CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 761122Orig1s000 OTHER REVIEW(S) Center for Drug Evaluation and Research Office of Pharmaceutical Quality Office of Biotechnology Products LABELS AND LABELING ASSESSMENT Date of assessment: May 16, 2019 Assessor: Scott Dallas, RPh, Labeling Assessor Office of Biotechnology Products (OBP) Through: Lymarie Maldonado-Baez, PhD, Product Quality Reviewer OBP/Division of Biotechnology Review and Research I Application: BLA 761122 Applicant: GlaxoSmithKline LLC Submission Date: August 7, 2018; February 28, April 18 and May 9, 2019 Product: Nucala (mepolizumab) Dosage forms: Injection Strength and 100 mg/mL, single-dose prefilled autoinjector or single-dose prefilled Container-Closure: syringe (proposed under BLA 761122) Purpose of The Applicant submitted a biologics license application for a liquid assessment: formulation of Nucala (mepolizumab) to be administered subcutaneously via an autoinjector or a safety syringe device. Recommendations: The prescribing information, patient information, instructions for use, container labels, and carton labeling are acceptable from an OBP labeling perspective. Materials Considered for this Label and Labeling Assessment Materials Assessed Appendix Section Proposed Labels and Labeling A Evaluation Tables B Acceptable Labels and Labeling C DISCUSSION We evaluated the proposed labels and labeling for compliance with applicable requirements in the Code of Federal Regulations (see Appendix B). Please note the Prescribing Information for this BLA is to be combined with the approved labeling for BLA 125526 Nucala (mepolizumab) for injection, 100 mg/vial, approved on November 4, 2015. CONCLUSION The prescribing information, patient information, instructions for use, container labels, and carton labeling submitted on April 18 and May 9, 2019 were assessed and found to be acceptable (see Appendix C) from an OBP labeling perspective. Page 1 of 9 APPENDICES Appendix A: Proposed Labeling Prescribing Information and Patient Information (submitted on August 7, 2018) \\cdsesub1\evsprod\bla761122\0001\m1\us\114-labeling\1141-draft\draft-annotated.pdf Instructions for Use - Autoinjector (submitted on August 7, 2018) \\cdsesub1\evsprod\bla761122\0001\m1\us\114-labeling\1141-draft\draft-auto-ifu- 100mg.pdf Instructions for Use - Syringe (submitted on August 7, 2018) \\cdsesub1\evsprod\bla761122\0001\m1\us\114-labeling\1141-draft\draft-syr-ifu- 100mg.pdf (b) (4) 2 Pages of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page Page 2 of 29 Appendix B: Evaluation Tables Evaluation Tables: Label1·2 and Labeling3 Standards Container4 Label Evaluation Commercial and Sample Container Labels Proner Name (for container ofa product capable of bearino a full label) Accentable 21 CFR 610.60, 21 CFR 201.50, 21 CFR 201.10 ./ Yes D No D N/A Comment/ Recommendation: Autoinjector - acceptable Syrinae- acceptable Recommended labeling practices (placement of dosage form below the proper ./Yes name) : D No D N/A Comment/ Recommendation: Autoinjector - acceptable Syrinae - acceptable Manufacturer name, address, and license number Acceptable (for container ofa oroduct caoable of bearino a full label) 21CFR610.60 (a)(2), 21 CFR 201, 21CFR201. l(a), 21 CFR 201.l(h)(S), 21 ./ Yes CFR 201.1(h)(6), 21 CFR 201.lOO(e) D No D N/A Comment/ Recommendation: Autoinjector - acceptable, but no license number which is acceptable because it's a partial label Syringe - acceptable, but no license number which is acceptable because it's a partial label Recommended labeling practices (using the following qualifying statement D Yes "Manufactured by: NJ: D No 1:81 N/ A Comment/ Recommendation: Autoinjector -NA it's a partial label Syringe - NA it's a partial label 1 Per 21 CFR 1.3(b) Label means any display of written, printed, o r graphic matter on the immediat e container of any article, or any such matter affixed to a ny consumer commodity or affixed to or appearing upon a package containing any consumer commodity. 2 Per CFR 600.3(dd) Label means any writte n, printed, or graphic matter on t he container or package or any such matter clearly visible t hrough t he immediate carton, receptacle, or wrapper. 3 Per 21 CFR 1.3(a) Labeling includes all writte n, printed, or graphic matte r accompanying an article at any t ime while such article is in interstate commerce or held for sale after shipment or delivery in interstate commerce. 