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MEMORANDUM REVIEW OF REVISED LABEL AND LABELING

Division of Medication Error Prevention and Analysis (DMEPA) Office of Medication Error Prevention and Risk Management (OMEPRM)

Office of Surveillance and Epidemiology (OSE) Center for Drug Evaluation and Research (CDER)

Date of This Memorandum: February 28, 2018

Requesting Office or Division: Division of Anesthesia, Analgesia, and Addiction Products (DAAAP)

Application Type and Number: NDA 207962

Product Name and Strength: Ztlido (lidocaine topical system), 1.8%

Applicant/Sponsor Name: Scilex Pharmaceuticals, Inc.

FDA Received Date: February 28, 2018

OSE RCM #: 2017-1869-2

DMEPA Safety Evaluator: Millie Shah, PharmD, BCPS

DMEPA Team Leader: Otto L. Townsend, PharmD

1 PURPOSE OF MEMORANDUM The Division of Anesthesia, Analgesia, and Addiction Products (DAAAP) requested that we review the revised container label and carton labeling for Ztlido (lidocaine topical system) (Appendix A) to determine if they are acceptable from a medication error perspective. The revisions are in response to recommendations that we made during a previous label and labeling review.a

2 CONCLUSION The revised container labeling and carton labeling for Ztlido are acceptable from a medication error perspective. We have no further recommendations at this time.

3 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page

a Shah M. Label and Labeling Review for Ztlido (NDA 207962). Silver Spring (MD): FDA, CDER, OSE, DMEPA (US); 2018 JAN 29. RCM No.: 2017-1869-1.

1

Reference ID: 4227924

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This is a representation of an electronic record that was signedelectronically and this page is the manifestation of the electronicsignature.

/s/

MILLIE C BRAHMBHATT 02/28/2018

OTTO L TOWNSEND 02/28/2018


Department of Health and Human ServicesPublic Health Service

Food and Drug AdministrationCenter for Drug Evaluation and Research

Office of Medical Policy

PATIENT LABELING REVIEW

Date: February 12, 2018

To: Sharon Hertz, MD Director Division of Anesthesia, Analgesia, and Addiction Products (DAAAP)

Through: LaShawn Griffiths, MSHS-PH, BSN, RN Associate Director for Patient Labeling Division of Medical Policy Programs (DMPP)

Barbara Fuller, RN, MSN, CWOCN Team Leader, Patient Labeling Division of Medical Policy Programs (DMPP)

From: Morgan Walker, PharmD, MBA, CPH Patient Labeling Reviewer Division of Medical Policy Programs (DMPP) L. Shenee’ Toombs, PharmD Regulatory Review Officer Office of Prescription Drug Promotion (OPDP)

Subject: Review of Patient Labeling: Patient Package Insert (PPI) and Instructions for Use (IFU)

Drug Name (established ZTLIDO (lidocaine topical system)name), Dosage Form and Route:

Application 207962 Type/Number:

Applicant: Scilex Pharmaceuticals Inc.


1 INTRODUCTION On August 28, 2017, Scilex Pharmaceuticals Inc. submitted for the Agency’s review a 505(b)(2) New Drug Application (NDA) 207962 for ZTLIDO (lidocaine topical system) which references NDA 020612 Lidoderm Patch 5%. This application is a Class 2 resubmission in response to an Agency-issued Complete Response (CR) letter sent to the Applicant on May 10, 2016 due to several deficiencies. The proposed indication for ZTLIDO (lidocaine topical system) is for the relief of pain associated with post-herpetic neuralgia.

This collaborative review is written by the Division of Medical Policy Programs (DMPP) and the Office of Prescription Drug Promotion (OPDP) in response to a request by the Division of Anesthesia, Analgesia, and Addiction Products (DAAAP) on January 30, 2018 for DMPP and September 15, 2017 for OPDP to review the Applicant’s proposed Patient Package Insert (PPI) and Instructions for Use (IFU) for ZTLIDO (lidocaine topical system).

2 MATERIAL REVIEWED

x Draft ZTLIDO (lidocaine topical system) PPI and IFU received on August 28, 2017, and received by DMPP on January 30, 2018 and OPDP on January 31, 2018

x Draft ZTLIDO (lidocaine topical system) Prescribing Information (PI) received on August 28, 2017, revised by the Review Division throughout the review cycle, and received by DMPP on January 31, 2018 and OPDP on January 31, 2018

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.

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 reformatted the PPI and IFU document using the Arial font, size 10.

In our collaborative review of the PPI and IFU we:

x simplified wording and clarified concepts where possible

x ensured that the PPI and IFU is consistent with the Prescribing Information (PI)

x removed unnecessary or redundant information

x ensured that the PPI and IFU is free of promotional language or suggested revisions to ensure that it is free of promotional language


x ensured that the PPI and IFU meets the criteria as specified in FDA’s Guidance for Useful Written Consumer Medication Information (published July 2006)

4 CONCLUSIONS The PPI and IFU are acceptable with our recommended changes.

5 RECOMMENDATIONS

x Please send these comments to the Applicant and copy DMPP and OPDP on the correspondence.

x Our collaborative review of the PPI and IFU is appended to this memorandum. Consult DMPP and OPDP regarding any additional revisions made to the PI to determine if corresponding revisions need to be made to the PPI and IFU.

Please let us know if you have any questions.



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/s/

MORGAN A WALKER 02/12/2018

LATOYA S TOOMBS 02/12/2018

BARBARA A FULLER 02/13/2018

LASHAWN M GRIFFITHS 02/13/2018


FOOD AND DRUG ADMINISTRATIONCenter for Drug Evaluation and ResearchOffice of Prescription Drug Promotion

****Pre-decisional Agency Information****

Memorandum Date: February 13, 2018

To: Sepideh Haghpanah, Clinical Reviewer Division of Anesthesia, Analgesia, and Addiction Products (DAAAP)

Allison Meyer, Regulatory Project Manager, (DAAAP)

Lisa Basham, Associate Director for Labeling, (DAAAP)

From: L. Shenee Toombs, Regulatory Review OfficerOffice of Prescription Drug Promotion (OPDP)

CC: Sam Skariah, Team Leader, OPDP

Subject: OPDP labeling comments for ZTlidoTM (lidocaine topical system)

NDA/BLA: NDA 207962

In response to DAAAP’s consult request dated September 15, 2017, OPDP has reviewed the proposed product labeling (PI), patient package insert (PPI)/Instructions for Use and carton and container labeling for the original NDA/BLA submission for ZTlido.

