Justification Submitted as General Correspondent and in the Annual Report

Guidance for Industry

Updating Labeling for Susceptibility

Test Information in Systemic

Antibacterial Drug Products and

Antimicrobial Susceptibility Testing

Devices

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

Center for Devices and Radiological Health (CDRH)

June 2009

Labeling

OMB Control No. 0910-0638

Expiration Date: 11/30/2014

(Expiration date will be updated periodically.)

See additional PRA statement in section VI of this guidance.

Guidance for Industry

Updating Labeling for Susceptibility

Test Information in Systemic

Antibacterial Drug Products and

Antimicrobial Susceptibility Testing

Devices

Additional copies are available from:

Office of Training and Communications

Division of Drug Information

Center for Drug Evaluation and Research

Food and Drug Administration

10903 New Hampshire Ave., Bldg. 51, rm. 2201

Silver Spring, MD 20993-0002

(Tel) 301-796-3400

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm

or

Office of Communication, Education, and Radiation Programs

Division of Small Manufacturers Assistance, HFZ-220

Center for Devices and Radiological Health

Food and Drug Administration

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Rockville, MD 20850-4307

E-mail: dsma@cdrh.fda.gov

Fax: 301-443-8818

(Tel) Manufacturers Assistance: 800-638-2041 or 301-443-6597

(Tel) International Staff Phone: 301-827-3993

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/default.htm

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

Center for Devices and Radiological Health (CDRH)

June 2009

Labeling

TABLE OF CONTENTS
I.

INTRODUCTION............................................................................................................. 1

II.

BACKGROUND ............................................................................................................... 2

A.

The Importance of Susceptibility Test Interpretive Criteria ..................................................... 2

B.

Antibacterial Drug Product Labeling .......................................................................................... 3

III.

SECTION 1111 OF FDAAA AND HOW FDA INTENDS TO COMPLY.................. 4

IV.

UPDATING SUSCEPTIBILITY TEST INFORMATION IN ANTIBACTERIAL

DRUG PRODUCT LABELING...................................................................................... 5

A.

Periodic Evaluation of Information in the Microbiology Subsection......................................... 5

B.

Approaches to Updating the Labeling ......................................................................................... 5

C.

If the Applicant Believes No Change to the Labeling Is Needed ............................................... 7

D.

Addressing the Status of the Microbiology Subsection in the Annual Report .......................... 7

E.

The Labeling Submission .............................................................................................................. 7

F.

Public Availability of Updated Microbiology Subsection Labeling ........................................... 7

V.

UPDATING SUSCEPTIBILITY TEST INFORMATION FOR IN VITRO

DIAGNOSTIC AST DEVICES ....................................................................................... 8

VI.

PAPERWORK REDUCTION ACT OF 1995................................................................ 9

i

Contains Nonbinding Recommendations

Guidance for Industry1
Updating Labeling for Susceptibility Test Information in Systemic

Antibacterial Drug Products and Antimicrobial Susceptibility

Testing Devices

This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this topic. It
does not create or confer any rights for or on any person and does not operate to bind FDA or the public.
You can use an alternative approach if the approach satisfies the requirements of the applicable statutes
and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for
implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate
number listed on the title page of this guidance.

I.

INTRODUCTION

The purpose of this guidance is to inform industry of how the FDA intends to comply with
section 1111 of the Food and Drug Administration Amendments Act (FDAAA), which requires
FDA to identify and periodically update susceptibility test interpretive criteria2 for antibacterial
drug products and to make those findings publicly available. Because susceptibility test
interpretive criteria, susceptibility test methods, and quality control parameters are interrelated,
this guidance addresses procedures for updating all three of these elements of labeling of
antibacterial drug products for human use. The guidance is also intended to remind drug
application holders of their responsibility to update this information in the labeling of their
antibacterial drug products (see 21 CFR 201.56(a)(2)). In addition, this guidance provides
directions to manufacturers of antimicrobial susceptibility testing (AST) devices for updating
labeling regarding susceptibility testing information.
FDA’s guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should
be viewed only as recommendations, unless specific regulatory or statutory requirements are
1

This guidance has been prepared by the Office of Antimicrobial Products in the Center for Drug Evaluation and
Research (CDER) and the Office of In Vitro Diagnostic Device Evaluation and Safety in the Center for Devices and
Radiological Health (CDRH) at the Food and Drug Administration.

