1. Labeling and Electronic Initiatives Rachel E. Behrman M.D., M.P.H. Deputy Director, Office of Medical Policy CDER FDA Science Board, April 15, 2005

2. Authority Sec. 502(a) – A drug or device shall be deemed to be misbranded if its labeling is false or misleading in any particular Sec. 505(d)(7) – If the Secretary finds…such labeling is false or misleading in any particular; he shall issue an order refusing to approve the application 21CFR 201.57 – Specific requirements on content and format of labeling for human prescription drugs

3. Current Labeling Description Clinical Pharmacology Indications and Usage Contraindications Warnings Precautions Adverse Reactions Drug Abuse and Dependence Overdosage Dosage and Administration How Supplied May Contain: –Animal Pharmacology &/or Toxicology –Clinical Studies –References

4. Physician Labeling Rule - Background Goal - more informative and accessible labeling, resulting in a better risk communication and management tool Development process included –Focus groups –National physician survey –Public meeting Formal notice and comment rulemaking process with review of comments on proposed rule

5. Complete Prescribing Information Boxed Warning 1 Indications & Usage 2 Dosage & Administration 3 Contraindications 4 Warnings & Precautions 5 Adverse Reactions 6 Drug Interactions 7 Use in Specific Populations 8 Drug Abuse & Dependence 9 Overdosage 10 Description 11 Clinical Pharmacology 12 Nonclinical Toxicology 13 Clinical Studies 14 References 15 How Supplied/Storage & Handling 16 Patient Counseling Information

6. Highlights Limitations Statement Product Names Boxed Warning Recent Changes Indications and Usage Dosage & Administration Contraindications Warnings & Precautions Adverse Reactions Drug Interactions Use in Specific Populations Patient Counseling Information Statement

7. Some Format Innovations Establish format requirements –Minimum 8-point font (note comments to exempt trade labeling that accompanies drug product) –Standardized bolding and “white space” Reorder and reorganize sections –Frequently referenced information moved forward –Consolidate safety information into new Warnings and Precautions section

8. Some Content Innovations Highlights –Limit to ½ page –Bullet information Index –Allow easy reference to full prescribing information –Allow hyperlinks in electronic formats Identify and date major changes Emphasize “Patient Counseling Information” Provide greater clarity in requirements (e.g., Adverse Reactions)

9. Index Boxed Warning 1 Indications & Usage 2 Dosage & Administration 3 Contraindications 4 Warnings & Precautions 5 Adverse Reactions 6 Drug Interactions 7 Use in Specific Populations 8 Drug Abuse & Dependence 9 Overdosage 10 Description 11 Clinical Pharmacology 12 Nonclinical Toxicology 13 Clinical Studies 14 References 15 How Supplied/Storage & Handling 16 Patient Counseling Information

10. Companion Initiatives Guidance –Labeling Content and Format –Adverse Reactions –Clinical Studies –Warning and Precautions, Contraindications and Boxed Warning Health Information Technology PLR provides concise, consistent, reliable information that can be manipulated electronically

11. Structured Product Labeling SPL Content of labeling in a standardized electronic file format with tagged blocks of text and data elements –Substance Registration System (SRS) and Unique Ingredient Identifiers (UNII) –ELIPs (processing system) DailyMed Electronic repository of current labeling managed by NLM updated daily by FDA Medicare Modernization Act Requires uniform standards for medication information

12. Example This is how the product is supplied This is the indication of the product This is the description of this product These are the contraindications These are the warnings Description: This is the description of the product Indications and Usage: This is the indication for use of this product Contraindications: These are the contraindications Warnings: These are the warnings. How supplied: This is how the product is supplied. PDFSPL 12

13. ELIPs - Functions Receive SPL –Validate –Reject –Notify labeling authority Provide review tools –Search –View –Compare –Edit Transmit SPL after 1 business day lag 13

14. Overview of Information Flow Applicant SPL + supporting documents EDR COMIS ELIPS NLM CDR SPL + Electronic documents Tracking information with submission identifier SRS/CID UNII SPL SPL + metadata

15. SPL Project Phase I: SPL for approved prescription drugs –Target: October 2005 –Systems Electronic Labeling Information Processing System (ELIPs) Substance Registration System (SRS) Phase II – SPL for unapproved prescription and OTC drugs –Target: August 2006 –Systems Electronic Listing System (eList) Drug Facility Registration Module (DFRM) 15

16. Summary FDA will provide accurate, up-to-date drug information (labeling) –In a readable, accessible format –In a electronically manipulatable form (SPL), delivered daily to NLM (Daily Med) Drug information initiatives support –Electronic prescribing –Electronic health record –Decision support software