitable 
for a direct final rule. The repeal of section 507 of the act 
eliminates the statutory provision on which the agency relied to 
certify antibiotic drugs. FDA will, therefore, remove all provisions of 
Title 21 of the CFR that were issued primarily to carry out the 
agency's program for the certification of antibiotic drugs under former 
section 507 of the act. The actions taken should be noncontroversial 
and the agency does not anticipate receiving any significant adverse 
comments on this rule.
    If FDA does not receive significant adverse comment on or before 
July 27, 1998, the agency will publish a document in the Federal 
Register before August 25, 1998, confirming the effective date of the 
direct final rule. A significant adverse comment is one that explains 
why the rule would be inappropriate, including challenges to the rule's 
underlying premise or approach, or would be ineffective or unacceptable 
without a change. A comment recommending a rule change in addition to 
this rule will not be considered a significant adverse comment, unless 
the comment states why this rule would be ineffective without the 
additional change. If timely significant adverse comments are received, 
the agency will publish a notice of significant adverse comment in the 
Federal Register withdrawing this direct final rule before August 25, 
1998.
    Elsewhere in this issue of the Federal Register, FDA is publishing 
a companion proposed rule, which is identical to the direct final rule, 
that provides a procedural framework within which the rule may be 
finalized in the event the direct final rule is withdrawn because of 
significant adverse comment. The comment period for the direct final 
rule runs concurrently with that of the companion proposed rule. Any 
comments received under the companion proposed rule will be treated as 
comments regarding the direct final rule. Likewise, significant adverse 
comments submitted to the direct final rule will be considered as 
comments to the companion proposed rule and the agency will consider 
such comments in developing a final rule. FDA will not

[[Page 26067]]

provide additional opportunity for comment on the companion proposed 
rule.
    If a significant adverse comment applies to part of this rule and 
that part may be severed from the remainder of the rule, FDA may adopt 
as final those parts of the rule that are not the subject of a 
significant adverse comment. A full description of FDA's policy on 
direct final rule procedures may be found in a guidance document 
published in the Federal Register of November 21, 1997 (62 FR 62466).

