1. Generic Drug Labeling: Generic Drug Labeling: 2011 USPHS Symposium 2011 USPHS Symposium Pharmacy Category Day Pharmacy Category Day June 21, 2011 June 21, 2011 Presented by: CAPT Lillie D. Golson, MSA, PharmD Team Leader, Labeling Review Branch Office of Generic Drugs Food and Drug Administration Unraveling the Mysteries

2. Learning Objectives  Provide an overview of the labeling review process in FDA’s Office of Generic Drugs  Describe the types of errors often attributed to labeling  Present graphic examples highlighting ways labeling can both contribute to and prevent medication errors  Provide tips to better understand characteristics unique to generic labeling  Heighten awareness of the use of labeling statements to communicate important information to practitioners

3. Overview: Labeling Review Branch Office of Generic Drugs (OGD)

4. Staffing 22 Pharmacists: 19 Reviewers 19 Reviewers 3 Team Leaders 3 Team Leaders

5. Responsibilities Ensure that the proposed generic labeling is the “same as” that of the branded equivalent or Reference Listed Drug (RLD) Ensure that the proposed generic labeling is the “same as” that of the branded equivalent or Reference Listed Drug (RLD) Ensure that healthcare practitioners are provided sufficient information to safely use the product Ensure that healthcare practitioners are provided sufficient information to safely use the product

6. Review Tools

7. Primary Focus Areas of OGD Labeling Reviews Labeling Text Labeling Text Packaging Packaging Pharmacy practice (as related to safety and the prevention of medication errors) Pharmacy practice (as related to safety and the prevention of medication errors)

8. Labeling Text Focus: Labeling Text Focus: Is the generic name correct? Is the generic name correct? Does font size meet regulatory standards? Does font size meet regulatory standards? Are inappropriate abbreviations used? Are inappropriate abbreviations used? Are dyes and coloring agents listed in the DESCRIPTION section? Are dyes and coloring agents listed in the DESCRIPTION section? Do solid oral dosage forms have unique identifiers described in the HOW SUPPLIED section? Do solid oral dosage forms have unique identifiers described in the HOW SUPPLIED section?

9. Packaging Focus: Packaging Focus: Does the package container differ from the RLD (e.g., prefilled syringe vs. vial)? Does the package container differ from the RLD (e.g., prefilled syringe vs. vial)? Is the container color appropriate (e.g., cap color for ophthalmics, potassium chloride)? Is the container color appropriate (e.g., cap color for ophthalmics, potassium chloride)? Are individual cartons required (e.g., contains special dosing instructions)? Are individual cartons required (e.g., contains special dosing instructions)? Is proposed package size mismatched with the recommended dose? Is proposed package size mismatched with the recommended dose? How will medication guides and patient information leaflets accompany the product? How will medication guides and patient information leaflets accompany the product?

10. Pharmacy Practice Focus: Pharmacy Practice Focus: Are adequate instructions provided to ensure the correct use of a product when package differs from the RLD? Is the difference acceptable from a safety standpoint? Are adequate instructions provided to ensure the correct use of a product when package differs from the RLD? Is the difference acceptable from a safety standpoint? Are the established name and strength the most prominent text appearing on the label/labeling? Are the established name and strength the most prominent text appearing on the label/labeling? Is the layout of the labeling cluttered or confusing? Is the layout of the labeling cluttered or confusing? How is the product and labeling being used in the real world? How is the product and labeling being used in the real world? Are products sufficiently differentiated? Are products sufficiently differentiated?

11. Labeling and Medication Errors

12. 2006 IOM Report Indicated that major med error problems involved drug naming, labeling, and packaging of products Indicated that major med error problems involved drug naming, labeling, and packaging of products 33% of errors caused by labeling and packaging 33% of errors caused by labeling and packaging 30% of fatalities reported involved labeling and packaging 30% of fatalities reported involved labeling and packaging 10% of all errors were attributed to drug name confusion 10% of all errors were attributed to drug name confusion

13. Ways The Labeling and Packaging Cause Confusion Expression of Strength Expression of Strength Prominence of Information Prominence of Information Legibility of Information Legibility of Information Trade Dress Trade Dress Packaging Configurations Packaging Configurations Packaging Design Packaging Design Product Design Product Design

