Transcript Clin Pharmacol Ther. 2013 - OSMAP and The Forum for Medical Affairs

Drug Shortage Update
Progress Towards Solutions
Erin R. Fox, PharmD, FASHP
Director, Drug Information Service
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.
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/shortage
– Partners since 2001
– Receive voluntary reports submitted via web
– Frequent communication with FDA drug
shortage team
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
Timeline Towards Progress
2002
AMA/ASHP
2011 FDA
Workshop
2010
Summit
2011
Executive
Order
2011
AMA Policy
2012
FDASIA
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
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!
Making a Difference?
+ FDA prevents hundreds – Ongoing shortages
not resolving
of shortages
+ More suppliers choose – Manufacturing
problems
to work with FDA early
+ Decreased rate of new – Continued patient
impact
shortages
Current Trends
New Shortages by Year
January 2001 to September 30, 2014
300
267
250
211
204
200
150
149
140 145
129
120
88
100
166
73
58
74
70
05
06
50
0
01
02
03
04
07
08
09
10
11
12
13
14
Note: Each column represents the number of new shortages identified during
that year. University of Utah Drug Information Service
[email protected], @foxerinr
Active Shortages by Quarter
350
300
239
250
273
299 295 299 294 288
320
260
211
200
150
246 256
282
305 306
152
167 176
188
100
50
0
Note: Each column represents the number of active shortages at the end of
each quarter. University of Utah Drug Information Service
[email protected], @foxerinr
Top 5 Drug Classes
Active Shortages 9/30/14
60
50
40
30
20
10
0
52
47
41
30
30
University of Utah Drug Information Service
[email protected], @foxerinr
Shortages of Basics
• Frequent fliers
• 10 medications short > 50 times between
2001 and 2013
– Dextrose, diazepam, epinephrine, fentanyl,
lorazepam, morphine, ondansetron,
nalbuphine, naloxone, promethazine
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
Why is this happening?
Drug Manufacturing is a Business
•
•
•
•
•
•
Profitability
Manufacturing fixes
Capacity – most factories running 24/7
Prioritization (new opportunities)
Forecasting (contracts)
Aging facilities
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
17
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
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
How did we get here?
Cascade of Events
Early 2000’s
“Find production
efficiencies”
2008
Dr. Hamburg
FDA increases
scrutiny
2009
Irvine plant closes
New York plant
closes
Heparin
Warning letters,
483’s document
serious quality
problems
2010+
30% manufacturing
capacity is closed
Ohio plant
closes
Economic Drivers of Drug Shortages
Quality
No
Incentive
Clin Pharmacol Ther. 2013;93:170-176
Clin Pharmacol Ther. 2013; 93:145-147
Not
Transparent
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
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
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
New Ideas for Solutions
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
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
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
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
[email protected]
Twitter: @foxerinr