PI and PPI/Medication Guide/IFU: OPDP’s comments on the proposed labeling are based on the draft PI received by electronic mail from DAAAP on January 31, 2018, and are provided below.

A combined OPDP and Division of Medical Policy Programs (DMPP) review will be completed, and comments on the proposed PPI/Medication Guide/IFU will be sent under separate cover.

Carton and Container Labeling: OPDP has reviewed the attached proposed carton and container labeling submitted by the Sponsor to the electronic document room on November 17, 2017, and we have the following comments:

OPDP recommends revising the step by step directions for use included on the carton and container labels/labeling in a manner consistent with the step by step directions included in the instructions for use patient labeling document. For example, revise the labels and labeling to include material information such as, but not limited to, the following: x “ZTLIDO should only be applied to clean, dry, and intact skin to cover the most painful area”


x “Avoid contact of your hands or finger with your eyes until hands are washed.”

Thank you for your consult. If you have any questions, please contact Sheneé Toombs at (301) 796-4174 or [email protected].



mailto:[email protected]

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/s/



________________________________________________________________

________________________________________________________________

M E M O R A N D U M DEPARTMENT OF HEALTH AND HUMAN SERVICES PUBLIC HEALTH SERVICE

FOOD AND DRUG ADMINISTRATIONCENTER FOR DRUG EVALUATION AND RESEARCH

DATE: February 6, 2018

TO: Sharon Hertz, M.D.Director Division of Anesthesia, Analgesia, and AddictionProducts Office of Drug Evaluation II, OND

FROM: Himanshu Gupta, Ph.D.Division of Generic Drug Bioequivalence EvaluationOffice of Study Integrity and Surveillance (OSIS)

THROUGH: John A. Kadavil, Ph.D.Deputy Director (Acting)Division of Generic Drug Bioequivalence EvaluationOffice of Study Integrity and Surveillance (OSIS)

SUBJECT: inspection of (b) (4)

Addendum to the review for the analytical surveillance

Inspection Summary:

(Attachment 2). Our final classification in theoriginal EIR review remains unchanged.

This is an addendum to the EIR review finalized on January 12,2018 for NDA 207962 (Attachment 1). This addendum updates theresponse and review for findings under Form FDA 483 observation2, after the firm provided additional information dated (b) (4)

Observation 2- edited from the original version (b) (4)

Firm’s response:

(b) (4)


Addendum-Review of EIR for (b) (4)

(b) (4)

Conclusion After reviewing the inspectional findings and the firm’s response to observation 2 of Form FDA 483, this reviewer recommends to

(b) (4)accept the data from the lidocaine residual study.

Therefore, the lidocaine residual studydata is acceptable.

(b) (4)

(b) (4)

Final Site Classification: VAI – FEI:

(b) (4)

(b) (4)

cc: OSIS/Kassim/Choe/Haidar/Mitchell/Nkah/Fenty-StewartOSIS/DGDBE/Cho/Kadavil/Choi/Skelly/Au/GuptaOSIS/DNDBE/Bonapace/Dasgupta/Ayala/Biswas

Draft: HG 02/01/2018, 02/05/18, 02/6/18Edit: SA 2/1/2018, 2/6/18; JAK 2/6/2018

ECMS: Cabinets/CDER_OC/OSI/OSIS--Office of Study Integrity andSurveillance/INSPECTIONS/BE Program/ANALYTICAL SITES/ (b) (4)


Addendum-Review of EIR for (b) (4)

/NDA207962_Ztlido Patch, 1.8.% (lidocaine patch, 1.8%-FY 2018

(b) (4)

Inspection

OSI file #: FACTS: (b) (4)

(b) (4)

Himanshu Gupta, Ph.D.Division of Generic Drug Bioequivalence Evaluation

Stanley Au, Pharm.D., BCPSDivision of Generic Drug Bioequivalence Evaluation

John Kadavil, Ph.D.Division of Generic Drug Bioequivalence Evaluation

Attachments: Attachment 1– Initial EIR review Attachment 2- Additional Form FDA 483 response from firm, dated

. (b) (4)

109 Page(s) have been Withheld in Full as b4 (CCI/TS) immediately following this page


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/s/

HIMANSHU GUPTA 02/06/2018

STANLEY AU 02/06/2018 Acting Team Lead

JOHN A KADAVIL 02/06/2018





Date of This Memorandum: January 29, 2018





FDA Received Date: August 28, 2017 and November 17, 2017

OSE RCM #: 2017-1869-1



1 PURPOSE OF MEMO We previously provided recommendations in our label and labeling review for Ztlido (lidocaine topical system).a Our review included a recommendation to add a strength equivalency statement to the principal display panel of the container label and carton labeling to indicate that Ztlido 1.8% provides equivalent lidocaine exposure as Lidoderm 5%, despite the difference in strength. However, since our previous review, we have had internal discussions with the Office of Policy for Pharmaceutical Quality (OPPQ) and DAAAP and determined that a different version of the equivalency statement would better convey this message. Thus, we provide recommendations for Scilex Pharmaceuticals below.

2 CONCLUSION We revised our recommendations regarding the strength equivalency statement for the container label and carton labeling to promote safe use of this product.

a Shah M. Label and Labeling Review for Ztlido (NDA 207962). Silver Spring (MD): FDA, CDER, OSE, DMEPA (US); 2017 DEC 07. RCM No.: 2017-1869.

1


3 RECOMMENDATIONS FOR SCILEX PHARMACEUTICALS, INC. We recommend the Applicant implement the following prior to approval of this NDA:

A. Container Label and Carton Labeling (including Professional Sample) 1. There is risk for medication errors because the strength of Ztlido (1.8%) is lower than

the listed drug, Lidoderm (5%). Thus, users may interpret the lower strength of Ztlido as being less potent than Lidoderm, to which Ztlido provides equivalent lidocaine exposure. Therefore, we recommend you provide further information about this equivalency, by adding an asterisk after the strength statement (1.8%*) and by adding the following statement under the statement “For topical use only” on the principal display panel:

“*One Ztlido (lidocaine topical system) 1.8% provides equivalent lidocaine exposure to one Lidoderm® (lidocaine patch 5%).”