2

Section 1111 of FDAAA uses the term clinically susceptible concentrations and defines that term as “specific
values which characterize bacteria as clinically susceptible, intermediate, or resistant to the drug (or drugs) tested”
(Public Law 110-85). Because the term is more commonly used in clinical microbiology laboratories, FDA uses the
term susceptibility test interpretive criteria to describe the drug concentrations where a type of bacteria is
categorized as susceptible, intermediate, or resistant. Therefore, throughout this guidance, we use the term
susceptibility test interpretive criteria rather than the statutory term clinically susceptible concentrations, but we
intend for these two terms to have the same meaning.

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Contains Nonbinding Recommendations
cited. The use of the word should in Agency guidances means that something is suggested or
recommended, but not required.
II.

BACKGROUND

On September 27, 2007, the President signed FDAAA into law. Section 1111 of FDAAA
requires FDA to identify and periodically update susceptibility test interpretive criteria for
antibacterial drug products and to make those findings publicly available.3 By enacting section
1111 of FDAAA, Congress recognized the importance of maintaining updated susceptibility test
interpretive criteria.4
A.

The Importance of Susceptibility Test Interpretive Criteria

Antibacterial susceptibility testing is used to determine if bacteria that are isolated from a patient
with an infection are likely to be killed or inhibited by a particular antibacterial drug product at
the concentrations of the drug that are attainable at the site of infection using the dosing
regimen(s) indicated in the drug product’s labeling. The results from antibacterial susceptibility
testing generally categorize bacteria as “susceptible,” “intermediate,” or “resistant” to each
antibacterial drug tested.5 When available, culture and susceptibility testing results are one of the
factors that physicians consider when selecting an antimicrobial drug product for treating a
patient.
The numerical values generated by susceptibility testing to determine whether a particular
microorganism is susceptible to a particular antimicrobial drug — the antimicrobial
susceptibility test interpretive criteria — are commonly referred to as breakpoints. These
breakpoints are specified in the antimicrobial drug product’s label. The antimicrobial
susceptibility test interpretive criteria can be used to interpret results from either manual or
automated AST devices.
For labeling AST devices, CDRH, the component of FDA that regulates AST devices,
recognizes the importance of having antimicrobial susceptibility test interpretive criteria that
conform to antimicrobial drug product labeling.6 However, in cases where antibacterial drug
product labels are out-of-date, AST devices sometimes have nonconforming labeling.
Inconsistencies between antibacterial drug product labels and AST device labels are not
3

This guidance applies to systemic antibacterial drug products for human use. We note that susceptibility test
interpretive criteria have not been developed for nonsystemic antibacterial drug products because the dosing is less
precise and typically involves local exposure of the infected area to high concentrations of the antibacterial agents.

4

FDA notes that the accuracy of susceptibility test interpretive criteria is dependent on the application of appropriate
test methods and associated quality control parameters.
5

We also note that in circumstances where criteria for intermediate and/or resistant bacteria have not been
established, bacteria categorized as other than “susceptible” are referred to as “nonsusceptible.”
6

See March 5, 2007, response to the June 21, 2006, citizen petition from the Clinical Laboratory Standards Institute,
Docket No. FDA-2006-P-0287 (formerly Docket No. 2006P-0271) available at http://www.regulations.gov.

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Contains Nonbinding Recommendations
desirable. Having up-to-date labeling for antibacterial drug products will better ensure the
consistency of antibacterial drug and AST device labels.
B.

