1. Drug Shortage Update Progress Towards Solutions Erin R. Fox, PharmD, FASHP Director, Drug Information Service

2. Disclosure This presentation represents my own opinions. University of Utah Drug Information Service receives some funding from Novation LLC for drug shortage content. No funds are directly paid to Erin Fox.

3. National Shortages and University of Utah Drug Information Service UU DIS provides drug shortage content to American Society of Health-System Pharmacists Public website at www.ashp.org/shortagewww.ashp.org/shortage –Partners since 2001 –Receive voluntary reports submitted via web –Frequent communication with FDA drug shortage team

4. Shortage Website Differences ASHP www.ashp.org/shortage Drugs impacting clinical practice (biologics, devices, dosage forms) What is available at NDC level How to access Frequent updates Alternatives Contract information FDA www.fda.gov/cder Medically necessary drugs Information from manufacturer

5. Timeline Towards Progress 2002 AMA/ASHP 2010 Summit 2011 FDA Workshop 2011 AMA Policy 2011 Executive Order 2012 FDASIA

6. FDA Strategic Plan for Shortages Mandated as part of FDASIA law –Enhance mitigation efforts –Develop long-term prevention Suggestions for external stakeholders –Manufacturing incentives –Use quality data when purchasing –Capacity, redundancy

7. FDA’s Mitigation Tool Kit Regulatory discretion –Require filters Ask others to increase production Expedite reviews (new product, longer expiration, new raw material, new manufacturing sites Imports –Less than ideal, but helpful NB – FDA can’t make any drug!

8. Making a Difference? +FDA prevents hundreds of shortages +More suppliers choose to work with FDA early +Decreased rate of new shortages –Ongoing shortages not resolving –Manufacturing problems –Continued patient impact

9. Current Trends

10. New Shortages by Year January 2001 to September 30, 2014 Note: Each column represents the number of new shortages identified during that year. University of Utah Drug Information Service Erin.Fox@hsc.utah.eduErin.Fox@hsc.utah.edu, @foxerinr

11. Active Shortages by Quarter Note: Each column represents the number of active shortages at the end of each quarter. University of Utah Drug Information Service Erin.Fox@hsc.utah.eduErin.Fox@hsc.utah.edu, @foxerinr

12. Top 5 Drug Classes University of Utah Drug Information Service Erin.Fox@hsc.utah.eduErin.Fox@hsc.utah.edu, @foxerinr

13. Shortages of Basics Frequent fliers 10 medications short > 50 times between 2001 and 2013 –Dextrose, diazepam, epinephrine, fentanyl, lorazepam, morphine, ondansetron, nalbuphine, naloxone, promethazine

14. What do these numbers mean? The rate of new shortages has decreased, but recently has increased The ongoing shortages are not resolving Continued daily impact for patients, clinicians, health systems, health care http://www.gao.gov/products/GAO-14-194 Twitter: @foxerinr

15. Why is this happening?

16. Drug Manufacturing is a Business Profitability Manufacturing fixes Capacity – most factories running 24/7 Prioritization (new opportunities) Forecasting (contracts) Aging facilities

17. 17 Fragile Supply Chain Generic Injectables Few suppliers 3 manufacturers supply 71% of market Only 1 or 2 manufacturers for > 1/3 products Capacity is limited –Concentrated, “just in time” production –Multiple products made on single line –No back up manufacturing lines

19. IV Fluids, Irrigations Shortage 3 suppliers All suppliers state “increased demand” Real reason behind the increased demand is unclear Rolling shortages, unclear allocations (expect problems through 2015?) –Available fluid type, volume will vary –Imports – costs, access, packaging

20. No Quick and Easy Fix Complex manufacturing process –Quality problems are difficult to fix –Investigation of root cause takes time –Changes take time –Capacity or redundancy not available

21. How did we get here?

22. Cascade of Events 2008 2009 2010+ Early 2000’s “Find production efficiencies” Heparin Dr. Hamburg FDA increases scrutiny Warning letters, 483’s document serious quality problems Irvine plant closes Ohio plant closes New York plant closes 30% manufacturing capacity is closed

23. Economic Drivers of Drug Shortages Quality Not Transparent No Incentive Clin Pharmacol Ther. 2013;93:170-176 Clin Pharmacol Ther. 2013; 93:145-147

24. Why Doesn’t the Free Market Fix the Problem? Supply and demand doesn’t work for drugs Consumers don’t choose products Misaligned incentives No suppliers to step in when others can’t produce Shortages generally don’t impact profits Patient impact, not suppliers

25. No Requirement to Report Manufacturer of Product Contract manufacturing means we don’t always know who makes the product No requirement to disclose manufacturer (or location) in product label (or 483) Your brand product may be manufactured by a generic company

26. Import Bans Ranbaxy, Wockhardt, import bans Massive recalls due to falsified data, tablets that won’t dissolve India’s Drug Controller General says US standards too strict

27. New Ideas for Solutions

28. International Society for Pharmaceutical Engineering Survey -2013 – Key deficits in quality systems, aseptic processing equipment Shortage initiative – Root causes of manufacturing problems Prevention Plan (October 2014) –6 dimension plan http://www.ispe.org/drug-shortages-initiative

29. New Ideas for Manufacturing Janet Woodcock advocates continuous manufacturing for: –Faster, improved quality, lower prices, fewer shortages –Domestic plants – fully integrated from API to finished product

30. Too little, too late Hospitals are functioning in disaster mode Patient care decisions based on incomplete information Clinicians no longer trust critical therapies will be available for patients Industry must fix itself

31. Contact Information Erin R. Fox, PharmD, FASHP Director, Drug Information Service University of Utah Health Care Adjunct Associate Professor, University of Utah College of Pharmacy, Dept. of Pharmacotherapy 801-587-3621 erin.fox@hsc.utah.edu Twitter: @foxerinr