Use the same font size and style for the statement above as the other information presented after the statement “For topical use only.”


2


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/s/




DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service Food and Drug Administration Center for Devices and Radiological Health Office of Compliance, Division of Manufacturing & Quality Physical Medicine, Orthopedic, Neurology, Dental

Date: January 25, 2018

To: Cassandra Abellard, OMPT/CDER/OPQ/OPF/DIA/IABII [email protected]

Julia Pinto, OMPT/CDER/OPQ/ONDP/DNDPII/NDPBIV [email protected]

Office of Combination Products at [email protected]

RPM: Steven Kinsley

Through: Kendra Y. Jones, Lead Consumer Safety Officer, DPLC, OC, CDRH

___________________________________

From: Robert Kang, POND, DMQ, OC, CDRH

Applicant: Scilex Pharmaceuticals, Inc. 301 Linden Drive, Ste 300 Malvern, PA 19355 FEI#: 3012645358

Application # NDA 207962

Consult # ICC1700742

Product Name: ZTlido

Combination Product Intended Use: Relief of pain associated with post-herpetic neuralgia (PHN)

Pre-Approval Inspection: Yes

Documentation Review: No Additional Information Required

1


Final Recommendation: Approvable

The Office of Compliance (OC) at the Center for Devices and Radiological Health (CDRH) received a consult request from CDER to evaluate the applicant’s compliance with applicable Quality System Requirements for the approvability of NDA 207962.

PRODUCT DESCRIPTION The drug product, lidocaine patch, 1.8%, consists of lidocaine drug substance compounded in an anhydrous adhesive patch (NCI Code: C42968) intended for cutaneous route of administration (NCI Code: C38675). The drug product comprises an adhesive material containing 1.8% lidocaine is applied to a nonwoven cloth and covered with a polyethylene terephthalate separator. The release liner is removed prior to application to the skin. The size of the patch is 10 cm x 14 cm. Each adhesive patch contains 36 mg of lidocaine (18 mg per gram adhesive or 1.8%) in an anhydrous base.

REGULATORY HISTORY The following facilities was identified as being involved in the manufacturing and/or development of the ZTlido in NDA 207962:

1. Oishi Koseido Co., Ltd. 2539-1 Yamaura-Machi Tosu, Saga Japan FEI# 3010166685

Responsibility – Drug product manufacture; Drug product QC release and testing; Drug product stability testing; Packaging

Inspectional History – An analysis of the firm’s inspection history over the past 2 years showed that an initial inspection was conducted from 01/25/2016 to 01/29/2016. The inspection covered drug GMP and was classified OAI.

Inspection Recommendation: An inspection is required because: x The firm is responsible for major activities related to the manufacturing and/or

development of the final combination involving the device constituent part; and, x A recent medical device inspection of the firm has not been performed.

2. Scilex Pharmaceuticals, Inc. 301 Lindenwood Drive, Ste 300 Malvern PA 19355-1774 FEI# 3012645358

2


Responsibility – Drug product applicant/ specification developer

Inspectional History – An analysis of the firm’s inspection history over the past 2 years showed it has never been inspected.

Inspection Recommendation: An inspection is not required because: x The firm is not responsible for major activities related to the manufacturing and/or

development of the final combination. The firm is the licensed initial importer of the combination product, but does not perform any manufacturing activities.

DOCUMENTATION REVIEW The application was searched for documents pertaining to applicable 21 CFR part 820 regulations for this combination product.

(b) (4)

7 Page(s) have been Withheld in Full as b4 (CCI/TS) immediately following this page3


(b) (4)

RECOMMENDATION

The Office of Compliance at CDRH has completed the evaluation of application NDA207962 and has the following recommendations:

Application NDA207962 is approvable from the perspective of the Medical Device Regulations.

Pre-approval inspections were conducted at two facilities noted below and both were classified NAI with no 483 observations. The inspection report indicated that the Quality System was covered and no deficiencies identified. The areas covered included Product Specifications and Testing, Annual Product Review,

included CAPA. However, it did not specifically discuss Change Control, and Deviations/Investigations (Non-Conformances) which

(b) (4)

11


(b) (4)

(b) (4). It is recommended that the next scheduled inspection (pre or post) cover for medical devices.

In addition, the report indicated that process validation (PV) was not completed at the time of the inspection although a draft PV protocol was available for review. The decision for approval in light of an incomplete PV report is deferred to CDER.

Facilities Inspected: a. Combination Product Contract ManufacturerOishi Koseido Co., Ltd.2539-1 Yamaura-MachiTosu, Saga, JapanFEI: 3010166685

b. Quality Control Testing Laboratory1 Chrome 933 Hon-MachiTosu, Saga, JapanFEI: 3006786747

__________________________

12


Prepared: RKang: 10/5/17; 11/6/17 Reviewed: KJones: 10/25/17 IR Response Review: RKang: 1/25/18

CTS No.: ICC1700742 NDA 207962

Review Cycle Meeting Attendance: Month/Day/Year Month/Day/Year Month/Day/Year


13

Inspectional Guidance

CDRH recommends a preapproval inspection under the applicable Medical Device Regulations of Oishi Koseido Co., Ltd. 2539-1 Yamaura-Machi FEI: 3010166685

A comprehensive baseline Level 2 inspection is recommended focusing on Management Responsibility (21 CFR 820.20), Purchasing Controls (21 CFR 820.50), CAPA (21 CFR 820.100), Final Acceptance Activities (21 CFR 820.80), and Design Controls (21 CFR 820.30)

Additionally, evaluate the manufacturing activities associated with the manufacturing/assembly of the finished combination product, including in process and final acceptance activities.

REGULATORY STRATEGY The establishment inspection report (EIR) for the firm should be shared with CDRH (The EIR should be assigned to CDER and then sent to CDRH as a consult for review). If the inspection is being classified Official Action Indicated (OAI), the District should consider recommending appropriate regulatory action with consultation from CDER and CDRH and whether the violation is drug or device related.

