Repeal of Section 507 of the Federal Food, Drug and Cosmetic Act _1

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

Guidance for Industry
and Reviewers
Repeal of Section 507 of the Federal
Food, Drug, and Cosmetic Act
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Procedural 1
Revised, May 1998

Guidance for Industry
and Reviewers
Repeal of Section 507 of the Federal
Food, Drug, and Cosmetic Act
Additional copies are available from:
Office of Training and Communications
Division of Communications Management
The Drug Information Branch, HFD-210
5600 Fishers Lane
Rockville, MD 20857
(Tel) 301-827-4573
(Internet) http://www.fda.gov/cder/guidance/index.htm
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Procedural 1
Revised, May 1998

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Table of Contents
I. INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
II. SUMMARY OF SECTION 125 OF THE FDAMA . . . . . . . . . . . . . . . . . . . . . . . . . . 1
III. POLICIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
A. Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
B. Application Numbering Conventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
C. Applications Subject to Section 125 Exemptions . . . . . . . . . . . . . . . . . . . . . . 3
D. Action Letters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
E. Monographs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
F. Bulk Drug Applications (Pending and Approved) . . . . . . . . . . . . . . . . . . . . . 5

This guidance has been prepared by the Antibiotic Working Group of the Center for Drug Evaluation and	1
Research (CDER) at the Food and Drug Administration. This guidance document represents the Agency’s current
thinking on the implementation of the repeal of section 507 of the Federal Food, Drug, and Cosmetic Act. It does not
create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach
may be used if such approach satisfies the requirements of the applicable statute, regulations, or both.
GUIDANCE FOR INDUSTRY AND REVIEWERS1
Repeal of Section 507 of
the Federal Food, Drug, and Cosmetic Act
I. INTRODUCTION
Section 125 of Title I of the Food and Drug Administration Modernization Act of 1997 (the
Modernization Act), signed into law by President Clinton on November 21, 1997, repealed
section 507 of the Federal Food, Drug, and Cosmetic Act (the Act). As a result of the repeal of
section 507, which took effect immediately, several of the Agency's administrative processes for
reviewing and approving antibiotic drug applications must be changed. This document is intended
to clarify, on an interim basis, the administrative processes that will be followed in implementing
section 125 of the Modernization Act. In the current revision, the Agency clarifies the procedures
applicable to bulk drug substances for products previously regulated under section 507.
II. SUMMARY OF SECTION 125 OF THE FDAMA
Prior to the enactment of the Modernization Act, the Agency approved antibiotic drug marketing
applications under section 507 of the Act. In addition, section 507 required the Agency to publish
regulations (antibiotic monographs) that set forth standards of identity, strength, quality, and
purity for each marketed antibiotic drug.
As a result of the repeal of section 507, the Agency’s legal obligation to publish antibiotic
monographs has been eliminated from the Act. Moreover, all antibiotic drug applications will
now be filed, reviewed, and approved under section 505 of the Act, as are all other new drugs.
Section 125 of the Modernization Act specifically provides that:
1. All full applications approved under section 507 on or before November 20, 1997, are
now deemed to have been submitted and filed under section 505(b) and approved for
safety and effectiveness under section 505(c).
2. All abbreviated applications approved under section 507 on or before November 20, 1997,
are now deemed to have been filed and approved under section 505(j). (The status of
antibiotic bulk drug applications that were submitted or approved under former section

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507 is discussed in section III.F., below.)
3. All applications for drugs that contain an antibiotic that was the subject of any marketing
application received by the Secretary on or before November 20, 1997, (hereafter referred
to as an "old" antibiotic) are exempt from the patent listing, patent certification, and
exclusivity provisions in section 505. (See section III.C, below.) The effects of this
exemption provision include the following:
a. Antibiotic drug marketing applications that were pending in FDA on or before
November 20, 1997, need not be updated with the patent information required
under section 505(b)(1) and would not be eligible to claim exclusivity under
sections 505(c) or 505(j).
b. Already approved antibiotic drug marketing applications need not be updated with
patent information and cannot seek exclusivity under sections 505(c) or 505(j).
c. New applications (those received on or after November 21, 1997) under section
505(b) or 505(j) for drugs that contain “old” antibiotics need not include patent
information and are not eligible for exclusivity under sections 505(c) or 505(j).
d. An application received on or after November 21, 1997, that does not contain an
"old" antibiotic would be required to file patent information and could seek
exclusivity, as appropriate, under sections 505(c) or 505(j).
e. An abbreviated application under section 505(j) or an application under section
505(b)(2) that refers to a drug that does not contain an "old" antibiotic would be
required to include appropriate patent certifications and may be subject to the
exclusivity provisions in sections 505(c) or (j), as appropriate.
4. Finally, section 125 preserves for all products containing an antibiotic drug the special
export status that has been allowed over the years for antibiotic drugs.
III. POLICIES
A. Definitions
For purposes of section 125 of the Modernization Act, the "date of the enactment of this
Act" is November 21, 1997. Before the date of the enactment of this Act means on or
before November 20, 1997.
B. Application Numbering Conventions

