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Updating ANDA Labeling After the Marketing Application for the Reference Listed Drug Has Been Withdrawn

Updating ANDA Labeling

After the Marketing Application

for the Reference Listed Drug

Has Been Withdrawn Guidance for Industry

DRAFT GUIDANCE

This guidance document is being distributed for comment purposes only.

Comments and suggestions regarding this draft document should be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit electronic comments to http://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register.

For questions regarding this draft document, contact (CDER) Emily Helms Williams, 301-796- 3600.

U.S. Department of Health and Human Services Food and Drug Administration
Center for Drug Evaluation and Research (CDER)

July 2016 Generics

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Updating ANDA Labeling

After the Marketing Application

for the Reference Listed Drug

Has Been Withdrawn Guidance for Industry

Additional copies are available from:
Office of Communications, Division of Drug Information Center for Drug Evaluation and Research

Food and Drug Administration th 10001 New Hampshire Ave., Hillandale Bldg., 4

Floor

Silver Spring, MD 20993-0002
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353
Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm

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U.S. Department of Health and Human Services Food and Drug Administration
Center for Drug Evaluation and Research (CDER) July 2016
Generics

I. II. III. IV.

A. B. C.

1. 2.

Contains Nonbinding Recommendations

Draft — Not for Implementation

TABLE OF CONTENTS

INTRODUCTION............................................................................................................. 1 BACKGROUND ............................................................................................................... 2 SCOPE OF GUIDANCE .................................................................................................. 4 UPDATING LABELING OF ANDAs THAT RELY ON WITHDRAWN RLDs ...... 4 Examples of Labeling Updates for ANDAs That Rely on Withdrawn RLDs........................... 5 Process for Labeling Updates ....................................................................................................... 7 Relationship of this Guidance to Existing Authorities and Processes ....................................... 7

Safety Labeling Changes Under Section 505(o)(4) of the FD&C Act ............................................. 7 Section 409I of the Public Health Services Act................................................................................ 8

Contains Nonbinding Recommendations

Draft — Not for Implementation

  1. 1 Updating ANDA Labeling After the Marketing Application for the

  2. 2 Reference Listed Drug Has Been Withdrawn

34 Guidance for Industry1

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I. INTRODUCTION 16

  1. 17  This guidance describes a process for updating labeling for abbreviated new drug applications

  2. 18  (ANDAs) in cases where FDA has withdrawn approval of the new drug application (NDA)2 for

  3. 19  the ANDA’s reference listed drug (RLD)3 for reasons other than safety or effectiveness. Where

  4. 20  approval of the NDA for the RLD has been withdrawn by FDA under these circumstances

  5. 21  (referred to in this guidance as a “withdrawn RLD”), and ANDAs are pending or generic drugs

  6. 22  continue to be marketed under one or more ANDAs that rely on the withdrawn RLD, the

  7. 23  labeling of those pending or marketed ANDA products may need to be updated to reflect

  8. 24  changes that would have been necessary had the NDA for the RLD not been withdrawn.

25

  1. 26  This guidance sets forth ways in which FDA may seek to facilitate the revision of labeling to

  2. 27  reflect updated information for ANDAs that rely on withdrawn RLDs. This guidance will be of

  3. 28  interest to the holders of pending or approved ANDAs that rely upon a withdrawn RLD, as well

  4. 29  as to applicants seeking to submit ANDAs relying on withdrawn RLDs. We anticipate that this

  5. 30  guidance will help facilitate labeling updates for approved ANDAs as well as the approval of

  6. 31  certain pending ANDAs where the NDA for the RLD has been withdrawn.

32

  1. 33  In general, FDA’s guidance documents do not establish legally enforceable responsibilities.

  2. 34  Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only

  3. 35  as recommendations, unless specific regulatory or statutory requirements are cited. The use of

    1 This guidance has been prepared by the Office of Regulatory Policy, the Office of Generic Drugs, the Office of New Drugs, and the Office of Surveillance and Epidemiology in the Center for Drug Evaluation and Research at the Food and Drug Administration.
    2 For purposes of this guidance, we use the phrase “new drug application” or “NDA” to refer to an application approved under section 505(c) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355(c)), including applications based on a finding of effectiveness under the Drug Efficacy Study Implementation (DESI) review process.
    3 See 21 CFR 314.3 (defining reference listed drug and listed drug); see also “Abbreviated New Drug Applications and 505(b)(2) Applications” (Proposed Rule), 80 FR 6802 at 6814 (February 6, 2015).

