CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`202324Orig1s000
`
`
`OTHER REVIEW(S)
`
`

`

`
`
`PMR/PMC Development Template
`
`
`This template should be completed by the PMR/PMC Development Coordinator and included for each
`PMR/PMC in the Action Package.
`
`
`NDA #/Product Name:
`
`PMR/PMC Description:
`
`NDA 202324/Inlyta (axitinib) Tablets
`
`Provide the analytical methods and method validation for testing of
`and
` in the final drug substance
`
`
`
` NA
` NA
` 04/22/2012
` NA
`
`
`PMR/PMC Schedule Milestones: Final Protocol Submission:
`
`Study/Trial Completion:
`
`Final Report Submission:
`
`Other:
`
`
`1. During application review, explain why this issue is appropriate for a PMR/PMC instead of a
`pre-approval requirement. Check type below and describe.
` Unmet need
` Life-threatening condition
` Long-term data needed
` Only feasible to conduct post-approval
` Prior clinical experience indicates safety
` Small subpopulation affected
` Theoretical concern
` Other
`
`
`
` the drug substance which was
`The sponsor proposal included testing on
`fund to be unacceptable. Minor changes and validation to the method is needed for its use on the
`final drug substance. This has been identified as a low risk and should require minimal resource.
`
`
`2. Describe the particular review issue and the goal of the study/clinical trial. If the study/clinical trial is
`a FDAAA PMR, describe the risk. If the FDAAA PMR is created post-approval, describe the “new
`safety information.”
`
` the drug substance which was
`The sponsor proposal included testing on
`fund to be unacceptable. Minor changes and validation to the method is needed for its use on the
`final drug substance.
`
`PMR/PMC Development Template
`
`Last Updated 1/24/2012
`
`Page 1 of 3
`
`Reference ID: 3076355
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`
`3. If the study/clinical trial is a PMR, check the applicable regulation.
`If not a PMR, skip to 4.
`- Which regulation?
` Accelerated Approval (subpart H/E)
` Animal Efficacy Rule
` Pediatric Research Equity Act
` FDAAA required safety study/clinical trial
`
`
`
`- If the PMR is a FDAAA safety study/clinical trial, does it: (check all that apply)
` Assess a known serious risk related to the use of the drug?
` Assess signals of serious risk related to the use of the drug?
` Identify an unexpected serious risk when available data indicate the potential for a serious
`risk?
`
`
`- If the PMR is a FDAAA safety study/clinical trial, will it be conducted as:
` Analysis of spontaneous postmarketing adverse events?
`Do not select the above study/clinical trial type if: such an analysis will not be sufficient to
`assess or identify a serious risk
`
`
`
` Analysis using pharmacovigilance system?
`Do not select the above study/clinical trial type if: the new pharmacovigilance system that the
`FDA is required to establish under section 505(k)(3) has not yet been established and is thus
`not sufficient to assess this known serious risk, or has been established but is nevertheless not
`sufficient to assess or identify a serious risk
`
` Study: all other investigations, such as investigations in humans that are not clinical trials as
`defined below (e.g., observational epidemiologic studies), animal studies, and laboratory
`experiments?
`Do not select the above study type if: a study will not be sufficient to identify or assess a
`serious risk
`
`
`
`
`
` Clinical trial: any prospective investigation in which the sponsor or investigator determines
`the method of assigning investigational product or other interventions to one or more human
`subjects?
`4. What type of study or clinical trial is required or agreed upon (describe and check type below)? If the
`study or trial will be performed in a subpopulation, list here.
`Method validation report and analytical procedure for testing
`drug substance
`
` and
`
`in the final
`
`
`Required
` Observational pharmacoepidemiologic study
` Registry studies
` Primary safety study or clinical trial
` Pharmacogenetic or pharmacogenomic study or clinical trial if required to further assess safety
` Thorough Q-T clinical trial
` Nonclinical (animal) safety study (e.g., carcinogenicity, reproductive toxicology)
`
`PMR/PMC Development Template
`
`Last Updated 1/24/2012
`
`Page 2 of 3
`
`Reference ID: 3076355
`
`(b) (4)
`
`(b) (4)
`
`