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Because of the exemptions that apply to old antibiotics, we will continue to maintain our
numbering system for new drug applications to allow us to distinguish between
applications that contain old antibiotics and all other applications. Beginning November
21, 1997, we will apply our NDA numbering system as follows:
1. All applications (except bulk drug applications) assigned a series 50,000 or series
60,000 NDA number on or before November 20, 1997, will keep that number. As
discussed above, the exemption provisions in section 125 that exempt applications
for drugs that contain "old" antibiotic drugs from the patent listing, patent
certification, and exclusivity provisions in section 505 of the Act apply to these
applications. For bulk drug applications assigned series 60,000 numbers on or
before November 20, 1997, see section III.F, below.
2. Series 50,000 numbers will be assigned to all marketing applications submitted
under 505(b) on or after November 21, 1997, to which the section 125 exemptions
apply.
3. Series 60,000 numbers will be assigned to all marketing applications submitted
under 505(j) on or after November 21, 1997, to which the section 125 exemptions
apply.
4. Series 20,000 numbers will be assigned to all marketing applications submitted
under 505(b) on or after November 21, 1997, to which the section 125 exemptions
do not apply.
5. Series 70,000 or 40,000 numbers will be assigned to all marketing applications
submitted under 505(j) on or after November 21, 1997, to which the section 125
exemptions do not apply.
Example. The marketing application (NDA) for azithromycin was submitted to FDA (i.e.,
the Secretary) before November 21, 1997. If, on or after November 21, 1997, another
NDA is submitted for a new dosage form or a new indication for azithromycin, this newly
submitted NDA would be assigned a series 50,000 number because the drug (i.e.,
azithromycin) that is the subject of the new NDA was originally received by the Secretary
(see section C.2., below) prior to November 21, 1997.
C. Applications Subject to Section 125 Exemptions
Section 125 of the Modernization Act exempts from the patent listing, patent certification,
and sections 505(c) and (j) marketing exclusivity provisions, marketing applications for
drugs that contain old antibiotics. (See section 125(d)(2) of the Modernization Act for a
list of the specific provisions in section 505 of the Act that do not apply to applications
that contain old antibiotics.) For purposes of implementing this provision, consider these

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points in deciding whether an application is subject to the exemption.
1. The drug that is the subject of the application must contain (in whole or as part of
a combination) an antibiotic drug. As was the case prior to the repeal of section
507, an antibiotic drug is:
any drug (except drugs for use in animals other than humans) composed wholly or partly of
any kind of penicillin, streptomycin, chlortetracycline, chloramphenicol, bacitracin, or any
other drug intended for use by man containing any quantity of any chemical substance which
is produced by a micro-organism and which has the capacity to inhibit or destroy micro-
organisms in dilute solution (including the chemically synthesized equivalent of any such
substance) or any derivative thereof. (See new section 201(jj) of the Act.)
2. The antibiotic drug that is contained in the application must have been the subject
of a marketing application that was received by the Secretary on or before
November 20, 1997. For purposes of section 125 of the Modernization Act, this
would include any antibiotic application (including an old Form 5 or Form 6
application) that was:
a. Received by FDA (as evidenced by an Agency date stamp) on or before
November 20, 1997.
b. Filed or approved on or before November 20, 1997.
c. Received on or before November 20, 1997, and is presently under review.
d. The subject of an action letter on or before November 20, 1997 (e.g., AE,
NA, or WD), and is now back with the company.
e. Received on or before November 20, 1997, filed, reviewed, approved, and
then withdrawn from the market (either for safety or other reasons).
f. Received on or before November 20, 1997, and then withdrawn prior to
filing and has not been further submitted.
g. Received on or before November 20, 1997, and subsequently refused filing
and has not been further submitted.
h. Received on or before November 20, 1997, and was unacceptable for filing
under PDUFA for failure to submit the appropriate user fee and has not
been further submitted.
For purposes of section 125 of the Modernization Act received by the Secretary
does not mean (1) canceled applications (i.e., administrative errors) or (2)