Questions regarding this consult should be referred to one of the following individuals: Primary Contact Robert Kang, Compliance Officer POND/DMQ/OC/CDRH Office of Compliance, WO66 RM 3432 Phone: 301-796-6614

Secondary Contacts (if Primary is unavailable and a timely answer is required) Kendra Y. Jones DPLC/OC/CDRH Office of Compliance, WO66 RM 3631 Phone: 301-796-3917

THIS ATTACHMENT IS NOT TO BE PROVIDED TO THE FIRM OR SHOWN TO THEM DURING THE INSPECTION. THIS ATTACHMENT CONTAINS PREDECISIONAL INFORMATION

14


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/s/

STEVEN A KINSLEY 01/26/2018


________________________________________________________________

________________________________________________________________



DATE: January 12, 2018

TO: Sharon Hertz, M.D.Director Division of Anesthesia, Analgesia, and AddictionProducts Office of Drug Evaluation II, OND

FROM: Himanshu Gupta, Ph.D.Division of Generic Drug Bioequivalence EvaluationOffice of Study Integrity and Surveillance (OSIS)

THROUGH: John Kadavil, Ph.D.Deputy Director (Acting)Division of Generic Drug Bioequivalence EvaluationOffice of Study Integrity and Surveillance (OSIS)

SUBJECT: Surveillance inspection of (b) (4)

Inspection Summary: The Office of Study Integrity and Surveillance (OSIS) conducted

from .

(b) (4) (b) (4)

an inspection of study SCI-LIDO-PK-002A to support NDA 207962 at

Form FDA 483 was issued at the inspection close-out. The finalinspection classification is Voluntary Action Indicated (VAI).

Significant objectionable conditions were observed during thisinspection that impacted the reliability of a portion of theaudited studies. OSIS recommendations regarding the inspectionfindings are detailed in the conclusion section below.

Inspected Study NDA 207962 Study/Project #:Study Title:

SCI-LIDO-PK-002A Phase 1, Randomized ComparativePharmacokinetic Study of Lidocaine Patch


Review of EIR for (b) (4)

1.8% (ZTlido™) and Lidocaine Patch 5%(Lidoderm®) in Healthy Subjects

Sample Analysis date: Oct-Nov 2016

Analytical site : (b) (4)

From , CDER-OSIS reviewer Himanshu Gupta audited analytical data for lidocaine samples under study SCILIDO-PK-002A at

. The inspection included reviewing records relevant to the audited study, equipment calibration and maintenance, SOPs,

(b) (4)

(b) (4)

and sample tracking as well as data verification against source records.

There were four Form FDA 483 observations (Attachment 1) issuedat the closeout. OSIS received the email response to Form FDA

FDA 483 observations:

Observation 1 - edited from the original version

483 from on (Attachment 2). (b) (4) (b) (4)

(b) (4)

Firm’s response: (b) (4)



Review of EIR for (b) (4)

Conclusion Significant objectionable conditions were observed during thisinspection and Form FDA 483 was issued. The final inspectionclassification is Voluntary Action Indicated (VAI).

After reviewing the inspectional findings and the firm’s response to Form FDA 483, this reviewer recommends the following:

1. Accepting the data from SCI-LIDO-PK-002A

.

(b) (4)

2. Not accepting the data from the lidocaine residual study,

Final Site Classification:

3.

.

(b) (4)

(b) (4)

VAI – FEI:

(b) (4)

(b) (4)

cc: OSIS/Kassim/Choe/Haidar/Nkah/Fenty-Stewart/KadavilOSIS/DGDBE/Cho/Choi/Skelly/Au/GuptaOSIS/DNDBE/Bonapace/Dasgupta/Ayala/Biswas

Draft: HG 01/05/18, 01/10/18, 01/12/18Edit: SA 01/05/18 01/12/18; JAK 1/12/18

Inspection

OSI file #: FACTS: (b) (4)

(b) (4)

ECMS: Cabinets/CDER_OC/OSI/OSIS--Office of Study Integrity andSurveillance/INSPECTIONS/BE Program/ANALYTICAL SITES/

/NDA207962_Ztlido Patch, 1.8.% (lidocaine patch, 1.8%-FY 2018

(b) (4)


Review of (b) (4)

Himanshu Gupta, Ph.D.Division of Generic Drug Bioequivalence Evaluation

Stanley Au, Pharm.D., BCPSDivision of Generic Drug Bioequivalence Evaluation

John Kadavil, Ph.D.Division of Generic Drug Bioequivalence Evaluation

Attachments: Attachment 1– Form FDA 483 Attachment 2- Form FDA 483 response from firm, dated

Attachment 3- Protocol amendment and report amendment for REP0496

(b) (4)



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/s/

HIMANSHU GUPTA 01/12/2018

STANLEY AU 01/12/2018 Acting Team Lead

JOHN A KADAVIL 01/12/2018


LABEL AND LABELING REVIEW Division of Medication Error Prevention and Analysis (DMEPA)

Office of Medication Error Prevention and Risk Management (OMEPRM) Office of Surveillance and Epidemiology (OSE)

Center for Drug Evaluation and Research (CDER)

*** This document contains proprietary information that cannot be released to the public***

Date of This Review: December 7, 2017




Product Type: Single ingredient combination product

Rx or OTC: Rx


Submission Date: August 28, 2017 and November 17, 2017

OSE RCM #: 2017-1869



1


1 REASON FOR REVIEW

This review provides our evaluation of the proposed labels and labeling for Ztlido (lidocaine topical system) 1.8% from a medication error perspective. The Division of Anesthesia, Analgesia, and Addiction Products (DAAAP) requested this review as part of their evaluation of the 505(b)(2) NDA submission for Ztlido.

2 MATERIALS REVIEWED

We considered the materials listed in Table 1 for this review. The Appendices provide the methods and results for each material reviewed.

Table 1. Materials Considered for this Label and Labeling Review

Material Reviewed Appendix Section (for Methods and Results)

Product Information/Prescribing Information A

Previous DMEPA Reviews B

Human Factors Study C-N/A

ISMP Newsletters D-N/A

FDA Adverse Event Reporting System (FAERS)* E-N/A

Other F-N/A

Labels and Labeling G

N/A=not applicable for this review *We do not typically search FAERS for our label and labeling reviews unless we are aware of medication errors through our routine postmarket safety surveillance

3 OVERALL ASSESSMENT OF THE MATERIALS REVIEWED

We performed a risk assessment of the proposed container labels, carton labeling, and prescribing information to identify deficiencies that may lead to medication errors and to identify other areas that can be improved.