Antibacterial Drug Product Labeling

FDA regulations require that information on susceptibility testing be included in the labeling for
antibacterial drug products (see 21 CFR 201.57(c)(2)(i)(C)). The INDICATIONS AND USAGE
section of labeling for antibacterial drugs includes the condition(s) for which the product has
been found to be safe and effective if used as described in the product labeling. The
INDICATIONS AND USAGE section also includes a list of specific microbial organisms for the
particular indicated condition(s). The results from culture and susceptibility testing can be used
to guide selection of an appropriate antibacterial drug product.
In general, FDA currently establishes susceptibility test interpretive criteria in the context of an
individual new drug application (NDA), and corresponding information is included in the
approved labeling for the drug product, based on in vivo and in vitro information provided by the
applicant. Specific information on susceptibility test interpretive criteria, and associated test
methods and quality control standards, is generally included in the Microbiology subsection of
the CLINICAL PHARMACOLOGY section of labeling. The labeling informs health care
providers on appropriate use of the antibacterial drug product when culture and susceptibility test
results are available. Generally, drug product labeling is publicly available at the DailyMed Web
site or at the Drugs@FDA Web site.7
Over time, additional information may become available and/or changes may occur regarding the
susceptibility of certain bacteria to antibacterial drugs. For example:
● Additional data on susceptibility of bacteria and response to therapy may show an altered
relationship over time between a particular bacterial species and a particular antibacterial
drug. Furthermore, the development of new mechanisms of resistance in bacteria may result
in decreased susceptibility to a particular antibacterial agent. Decreased susceptibility may
raise efficacy or safety concerns when out-of-date susceptibility test interpretive criteria are
used in guiding treatment of patients with the indicated infection(s).
● Microbiological testing methods and their respective quality control parameters may be
refined to improve performance or better assess the quality control of susceptibility testing.
Consequently, it is important that the in vitro susceptibility test methods, the susceptibility test
interpretive criteria, and the quality control parameters listed in the labeling for a product be
reviewed on a regular basis and updated to reflect the most current information.
Although sponsors are required to update susceptibility test interpretive criteria when
appropriate, FDA has found it difficult to ensure that the labeling of a number of antibacterial
drugs and the associated AST devices is current. Before the information in the Microbiology
7

DailyMed can be accessed at http://dailymed.nlm.nih.gov/dailymed/about.cfm. Product labeling is also available
on the Drugs@FDA Web site at http://www.accessdata.fda.gov/scripts/cder/drugsatfda.

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Contains Nonbinding Recommendations
subsection in the drug labeling can be changed, the application holder, in general, has to submit
an appropriate labeling supplement to the Agency for review and approval (see 21 CFR 314.70).
An internal FDA review of the Microbiology subsection of labeling for a large number of
antibacterial drug products confirmed that the product labeling often contains susceptibility test
methods, antimicrobial susceptibility test interpretive criteria, and/or quality control parameters
that have not been updated in many years. Also, FDA has received citizen petitions requesting
that the susceptibility test interpretive criteria for specific drug products be updated. FDA is also
aware that information in the Microbiology subsection of product labeling is sometimes
inconsistent with the standards relied on by many microbiology laboratories. This guidance
document addresses concerns about these inconsistencies.
III.

SECTION 1111 OF FDAAA AND HOW FDA INTENDS TO COMPLY

Section 1111 took effect immediately when FDAAA was signed into law by the President
(September 27, 2007). The specific language of section 1111(b) requires FDA to “identify
(where such information is reasonably available) and periodically update” susceptibility test
interpretive criteria. Section 1111(c) requires FDA to make susceptibility test interpretive
criteria publicly available “not later than 30 days after the date of identification and any update
under . . . section [1111].”
FDA’s approach for updating susceptibility test interpretive criteria in the manner described in
this guidance is authorized by sections 502 and 505 of the Federal Food, Drug, and Cosmetic Act
(the Act) (21 U.S.C. 352 and 355) and section 1111 of FDAAA. FDA is using other sources, in
addition to applicant-initiated drug product labeling, to identify and update susceptibility test
interpretive criteria, and associated test methods and quality control parameters, particularly if
the antibacterial drug product labeling is out of date. Potentially useful sources for this
information are existing standards established by nationally or internationally recognized
standard development organizations.
Where appropriate, FDA intends to recognize susceptibility test interpretive criteria, and
associated test methods and quality control parameters, by publishing annually in a Federal
Register notice certain standards developed by one or more nationally or internationally
recognized standard development organizations.8 The Federal Register notice will constitute
notification that FDA has recognized a standard for devices. This approach is authorized by
FDA’s current authority in section 514(c) of the Act (21 U.S.C. 360d(c)) to recognize a standard
for devices by issuing a Federal Register notice.9 Under this approach, FDA retains the
authority to accept or reject for recognition (based on our scientific judgment) any susceptibility
test interpretive criteria, or associated susceptibility test method or quality control parameters,
developed by a standard development organization for a specific bacterium treated by a specific
approved antibacterial drug product. When a standard is recognized, FDA also intends to accept
8

The standards recognized by FDA will be available through a public source, such as the National Library of
Medicine (Bethesda, MD).