4 Per 21 CFR 600.3(bb) Container (referred to a lso as "final container") is t he immediat e unit, bott le, vial, ampule, tube, or other receptacle containing t he product as distributed for sale, barter, o r exchange. Page 5 of 29 Lot number or other lot identification Acceptable (container capable of bearing a full label shall bear) 21CFR610.60, 21 CFR201.18, 21CFR201.100 ./ Yes D No D N/A Comment/ Recommendation: Autoinjector - Please verify the lot number will be provided on t he label per 21 CFR 610.60(a)(3) and indicate where this information will appear. Syringe- acceptable April 18, 2019: The revised autoinjector container labels include the words "Lot" and "Exp", and GSK confirmed t his information will appear on t he label. FDA response: GSK's revisions are acceptable. Exniration date fcontainer capable ofbearino a full label shall bear) Accentable 21CFR610.60, 21 CFR201.17 ./ Yes D No D N/A Comment/ Recommendation: Autoinjector - Please verify the expiration date will be provided on t he label per 21 CFR 610.60(a)(4) and indicate where this information will appear. Syringe - acceptable April 18, 2019: The revised autoinj ector container labels include the words " Lot" and "Exp", and GSK confirmed t his information will appear on t he label. FDA response: GSK's revisions are acceptable. Recommended labeling practices (the expiration date appears on all aspects of o Yes the package): o No l:8J N/A Product Strennth Accentable 21 CFR 201.lO(d)(l), 21 CFR 201.100(b)(4) ./ Yes D No D N/A Comment/ Recommendation: Autoinjector - acceptable Svrinae - acceptable Recommended labeling practices (expression of strength for injectable drugs): Reference: Draft Guidance Safety Considerations for Container Labels and Carton Labeling Design to Minimize Medication Error~ April 2013 line176 USP General Chapters: <7> Labelino Autoinjector - acceptable ./ Yes D No Syringe - acceptable D N/A Page 6 of 29 AcceRtable MultiRle dose containers {recommended individual dose} 21 CFR 610.60, 21 CFR 201.55 D Yes D No l&1 N/A Statement: "Rx onlv" Accentable 21 CFR 610.60, 21 CFR 201. 100 D Yes D No l&1 N/A Comment/ Recommendation: Autoinjector - no Rx only statement, but it's acceptable, because it can be considered a partial label Syringe- no Rx only statement, but it's acceptable, because it can be considered a partial label Recommended labeling practices : D Yes D No l&1 N/ A Medication Guide Accentable 21 CFR 610.60, 21 CFR 208.24 D Yes D No l&1 N/A No Packane for container Accentable 21 CFR 610.60 D Yes D No l&1 N/A Recommended labeling practices : D Yes (U.S license number for container bearing a partial label) D No l&1 N/A Comment/Recommendation: Dartial label No container label Accentable 21 CFR 610.60 D Yes D No l&1 N/A Comment/ Recommendation: Autoinjector - ok, it has a carton Svrinae - ok it has a carton Ferrule and can oversea! (for vials onlvJ Accentable Recommended labeling practices: D Yes United States Pharmacopeia (USP)/ General Chapters: <7> Labeling (Ferrules D No and Cap Overseals) l&1 N/A Page 7 of 29 Visual insnection ffor vials on/vJ Accentable 21 CFR 610.GO(e) ./ Yes D No D N/A Comment/ Recommendation: Autoinjector and Syringe - provide an inspection window NOC numbers Accentable 21 CFR 201.2, 21 CFR 207.35 ./ Yes D No D N/A Comment/ Recommendation: Autoinjector - acceptable, has a NDC Syringe- acceptable, does not contain a NDC, but it is a partial label Route of administration Accentable 21 CFR 201.5, 21 CFR201. 100 ./ Yes D No D N/A Comment/ Recommendation: Autoinjector - acceptable Syringe- acceptable, does not contain a ROA, but it is a partial label Recommended labeling practices : D Yes route of administration statement to appear after the strength statement on D No the principal display panel l:8J N/A Comment/ Recommendation: Autoinjector - space/design does not permit this format Syringe- NA, partial label Prenaration instructions Accentable 21CFR201.5 D Yes D No l:8J N/A Comment/ Recommendation: Autoinjector - not required partial label Syringe - not required partial label Page 8 of 29 Recommended labeling practices : D Yes Draft Guidance Safety Considerations for Container Labels and Carton Labeling D No Design to Minimize Medication Errors, April 2013 (lines 426-430) l&1 N/A Please note OPDP recommended removal of the partial instruction graphics on the container label. Package :W~ term AcceRtable Recommended labeling practices: Guidance for Industry: Selection of the ./ Yes Appropriate Package Type Terms and Recommendations for Labeling D No Injectable Medical Products Packaged in Multiple-Dose/ Single-Dose/ and D N/A Single-Patient-Use Containers for Human Use. USP chapter <659> Packaging and Storage Requirements I Comment/ Recommendation: Autoinjector -acceptable Svrinae- not reauired partial label Misleadina statements Accentable 21CFR201.6 D Yes D No l&1 N/A Comment/ Recommendation: Autoinjector -NA Svrinae- NA Prominence of r~uired label statements Accentable 21 CFR 201.15 ./ Yes D No D N/A Comment/ Recommendation: Autoinjector - acceptable Syringe- acceptable Snanish-lanauaae lDruasl Accentable 21 CFR 201.16 D Yes D No l&1 N/A FD&C Yellow No. 5 and/or FD&C Yellow No. 6 Accentable 21 CFR 201.20 D Yes D No l&1 N/A Phenvlalanine as a comnonent of asnartame Accentable 21 CFR 201.21 D Yes D No l&1 N/A Page 9 of 29 Sulfites~ renuired warninn statements Accentable 21 CFR 201.22 D Yes D No l:8J N/A Bar code label renuirements Accentable 21 CFR 201.25, 21 CFR 610.67 ./ Yes D No D N/A Comment/ Recommendation: Autoinjector - acceptable Note: The sample autoinj ector label does not contain a linear bar code.