Container Label and Carton Labeling

Our review of the container label and carton labeling determined that there may be risk of confusion due to the strength of Ztlido (1.8%) being lower than the strength of the listed drug, Lidoderm (5%), to which Ztlido is bioequivalent. Due to differences in formulations, Ztlido 1.8% has the same therapeutic effect as Lidoderm 5%. The concern is that users may interpret the lower strength of Ztlido to be less potent than Lidoderm, which may lead to medication errors. We concur with the Office of Pharmaceutical Quality (OPQ) that a labeling statement is necessary to convey that Ztlido is equivalent to topical systems that contain lidocaine 5%. Therefore, we recommend the Applicant add the following statement in large, red font immediately after the strength statement on the container label and carton labeling: “*Equivalent to other topical systems containing 5% lidocaine.”

2


Our review of the prescribing information identified the statement, “ ” under the Dosage Forms and Strengths section. This statement may lead to

(b) (4)

We do not have recommendations to the patient instructions on the carton labeling at this time; however, if the Patient Labeling Team (PLT) makes changes to the patient instructions, we recommend those changes be implemented on the carton label for consistency and to minimize the risk for confusion.

Prescribing Information

confusion because the strength is 1.8%. Thus, we recommend

(b) (4)

removing this statement to minimize the risk for confusion.

To minimize the risk for medication errors due to the lower strength of Ztlido compared to the listed drug, Lidoderm, and appearing less potent, we recommend adding the statement, “One Ztlido (lidocaine topical system) 1.8% provides equivalent lidocaine exposure to one Lidoderm® (lidocaine patch 5%)” to the Dosage and Administration section of the Highlights of Prescribing Information. Additionally, we recommend relocating the statement, “Because of the difference in bioavailability of ZTlido compared to Lidoderm® (lidocaine patch 5%), a different dosage strength is required to be administered to the patient. One ZTlido (lidocaine topical system) 1.8% provides equivalent lidocaine exposure to one Lidoderm® (lidocaine patch 5%).” from its current location at the end of the Dosage and Administration section of the Full Prescribing Information to a more prominent location at the beginning of the Dosage and Administration section.

4 CONCLUSION & RECOMMENDATIONS

We identified areas in the proposed container label, carton labeling, and prescribing information that can be improved to promote the safe use of this product.

If you have further questions or need clarifications, please contact Davis Mathew, OSE Project Manager, at 240-402-4559.

4.1 RECOMMENDATIONS FOR THE DIVISION

We provide recommendations below for review and consideration by DAAAP.

A. Highlights of Prescribing and Full Prescribing Information 1. We recommend removing the statement, “

under the Dosage Forms and Strengths section. This statement may lead to ” (b) (4)

confusion because the strength is 1.8%. (b) (4)

2. We recommend adding the statement, “One Ztlido (lidocaine topical system) 1.8% provides equivalent lidocaine exposure to one Lidoderm® (lidocaine patch 5%)” to the Dosage and Administration section of the Highlights of Prescribing Information to minimize the risk for medication errors due to the lower strength of Ztlido compared to the listed drug, Lidoderm, and appearing less potent.

3


3. We recommend relocating the statement, “Because of the difference in bioavailability of ZTlido compared to Lidoderm® (lidocaine patch 5%), a different dosage strength is required to be administered to the patient. One ZTlido (lidocaine topical system) 1.8% provides equivalent lidocaine exposure to one Lidoderm® (lidocaine patch 5%).” from its current location at the end of the Dosage and Administration section of the Full Prescribing Information to a more prominent location at the beginning of the Dosage and Administration section.

4.2 RECOMMENDATIONS FOR SCILEX PHARMACEUTICALS, INC.

A. Container Label and Carton Labeling (including Professional Sample) 1. There is risk for medication errors because the strength of Ztlido (1.8%) is lower than

the listed drug, Lidoderm (5%). Thus, users may interpret the lower strength of Ztlido as being less potent than Lidoderm, to which Ztlido is bioequivalent. Therefore, we recommend you add the following statement in large, red font immediately following the strength statement: ZTlido (lidocaine topical system) 1.8%* *Equivalent to other topical systems containing 5% lidocaine

4


APPENDICES: METHODS & RESULTS FOR EACH MATERIALS REVIEWED

APPENDIX A. PRODUCT INFORMATION/PRESCRIBING INFORMATION

Table 2 presents relevant product information for Ztlido that Scilex Pharmaceuticals submitted on August 28, 2017 and November 17, 2017, and the listed drug (LD).

Table 2. Relevant Product Information for Ztlido and the Listed Drug

Product Name Ztlido Lidoderm

Initial Approval Date N/A March 19, 1999

Active Ingredient Lidocaine lidocaine

Indication relief of pain associated with relief of pain associated with post-herpetic neuralgia post-herpetic neuralgia

Route of Topical Topical Administration Dosage Form Topical system Patch

Strength 1.8% 5%

Dose and Frequency Apply the prescribed number of Apply the prescribed number patches (up to three) only once of patches (maximum of 3), for up to 12 hours in a 24-hour only once for up to 12 hours period within a 24 hour period

How Supplied/ Carton of 30 patches, packaged Carton of 30 patches, Container Closure into individual child-resistant packaged into individual child-

resistant envelopes

Store at 25°C (77°F); excursionsStorage permitted to 15°-30°C (59°86°F). [See USP Controlled Room Temperature].

envelopes. (b) (4)

Store at 25°C (77°F); excursions permitted to 15°30°C (59°-86°F). [See USP Controlled Room Temperature].

5


APPENDIX B. PREVIOUS DMEPA REVIEWS

On November 3, 2017, we searched DMEPA’s previous reviews using the term, Ztlido. Our search identified two previous reviews relevant to the current reviewa,b, and we confirmed that our previous recommendations were implemented or considered. APPENDIX C. N/A APPENDIX D. N/A APPENDIX F. N/A

APPENDIX G. LABELS AND LABELING G.1 List of Labels and Labeling Reviewed

Using the principles of human factors and Failure Mode and Effects Analysis,c along with postmarket medication error data, we reviewed the following Ztlido labels and labeling submitted by Scilex Pharmaceuticals on November 17, 2017.