Section 125 of the Modernization Act also authorizes the Secretary to publish the established name of each2
antibiotic drug that is subject to the section 125 exemption (i.e., each "old" antibiotic drug). The Agency has not yet
decided how it will implement this authority.
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applications for which only a presubmission was received without a full submission
ever having been received subsequently by the Agency. (See also 21 CFR
314.101(d).)
3. Other factors, such as the extent to which derivatives of the active moiety of an old
antibiotic are also considered to be old antibiotics, are beyond the scope of this
administrative guidance and may be addressed as part of an Agency rulemaking
proceeding.2
D. Action Letters
Beginning November 21, 1997, the action letter templates for 507 drugs will no longer be
used. Section 507 no longer provides a statutory basis for approval of a drug product.
All action letters must use the 505(b) or 505(j) templates, even for drugs that originally
were submitted under section 507, but are the subject of Agency action on or after
November 21, 1997.
For action letters on marketing applications to which the section 125 exemptions apply,
the following sentence should be added after the initial reference to section 505: "We note
that this application is subject to the exemption provisions contained in section 125(d)(2)
of Title I of the FDA Modernization Act of 1997."
E. Monographs
On and after November 21, 1997, FDA will no longer publish or maintain antibiotic
monographs in the Code of Federal Regulations (CFR). Products approved under section
505 do not require such monographs. The Agency recently published a direct final rule to
remove the antibiotic monographs from the CFR (63 FR 26066, May 12, 1998).
F. Bulk Drug Applications (Pending and Approved)
Prior to the repeal, the Agency consistently read section 507 to require that bulk antibiotic
drug substances must be either batch certified or exempted from batch certification
through the approval of an antibiotic drug application. Applications for bulk antibiotic
drugs were previously assigned 60,000 application numbers. The Agency, however, has
not required the filing or approval of such an application under section 505 for bulk drug
substances used in the manufacture of non-antibiotic new drug products. Rather, in
accordance with 21 CFR 314.420, information about drug substances, drug substance
intermediates, and materials used in their preparation or in the preparation of new drug

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products may be filed and maintained as Type II Drug Master Files (DMFs).
Alternatively, drug substance information may be filed as part of the marketing application
for the finished dosage form of the drug.
In light of the repeal of section 507 and the Agency’s longstanding regulatory approach to
handling bulk drug substances under section 505, the Agency intends to administratively
convert all antibiotic bulk drug substance applications (“bulk applications”) into DMFs.
Action — After August 31, 1998, all unapproved bulk applications that were pending in
CDER as of November 21, 1997, will be administratively converted into DMFs.
Likewise, after August 31, 1998, FDA will begin administratively converting all approved
bulk applications into DMFs. Any bulk application received by CDER after November 21,
1997, will be returned to the applicant. The agency has not approved any bulk
applications since the repeal of section 507 went into effect on November 21, 1997.
Following issuance of this revised guidance, the Agency will provide written notice to
each sponsor of a bulk application of the Agency’s intention to convert the application
into a DMF. Following the conversion of each application, the Agency will notify the
sponsor of the newly assigned DMF reference number.
The Agency does not intend at this time to require sponsors of converted bulk applications
to submit new letters of authorization for each of the dosage form manufacturers who may
reference the DMF. Similarly, the Agency does not expect to require dosage form
manufacturers to amend their marketing applications to reference the newly assigned DMF
number. However, following conversion of a bulk application, any new letters of
authorization or other correspondence relating to the bulk substance will be expected to
reference the new DMF number, in accordance with 21 CFR 314.420(b).
Sponsors of bulk applications need not take any action for their applications to be
converted. The Agency expects most, if not all, bulk applications will be handled under
this process. However, if a sponsor does not wish to maintain a DMF for a particular bulk
drug substance, the information in the bulk application may be merged into one or more
dosage form applications, or the Agency may cancel and retire the application in
accordance with Agency record keeping practices. The Agency also would consider
requests for more expeditious conversion of bulk applications to DMFs from sponsors
who would like their applications converted before August 31, 1998. Sponsors interested
in one of these alternatives should contact Jerry Phillips, Director, Division of Labeling
and Program Support, CDER, at 301-827-5846, before August 31, 1998.