An Epic Battle Pharmacist Heroes vs. Shortages

Transcription

1 An Epic Battle Pharmacist Heroes vs. Shortages Erin R. Fox, PharmD, BCPS, FASHP mmpharmd Disclosure This presentation represents my own opinions. University of Utah Drug Information Service receives some funding from Vizient to provide drug shortage content. Drug Shortages 1

2 Learning Objectives 1. Explain current trends in drug shortages. 2. Discuss federal regulations related to manufacturing and how recent quality trends relate to drug shortages. 3. Review federal laws related to drug shortages including advocacy opportunities for change University of Utah Drug Information and Drug Shortages Provide drug shortage content for ASHP Public website at Partners since 2001 Voluntary reports are confirmed with manufacturers Collaborate with FDA s drug shortage team Drug Shortages 2

3 National Drug Shortages New Shortages by Year January 2001 to March 31, National Drug Shortages Active Shortages by Quarter Drug Shortages 3

4 Active Shortages Top 5 Drug Classes Active Shortages March 31, Antimicrobials Chemotherapy Cardiovascular CNS E-Lytes, Nutrition, Fluids What do these numbers mean? The rate of new shortages is fairly consistent, however critical shortages are severely impacting patient care and pharmacy operations Long-term active and ongoing shortages are not resolving The most basic products required for patient care are short: saline, dextrose, hydromorphone, morphine, fentanyl, ketamine, and sterile water Drug Shortages 4

5 What s making current numbers feel worse? Shortages of basic products impacting most patients High risk medications (opioids) EHR, automation, smart pumps All designed to require the use of the same product, all of the time Large amounts of product needed Uncertainty about compounding regulations Disruption in 503b market Quality Drug Shortages 5

6 June 2016 Government Accountability Office Analysis Few suppliers Warning letter Injectable Low profit Manufacturing / Quality Issues Quality Leaks Mold Equipment Product Defect Sterility Particles Overfill Shortages Recalls Closures Drug Shortages 6

7 What are the laws regarding manufacturing? Current Good Manufacturing Practice (CGMP) Regulations Code of Federal Regulations (CFR) Title 21 (Food and Drugs) 21 C.F.R CGMP manufacturing, packing, holding, general 21 C.F.R CGMP for finished pharmaceuticals 21 C.F.R Human drug compounding Browse online at Guidance from FDA on meeting CGMP /ucm htm CGMP Inspections Title VII Food and Drug Safety and Innovation Act (FDASIA) 705 Risk-based Inspection Frequency Routine For cause Drug Shortages 7

8 How to review inspection data? Office of Regulatory Affairs FOIA Electronic Reading Room Domestic inspections filter and sort by date, record type, state etc. Warning Letters Link on main CDER page Select Year Select Office Prescription Drug Promotion Compliance/Immediate Office Manufacturing Quality Scientific Investigations Drug Security, Integrity, Recalls Drug Shortages 8

9 Other Warnings and Inspections District Office Warning Letters Compounding and Outsourcing Facilities Drug Shortages 9

10 Lack of Transparency Contract manufacturing means we don t always know who makes the product No requirement to disclose manufacturer (or location) in product label (or 483) Cannot purchase based on quality Labeling Laws 21 C.F.R Drugs; name and place of business of manufacturer, packer, or distributor Drug Shortages 10

11 What does quality mean? Difficult to observe Microbial contamination difficult to detect (non-uniform, patients already sick) Purchasers rely on FDA to ensure quality FDA inspects, but relies on manufacturer to self-report between inspections Does quality = availability? Economic drivers of drug shortages Quality No Incentive Not Transparent Clin Pharmacol Ther. 2013;93: Mayo Clinic Proc (3): Drug Shortages 11

12 Quality metrics goals Modernize drug quality oversight Risk based inspection scheduling Predict drug shortages Objective criteria including: Lot acceptance rate Product quality complaint rate Drug Shortages 12

13 Fixing the shortage problem Are shortages FDA s fault? NO FDA shortage team is extremely collaborative Violations must be extreme for a shut-down (safety first!) Work diligently to prevent shortages YES Enforcement actions can cause shortages Manufacturers may have trouble complying with regulations Regulatory discretion = unintended consequences? Drug Shortages 13