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This draft guidance, when finalized, will represent the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the title page.

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  1. 36  the word should in Agency guidances means that something is suggested or recommended, but

  2. 37  not required.

38 39

40 II. BACKGROUND 41

  1. 42  A generic drug is required to have the same labeling as the RLD at the time of approval, except

  2. 43  for changes required because of differences approved under a suitability petition (see section

  3. 44  505(j)(2)(C) of the FD&C Act and 21 CFR 314.93) or because the generic drug and the RLD are

  4. 45  “produced or distributed by different manufacturers” (see section 505(j)(2)(A)(v) of the FD&C

  5. 46  Act). FDA regulations provide examples of permissible differences in labeling that may result

  6. 47  where a proposed generic drug and the RLD are “produced or distributed by different

  7. 48  manufacturers,” including the omission of an indication or other aspect of labeling protected by

  8. 49  patent or exclusivity and “labeling revisions made to comply with current FDA labeling

  9. 50  guidelines or other guidance.” 21 CFR 314.94(a)(8)(iv).

51

  1. 52  As a general matter, all holders of marketing applications for drug products (both NDAs and

  2. 53  ANDAs) have an ongoing obligation to ensure their product labeling is accurate, and not false or

  3. 54  misleading. When new information becomes available that causes the labeling to become

  4. 55  inaccurate, false or misleading, the application holder must take steps to update its labeling (see,

  5. 56  e.g., 21 CFR 201.56(a)(2)). Any drug is misbranded if its labeling is false or misleading, or does

  6. 57  not provide adequate directions for use and adequate warnings (sections 301(a) and (b), and

  7. 58  502(a), (f), and (j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 331(a)

  8. 59  and (b), and 352(a), (f), and (j))).

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  1. 61  Where the NDA for the RLD has not been withdrawn, RLD holders often propose changes to the

  2. 62  labeling by submitting them to the NDA. ANDA holders are expected to update their labeling

  3. 63  after FDA has approved relevant changes to the labeling for the corresponding NDA RLD. FDA

  4. 64  may withdraw approval of an ANDA if it finds that the labeling for the drug product that is the

  5. 65  subject of the ANDA is no longer consistent with that for the RLD (section 505(e) of the FD&C

  6. 66  Act and 21 CFR 314.150(b)(10)).

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  1. 68  FDA believes ANDA applicants are familiar with the mechanisms for updating labeling for

  2. 69  pending and marketed ANDAs where the NDAs for the RLDs have not been withdrawn.

  3. 70  However, there has been confusion regarding the process for updating labeling for ANDAs

  4. 71  referencing RLDs where the NDAs have been withdrawn.

72

  1. 73  NDAs for RLDs may be withdrawn voluntarily, at the NDA holder’s request, for reasons other

  2. 74  than safety and effectiveness. Specifically, FDA will withdraw approval of an NDA at the

  3. 75  applicant’s request where the drug that is the subject of the application is no longer being

  4. 76  marketed, and if certain other conditions are satisfied, including the absence of any FDA finding

  5. 77  that the drug is unsafe or ineffective for its approved conditions of use (see, e.g., § 314.150(c)

2

Contains Nonbinding Recommendations

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  1. 78  (21 CFR 314.150(c))).4 As noted above, withdrawal of an NDA RLD under these circumstances

  2. 79  is referred to in this guidance as a “withdrawn RLD.”5

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  1. 81  Where an RLD has been withdrawn, ANDA products that were approved in reliance on the

  2. 82  withdrawn RLD may continue to be marketed, and new ANDAs must refer to the withdrawn

  3. 83  RLD as the basis for ANDA submission (provided that there has been a determination that the

  4. 84  NDA RLD was not withdrawn for reasons of safety or effectiveness) (see § 314.122(c) (21 CFR

  5. 85  314.122(c))).