`

`
`
`
`
`Continuation of Question 4
`
`
` Nonclinical study (laboratory resistance, receptor affinity, quality study related to safety)
` Pharmacokinetic studies or clinical trials
` Drug interaction or bioavailability studies or clinical trials
` Dosing trials
` Additional data or analysis required for a previously submitted or expected study/clinical trial
`(provide explanation)
`
` Meta-analysis or pooled analysis of previous studies/clinical trials
` Immunogenicity as a marker of safety
` Other (provide explanation)
`
`
`Agreed upon:
` Quality study without a safety endpoint (e.g., manufacturing, stability)
` Pharmacoepidemiologic study not related to safe drug use (e.g., natural history of disease,
`background rates of adverse events)
` Clinical trials primarily designed to further define efficacy (e.g., in another condition,
`different disease severity, or subgroup) that are NOT required under Subpart H/E
` Dose-response study or clinical trial performed for effectiveness
` Nonclinical study, not safety-related (specify)
`
` Other
`
`
`
`5. Is the PMR/PMC clear, feasible, and appropriate?
` Does the study/clinical trial meet criteria for PMRs or PMCs?
` Are the objectives clear from the description of the PMR/PMC?
` Has the applicant adequately justified the choice of schedule milestone dates?
` Has the applicant had sufficient time to review the PMRs/PMCs, ask questions, determine
`feasibility, and contribute to the development process?
`
`
`PMR/PMC Development Coordinator:
` This PMR/PMC has been reviewed for clarity and consistency, and is necessary to further refine
`the safety, efficacy, or optimal use of a drug, or to ensure consistency and reliability of drug
`quality.
`
`
`_______________________________________
`(signature line for BLAs)
`
`PMR/PMC Development Template
`
`Last Updated 1/24/2012
`
`Page 3 of 3
`
`Reference ID: 3076355
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`DON L HENRY
`01/24/2012
`
`RICHARD T LOSTRITTO
`01/24/2012
`
`Reference ID: 3076355
`
`

`

`
`
`Lisa Skarupa – Regulatory Project Manager
`Division of Oncology Products 1 (DOP 1)
`Office of Hematology Oncology Products
`
`Michelle Safarik, PA-C – Regulatory Review Officer
`Division of Direct-to-Consumer Promotion (DDTCP)
`Office of Prescription Drug Promotion (OPDP)
`
`FOOD AND DRUG ADMINISTRATION
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`Division of Direct-to-Consumer Promotion
`
`****Pre-decisional Agency Information****
`
`
`
`
`
`Memorandum
`
`Date:
`January 4, 2012
`
`
`To:
`
`
`
`
`
`
`From:
`
`
`
`
`
`Subject:
`
`
`
`
`
`This review is in response to DOP 1’s consult request dated April 25, 2011, for
`OPDP review of the proposed Package Insert (PI) and proposed Patient
`Package Insert (PPI) for Inlyta.
`
`Reference is made to OPDP’s review of the proposed PI dated December 21,
`2011. Reference is also made to the Division of Medical Policy Program’s
`(DMPP) review of the proposed PPI on January 3, 2012. Both reviews utilized
`the substantially complete version of the proposed PI dated December 20, 2011.
`
`DDTCP has reviewed DMPP’s comments on the proposed PPI, and has no
`further comments from a promotional perspective at this time.
`
`Thank you for your consult.
`
`
`
`
`
`Comments on draft labeling for INLYTA (axitinib) tablets for oral
`administration (Inlyta), NDA 202324
`
`
`
`
`
`
`
`Reference ID: 3066880
`
`1
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`MICHELLE L SAFARIK
`01/04/2012
`
`Reference ID: 3066880
`
`

`

`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Medical Policy Initiatives
`Office of Medical Policy Programs
`
`PATIENT LABELING REVIEW
`
`January 3, 2012
`
`Robert Justice, MD, Director
`Division of Oncology Products 1 (DOP 1)
`
`LaShawn Griffiths, RN, MSHS-PH, BSN
`Team Leader, Patient Labeling Team
`Division of Medical Policy Programs (DMPP)
`
`Barbara Fuller, RN, MSN, CWOCN
`Team Leader, Patient Labeling Team
`Division of Medical Policy Programs
`
`Latonia M. Ford, RN, BSN, MBA
`Patient Labeling Reviewer
`Division of Medical Policy Programs
`
`Date:
`
`To:
`
`Through:
`
`From:
`
`Subject:
`
`DMPP Review of Patient Labeling (Patient Package Insert)
`
`Drug Name (established
`name):
`Dosage Form and Route:
`
`INLYTA (axitinib)
`
`tablets for oral administration
`
`NDA 202324
`
`Pfizer, Inc
`
`2011-1289
`
`Application
`Type/Number:
`Applicant:
`
`OSE RCM #:
`
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 3066041
`
`
`
`

