CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 022063Orig1s000 OTHER REVIEW(S) Reference ID: 4119537 Reference ID: 4119537 Reference ID: 4119537 Reference ID: 4119537 Reference ID: 4119537 Reference ID: 4119537 Reference ID: 4119537 Reference ID: 4119537 Reference ID: 4119537 Reference ID: 4119537 Reference ID: 4119537 Reference ID: 4119537 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 Review: June 20, 2017 Requesting Office or Division: Division of Psychiatry Products (DPP) Application Type and Number: NDA 022063 Product Name and Strength: Mydayis (Mixed Salts of a Single-Entity Amphetamine) (b) (4) release capsule 12.5 mg, 25 mg, 37.5 mg, 50 mg Product Type: Single-Ingredient Product Rx or OTC: Rx Applicant/Sponsor Name: Shire Development LLC Submission Date: December 20, 2016 OSE RCM #: 2017-125-2 DMEPA Primary Reviewer: Briana Rider, PharmD DMEPA Team Leader: Lolita White, PharmD 1 PURPOSE OF MEMO The Division of Psychiatry Products (DPP) requested that we review the revised container labels for Mydayis (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 labels for Mydayis are acceptable from a medication error perspective. We have no further recommendations at this time. a Rider B. Label and Labeling Review Memorandum for Mydayis (NDA 022063). Silver Spring (MD): FDA, CDER, OSE, DMEPA (US); 2017 JUN 19. RCM No.: 2017-125-1. 1 Reference ID: 4113842 APPENDIX A. LABEL AND LABELING SUBMITTED ON JUNE 20, 2017 Container Label: 12.5 mg (b) (4) 2 Reference ID: 4113842 Container Label: 37.5 mg (b) (4) 3 Reference ID: 4113842 --------------------------------------------------------------------------------------------------------- This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------- /s/ ---------------------------------------------------- BRIANA B RIDER 06/20/2017 LOLITA G WHITE 06/21/2017 Reference ID: 4113842 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 Review: June 19, 2017 Requesting Office or Division: Division of Psychiatry Products (DPP) Application Type and Number: NDA 022063 Product Name and Strength: Mydayis (Mixed Salts of a Single-Entity Amphetamine) (b) (4) release capsule 12.5 mg, 25 mg, 37.5 mg, 50 mg Product Type: Single-Ingredient Product Rx or OTC: Rx Applicant/Sponsor Name: Shire Development LLC Submission Date: December 20, 2016 OSE RCM #: 2017-125-1 DMEPA Primary Reviewer: Briana Rider, PharmD DMEPA Team Leader: Lolita White, PharmD 1 PURPOSE OF MEMO The Division of Psychiatry Products (DPP) requested that we review the revised container labels for Mydayis (Appendix A) to determine if it is 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 labels are unacceptable from a medication error perspective. In a previous label and labeling review,a we expressed concern that Mydayis may be inappropriately substituted for Adderall XR since both products have the same established name, have an overlapping strength of 25 mg, and are both dosed once daily. We have since considered several potential strategies to help differentiate the container labels from those of Adderall XR. a Rider B. Label and Labeling Review for Mydayis (NDA 022063). Silver Spring (MD): FDA, CDER, OSE, DMEPA (US); 2017 MAY 18. RCM No.: 2017-125. 1 Reference ID: 4113248 After consultation with OGD, OCC, and OPDP we have determined that the addition of the statement ‘Do not substitute for Adderall XR’ to the Principal Display Panel (PDP) of the Mydayis container labels would be appropriate to help minimize the risk of wrong drug medication errors. 3 RECOMMENDATIONS FOR SHIRE DEVELOPMENT LLC We recommend the following be implemented prior to approval of this NDA: A. As presented, the container labels do not adequately convey to the end user that the product is not substitutable for Adderall XR. We are concerned that Mydayis may be inappropriately substituted for Adderall XR products since Mydayis and Adderall XR have the same established name, have an overlapping dose of 25 mg and are both dosed once daily. We recommend that you add the following statement to the Principal Display Panel on the container labels under the net quantity statement. i. Do not substitute for Adderall XR. 2 Reference ID: 4113248 APPENDIX A. LABEL AND LABELING SUBMITTED ON JUNE 6, 2017 Container Label: 12.5 mg (b) (4) 3 Reference ID: 4113248 Container Label: 37.5 mg (b) (4) 4 Reference ID: 4113248 --------------------------------------------------------------------------------------------------------- This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------- /s/ ---------------------------------------------------- BRIANA B RIDER 06/19/2017 LOLITA G WHITE 06/19/2017 Reference ID: 4113248 M E M O R A N D U M Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research Date: June 20, 2017 To: Mitch Mathis, MD, Director Division of Psychiatry Products (DPP) Through: Silvia Calderon, Ph.D., Senior Pharmacologist Martin Rusinowitz, M.D., Senior Medical Officer Controlled Substance Staff From: Edward Hawkins, PhD, Pharmacologist Controlled Substance Staff Subject: SHP 465 (mixed salts of a single entity amphetamine), NDA 22-063 Trade Name, dosages, formulations, routes: Mydayis capsules, 12.5 mg, 25 mg, 37.5 mg, and 50 mg, for oral administration once a day IND Number: 58,037 Indication(s): Treatment of attention deficit hyperactivity disorder (ADHD) Sponsor: Shire PDUFA Goal Date: June 20, 2017 Materials Reviewed: • 1.14.1.3 Draft labeling text • 1.16.1 Abuse potential evaluation report • 2.3 Drug product and substance • 2.7 Clinical summary • 5.3.3 Reports of human PK studies • 5.3.5 Reports of efficacy and safety studies Table of Contents I. SUMMARY .........................................................................................................................................3 1. Background.......................................................................................................................................3 2. Conclusions.......................................................................................................................................3 3. Recommendations.............................................................................................................................4 II. DISCUSSION...................................................................................................................................5 1. Chemistry..........................................................................................................................................5 Reference ID: 4110964 Mydayis [Mixed salts of a single entity amphetamine] [NDA 022063] 1.1 Substance Information...............................................................................................................5 1.2 Potential Drug Isomers..............................................................................................................7 1.3 In Vitro Manipulation and Extraction Studies for Products with Abuse-Deterrent Features ..7 2. Nonclinical Pharmacology................................................................................................................7 3. Clinical Pharmacology......................................................................................................................8 3.1 Absorption, Distribution, Metabolism, Elimination (ADME) ..................................................9 3.2 Drug/Product Interactions .........................................................................................................9 4. Clinical Studies...............................................................................................................................10 4.1 Human Abuse Potential Studies..............................................................................................11 4.2 Adverse Event Profile Through all Phases of Development...................................................11 4.3 Safety Profile...........................................................................................................................13 4.4 Evidence of Abuse, Misuse and Diversion in Clinical Trials .................................................13 4.5 Tolerance and Physical Dependence Studies in Humans........................................................14 5. Regulatory Issues and Assessment .................................................................................................14