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  1. 87  Under these circumstances, where approval of the NDA for an RLD has been withdrawn, the

  2. 88  NDA holder can no longer update labeling for the withdrawn RLD.6 Yet as a drug is used over

  3. 89  time, the scientific community’s understanding of the drug may evolve based on data from

  4. 90  various sources, including published literature and postmarketing data. Therefore, the labeling

  5. 91  of ANDAs that rely on the withdrawn RLD might eventually become inaccurate and outdated,

  6. 92  resulting in labeling that is false and/or misleading, for example. Likewise, new original

  7. 93  ANDAs that rely on the withdrawn RLD might include proposed labeling based on the last

  8. 94  approved RLD labeling that includes outdated information that is false and/or misleading.

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  1. 96  If an NDA for a certain drug has been withdrawn, there may be other drugs that contain the same

  2. 97  active ingredient (or an active ingredient in the same pharmacologic or therapeutic class) for

  3. 98  which approval of the NDA has not been withdrawn. The labeling of those other drugs, as well

  4. 99  as the labeling of any corresponding ANDAs, may have been updated to reflect any new

  5. 100  scientific information that is needed for the safe and effective use of the drug. This creates a

  6. 101  situation in which certain NDAs and ANDAs for a given active ingredient have up-to-date

  7. 102  labeling, while other ANDAs do not, simply because those other ANDAs rely on an RLD for

  8. 103  which approval of the NDA has been withdrawn. In such cases the labeling of pending ANDAs

  9. 104  or marketed ANDAs products may need to be updated to reflect changes that would have been

  10. 105  necessary had the NDA for the RLD not been withdrawn.

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4 If the NDA for the RLD has been withdrawn for reasons other than safety or effectiveness, a therapeutically equivalent drug product approved under an ANDA may be designated as the reference standard for use in conducting an in vivo study to demonstrate bioequivalence.
5 Withdrawal of approval of an NDA is considered effective upon the date specified in the notice of withdrawal published in the Federal Register. Until that date, an NDA holder that has submitted a request under 21 CFR 314.150 to withdraw the approval of an NDA will continue to be responsible for ensuring that the labeling of the drug product approved under the NDA remains accurate and up to date.

6 In cases where marketing of the RLD product has been discontinued but approval of the NDA has not been withdrawn under § 314.150 or section 505(e) of the FD&C Act (referred to in this guidance as a “discontinued RLD”), the NDA holder must still comply with applicable statutory and regulatory requirements. These requirements include, for example, proposing any necessary revisions to update product labeling for the discontinued RLD (see, e.g., § 201.56(a)(2)). ANDA products approved in reliance on a discontinued RLD may continue to be marketed, and new ANDAs must refer to the discontinued RLD as the basis for ANDA submission (see § 314.122(c)). The Agency will continue to list discontinued RLD drug products on the “Discontinued Drug Product List” in FDA’s “Approved Drug Products With Therapeutic Equivalence Evaluations” (the “Orange Book”), unless FDA determines that the drug product was withdrawn from sale for reasons of safety or effectiveness, in which case the drug product will be removed from the Orange Book.

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Contains Nonbinding Recommendations

Draft — Not for Implementation

  1. 107  In this guidance, FDA clarifies that consistent with the statute, where the RLD is withdrawn, 7

  2. 108  certain labeling changes may continue to be made for pending ANDAs and marketed ANDAs.

109 110

111 III. SCOPE OF GUIDANCE 112

  1. 113  This guidance is limited to labeling updates for generic drugs that are the subject of new original,

  2. 114  pending ANDAs or approved ANDAs that rely on an RLD for which approval of the NDA has

  3. 115  been withdrawn for reasons other than safety or effectiveness.

116

  1. 117  Consistent with this guidance, FDA may seek to facilitate certain updates to the labeling for a

  2. 118  new original, pending ANDA or an already-approved ANDA that relies on a withdrawn RLD

  3. 119  when the previously approved labeling for the withdrawn RLD has become outdated and such

  4. 120  changes would have been necessary had the RLD not been withdrawn.