• Pouch Label • Carton Labeling • Professional Sample Pouch Label • Professional Sample Carton Labeling • Prescribing Information (Image not shown)

a Shah, M. Label and Labeling Review for Ztlido (NDA 207962). Silver Spring (MD): FDA, CDER, OSE, DMEPA (US);2016 FEB 24. RCM No.: 2015-2396. b Shah, M. Label and Labeling Memo for Ztlido (NDA 207962). Silver Spring (MD): FDA, CDER, OSE, DMEPA (US);2016 MAR 18. RCM No.: 2015-2396. c Institute for Healthcare Improvement (IHI). Failure Modes and Effects Analysis. Boston. IHI:2004. 3 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following

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DATE: 10/11/2017

TO: Division of Anesthesia Analgesia and Addiction Products Office of Drug Evaluation II

FROM: Division of New Drug Bioequivalence Evaluation (DNDBE) Office of Study Integrity and Surveillance (OSIS)

SUBJECT: Recommendation to accept data without an on-site inspection

RE: NDA 207962

The Division of New Drug Bioequivalence Evaluation (DNDBE) within the Office of Study Integrity and Surveillance (OSIS) recommends accepting data without an on-site inspection. The rationale for this decision is noted below.

Rationale OSIS recently inspected the site listed below. The inspectional outcome from the inspection was classified as No Action Indicated (NAI).

Inspection Site

Facility Type Facility Name Facility Address

Clinical TKL Research, Inc. One Promenade Boulevard, Suite 1201, Fair Lawn, NJ


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SHILA S NKAH 10/13/2017


FOOD AND DRUG ADMINISTRATION Center for Drug Evaluation and Research Office of Prescription Drug Promotion

****Pre-decisional Agency Information****

Memorandum

Date: July 14, 2016

To: Hina Mehta, Regulatory Project Manager Division of Anesthesia, Analgesia, and Addiction Products (DAAAP)

From: L. Shenee Toombs, Regulatory Review Officer (OPDP)

CC: Olga Salis, Senior Regulatory Health Project Manager (OPDP) Michael Wade, Regulatory Health Project Manager (OPDP)

Subject: NDA 207962 OPDP labeling comments for ZTlido (Lidocaine) Patch

OPDP acknowledges receipt of your August 28, 2015, consult request for the proposed Package Insert for ZTlido (Lidocaine) Patch. Reference is made to the May 10, 2016, Compete Response (CR) letter. As a result, OPDP will provide comments regarding labeling for this application during a subsequent review cycle. OPDP requests that DAAAP submit a new consult request during the subsequent review cycle.

Thank you for the opportunity to comment on these proposed materials.

If you have any questions, please contact Shenee’ Toombs at (301) 796-4174 or [email protected].


mailto:[email protected]

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____________________________________________________________________________



DATE: March 23, 2016

TO: Sharon Hertz, M.D.Director Division of Anesthesia, Analgesia, and AddictionProducts (DAAAP)Office of New Drugs

Dale Conner, Pharm.D.Director (Acting)Office of Bioequivalence (OB)Office of Generic Drugs

FROM: Srinivas R. Chennamaneni, Ph.D.Staff Fellow Division of New Drug Bioequivalence Evaluation (DNDBE)Office of Study Integrity and Surveillance (OSIS)Office of Translational Sciences

Yiyue Zhang, Ph.D.Visiting AssociateDivision of New Drug Bioequivalence Evaluation (DNDBE)Office of Study Integrity and Surveillance (OSIS)Office of Translational Sciences

Michael F. Skelly, Ph.D.Lead PharmacologistDivision of Generic Drug Bioequivalence Evaluation(DGDBE)Office of Study Integrity and Surveillance (OSIS)Office of Translational Sciences

THROUGH: Charles Bonapace, Pharm.D.Director Division of New Drug Bioequivalence Evaluation (DNDBE)Office of Study Integrity and Surveillance (OSIS)

Seongeun Cho, Ph.D.Director Division of Generic Drug Bioequivalence Evaluation(DGDBE)Office of Study Integrity and Surveillance (OSIS)


Review of EIRs for TKL Research, Inc., Fair Lawn, NJand (b) (4)

SUBJECT: Review of EIRs for TKL Research, Inc., Fair Lawn, NJ (Clinical Site) and

(Bioanalytical site) (b) (4)

Inspection Summary:

The Office of Study Integrity and Surveillance (OSIS) arrangedan inspection of the clinical portion of studies

NON-RESPONSIVE

SCI-LIDO-PK-001 and at TKL Research, Inc., Fair Lawn, NJ and

SCI-LIDO-PK-001 atNo significant deficiencies were observed and no

conducted an inspection of the analytical portion of study(b) (4)

Form FDA 483 was issued at TKL Research, Inc. The final

(NAI). Following the inspection of , Form FDA 483 containing three observations was issued. The

(b) (4)

(b) (4)

classification for TKL Research, Inc. is No Action Indicated

final classification for is Voluntary Action Indicated (VAI). Based on the inspectional outcomes and our review, these reviewers recommend thefollowing: x Data from the clinical portion of studies SCI-LIDO-PK-001

should be accepted for further agency review. and NON-RESPONSIVE

x Data from the pharmacokinetic portion of studySCI-LIDO-PK-001 should be accepted for agency review,subject to the evaluation of the experimental design (timing of heat application and exercise) and dosimetry.

x Data from the residual drug in used patches from studySCI-LIDO-PK-001 should not be accepted for further agency review.

Studies Audited during the Inspections:

NDA 207962

Study Number: SCI-LIDO-PK-001 Study Title: “Phase 1, Randomized, Comparative

Pharmacokinetic Study of Bolus IntravenousLidocaine 0.7 mg/kg, Lidocaine Patch 1.8%, andLidocaine Patch 5% (Lidoderm) in HealthySubjects and an Evaluation on the Effects of Heat and Exercise on the Pharmacokinetics of Lidocaine Patch 1.8% in Healthy Subjects”

Study Conduct: April 28 – July 24, 2014



NON-RESPONSIVE

Clinical Site: TKL Research, Inc.Fair Lawn, NJ

Audited studies: SCI-LIDO-PK-001 and NON-RESPONSIVE

The inspection of TKL Research, Fair Lawn, NJ was performed byORA investigator Peter R Lenahan (NWJ-DO) from November 16–17,19-20, 23-24, and December 22, 2015. The audit covered a review of study protocols and amendments, informed consent forms (ICFs), IRB submission and correspondence, subject selection criteria, electronic case report forms (eCRFs), source documents, selection and training of clinical personnel,monitoring procedures and activities, serious adverse events(SAEs) reporting, records retention and investigational drug accountability. No discrepancies were observed. No underreporting of AEs was observed. The treatment randomizationschedule was compared to the case report forms; no discrepancies were observed. No Form FDA 483 was issued at the conclusion of the inspection.