9

Under section 514(c) of the Act, FDA has authority to recognize a standard for use by device manufacturers. The
procedures for devices are described, in general, in a separate guidance from CDRH on Recognition and Use of
Consensus Standards available at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/default.htm.

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Contains Nonbinding Recommendations
the recognized susceptibility test interpretive criteria, or associated test methods or quality
control parameters, to update the drug product labeling. Applicants and manufacturers have the
option to rely on the FDA-recognized standards as one approach to updating their product
labeling (see section IV.B). Under existing regulations, an application holder is responsible for
updating its labeling whenever new information becomes available that causes the labeling to
become false or misleading (see § 201.56(a)(2)). FDA’s final decision regarding the appropriate
susceptibility test information for a particular drug product will be publicly available in approved
product labeling (see section IV.F).
IV.

UPDATING SUSCEPTIBILITY TEST INFORMATION IN ANTIBACTERIAL
DRUG PRODUCT LABELING
A.

Periodic Evaluation of Information in the Microbiology Subsection

Holders of new drug applications (NDAs) and abbreviated new drug applications (ANDAs) that
are designated as a reference listed drug (RLD) for systemic antibacterial drug products should
review their product labeling at least annually to evaluate whether the Microbiology subsection is
up to date. When FDA recognizes a standard that is different from the information in the
Microbiology subsection of the labeling for the application holder’s product, the differences
should be specifically evaluated by the applicant (§ 201.56(a)(2)). Within 90 days following
FDA publicly recognizing a standard that is relevant to the application holder’s product, the
application holder should submit updated labeling (see section IV.B) or provide a written
explanation why it believes the standard is not applicable to its antibacterial drug product (see
section IV.C).10
B.

Approaches to Updating the Labeling

This guidance describes two approaches for application holders to update labeling as follows:




updating information in the Microbiology subsection of product labeling by
submitting revised product labeling that is in conformance with a standard that has
been recognized by the Agency
or
submitting data that support a change in the information in the Microbiology
subsection of product labeling that differs from the Agency’s recognized standard.

10

We anticipate that this amount of time will be adequate for application holders to evaluate whether to rely on a
recognized standard or submit data to support a different labeling change or maintain the information in the
Microbiology subsection of product labeling. In general, before FDA recognizes a standard, there will be a public
process to discuss changes to an accepted standard. For example, any standard development organization would
likely discuss proposed changes (and the supporting data) to an existing standard at an open meeting, and discussion
may continue at additional meetings prior to adoption of a standard. It would be prudent for any application holder
to begin considering the appropriateness of its susceptibility test information, quality control parameters, and test
methods in its product labeling whenever revised standards that apply to a particular application are being
considered by a relevant standard development organization.

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Contains Nonbinding Recommendations
Either approach can be a suitable and sufficient route for application holders to provide
information to FDA for review by the FDA to determine the appropriate updating of the
Microbiology subsection in product labeling.
1.