121

  1. 122  The process described in this guidance is intended to complement existing Agency authorities

  2. 123  and processes, including FDA’s authority under the Food and Drug Administration Amendments

  3. 124  Act of 2007 (FDAAA) to require certain safety labeling changes (SLCs) to the labeling of certain

  4. 125  prescription drug products. The relationship of this guidance to certain existing FDA authorities

  5. 126  and processes is further discussed in section IV.C below.

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IV. UPDATING LABELING OF ANDAs THAT RELY ON WITHDRAWN RLDs 130

  1. 131  ANDA holders are responsible for reviewing postmarketing data and published literature as

  2. 132  appropriate to satisfy applicable reporting requirements (e.g., 21 CFR 314.81, 314.98).

  3. 133  However, FDA (as well as ANDA holders and applicants) may be aware of data relevant to

  4. 134  labeling updates in a variety of situations. For example, relevant data may already be reflected in

  5. 135  the updated labeling of other drugs in the same pharmacologic or therapeutic class (e.g., class

  6. 136  labeling); in non-product specific literature; or in postmarketing information. The updates

  7. 137  contemplated by this guidance generally would not involve reliance on product-specific,

  8. 138  proprietary information about another drug. Any changes proposed under this guidance must be

  9. 139  consistent with the requirement that an ANDA include sufficient information to show that the

  10. 140  conditions of use have been previously approved for the RLD (section 505(j)(2)(A)(i)).

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7 The approach proposed in this guidance is consistent with FDA statements made in the context of determinations that certain drug products that have been withdrawn from sale were not withdrawn for reasons of safety or effectiveness, including statements to the effect that “[i]f FDA determines that labeling for these drug products should be revised to meet current standards, the Agency will advise ANDA applicants to submit such labeling.” See, e.g., 80 FR 27320 at 27321 (May 13, 2015) (determining that SODIUM SULAMYD (sulfacetamide sodium) Ophthalmic Solution and Ophthalmic Ointment were not withdrawn from sale for reasons of safety or effectiveness).

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Contains Nonbinding Recommendations

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A. Examples of Labeling Updates for ANDAs That Rely on Withdrawn RLDs

In general, the labeling changes contemplated under this guidance include changes necessary to ensure that labeling adequately describes information essential for safe and effective use; that labeling is accurate and meets current standards; and that labeling is not false or misleading under section 502 of the FD&C Act. Revisions described by this guidance may include changes based on data that have become available since the RLD was withdrawn, including published literature and other data that emerge after products have entered the market.

More specifically, the labeling changes contemplated under this guidance may be needed:

• •

To achieve consistency with the labeling of other products that have the same active ingredient or an active ingredient in the same pharmacologic or therapeutic class, or with the labeling of other products approved for the same indication, where appropriate;
To correct outdated information related to a previously approved indication; and/or
To achieve consistency with applicable regulations and current FDA labeling guidelines or other guidance (as already contemplated under § 314.94(a)(8)(iv)).

Examples of the updates contemplated by this guidance might include the following (this list is not intended to be exhaustive):8

• •

Updating the indication statement in the INDICATIONS AND USAGE section to reflect current disease terminology (e.g., changing “Juvenile Rheumatoid Arthritis” to “Juvenile Idiopathic Arthritis”) or to modify the description of an outdated restriction on the use of the drug in specific situations.

For systemic antibacterial drug products, including the required statement about antimicrobial resistance in the INDICATIONS AND USAGE section (see 21 CFR 201.24(b)).

For parenteral products, including the following required statement or appropriate modification in the DOSAGE AND ADMINISTRATION section: “Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit” (see 21 CFR 201.57(c)(3)(iv)).

Removing a risk from the CONTRAINDICATIONS section if the benefit outweighs the risk of use in the situation or subpopulation (e.g., the risk is theoretical) (see 21 CFR 201.57(c)(5)).

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8 FDA intends to use the process outlined in section IV.B to address these types of labeling changes, unless, in particular circumstances, such changes fall within FDA’s authority to require SLCs pursuant to section 505(o)(4) of the FD&C Act. As noted above in section III, the process described in this guidance is intended to complement existing Agency authorities and processes, including FDA’s authority to require SLCs.