`

`1
`
`INTRODUCTION
`This review is written in response to a request by the Division of Oncology 1 (DOP
`1) for the Division of Medical Policy Programs (DMPP) to review the Applicant’s
`proposed Patient Package Insert (PPI) for Inlyta (axitinib) tablets for oral
`administration.
`On April 14, 2011, Pfizer, Inc. submitted original New Drug Application (NDA),
`202324 for Inlyta (axitinib) tablets for oral administration. The purpose of the
`Applicant’s submission is to seek approval for the proposed indication of the
`treatment of patients with advanced renal cell carcinoma.
`2 MATERIAL REVIEWED
` Draft Inlyta (axitinib) tablets for oral administration Patient Package Insert
`received April 14, 2011, and revised by the review division throughout the current
`review cycle and received by DMPP on December 20, 2011.
` Draft Inlyta (axitinib) tablets for oral administration Prescribing Information (PI)
`received April 14, 2011, and revised by the review division throughout the current
`review cycle and received by DMPP on December 20, 2011.
`
`
`3 REVIEW METHODS
`To enhance patient comprehension, materials should be written at a 6th to 8th grade
`reading level, and have a reading ease score of at least 60%. A reading ease score of
`60% corresponds to an 8th grade reading level. In our review of the PPI the target
`reading level is at or below an 8th grade level.
`
`
`
`Additionally, in 2008 the American Society of Consultant Pharmacists Foundation
`(ASCP) in collaboration with the American Foundation for the Blind (AFB)
`published Guidelines for Prescription Labeling and Consumer Medication
`Information for People with Vision Loss. The ASCP and AFB recommended using
`fonts such as Verdana, Arial or APHont to make medical information more
`accessible for patients with vision loss. We have reformatted the PPI document
`using the Verdana font, size 11.
`In our review of the PPI we have:
`
`simplified wording and clarified concepts where possible
`
`ensured that the PPI is consistent with the prescribing information (PI)
`
`removed unnecessary or redundant information
`
`ensured that the PPI, meets the criteria as specified in FDA’s Guidance for
`Useful Written Consumer Medication Information (published July 2006)
`
`
`4 CONCLUSIONS
`The PPI is acceptable with our recommended changes.
`
`
`
`
`
`Reference ID: 3066041
`
`
`
`

`

`
`5 RECOMMENDATIONS
` Please send these comments to the Applicant and copy DMPP on the
`correspondence.
` Our annotated versions of the PPI are appended to this memo. Consult DMPP
`regarding any additional revisions made to the PI to determine if corresponding
`revisions need to be made to the PPI.
`
`
`Please let us know if you have any questions.
`
`
`
`
`
`Reference ID: 3066041
`
`
`
`13 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following
`this page
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`LATONIA M FORD
`01/03/2012
`
`BARBARA A FULLER
`01/03/2012
`
`LASHAWN M GRIFFITHS
`01/03/2012
`
`Reference ID: 3066041
`
`

`

`FOOD AND DRUG ADMINISTRATION
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`Division of Professional Promotion
`
`****Pre-decisional Agency Information****
`
`
`
`
`
`Memorandum
`
`Date:
`December 21, 2011
`
`
`To:
`
`
`CC:
`
`
`
`From:
`
`
`
`Subject:
`
`Lisa Skarupa, RPM, DOP1
`
` Karen Rulli, Professional Review Group II Leader, OPDP
` Amy Toscano, DTC Review Group IV Leader, OPDP
` Michelle Safarik, Regulatory Review Officer
`
` Marybeth Toscano, Regulatory Reviewer Officer
` Office of Prescription Drug Promotion (OPDP)
` Division of Professional Promotion (DPP)
`
`Comments on draft labeling (Package Insert) for axitinib tablets for
`oral administration, NDA 202324
`
`
`
`
`
`In response to your consult request dated April 25, 2011, we have reviewed the
`draft version of the Package Insert for axitinib tablets. OPDP’s comments have
`been addressed during labeling meetings. We have no additional comments on
`the proposed draft version of the PI.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 3061820
`
`1
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`MARYBETH TOSCANO
`12/21/2011
`
`Reference ID: 3061820
`
`