Updating Through Reliance on a Standard Recognized by the FDA

If the standards recognized in the Federal Register notice differ from the information in an
applicant’s current product labeling, the applicant can submit proposed labeling to the Agency
that is in conformance with the FDA-recognized standards. The applicant should submit a “Prior
Approval” labeling supplement containing the appropriate changes. Labeling changes
referencing an FDA-recognized standard should not be combined with any “Changes Being
Effected (CBE)” or other “Prior Approval” labeling revisions being submitted. We recommend
that such supplements for adopting FDA-recognized standards be sent to the Agency within 90
days following the publication of the Federal Register notice. The applicant should clearly state
that the purpose of the labeling supplement is to change the Microbiology subsection of labeling
in conformance with an FDA-recognized standard and cite the relevant Federal Register notice
in which the standard is recognized.
Note that when relying on a recognized standard, the updating applies only to organisms that are
currently listed in the INDICATIONS AND USAGE section of the product label. For example,
it is appropriate to update the existing susceptibility interpretive criteria, methods, and quality
control for the organisms listed in the INDICATIONS AND USAGE section. It is not
appropriate to add indications or new organisms within the INDICATIONS AND USAGE
section or the in vitro data only list in the Microbiology subsection of the CLINICAL
PHARMACOLOGY section (commonly referred to as the “second list”) based solely upon a
standard that FDA has recognized.
2.

Updating Through Submission of Information that Supports Labeling Different
from a Standard Recognized by FDA

Application holders who wish to update their product’s labeling with susceptibility test
information that differs from the standards that the FDA recognizes in the Federal Register
should submit proposed labeling as a supplement to their application, within 90 days following
the publication of the Federal Register notice. The applicant should submit a “Prior Approval”
labeling supplement containing any proposed change to the Microbiology subsection, along with
information that supports a change to the susceptibility test interpretive criteria and associated in
vitro susceptibility test methods and/or quality control parameters.
The applicant should clearly state that the purpose of the labeling supplement is to change the
Microbiology subsection based on the submitted information. This labeling supplement should
not be combined with any “Changes Being Effected (CBE)” or other “Prior Approval” labeling
revisions being submitted.
Even if FDA has not recognized a standard with different susceptibility test interpretive criteria
and associated in vitro susceptibility test methods and/or quality control parameters for a specific
drug, applicants can update their labeling by providing additional information to support the

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proposed change. Application holders should submit a “Prior Approval” labeling supplement
whenever they have information that indicates the Microbiology subsection of their product
labeling needs to be updated.
C.

If the Applicant Believes No Change to the Labeling Is Needed

If the information in the applicant’s product labeling differs from the standards recognized by the
Agency and the applicant believes that changes to the labeling are not needed, the applicant
should provide written justification to the FDA within 90 days following the publication of the
Federal Register notice. For example, additional scientific information may justify not applying
the recognized standard to an applicant’s specific drug product. An applicant who believes a
change in the product labeling is not needed should submit the justification as general
correspondence to its application. The applicant should clearly state that the purpose of the
correspondence is to provide a justification for not changing the Microbiology subsection of
labeling in accordance with an FDA-recognized standard.
D.

Addressing the Status of the Microbiology Subsection in the Annual Report

Application holders should also include in their annual report an assessment of whether the
information in the Microbiology subsection of their product labeling is current or changes are
needed (21 CFR 314.81(b)(2)(i) and 314.98(c)).
E.

The Labeling Submission

All supporting documents (including current package insert) for revision of the labeling should
be included in the submission. Submit the revised content of labeling (21 CFR 314.50(1)(l)(i)) in
structured product labeling (SPL) format.11
F.

Public Availability of Updated Microbiology Subsection Labeling

Section 1111(c) requires FDA to make susceptibility test interpretive criteria publicly available
not later than 30 days after the date of identification and any update. As described in section III
of this guidance, FDA intends to issue annually a Federal Register notice recognizing
appropriate susceptibility test interpretive criteria, quality control parameters, and methods
developed by one or more nationally or internationally recognized standard development
organizations. The Federal Register notice will provide references to the standards recognized
by the Agency, but will not describe individual susceptibility test interpretive criteria for each
approved drug product. The susceptibility test interpretive criteria will be available from the
standard development organization(s).12
Because drug application holders can choose different approaches for responding to the notice of
FDA-recognized standards, FDA will consider the key date under FDAAA for identification and
11

See http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm.

12

See footnote 8.

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Contains Nonbinding Recommendations
update of susceptibility test interpretive criteria to be the date the Agency approves a labeling
supplement for an antibacterial product. Approved updated product labeling for antibacterial
drug products will be made publicly available at the Drugs@FDA Web site or at the DailyMed
Web site.13 Antibacterial drug labeling with updated information on susceptibility test
interpretive criteria in the Microbiology subsection will be posted on one of these public Web
sites within 30 days of an approval action for the application holder’s labeling supplement that
effects the change.
V.