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Revising the WARNINGS AND PRECAUTIONS section to include current steps to prevent, mitigate, monitor for, or manage a clinically significant adverse reaction or risk.

Revising the ADVERSE REACTIONS section to include a new adverse reaction based on postmarketing experience.

Revising the ADVERSE REACTIONS section to include the following recommended statement or appropriate modification before the presentation of adverse reactions from spontaneous reports:

The following adverse reactions have been identified during postapproval use of drug X. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

See FDA guidance for industry, Adverse Reactions Section of Labeling for Human Prescription Drug and Biological Products — Content and Format. 9

Adding a new clinically significant drug interaction in the DRUG INTERACTIONS section based on postmarketing data showing that a newly approved product interacts with the active ingredient in the ANDA product or with products in the ANDA product’s class.

Revising the OVERDOSAGE section to include overdose management strategies that are consistent with current Poison Control recommendations.

For systemic antibacterial drug products, updating susceptibility test interpretive criteria, susceptibility test methods, and quality control parameters in the Microbiology subsection of the CLINICAL PHARMACOLOGY section. See FDA guidance for industry, Updating Labeling for Susceptibility Test Information in Systemic Antibacterial Drug Products and Antimicrobial Susceptibility Testing Devices;10 see also section 1111 of FDAAA.

Making changes to keep up to date with class Medication Guides (e.g., if there is a class Medication Guide for nonsteroidal anti-inflammatory drugs (NSAIDs), all ANDA NSAID products -- including those with withdrawn NDA RLDs -- should have the current version of the class NSAID Medication Guide).

Making changes requested by FDA prior to withdrawal of an NDA RLD that are determined to be necessary for safe and effective use.

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9 We update guidances periodically. To make sure you have the most recent version of a guidance, check the FDA Drugs guidance Web page at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
10 Available at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.

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  1. 228  ANDA holders have the ability to submit any of the labeling updates contemplated by this

  2. 229  guidance, i.e. those changes needed to ensure that labeling is accurate and meets current

  3. 230  standards for an ANDA whose RLD is withdrawn, through the submission of a prior approval

  4. 231  supplement (PAS). If FDA determines that a change proposed in this manner is appropriate and

  5. 232  approves the supplement, the Agency may request that other ANDA holders and any ANDA

  6. 233  applicants relying on the same withdrawn RLD make the same updates, where appropriate. This

  7. 234  latter step is intended to ensure that labeling remains uniform across generic drugs that rely on

  8. 235  the same RLD.

236

  1. 237  FDA may also request a changes being effected (CBE-0) supplement from ANDA holders (see

  2. 238  21 CFR 314.70(c)(6)(iii)(E)) if FDA becomes aware of labeling updates that are needed to

  3. 239  ensure that labeling is accurate and meets current standards for an ANDA or ANDAs whose

  4. 240  RLD is withdrawn.11 Under these circumstances, the Agency would also solicit an amendment

  5. 241  reflecting the needed updates from any ANDA applicants seeking initial approval that rely on the

  6. 242  same RLD. Such an amendment would be necessary prior to ANDA approval.

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C. Relationship of This Guidance to Existing Authorities and Processes 245

  1. 246  The process described in this guidance is intended to complement existing Agency authorities

  2. 247  and processes. Two of these are described below.

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1. Safety Labeling Changes Under Section 505(o)(4) of the FD&C Act 250

  1. 251  The Food and Drug Administration Amendments Act of 2007 (FDAAA) gave FDA explicit

  2. 252  authority to require certain safety labeling changes (SLCs) to the labeling of prescription drug

  3. 253  products marketed under NDAs and under ANDAs whose RLD is not currently marketed (i.e.,

  4. 254  ANDAs with a “withdrawn RLD” or “discontinued RLD” as described in the Background

  5. 255  section of this guidance). If FDA becomes aware of “new safety information”12 that it believes

    11 FDA has issued a proposed rule that would allow ANDA holders to independently submit CBE-0 supplements making certain safety-related updates to their labeling, based on newly acquired information. See 78 FR 67985 (November 13, 2013). That proposed rule, along with comments received, remains under review. If the proposed rule is finalized, the final rule will govern the process for carrying out labeling updates that are within the scope of the rule. The process described in this guidance would not alter ANDA holders’ obligation to maintain up-to-date labeling, whether under the current regulatory framework or a future scenario at such time as the proposed rule is finalized.