`

`
`
`M E M O R A N D U M DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`PUBLIC HEALTH SERVICE
`
`FOOD AND DRUG ADMINISTRATION
`
`CENTER FOR DRUG EVALUATION AND RESEARCH
`____________________________________________________________________________
`
`
`
`CLINICAL INSPECTION SUMMARY
`
`
`DATE: December 20, 2011
`
`TO:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Amy McKee, Reviewing Medical Officer
`John Johnson, Clinical Team Leader
`Lisa Skarupa, RHPM
`Division of Oncology Products I
`
`Robert Young
`Good Clinical Practice Assessment Branch
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigations
`
`FROM:
`
`
`
`
`
`
`
`THROUGH:
`
`
`
`
`
`
`
`
`Susan Leibenhaut, M.D.
`Acting Team Leader, Good Clinical Practice Assessment Branch
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigations
`
`Tejashri Purohit-Sheth, M.D.
`Acting Division Director
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigations
`
`Evaluation of Clinical Inspections
`
`
`
`
`
`
`
`
`THROUGH:
`
`
`
`
`SUBJECT:
`
`NDA: 202324
`APPLICANT:
`Pfizer Inc.
`10646 Science Center Drive
`San Diego, CA 92121
`
`
`
`axitinib (Inlyta)
`
`DRUG:
`
`
`
`Yes
`NME:
`THERAPEUTIC CLASSIFICATION:
`standard
`
`INDICATION:
`
`CONSULTATION REQUEST DATE:
`DIVISION ACTION GOAL DATE:
`PDUFA DATE:
`
`treatment of advanced renal cell carcinoma
`
`17 May 2011
`14 Feb 2012
`14 Feb 2012
`
`
`
`
`Reference ID: 3061300
`
`

`

`Clinical Inspection Summary
`
`Page 2
` NDA 202324 axitinib (Inlyta)
`
`
`
`
`BACKGROUND:
`
`
`
`
`
`
`
`Pfizer, Inc. submitted this application for the use of axitinib as second line treatment of
`metastatic renal cell carcinoma (RCC). About 80% of renal cell carcinomas are clear cell RCC
`and frequently have an allelic loss on chromosome 3p or mutational inactivation of the von
`Hippel-Lindau tumor suppression gene. The latter is characterized by vascularity of and the
`production of high levels of vascular endothelial growth factor (VEGF) by the tumor. Axitinib
`is a potent selective tyrosine kinase inhibitor of several VEGF receptors.
`
`The adequate and well controlled study supporting this application was Protocol A4061032
`entitled " Axitinib [AG-013736] as Second-Line Therapy for Metastatic Renal Cell Cancer:
`Axis Trial”, a randomized, open label, multicenter study of axitinib starting at 5 mg twice daily
`v sorafenib starting at a dose of 400 mg twice daily in subjects that had failed one prior first
`line drug: sunitinib, bevacizumab plus IFN-alpha, temsirolimus or cytokines(s). The study
`continued until disease progression, intolerable toxicity or patient withdrawal. Disease status
`was followed first at 6 week intervals and then at 8 week intervals by tumor imaging.
`
`
`The adverse reactions reported in the proposed package insert include: hypertension, thyroid
`dysfunction, arterial thromboembolic events, venous thromboembolic events, elevation of
`hemoglobin or hematocrit, hemorrhage, gastrointestinal perforation, wound healing
`complications, RPLS, proteinuria, elevation of liver enzymes, and animal abnormal fetal
`development.
`
`The study was conducted at 175 sites in 22 countries and 723 subjects were randomized. Only
`a quarter of the subjects were from the US. Four clinical investigator sites, two foreign and two
`domestic were selected for inspection based on high enrollment.
`
`I.
`
`
`
`
`
`
`
`Reference ID: 3061300
`
`