Audited studies: SCI-LIDO-PK-001

and handling, examination of facilities and equipment, employeetraining, interviews and discussions with firm’s management andstaff. At the conclusion of the inspection, Form FDA 483 with

Analytical Site: (b) (4)

The inspection ofwas performed by OSIS scientists Srinivas R. Chennamaneni,

Ph.D., Yiyue (Cynthia) Zhang, Ph.D., and Michael F. Skelly, Ph.Dfrom . The audit included a thorough review of study records, documentation and audit trails, sample receipt

(b) (4)

(b) (4)

three observations was issued to (Attachment 1). responded to the observations on

(b) (4)

(b) (4)


Review of EIRs for TKL Research, Inc., Fair Lawn, NJ

(Attachments 2 and 3, respectively). The Form FDA 483 observations, the firm’sresponses, and our evaluation follow.

and (b) (4)

and (b) (4) (b) (4)

(b) (4)

1 Page(s) has been Withheld in Full as b4 (CCI/TS) immediately following this page



Additional Comments:

(b) (4)

Recommendations:

Following review of the EIR and inspectional findings, theclinical data from the audited studies at TKL Research, Inc., Fair Lawn, NJ were found to be reliable. Therefore, we recommendthat the data for the clinical portion of studies

NON-RESPONSIVE NON-RESPONSIVE

SCI-LIDO-PK-001 and submitted under NDA 207962 and be accepted for further agency review.

Following review of the EIR, inspectional findings, and theresponse to Form FDA 483, the bioanalytical data for the

NDA 207962 be accepted for further agency review, subject to the evaluation of the experimental design (timing of heat application and exercise) and dosimetry.

Following review of documentation for quantification of residualdrug in used lidocaine patches, we found that the data areincomplete and not reliable. Therefore, the data from the

pharmacokinetic portion of the audited study atwere found to be reliable. Therefore,

we recommend that the bioanalytical data from thepharmacokinetic portion of study SCI-LIDO-PK-001 submitted under

(b) (4)



residual drug analysis for study SCI-LIDO-PK-001 submitted under NDA 207962 should not be accepted for further agency review.

Srinivas R. Chennamaneni, Ph.D.DNDBE, OSIS

Yiyue Zhang, Ph.D.DNDBE, OSIS

Michael F. Skelly, Ph.D.DGDBE, OSIS

Final Classification:

Clinical Site:

NAI: TKL Research, Inc., Fair Lawn, NJ

Analytical Site:

Attachment:

Attachment 1:

(b) (4)

(b) (4)

(b) (4)

(b) (4)

(b) (4)

Form FDA 483 “Inspectional Observations”Attachment 2: response to Form FDA 483 dated:

Attachment 3: response to Form FDA 483 dated

Attachment 4:

Attachment 5:

Attachment 6:

VAI: (b) (4)

CC: OTS/OSIS/Kassim/Taylor/Fenty-Stewart/Nkah/Miller/Kadavil/JohnsonOTS/OSIS/DNDBE/Bonapace/Dasgupta/Chennamaneni/ZhangOTS/OSIS/DGDBE/Cho/Haidar/Skelly/ChoiOND/DAAAP/Hertz/MeyerOGD/OB/Conner/Potter


and (b) (4)

Page 8 – Review of EIRs for TKL Research, Inc., Fair Lawn, NJ

ORA/NWJ-DO/BIMO/Lenahan/HarlanDraft: SRC 3/8/2016; YZ 3/15/2016, 3/21/2016; MFS 3/15/2016Edit: MFS 3/22/2016; CRB 3/22/2016; JC 3/22/2016

ECMS: Cabinets/CDER_OC/OSI/Division of Bioequivalence & Good

Sites/TKL Research, Inc., Fair Lawn, NJ//TKL Research, Inc., Fair Lawn, NJ/NDA

NON-RESPONSIVE

Laboratory Practice Compliance/INSPECTIONS/BE Program/Clinical

207962_Lidocaine Patch Cabinets/CDER_OC/OSI/Division of Bioequivalence & GoodLaboratory Practice Compliance/INSPECTIONS/BE Program/Analytical

OSIS: BE 6957 (NDA 207962)

Sites/207962_Lidocaine Patch

(b) (4)

FACTS: 11546112 (TKL Research, Inc.) NON-RESPONSIVE

(b) (4)



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SRINIVAS RAO N CHENNAMANENI 03/24/2016

YIYUE ZHANG 03/24/2016

MICHAEL F SKELLY 03/24/2016

CHARLES R BONAPACE 03/24/2016

SEONGEUN CHO 03/24/2016





Date of This Memorandum: March 18, 2016



Product Name and Strength: Ztlido (lidocaine) topical patch, 1.8%

Submission Date: March 14, 2016

Applicant/Sponsor Name: Scilex Pharmaceuticals

OSE RCM #: 2015-2396

DMEPA Primary Reviewer: Millie Shah, PharmD, BCPS

DMEPA Team Leader: Vicky Borders-Hemphill, PharmD

1 PURPOSE OF MEMO The Division of Anesthesia, Analgesia, and Addiction Products (DAAAP) requested that we review the revised container labels and carton labeling for Ztlido (lidocaine) topical patch (Appendix A) to determine if they are acceptable from a medication error perspective. The revisions are in response to recommendations that we made during a previous label and labeling review.1

2 CONCLUSION The revised container labels and carton labeling for Ztlido (lidocaine) topical patch are acceptable from a medication error perspective. We have no further recommendations at this time. APPENDIX A. LABEL AND LABELING SUBMITTED ON MARCH 14, 2016

1 Shah M. Label and Labeling Review for Ztlido (NDA 207962). Silver Spring (MD): Food and Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Division of Medication Error Prevention and Analysis (US); 2016 FEB 24. 10 p. OSE RCM No.: 2015-2396.