14. Expression of Strength and Total Drug Content www.medicalinspection.net/.../02/Figure31.png

15. Lack of Prominence of Vital Information www.medicalinspection.net/.../02/Figure12.png

16. Poorly Legible Information

17. Labeling and Packaging Trade Dress http://abcnews.go.com/Blotter/slideshow?id=9981722

18. Poor Packaging Design

19. Poor Product Design

20. Ways nomenclature can cause confusion

21. Sound alike – look alike names Sound alike – look alike names Brand name/brand name confusion Brand name/brand name confusion Generic name/generic name confusion Generic name/generic name confusion Brand to generic name confusion Brand to generic name confusion Generic names lacking unique/brand identity Generic names lacking unique/brand identity Use of abbreviations, acronyms, dose designations, and various symbols Use of abbreviations, acronyms, dose designations, and various symbols

22. Brand To Generic Name Confusion Brand To Generic Name Confusion Established names used more with generic products. Established names used more with generic products. Branded product frequently uses “fanciful” terms (e.g., sprinkles, rapidly disintegrating, caplets, spansules). Branded product frequently uses “fanciful” terms (e.g., sprinkles, rapidly disintegrating, caplets, spansules). RLD slow to change common/usual names to compendial names. RLD slow to change common/usual names to compendial names. RLD frequently uses “non-official” dosage forms in its proprietary names (e.g., sustained-release, dispersible, long-acting, controlled-release). RLD frequently uses “non-official” dosage forms in its proprietary names (e.g., sustained-release, dispersible, long-acting, controlled-release).

23. Brand to Generic Confusion (LA, CD, SR are not official dosage forms) Brand to Generic Confusion (LA, CD, SR are not official dosage forms) RLDRitalin Ritalin LA Metadate CD Ritalin SR Metadate ER Concerta Methylin ER Generic Methylphenidate HCL Tablets Methylphenidate HCL Extended-Release Capsules Methylphenidate HCL Extended-Release Tablets

24. RLDWellbutrinZyban Wellbutrin SR Wellbutrin XL Generic Bupropion HCL Tablets Bupropion HCL Extended-release Tablets Brand to Generic Confusion (SR not an official dosage form in USP) Brand to Generic Confusion (SR not an official dosage form in USP)

25. Brainstorming

27. Ways FDA Tries to Communicate With The Pharmacist and Technician

28. Cross reference common names with compendial names

32. Place important information on container and carton labeling

34. Tall Man Lettering Tall Man Lettering

35. Color Differentiate Products

36. Use USP Labeling Statements Protect from light Protect from light Not for injection Not for injection Not for intrathecal use Not for intrathecal use Must be chewed before swallowing Must be chewed before swallowing Must be diluted Must be diluted Warning: Paralyzing Agent Warning: Paralyzing Agent

37. Use CFR Labeling Statements

38. 21 CFR 201.20 Declaration of presence of FD&C Yellow No. 5 and/or FD&C Yellow No. 6 in certain drugs for human use Contains FD&C Yellow #5 (tartrazine)

39. 21 CFR 201.21 Declaration of presence of phenylalanine as a component of aspartame in over-the-counter and prescription drugs for human use Phenylketonurics : Contains phenylalanine (4.5 mg per tablet)

40. 21 CFR 208.24 Distributing and Dispensing a Medication Guide

41. However…

45. Technicians: Technicians: Familiarize yourselves with the general labeling format. Familiarize yourselves with the general labeling format. Scan the entire label for alerting statements and inform the pharmacist before filling the order. Scan the entire label for alerting statements and inform the pharmacist before filling the order. Try not to cover directions for use. Try not to cover directions for use. Try not to cover important information before pharmacist sees it. Try not to cover important information before pharmacist sees it. Never assume. Never assume. ATTENTION: CAUTION: PHARMACIST: WARNING: CONTAINS: BOXED STATEMENTS STATEMENTS IN RED LETTERS

46. Useful Links The Daily Med: http://dailymed.nlm.nih.gov/dailymed/about.cfm The Daily Med: http://dailymed.nlm.nih.gov/dailymed/about.cfm Drugs@FDA: Drugs@FDA:http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/ USP: http://www.usp.org/ USP: http://www.usp.org/ Medication Guides: http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm Medication Guides: http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm Orange Book: http://www.accessdata.fda.gov/Scripts/cder/ob/default.cfm Orange Book: http://www.accessdata.fda.gov/Scripts/cder/ob/default.cfm Medwatch: http://www.fda.gov/Safety/MedWatch/default.htm Medwatch: http://www.fda.gov/Safety/MedWatch/default.htm

48. Thank you!