`

`Clinical Inspection Summary
`
`Page 3
` NDA 202324 axitinib (Inlyta)
`
`
`
`
`
`
`II.
`
`RESULTS (by Site):
`
`
`Name of CI
`
`Protocol
`and # of
`Subjects
`A4061032/
`19
`
`Inspection Date
`
`October 3-7, 2011
`
`Final
`Classification
`
`Pending
`(Preliminary
`classification
`VAI)
`
`A4061032/
`22
`
`October 10-14, 2011
`
`NAI
`
`A4061032/
`15
`
`A4061032/
`15
`
`September 13-19, 2011
`
`NAI
`
`August 3-10, 2011
`
`NAI
`
`Bernard Escudier
`Institut Gustave Roussy
`Service d'Immunotherapie
`39 53 rue Camille
`Desmoulins
`VILLEJUIF CEDEX
`94805 FRANCE
`Sergey A. Ivanov
`(Note: Original Investigator
`at site was Andrey Kaprin)
`Radiology Department
`86 Profsoyusnaya str.
`Moscow 117997
`RUSSIAN FEDERATION
`
`Robert John Motzer
`Memorial Sloan-Kettering
`Cancer Center
`1275 York Avenue
`New York, NY 10065
`Marc Dror Michaelson
`Massachusetts General
`Hospital Cancer Center
`55 Fruit Street
`Boston, MA 02114
`Key to Classifications
`NAI = No deviation from regulations.
`VAI = Deviation(s) from regulations.
`OAI = Significant deviations from regulations.
`Pending = Preliminary classification based on information in 483 or preliminary
`communication with the field; EIR has not been received from the field, and complete
`review of EIR is pending.
`
`
`1. Bernard Escudier
`
`Institut Gustave Roussy, Service d'Immunotherapie, 39 53 rue Camille Desmoulins
` VILLEJUIF CEDEX, 94805 FRANCE
`
`Note: Observations noted are based on a preliminary review of the Establishment Inspection
`Report (EIR); an inspection summary addendum will be generated if conclusions
`change upon full review of the EIR.
`
`
`
`Reference ID: 3061300
`
`

`

`Clinical Inspection Summary
`
`Page 4
` NDA 202324 axitinib (Inlyta)
`
`
`
`
`
`
`a. What was inspected: At this site 29 subjects were screened and 19 were
`enrolled into the study. The case histories of 15 enrolled subjects were
`reviewed. Visits were made to the radiology department and pharmacy.
`
`
`b. General observations/commentary: The records appeared to be in good order.
`Based on preliminary information, the study appears to have been conducted
`adequately, except that nine subjects failed to sign an addendum to the informed
`consent form that updated information on side effects of the test article. This
`observation was the subject of a Form FDA 483 issued to the clinical
`investigator.
`
`
`
`c. Assessment of data integrity: The data generated at this site appears to be
`acceptable/reliable in support of the pending application. The major objectionable
`finding relates to the documentation of updated consent and not to data integrity.
`
`
`
`2. Sergey Ivanov
` Radiology Department, 86 Profsoyusnaya str.
` Moscow 117997, RUSSIAN FEDERATION
`
`a. What was inspected: At this site 25 subjects were screened, and of which 22
`subjects were entered into the trial. The case histories of ten subjects were
`reviewed.
`
`
`b. General observations/commentary: There was no evidence of under reporting
`of adverse events. No significant regulatory violations were found and a Form
`FDA 483 was not issued.
`
`
`c. Assessment of data integrity: The data generated at this site appears to be
`acceptable/reliable in support of the pending application.
`
`
`
`3. Robert Motzer
` Memorial Sloan-Kettering Cancer Center, 1275 York Avenue
`New York, NY 10065
`
`a. What was inspected: A total of 22 subjects were screened and of which 15
`were entered into the study. The case histories of ten subjects were reviewed.
`
`
`b. General observations/commentary: There was no evidence of under reporting
`of adverse events. No significant regulatory violations were found and a Form
`FDA 483 was not issued.
`
`
`c. Assessment of data integrity: The data generated at this site appears to be
`acceptable/reliable in support of the pending application.
`
`
`
`Reference ID: 3061300
`
`