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BRENDA V BORDERS-HEMPHILL 03/18/2016


LABEL AND LABELING REVIEW Division of Medication Error Prevention and Analysis (DMEPA)

Office of Medication Error Prevention and Risk Management (OMEPRM) Office of Surveillance and Epidemiology (OSE)

Center for Drug Evaluation and Research (CDER)

*** This document contains proprietary information that cannot be released to the public***

Date of This Review: February 24, 2016



Product Name and Strength: Ztlido (lidocaine) topical patch, 1.8%

Product Type: Single-ingredient combination product

Rx or OTC: Rx

Applicant/Sponsor Name: Scilex Pharmaceuticals

Submission Date: July 10, 2015

OSE RCM #: 2015-2396

DMEPA Primary Reviewer: Millie Shah, PharmD, BCPS

DMEPA Team Leader: Vicky Borders-Hemphill, PharmD

1


1 REASON FOR REVIEW Scilex Pharmaceuticals submitted NDA 207962 for Ztlido (lidocaine) topical patch. Thus, the Division of Anesthesia, Analgesia, and Addiction Products (DAAAP) requested we evaluate the container labels, carton labeling, instruction for use (IFU), and prescribing information (PI) for vulnerabilities that could lead to medication errors.

2 MATERIALS REVIEWED We considered the materials listed in Table 1 for this review. The Appendices provide the methods and results for each material reviewed.

Table 1. Materials Considered for this Label and Labeling Review

Material Reviewed Appendix Section (for Methods and Results)

Product Information/Prescribing Information A

Previous DMEPA Reviews B

Human Factors Study C-(N/A)

ISMP Newsletters D-(N/A)

FDA Adverse Event Reporting System (FAERS)* E-(N/A)

Labels and Labeling F

Prescribing Information G

N/A=not applicable for this review *We do not typically search FAERS for label and labeling reviews unless we are aware of medication errors through our routine postmarket safety surveillance

3 OVERALL ASSESSMENT OF THE MATERIALS REVIEWED We performed a risk assessment of the proposed container labels, carton labeling, PI, and IFU to identify deficiencies that may lead to medication errors and other areas for improvement.

Container Labels and Carton Labeling Our review of the container labels and carton labeling identified areas for improvement to increase clarity and prominence of important information. Thus, we provide recommendations in Section 4.2.

Prescribing Information (PI) Our review of the PI determined that the strength ( (b) (4)) is inconsistent with the strength presented on the container label and carton labeling. Therefore, we recommend revising the strength to 1.8% throughout the PI so that it is consistent with the container labels and carton labeling.

2


4 CONCLUSION & RECOMMENDATIONS We identified areas in the proposed labels and labeling that can be improved to increase clarity and prominence of important information to promote the safe use of this product.

If you have further questions or need clarifications, please contact Davis Mathew, OSE Project Manager, at 240-402-4559.

4.1 RECOMMENDATIONS FOR THE DIVISION

We have revised the Prescribing Information (See Appendix G) and have provided a detailed summary below for review and consideration by DAAAP.

A. Prescribing information 1. We recommend revising the current strength presentation ( (b) (4)) to 1.8% throughout

the prescribing information so that it is consistent with the container label and carton labeling.

4.2 RECOMMENDATIONS FOR SCILEX PHARMACEUTICALS We recommend the Applicant implement the following prior to approval of this NDA:

A. Carton labeling (30-patch package size and (b) (4)patch physician sample package size)

1. Change the font color of the established name and strength from (b) (4) to black to increase its prominence.1

2. Remove (b) (4) in accordance with 21 CFR 202.1(a)(1). As currently presented, it interferes with the ability to read the lowercase “i” in the proprietary name, ZTlido.

3. Decrease the size of the Rx only statement by decreasing its size. Relocate the Rx only statement to the bottom right corner of the principal display panel. As currently presented, the Rx only statement appears more prominent than other more important information.2

4. Revise the statement, “ ” to read, to match the

(b) (4)

(b) (4)

strength presentation with the established name.

1 Food and Drug Administration. Guidance for Industry: Safety Considerations for Container Labels and Carton Labeling Design to Minimize Medication Errors, April 2013. Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM349009.pdf.

2 Food and Drug Administration. Guidance for Industry: Safety Considerations for Container Labels and Carton Labeling Design to Minimize Medication Errors, April 2013. Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM349009.pdf.

3


http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM349009.pdf

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM349009.pdf

5. Revise the sentence in Step 3 in the Directions for Use from, “ ” to read, ” for clarity.

(b) (4)

(b) (4)

B. Pouch label (30-patch package size and (b) (4)patch physician sample package size)

1. See A.2 through A.5

APPENDICES: METHODS & RESULTS FOR EACH MATERIALS REVIEWED

APPENDIX A. PRODUCT INFORMATION/PRESCRIBING INFORMATION

4


(b) (4)

Table 2 presents relevant product information for Ztlido that Scilex Pharmaceuticals submitted on July 10, 2015.

Table 2. Relevant Product Information for Ztlido

Initial Approval Date N/A

Active Ingredient lidocaine

Indication relief of pain associated with post-herpetic neuralgia

Route of Administration topical

Dosage Form patch

Strength (b) (4)

Dose and Frequency Apply up to 3 patches once for 12 hours in a 24-hour period

How Supplied/ Container Closure

Carton of 30 patches, packaged into individual child-resistant envelopes Carton of patches, packaged into individual child-resistant envelopes

Storage Store at 25°C (77°F); excursions permitted to 15°-30°C (59°86°F). [See USP Controlled Room Temperature].

APPENDIX B. PREVIOUS DMEPA REVIEWS B.1 Methods On November 4, 2015, we searched the L:drive and AIMS using the term, Ztlido, to identify reviews previously performed by DMEPA.

B.2 Results Our search identified zero previous label/labeling reviews.

APPENDIX C. N/A APPENDIX D. N/A APPENDIX E. N/A

APPENDIX F. LABELS AND LABELING F.1 List of Labels and Labeling Reviewed Using the principles of human factors and Failure Mode and Effects Analysis,3 along with postmarket medication error data, we reviewed the following Ztlido labels and labeling submitted by Scilex Pharmaceuticals on February 2, 2016.

• Pouch label • Carton labeling

3 Institute for Healthcare Improvement (IHI). Failure Modes and Effects Analysis. Boston. IHI:2004. 5 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following

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BRENDA V BORDERS-HEMPHILL 02/24/2016


application number...1 introduction on august 28, 2017, scilex pharmaceuticals inc. submitted for...

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