1. Thomas Eingle, R.Ph. Inpatient Pharmacy Supervisor James A. Haley Veterans Hospital, Tampa, Fl

2. Disclosures  Thomas Eingle declares no conflicts of interest, real or apparent, and no financial interests in any company, product, or service mentioned in this program.

3. Objectives  List drugs affected by national drug shortage  Breakdown and discuss cited reasons for National Drug shortage  Discuss FDA response  Learn about resources to manage drug shortages  Discuss VAMC considerations in drug procurement to solve drug shortages

4. Senate Finance Committee Hearing on “Drug Shortages: Why They Happen and What They Mean” December 7, 2011 “In the past five years, shortages have rapidly escalated, increasing from 70 in 2006 to 231 as of this November, and there appears to be no end in sight. “

5. Hot off the Press!

6. Sampling of Drug Shortages affecting Inpatient Hospital setting Injectable Drug AmiodaroneFurosemide AtracuriumHaloperidol AtropineHeparin BumetanideHydromorphone Desmopressin injLevofloxacin Dexamethasone NaPO4Lorazepam DiazepamMagnesium sulfate DigoxinMannitol DiltiazemMetoclopramide FentanylMidazolam FluconazoleMorphine FosphenytoinPancuronium Several ingredients for TPNs

7. Chemotherapy BendamustineLeucovorin BleomycinMannitol CarboplatinMesna CytarabineMethotrexate DacarbazineMethylene Blue DaunorubicinOndansetron DexrazoxanePaclitaxel DoxorubicinSodium Thiosulfate FludarabineThiotepa FluorouracilVinblastine Sampling of Chemotherapy /Supportive Medication Shortages http://www.ashp.org/DrugShortages/Current

8. Drugs on Shortage  List of current drugs on shortage available at http://www.ashp.org/DrugShortages/Current/ http://www.ashp.org/DrugShortages/Current/ Lists Drugs on shortage with date revised If click on specific drug gives detailed information about: ○ Product affected ○ Reason for shortage ○ Available Products ○ Estimated Resupply dates ○ Related shortages

9. Drug Shortages by Primary Reason for Disruption in Production and Supply  [Food and Drug Administration, 10/31/11]  Key: API = Actual Pharmaceutical Ingredient

10. Dosage Forms and Drug Source Affected ismpinstitute.org

11. Cited Reasons for Drug Shortages  Supply/Demand issues  Production issues  Aging Manufacturing Plants  Shortage of Raw Materials  Generic manufacturing not profitable  Gray Market hoarding medications

12. A Matter of Simple Economics: Supply and Demand  Increased demand for certain drugs can be caused by: competing manufacturers that have discontinued or withdrawn the product from the marketplace shortage of raw materials ○ Foreign source ○ Manufacturer not relinquishing exclusive raw material contracts when the product is discontinued (usually because they are working on a “next generation” generic that will be soon marketed)

13. Supply/Demand Example http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm050792.htm

14. How manufacturing and supply chain issues can cause drug shortages. www.FDA.gov

15. Production Problems http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm050792.htm  Contamination – i.e Dexamethasone from American Regent  Limited Production of product  Manufacturing Line Prioritization – i.e. Ketorlac Carpuject all strengths

16. Aging Production Plants  Shortage of methotrexate and doxorubicin was triggered by an FDA inspection of a generic manufacturing plant in Ohio. The Ben Venue Laboratories flunked because there was mold on the walls, rust from aging equipment falling into the medication and other violations of good manufacturing practice.

17. The Perfect Storm that Creates Drug Shortages for Generic Products  Medicare restrictions on average sale prices (which can only be updated every six months) for generic medicines  just-in-time inventory supply practices at hospitals  reverse-auction contracts from large group purchasing organizations for supplying generic drugs  tougher FDA manufacturing and inspection standards for domestic companies (which can raise costs)  increased global competition from low-cost suppliers in India and China

18. Gray Market

19.  They buy up drugs for everything from cancer to infections, stockpile them, then sell them to hospitals at massive markups.  The average markup on drugs is 650%  FDA is accepting cases of gray market abuse that it would refer to the Department of Justice.  If you are experiencing issues with gray market suppliers, contact the FDA Drug Shortage Office.

20. FDA Response  Work with manufacturers that report drug shortage issues  If necessary, ask alternative manufacturers to increase production  Expedite the review of data to support approval of a new generic drug product  Allow importation of product from other countries until the shortage is resolved  Assist manufacturer in instituting a drug allocation program to limit distribution

21. FDA Response

22. Resources to Manage Drug Shortage  www.ashp.org/DrugShortages www.ashp.org/DrugShortages  http://www.fda.gov/Drugs/DrugSafety/Dr ugShortages/ucm050792.htm http://www.fda.gov/Drugs/DrugSafety/Dr ugShortages/ucm050792.htm

23. Issues Specifically Related to VAMC  VA can only order drug products that are made in countries listed on the TAA Designated Country list. Turkey and India are not on this list VAMC is not able to obtain emergency alternative medications as easily as other Non- VA hospitals.

24. Designated Countries

25. Conclusions  Drug Shortages affect patient safety  Resources are available to assist in managing the drug shortage  Best to research therapeutic alternatives proactively  Best to have an organizational agreement on prioritizing patients and/or placing restrictions for use  Best to not hoard drugs that are on shortage or their alternatives

26. Questions?