`

`Clinical Inspection Summary
`
`Page 5
` NDA 202324 axitinib (Inlyta)
`
`
`
`
`
`
`
`4. Marc Mitchaelson
` Massachusetts General Hospital Cancer Center, 55 Fruit Street
` Boston, MA 02114
`
`
`a. What was inspected: At this site 15 subjects were screened, and of that
`number 14 were entered into the study.
`
`
`b. General observations/commentary: No significant regulatory violations were
`found and a Form FDA 483 was not issued.
`
`
`c. Assessment of data integrity: The data generated at this site appears to be
`acceptable/reliable in support of the pending application.
`
`
`
`IV. OVERALL ASSESSMENT OF FINDINGS AND RECOMMENDATIONS
`
`
`A total of four clinical sites were inspected for this application. For the clinical sites of
`Drs. Ivanov, Motzer, and Michaelson, there were no violations noted. For Dr. Escudier’s
`site, the violations did not impact data integrity and the observations noted are based on a
`preliminary review of the EIR.
`
`There were no significant regulatory findings relating to data integrity from any of the four
`sites inspected. The data may be used in the evaluation of this application. An inspection
`summary addendum will be generated if conclusions change upon full review of the EIR
`for Dr. Escudier’s site.
`
`
`
`CONCURRENCE:
`
`
`
`
`Reference ID: 3061300
`
`{See appended electronic signature page}
`
`Robert Young
`Good Clinical Practice Assessment Branch
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigations
`
`
`{See appended electronic signature page}
`
`Susan Leibenhaut, M.D.
`Acting Team Leader
`Good Clinical Practice Assessment Branch
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigations
`
`{See appended electronic signature page}
`
`

`

`Clinical Inspection Summary
`
`Page 6
` NDA 202324 axitinib (Inlyta)
`
`
`
`
`
`
` Tejashri Purohit-Sheth, M.D.
`Acting Division Director
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigations
`
`
`
`
`
`
`Reference ID: 3061300
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ROBERT S K YOUNG
`12/20/2011
`
`SUSAN LEIBENHAUT
`12/20/2011
`
`TEJASHRI S PUROHIT-SHETH
`12/20/2011
`
`Reference ID: 3061300
`
`

`

`
`
`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Surveillance and Epidemiology
`Office of Medication Error Prevention and Risk Management
`
`Label and Labeling Review
`
`Date
`
`November 8, 2011
`
`Denise V. Baugh, PharmD, BCPS
`Reviewer
`
`Division of Medication Error Prevention and Analysis
`Lubna Merchant, PharmD, M.S.
`Team Leader
`Division of Medication Error Prevention and Analysis
`
`Carol Holquist, R.Ph.
`Division Director
`Division of Medication Error Prevention and Analysis
`
`Inlyta (Axitinib) Tablets, 1 mg and 5 mg
`Drug Name and Strengths
`Application Type/Number NDA 202324
`Applicant
`Pfizer, Inc.
`OSE RCM #
`2011-1316
`*** This document contains proprietary and confidential information that should not be
`released to the public.***
`
`
`
`
`
`
`Reference ID: 3041380
`
`

`

`1
`
`INTRODUCTION
`
`(5x4) and insert labeling for Inlyta (Axitinib)
`This review evaluates the container labels
`Tablets for areas of vulnerability that could lead to medication errors.
`
`1.1
`
`REGULATORY HISTORY
`
`Axith is the established name for the proposed proprietary name, Inlyta, which was
`found acceptable by DMEPA (OSE Review # 201 1—1314 dated July 7, 201 1).
`
`1.2
`
`PRODUCT INFORMATION
`
`Inlyta (axitinib) tablets is a tyrosine kinase inhibitor which will be indicated for the
`treatment of metastatic renal cell carcinoma afier disease progression on prior systemic
`therapy. The product will be available in 1 mg and 5 mg tablets. The intended starting
`dose for Inlyta will be 5 mg (one tablet) taken orally twice a day. The dose may be
`adjusted upward based on patient tolerance or downward based upon adverse drug effects
`to Inlyta. The other possible doses of Inlyta include 2 mg (2 x 1 mg tablets), 3 mg (3 x 1
`mg tablets), 7 mg (2 x 1 mg and l x 5 mg tablets) or 10 mg (2 x 5 mg tablets) taken
`twice daily. Inlyta will be available in bottles containing 60 or 180 tablets which will be
`stored at room temperature
`M"
`
`2
`
`METHODS AND MATERIALS REVIEWED
`
`Using Failure Mode and Effects Analysis1 and postmarketing medication error data, the
`Division of Medication Error Prevention and Analysis (DMEPA) evaluated the
`following:
`
`0 Container Labels submitted April 14, 2011 (see Appendix A)
`(m4)
`
`0
`
`Insert Labeling submitted April 14, 2011 (no image)
`
`(m4)
`
`3
`
`RESULTS AND DISCUSSION
`
`The following sections describe DMEPA’s evaluation of the proposed labels and labeling
`for Inlyta.
`
`3.1 GENERAL COMMENT
`
`(am) and cites USP
`The storage temperature is stated as
`Controlled Room Temperature to support this statement. However, this temperature
`statement is not consistent with the definition of Controlled Room Temperature per USP.
`
`1 Institute for Healthcare Improvement (IHI). Failure Modes and Effects Analysis. Boston. 1111:2004.
`
`Reference ID: 3041 380
`
`