III. Description of the Rule

    This rule eliminates Part 430--Antibiotic Drugs; General, in its 
entirety. Part 430 provided definitions used in the certification of 
antibiotic drugs and contains Sec. 430.10, which carried out former 
section 507(h) of the act and was intended to address the certification 
or release of antibiotic drugs affected by the Drug Amendments of 1962 
(Pub. L. 87-781).
    This rule also eliminates Part 431--Certification of Antibiotic 
Drugs, which provided various administrative and procedural 
requirements for the antibiotic certification program, established 
conditions on the effectiveness of a certification issued by the 
agency, and set the fees needed to maintain the agency's antibiotic 
certification program (see former section 507(b) of the act). Subpart D 
of Part 431--Confidentiality of Information, is also being eliminated 
because it is duplicative of the provisions in 21 CFR 312.130 governing 
the disclosure of information in or about an investigational new drug 
application.
    Part 433--Exemptions from Antibiotic Certification and Labeling 
Requirements is removed by this rule. Part 433 set the conditions for 
exempting antibiotic drugs from the general requirement of 
certification as well as from other, more specific, regulatory 
requirements (see former section 507(c) and (d) of the act).
    This rule eliminates Part 436--Tests and Methods of Assay of 
Antibiotic and Antibiotic-Containing Drugs. Part 436 contained 
sterility test methods, biological test methods, microbiological assay 
methods, and chemical tests for antibiotic drugs generally and for 
specific antibiotic drugs and antibiotic drug dosage forms. These tests 
and methods of assay established the means by which the agency would 
certify that a given batch of antibiotic drug was in compliance with 
applicable standards of identity, strength, quality, and purity (see 
former section 507(a) and (b) of the act).
    This rule also repeals the following parts: Part 440--Penicillin 
Antibiotic Drugs; Part 441--Penem Antibiotic Drugs; Part 442--Cepha 
Antibiotic Drugs; Part 443--Carbacephem Antibiotic Drugs; Part 444--
Oligosaccharide Antibiotic Drugs; Part 446--Tetracycline Antibiotic 
Drugs; Part 448--Peptide Antibiotic Drugs; Part 449--Antifungal 
Antibiotic Drugs; Part 450--Antitumor Antibiotic Drugs; Part 452--
Macrolide Antibiotic Drugs; Part 453--Lincomycin Antibiotic Drugs; Part 
455--Certain Other Antibiotic Drugs; and Part 460--Antibiotic Drugs 
Intended for Use in Laboratory Diagnosis of Disease. These parts 
contain the standards of identity, strength, quality, and purity that 
served as the agency's basis for batch certifying or otherwise 
authorizing the marketing of drugs that were subject to former section 
507 of the act, including the classes of penicillin; penem; cepha; 
carbacephem; oligosaccharide; tetracycline; peptide; antifungal; 
antitumor; macrolide; and lincomycin antibiotic drugs; several 
antibiotic drugs not included in the parts listed above; and antibiotic 
susceptibility discs, powders, and test panels, respectively (see 
former section 507(a) and (b) of the act).
    With the repeal of part 436 and parts 440 et seq., the test methods 
and assays contained in the approved marketing application and, when 
applicable, the United States Pharmacopeia (USP) will be used to 
determine if antibiotic drugs meet the standards of identity, strength, 
quality, and purity found in the approved marketing application for the 
drug and, when applicable, the USP.
    Finally, the agency is eliminating Part 432--Packaging and Labeling 
of Antibiotic Drugs, which sets forth special packaging requirements 
and additional labeling requirements (in addition to the requirements 
prescribed by 21 CFR 201.100) for drugs that were subject to batch 
certification or release under former section 507 of the act. With the 
repeal of section 507 of the act, there is no need to maintain separate 
or additional labeling and packaging requirements for antibiotic drug 
products. As with other drug products, labeling of antibiotic drugs 
will be governed by the agency's general labeling provisions found in 
21 CFR part 201 and by applicable over-the-counter drug monographs and 
approved marketing applications.
    Part 432 also included Sec. 432.9, which conditionally authorized 
the batch certification of antibiotic drugs intended for export, even 
if the drug failed to meet certain labeling requirements, and provided 
additional guidance on the labeling of antibiotic drugs for export. In 
light of the repeal of the batch certification requirement, Sec. 432.9 
may also be eliminated without affecting the export of antibiotic drug 
products.
    It should be noted, however, that differences remain between the 
application of the export provisions in sections 801 and 802 of the act 
(21 U.S.C. 381 and 382) to antibiotic drugs and the application of 
those provisions to other new drugs. Prior to the repeal of section 507 
of the act, these differences were based on the fact that antibiotic 
drugs were not subject to premarket approval under section 505 and, 
therefore, could be exported under section 801(e)(1) of the act. 
Antibiotic drugs did not have to meet the export requirements in 
section 802 that apply to unapproved new drugs. Thus, manufacturers 
could export antibiotic drugs that had not been certified, released, or 
exempted from certification, subject only to the provisions of section 
801(e)(1) of the act. Section 125(c) of FDAMA preserved the export 
status of antibiotic drugs (which are now subject to approval under 
section 505 of the act) by expressly exempting them from section 802. 
(Section 125(c) of FDAMA included the same exemption for insulin 
products.) In the second phase of the implementation of section 125 of 
FDAMA, the agency will consider making appropriate amendments to its 
regulations to reflect this difference between the application of the 
export provisions of the act to antibiotic drugs (and insulin products) 
as opposed to all other new drugs.
    The removal of parts 430 et seq. is not expected to result in any 
immediate, significant changes in the manufacturing, packaging, 
labeling, or marketing of antibiotic drug products. Since 1982, the 
agency has conditionally exempted all antibiotic drugs from batch 
certification (47 FR 39155, September 7, 1982). With limited 
exceptions, such as in the areas of export and generic drug approvals, 
the agency has imposed much the same regulatory requirements on 
exempted antibiotic drug products as it has on all other drug products.

IV. Environmental Impact

    The agency has determined under 21 CFR 25.30(h) 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.

V. Analysis of Impacts

    FDA has examined the impacts of the direct final rule under 
Executive Order 12866, the Regulatory Flexibility Act (5

[[Page 26068]]

