PF PRISM C.V.
`
`
` c/o Pfizer Inc.
` Attention: Nadia Kirzecky
`
` Director, Worldwide Safety and Regulatory
`
`235 East 42nd Street
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`
`
`New York, NY 10017-5755
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`
`
`Dear Ms. Kirzecky:
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`Please refer to your Supplemental New Drug Applications (sNDAs) submitted under section
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`505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for the following:
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` NDA#/Drug Name
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` Supplement
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` Number
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` Submission Date Date Received
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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 21-821/S-026 and S-031
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`Food and Drug Administration
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` Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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` S-026
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`S-031
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` September 30, 2009
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`February 11, 2011
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` September 30, 2009
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`February 11, 2011
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` NDA 21-821/Tygacil
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` (tigecycline) for
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` Injection
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`We acknowledge receipt of your amendments to these supplemental applications dated
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`November 29, 2011, February 7, 2012 [S-031 only], and February 13, July 3, and September 23,
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`2013.
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`Supplemental application S-026 is a “Prior Approval” supplement that provides for changes to
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`the INDICATIONS AND USAGE section stating that Tygacil is not indicated for the treatment
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`of diabetic foot infections.
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`Supplemental application S-031 is a “Changes Being Effected” supplement that provides for
`changes to the ADVERSE REACTIONS section of the labeling to include the adverse reactions
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`of pneumonia and severe skin reactions, including Stevens-Johnson syndrome.
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`In addition to the changes requested in the above supplements, the attached labeling also
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`includes the following changes as discussed with you via multiple electronic communications
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`(e-mails) and finalized in your submission containing revised draft labeling on September 23,
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`2013.
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`Reference ID: 3379756
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`

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` NDA 21-821/S-026 and S-031
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` P a g e | 2
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` • Addition of a “BOXED WARNING” to include information from meta-analysis of
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` clinical trials that showed an increased risk of mortality in Tygacil-treated patients and to
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` reserve Tygacil for use in situations when alternative treatments are not suitable.
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` • Addition of Limitations of Use (1.4) to include information that Tygacil is not indicated
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` for the treatment of diabetic foot infections and hospital-acquired or ventilator-associated
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` pneumonia.
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` • Revisions of the DOSAGE AND ADMINISTRATION section (2), Pediatric Patients
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` subsection (2.3) and USE IN SPECIFIC POPULATIONS section (8.0), Pediatric Use
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` subsection (8.4) to include information about use in the pediatric population.
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` • Revisions to the WARNINGS AND PRECAUTIONS section (5), All-Cause Mortality
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` subsection (5.1) regarding the increased risk of mortality.
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` • The following revisions to the ADVERSE REACTIONS section (6):
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`o Clinical Trials Experience subsection (6.1) to include information about an
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` increase in mortality in trials conducted for approved indications
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`o Post-Marketing Experience subsection (6.2), to include adverse reactions of
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` Stevens-Johnson syndrome and symptomatic hypoglycemia
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`o Revised the incidence of adverse reactions in Table 1.
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` • Addition of a Pharmacodynamics subsection (12.2), Cardiac Electrophysiology, to the
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` CLINICAL PHARMACOLOGY section (12).
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` • Minor editorial changes including updates to the REFERENCES (15) section.
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`APPROVAL & LABELING
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`We have completed our review of these supplemental applications, as amended. They are
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`approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-
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`upon labeling text.
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`CONTENT OF LABELING
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`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
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`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
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`automated drug registration and listing system (eLIST), as described at
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`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
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`of labeling must be identical to the enclosed labeling text for package insert, with the addition of
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`any labeling changes in pending “Changes Being Effected” (CBE) supplements, as well as
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`annual reportable changes not included in the enclosed labeling.
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`Reference ID: 3379756
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`

`

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` NDA 21-821/S-026 and S-031
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` P a g e | 3
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` Information on submitting SPL files using eList may be found in the guidance for industry titled
` “SPL Standard for Content of Labeling Technical Qs and As at
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`
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`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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` The SPL will be accessible from publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications that includes labeling changes
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`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
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`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
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`changes approved in these supplemental applications, as well as annual reportable changes and
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`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
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`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
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`should provide appropriate annotations, including supplement number(s) and annual report
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`date(s).
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`PROMOTIONAL MATERIALS
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`All promotional materials that include representations about your drug product must be promptly
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`revised to be consistent with the labeling changes approved in this supplement, including any
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`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
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`should include prominent disclosure of the important new safety information that appears in the
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`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
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`to comply with 21 CFR 314.70(a)(4) to the address above or by fax to 301-847-8444.
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
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`(21 CFR 314.80 and 314.81).
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`If you have any questions, call Carmen DeBellas, PharmD, R.Ph., Regulatory Project Manager,
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`at (301) 796-1203.
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`Sincerely,
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`
`{See appended electronic signature page}
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`
`
`Sumathi Nambiar, MD, MPH
`
`Acting Director
`
`
`Division of Anti-Infective Products
`
`Office of Antimicrobial Products
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`Center for Drug Evaluation and Research
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`ENCLOSURE:
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`Content of Labeling
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`
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`Reference ID: 3379756
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`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`SUMATHI NAMBIAR
`09/26/2013
`
`Reference ID: 3379756
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`