`

`3.2 CONTAINER LABEL
`A. Although the established name is at least half the size of the proprietary name, the
`
`proprietary name is presented in thick, black font whereas the established name is
`
`presented in thin black font and lacks prominence.
`
`B. The dosage form, ‘tablets’ appears after the statement of strength which is not the
`
`traditional sequence for identifying drug products.
`
`
`
`
`
`
`
`
`
`C. The logo, ‘Pfizer’ is presented in the same color scheme as the statement of
`
`strength and is located just above the proprietary name giving it more prominence
`
`than the important information used to identify the drug product.
`
`D. The proprietary name is presented in upper case letters making this information
`
`difficult to read.
`
`E. There is a blue banner containing the manufacturer’s name which is located
`
`vertically across the container labels for both strengths. This presentation
` minimizes the impact of the color differentiation between the strengths and makes
`
`the container labels appear similar. This presentation may contribute to selection
`
`errors.
`
`4
`CONCLUSIONS AND RECOMMENDATIONS
` introduce
`DMEPA concludes that the proposed container label
`vulnerability that can lead to medication errors. We recommend the following:
`
`A. GENERAL COMMENTS
` on the label and labeling to read “Store
`Revise the statement,
`at 20°C to 25°C (68°F to 77°F)” to be in accordance with the USP definition of
`Controlled Room Temperature (see USP 10.30.60 Controlled Room Temperature).
`
`B. CONTAINER LABELS (1 MG AND 5 MG)
`1. We acknowledge that the established name is at least half as large as the
`proprietary name, however, in accordance with 21 CFR 201.10(g)(2), the
`presentation of the established name should also “ . . . have a prominence
`commensurate with the prominence with which such proprietary name or
`designation appears, taking into account all pertinent factors, including
`typography, layout, contrast and other printing features”. Therefore, we
`request you revise the established name accordingly.
`
`
`2. The established name includes the active ingredient and the finished
`dosage form. We request you relocate the dosage form, ‘tablets’, to
`appear after axitinib.
`
`
`
`
`
`
`
`Reference ID: 3041380
`
`2
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`
`
`
`
`
`
`3. Relocate the logo, ‘Pfizer’ which appears above the proprietary name, to
`the lower third of the label/labeling. Additionally, remove the name from
`the color block.
`
`
`4. The proprietary name is presented in upper case letters (INLYTA). To
`increase its readability, revise the proprietary name so that it is presented
`in title case (Inlyta).
`
`5. Increase the prominence of the four middle numbers in the NDC number
`as this information is how the pharmacist identifies the correct strength for
`drug products. For example, NDC 0069-0151-11 should be revised to
`read 0069-0151-11 for the 5 mg strength.
`
`
`6. The blue banner containing the manufacturer name and logo that appears
`vertically across both the 1 mg and 5 mg labels minimizes the impact of
`the color differentiation between the strengths. To avoid selection errors,
`remove this banner.
`
`7. Relocate the ‘Rx only’ statement to the bottom of the principal display
`panel.
`
`
`
`
`
`Reference ID: 3041380
`
`3
`
`3 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following
`this page
`
`(b) (4)
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`DENISE V BAUGH
`11/08/2011
`
`LUBNA A MERCHANT
`11/08/2011
`
`CAROL A HOLQUIST
`11/08/2011
`
`Reference ID: 3041380
`
`

`

`
`
`NDA
`Generic Name
`Sponsor
`Indication
`Dosage Form
`Drug Class
`
`Interdisciplinary Review Team for QT Studies Consultation:
`Thorough QT Study Review
`202324
`AG-013736 (Axitinib)
`Pfizer Inc.
`Advanced Renal Cell Carcinoma (RCC)
`Tablets
`Kinase inhibitor of VEGF (vascular endothelial
`growth factor) receptors 1, 2, and 3
`5 mg b.i.d.
`Chronic
`Not established
`SDN 001