U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 
104-4). Executive Order 12866 directs agencies to assess all costs and 
benefits of available regulatory alternatives and, when regulation is 
necessary, to select regulatory approaches that maximize net benefits 
(including potential economic, environmental, public health and safety, 
and other advantages; distributive impacts; and equity). Executive 
Order 12866 classifies a rule as significant if it meets any one of a 
number of specified conditions, including having an annual effect on 
the economy of $100 million or adversely affecting in a material way a 
sector of the economy, competition, or jobs, or if it raises novel 
legal or policy issues. As discussed below, the agency believes that 
this final rule is consistent with the regulatory philosophy and 
principles identified in the Executive Order. In addition, the direct 
final rule is not a significant regulatory action as defined by the 
Executive Order and so is not subject to review under the Executive 
Order.
    The Regulatory Flexibility Act requires that if a rule has a 
significant impact on a substantial number of small entities, the 
agency must analyze regulatory options to minimize the economic impact 
on small entities. The agency certifies, for the reasons discussed 
below, that the direct final rule will not have a significant impact on 
a substantial number of small entities. Therefore, under the Regulatory 
Flexibility Act, no further analysis is required.
    The Unfunded Mandates Reform Act requires an agency to prepare a 
budgetary impact statement before issuing any rule likely to result in 
a Federal mandate that may result in expenditures by State, local, and 
tribal governments or the private sector of $100 million (adjusted 
annually for inflation) in any 1 year. The elimination of the 
regulations governing the certification of antibiotic drugs will not 
result in any increased expenditures by State, local, and tribal 
governments or the private sector. Because this rule will not result in 
an expenditure of $100 million or more on any governmental entity or 
the private sector, no budgetary impact statement is required.
    This rule is intended to eliminate regulatory procedures and 
standards that the agency, as a result of the repeal of section 507 of 
the act, is no longer required to maintain. The elimination of the 
above listed parts is expected to streamline the regulation of 
antibiotic drugs by making these products subject to the same 
regulatory standards as all other drugs for human use. Many of the 
provisions that are being eliminated by this rulemaking have not had a 
material impact on the marketing of antibiotic drugs since 1982, when 
all antibiotic drugs were conditionally exempted from the batch 
certification requirement. Other provisions, such as the standards of 
identity, strength, quality, and purity, have in some instances not 
been kept up-to-date, are duplicative of USP standards, or have been 
incorporated into approved marketing applications for specific 
antibiotic drug products. For these reasons, the agency believes that 
this rule is necessary and that it is consistent with the principles of 
Executive Order 12866; that it is not a significant regulatory action 
under that Order; that it will not have a significant impact on a 
substantial number of small entities; and that it is not likely to 
result in an annual expenditure in excess of $100 million.

VI. Paperwork Reduction Act of 1995

    This direct final rule contains no collection of information. 
Therefore, clearance by the Office of Management and Budget under the 
Paperwork Reduction Act of 1995 (Pub. L. 104-13) is not required.

VII. Request for Comments

    Interested persons may, on or before July 27, 1998, submit to the 
Dockets Management Branch (address above) written comments regarding 
this rule. 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 office 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 Part 431

    Administrative practice and procedure, Antibiotics, Confidential 
business information, Reporting and recordkeeping requirements.

21 CFR Part 432

    Antibiotics, Labeling, Packaging and containers.

21 CFR Part 433

    Antibiotics, Labeling, Reporting and recordkeeping requirements.

21 CFR Parts 436, 440, 441, 442, 443, 444, 446, 448, 449, 450, 452, 
453, 455, and 460

    Antibiotics.

    Therefore, under the Federal Food, Drug, and Cosmetic Act, the Food 
and Drug Administration Modernization Act, and under authority 
delegated to the Commissioner of Food and Drugs, 21 CFR chapter I is 
amended as follows:

PART 430--ANTIBIOTIC DRUGS; GENERAL

    1. Part 430 is removed.

PART 431--CERTIFICATION OF ANTIBIOTIC DRUGS

    2. Part 431 is removed.

PART 432--PACKAGING AND LABELING OF ANTIBIOTIC DRUGS

    3. Part 432 is removed.

PART 433--EXEMPTIONS FROM ANTIBIOTIC CERTIFICATION AND LABELING 
REQUIREMENTS

    4. Part 433 is removed.

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

    5. Part 436 is removed.

PART 440--PENICILLIN ANTIBIOTIC DRUGS

    6. Part 440 is removed.

PART 441--PENEM ANTIBIOTIC DRUGS

    7. Part 441 is removed.

PART 442--CEPHA ANTIBIOTIC DRUGS

    8. Part 442 is removed.

PART 443--CARBACEPHEM ANTIBIOTIC DRUGS

    9. Part 443 is removed.

PART 444--OLIGOSACCHARIDE ANTIBIOTIC DRUGS

    10. Part 444 is removed.

PART 446--TETRACYCLINE ANTIBIOTIC DRUGS

    11. Part 446 is removed.

PART 448--PEPTIDE ANTIBIOTIC DRUGS

    12. Part 448 is removed.

PART 449--ANTIFUNGAL ANTIBIOTIC DRUGS

    13. Part 449 is removed.

PART 450--ANTITUMOR ANTIBIOTIC DRUGS

    14. Part 450 is removed.

[[Page 26069]]

PART 452--MACROLIDE ANTIBIOTIC DRUGS

    15. Part 452 is removed.

PART 453--LINCOMYCIN ANTIBIOTIC DRUGS

    16. Part 453 is removed.

PART 455--CERTAIN OTHER ANTIBIOTIC DRUGS

    17. Part 455 is removed.

PART 460--ANTIBIOTIC DRUGS INTENDED FOR USE IN LABORATORY DIAGNOSIS 
OF DISEASE

    18. Part 460 is removed.

    Dated: May 1, 1998.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 98-12543 Filed 5-11-98; 8:45 am]
BILLING CODE 4160-01-F