UPDATING SUSCEPTIBILITY TEST INFORMATION FOR IN VITRO
DIAGNOSTIC AST DEVICES

Where appropriate, FDA intends to recognize susceptibility test interpretive criteria, and
associated test methods and quality control parameters, by publishing annually in a Federal
Register notice references to standards developed by one or more nationally or internationally
recognized standard development organizations. Once FDA has recognized a standard, NDA
holders should update their drug labeling as described in section IV and FDA will make the
approved, updated drug labeling publicly available. If the susceptibility test interpretive criteria
in the labeling for an AST device do not conform with the updated drug labeling, AST device
manufacturers should update their labeling to conform with the new, publicly available drug
labeling within 90 days. If the FDA approves drug labeling that differs from the FDArecognized standard as described in section IV.B.2, FDA intends to revoke the standard under
section 514(c)(2) of the Act.
While updating the susceptibility test interpretive criteria will significantly affect the safety and
effectiveness of the AST device and, therefore, ordinarily would require submission of a
premarket notification (510(k)) prior to updating device labeling (21 CFR 807.81(a)(3)(i)), FDA
intends to exercise enforcement discretion with regard to submission of a new 510(k) in certain
circumstances. To determine whether a particular AST device is within the scope of FDA’s
intended exercise of enforcement discretion, manufacturers should reevaluate previously
collected clinical trial data applying revised susceptibility test interpretive criteria or perform a
comparative study that demonstrates whether the updated susceptibility test interpretive criteria
affect performance of the device. If the updated interpretive criteria do not affect acceptable
device performance, as described in Class II Special Controls Guidance Document:
Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (the Class II
special controls guidance),14 and the only change to the AST labeling is updating susceptibility
test interpretive criteria, then FDA intends to exercise enforcement discretion with regard to the
510(k) requirement. If the updated susceptibility test interpretive criteria change the device
performance, and the manufacturer will update the interpretive criteria and change the device
performance portion of the labeling, then the device manufacturer should submit a new 510(k)
with the results of the comparative study or reevaluation of previously collected clinical trial data
13

See footnote 7.

14

The Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance
for Industry is available at
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm080564.htm. FDA
intends to update the Class II special controls guidance document to incorporate the information above.

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Contains Nonbinding Recommendations
applying revised susceptibility test interpretive criteria. See the Class II special controls
guidance document referenced above for information on acceptable device performance. The
comparative study should incorporate the following design elements:
 follow the design for the comparative study described in the Class II special controls
guidance
 use a similar group of organisms as those groups that provided the original Essential
Agreement or Category Agreement results
 include a representative number from all groups of organisms that might be affected
by modifications to the device
Manufacturers can report the results using the table format examples provided in the Class II
special controls guidance. Please contact the Division of Microbiology Devices, Office of
In Vitro Diagnostic Device Evaluation and Safety, at CDRH for details on the extent of the data
to be submitted.
VI.

PAPERWORK REDUCTION ACT OF 1995

This guidance contains information collection provisions that are subject to review by the Office
of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C.
3501-3520). The expiration date of the OMB control number will be updated periodically.
The time required to complete this information collection is estimated to average 16 hours per
response, including the time to review instructions, search existing data sources, gather the data
needed, and complete and review the information collection. Send comments regarding this
burden estimate or suggestions for reducing this burden to:
Office of Antimicrobial Products, Center for Drug Evaluation and Research, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 22, rm. 6212, Silver Spring, MD 209930002.
This guidance also refers to previously approved collections of information found in FDA
regulations. The collections of information in 21 CFR 201.56(a)(2) have been approved under
OMB Control No. 0910-0572; the collections of information in 21 CFR 314.70(b)(2)(v) and
314.81(b)(2)(i) have been approved under OMB Control No. 0910-0001.
An agency may not conduct or sponsor, and a person is not required to respond to, a
collection of information unless it displays a currently valid OMB control number. The
OMB control number for this information collection is 0910-0638 (expires 11/30/2014).

9