    12 See 21 U.S.C. 355-1(b)(3). The term “new safety information” includes certain information about a serious risk or an unexpected serious risk associated with the use of a drug that FDA has become aware of since the drug was approved, since a risk evaluation and mitigation strategy (REMS) was required, or since the last assessment of the approved REMS for the drug.

Making changes or updates described in Agency regulations, guidance, or Federal Register notices even if they do not specifically address the labeling of ANDAs where the NDA RLD is withdrawn.

B. Process for Labeling Updates

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  1. 256  should be included in labeling, FDA issues a safety labeling change notification letter, which

  2. 257  may include proposed labeling changes, to the affected application holder(s) (see section

  3. 258  505(o)(4) of the FD&C Act). Application holders must then submit either a supplement with the

  4. 259  proposed labeling changes, or a rebuttal statement explaining why the proposed changes are not

  5. 260  warranted, within 30 days. FDA reviews and acts on these supplements and rebuttal statement

  6. 261  within defined time frames (see FDA guidance for industry, Safety Labeling Changes –

  7. 262 Implementation of Section 505(o)(4) of the FD&C Act.13

  8. 263  The FDAAA SLC process is separate and distinct from the process described in this guidance.

  9. 264  FDA will continue to use its FDAAA SLC authorities where appropriate in situations where

  10. 265  FDA becomes aware of “new safety information” about a serious risk or an unexpected serious

  11. 266  risk that the Agency believes should be included in product labeling.

  12. 267  This guidance addresses certain situations in which needed updates to the labeling of ANDAs

  13. 268  that rely on withdrawn RLDs may not be captured by the FDAAA SLC process. For example:

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  1. 292  Under section 409I of the Public Health Service Act (42 U.S.C. § 284m), the National Institutes

  2. 293  of Health (NIH) and FDA implement a program for pediatric studies of drugs. NIH may under

  3. 294  certain circumstances award funds to an entity with appropriate expertise for the conduct of

  4. 295  studies needed to provide safety and efficacy information for pediatric labeling. Upon

    13 Available at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. 8

The FDAAA SLC authorities apply only to approved NDAs and ANDAs. When new original ANDAs are submitted that rely on a withdrawn RLD, the FDAAA SLC authorities do not extend to the draft labeling submitted as part of those pending applications. Under this guidance, FDA will consider the FDAAA SLC notification that is sent to the holders of approved applications to be “FDA labeling guidelines or other guidance” within the meaning of § 314.94(a)(8)(iv). Applicants with pending ANDAs will be able to submit amendments to their applications with labeling that reflects the safety labeling change made by the holders of approved ANDAs relying on the same RLD, and this will be considered a change made to comply with “current FDA labeling guidelines or other guidance” within the meaning of the regulation.

Before FDAAA came into effect on March 25, 2008, certain labeling updates had been accomplished through other regulatory procedures, including class labeling changes. Those updates were typically carried out in the first instance by updates to NDA RLD labeling that would then have been reflected in the labeling of ANDAs relying on that RLD. Where an RLD affected by the update was withdrawn, however, the corresponding ANDAs may have never adopted these updates. Where appropriate under the process described in this guidance (for example where labeling changes are not implemented through the FDAAA SLC process), FDA will ask ANDA holders that rely on withdrawn RLDs to make these updates to their labeling consistent with this guidance.

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2. Section 409I of the Public Health Service Act

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  1. 296  completion of these pediatric studies, a study report that includes all data generated in connection

  2. 297  with the studies is placed in a public docket assigned by FDA. FDA will review the data

  3. 298  generated, and if labeling changes are determined to be appropriate, FDA may request CBE-0

  4. 299  supplements from the affected application holders to reflect those changes. Affected application

  5. 300  holders may include holders of ANDAs that rely on withdrawn RLDs.

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302 The section 409I process will not be affected by this guidance. 303
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