14 FDA s strategy Prioritize medically necessary agents (determined on a case by case basis) Evaluate risks and benefits for patients Offer assistance and advise, but up to the manufacturer to fix Success hinges on early notification A Review of FDA's Approach to Medical Product Shortages. October 31, How does FDA prevent shortages? Regulatory discretion Require filters, double checks Ask others to increase production Expedite reviews (new product, longer expiration, new raw material, new manufacturing sites) Imports A Review of FDA's Approach to Medical Product Shortages. October 31, Drug Shortages 14

15 Imports Multiple examples since 2010 propofol, foscarnet, ethiodol, thiotepa, norepinephrine, capecitabine, leucovorin, levoleucovorin, methotrexate, doxorubicin liposomal, phentolamine, sodium bicarbonate, nitroglycerin, saline, bleomycin Limited by quantity available to share with US market May be difficult to access or use May not be an option for some clinical trials FDA strategic plan Mandated as part of FDASIA law 2 key goals Enhance mitigation efforts Develop long-term prevention Suggestions for external stakeholders Manufacturing incentives Use quality data when purchasing Capacity, redundancy Drug Shortages 15

16 FDA can only do so much FDA CAN require *notification of supply disruptions (FDASIA) FDA CANNOT require *continued production *increased production *disclosure of distribution Government Action President Obama Executive order October 2011 (notification) FDA Interim Final Rule December 2011 (notification) Senate / House Bills Food and Drug Administration Safety and Innovation Act (FDASIA) July 2012 User Fees (PDUFA V, MDUFA III, GDUFA, BsUFA) Innovation ( breakthrough designation, expedited programs) Title X shortage notifications Drug Shortages 16

17 ASPE Economic Analysis 2011 Limited capacity will take years to resolve Shortages due to expansion and volume of products without correlating capacity ASP + 6 pricing not specifically a contributing factor Advocating for change Drug Shortages 17

18 Strengthen Title X of FDASIA Discontinuance or interruption in the production of lifesaving drugs Provide reason for shortage to FDA with notification Extend notification to all shortages, not just life-saving Contingency Planning Encourage manufacturers to plan ahead FDA could include contingency planning as part of the approval process or routine inspections istockphoto.com/alexlmx Drug Shortages 18

19 Critical Infrastructure Consider drug shortages as a national security threat Support shortage prevention efforts by HHS / DHS Interagency Committee formation Authorize FTC / DOJ / FDA to form an interagency committee Suspend or stop merger or acquisition if it may cause shortages or harm public health Determine if remaining factories are functioning (cgmp) Consent orders with FTC to require business continuity planning Drug Shortages 19

20 DEA Quota System Implement GAO recommendations Improve cooperation between FDA and DEA Speed reallocation of quota on notification Advocacy Agenda ASHP roundtable report 11 recommendations Committee hearings? Contact your representatives Be specific Patient impact Health-system impact Offer suggestions Drug Shortages 20

21 Review of self assessment questions The most current trend for drug shortages is? a. Decreasing active shortages with an increase in specialty drug shortages b. Increasing active shortages with a decrease of shortages of basic products c. Increasing active shortages with an increase in specialty drug shortages d. Decreasing active shortages with an increase in basic product shortages. Drug Shortages 21

22 National Drug Shortages Active Shortages by Quarter Package inserts must include which of the following by law? a. Name of the company selling the product b. Location and name of the factory where product was manufactured c. Name of company that provides the active pharmaceutical ingredient (API) d. Name of the company that manufactured the product Drug Shortages 22

23 Lack of Transparency Contract manufacturing means we don t always know who makes the product No requirement to disclose manufacturer (or location) in product label (or 483) Cannot purchase based on quality FDA works to prevent some shortages by: a. Requiring companies to continue to produce products in short supply b. Prioritizing approvals of new products c. Decreasing drug prices d. Requiring other companies to increase production Drug Shortages 23

24 A potential strategy to improve drug shortages in the future is: a. Require manufacturers to have business continuity plans as part of the FDA approval process b. Ask FTC / FDA / DOJ to form an interagency committee to review potential public health concerns due to mergers c. Consider medication supply to be part of national security d. All of the above Contact Erin R. Fox, PharmD, BCPS, FASHP Senior Director, Drug Information Service University of Utah Health erin.fox@hsc.utah.edu Drug Shortages 24