MEDICINES SHORTAGES
PROGRESS AND
IN MANUFACTURING
FUTURE AGENDA
"GLOBAL STOCK OUTS"
Lisa Hedman
Department of Essential Medicines and Health Products
1 | Medicine shortages
Overview of global stock outs
 Defined as shortages or stock outs caused by
manufacturing insufficiency
 Similar incidence between branded versus generics
 Higher incidence in older generics, sterile injectables,
oncology medicines
 Affects countries of all income levels
 Can be confused with supply chain stock outs in some
situations
2 | Medicine shortages
Increasing trend
Example of trends from USA
United States Food and Drug Administration accessed 22 October 2013 http://aspe.hhs.gov/sp/reports/2011/DrugShortages/ib.shtml
3 | Medicine shortages
Current oncology medicines shortages

Deferoxamine Mesylate for Injection (Desferal) (Discontinuation)

Denileukin Diftitox (Ontak) Injection (Discontinuation)

Doxorubicin (Adriamycin) Injection (Shortage)

Ethiodized Oil (Lipiodol) Injection (Shortage)

Leucovorin Calcium Lyophilized Powder for Injection (Shortage)

Leuprolide Acetate Injection (Shortage)

Mesna Injection (Discontinuation)

Ondansetron (Zofran) Injection (Discontinuation)

Thiotepa (Thioplex) for Injection (Shortage)

Tositumomab and Iodine I 131 Tositumomab (Bexxar) (Discontinuation)
4 | Medicine shortages
USFDA 28 October 2015:
http://www.accessdata.fda.gov/scripts/
drugshortages/default.cfm
Current shortages:
Dosage forms for children
Ammonium Chloride Injection (Shortage)
Atropine Sulfate Injection (Shortage)
Atropine Sulfate Injection (Discontinuation)
alcium Chloride Injection, USP (Shortage)
Calcium Gluconate Injection (Shortage)
Fentanyl Citrate (Sublimaze) Injection
(Shortage)
Ondansetron (Zofran) Injection
(Discontinuation)
Leucovorin Calcium Lyophilized Powder for
Injection (Shortage)
Pancuronium Bromide Injection (Shortage)
Leuprolide Acetate Injection (Shortage)
Levetiracetam (Keppra) Injection (Shortage)
Cefazolin Injection (Shortage)
Cefepime Injection (Shortage)
Lidocaine Hydrochloride (Xylocaine) Injection
(Shortage)
Cefotaxime Sodium (Claforan) Injection
(Shortage)
Liotrix (Thyrolar) Tablets (Shortage)
Chloramphenicol Sodium Succinate Injection
(Shortage)
Lorazepam (Ativan) Injection
(Discontinuation)
Peritoneal Dialysis Solutions (Shortage)
Piperacillin and Tazobactam (Zosyn)
Injection (Shortage)
Potassium Chloride Injection (Shortage)
Reserpine Tablets (Shortage)
Sodium Chloride 0.9% Injection Bags
(Shortage)
Magnesium Sulfate Injection (Shortage)
Sodium Chloride 23.4% Injection
(Shortage)
Cidofovir Injection (Discontinuation)
Mecasermin [rDNA origin] (Increlex) Injection
(Shortage)
Sodium Chloride 23.4% Injection
(Discontinuation)
Dexamethasone Sodium Phosphate Injection
(Shortage)
Meloxicam (Mobic) Oral Suspension
(Discontinuation)
Sufentanil Citrate (Sufenta) Injection
(Shortage)
Dextrose 5% Injection Bags (Shortage)
Meropenem for Injection, USP (Shortage)
Thiotepa (Thioplex) for Injection (Shortage)
Doxorubicin (Adriamycin) Injection
(Shortage)
Methyldopate Hydrochloride Injection
(Shortage)
Tiopronin (Thiola) (Shortage)
Epinephrine 1mg/mL (Preservative Free)23
(Shortage)
Methylin Chewable Tablets (Shortage)
Chloroquine Phosphate Tablets (Shortage)
Epinephrine Injection (Shortage)
5 | Medicine shortages
Methylphenidate Hydrochloride ER
Capsules/Tablets24 (Shortage)
USFDA 28 October 2015:
http://www.accessdata.fda.gov/scripts/
drugshortages/default.cfm
Tobramycin Injection (Shortage)
Trace Elements (Shortage)
Vancomycin Hydrochloride for Injection,
USP (Shortage)
Most commonly cited causes
 Regulatory decisions e.g., plant closures
 Insufficient manufacturing base (3 or fewer manufacturers)
 Market failures, including unaffordability and low-margins
 Competition for production capacity with higher margin
products
 Poor visibility into demand cycles
 Less than full batch order quantities
 Poor procurement practices, eg payment and other terms
6 | Medicine shortages
Solutions in use for
national level management
 Advance reporting to regulatory agencies from
manufacturers
 Fast track regulatory assessments to manage risk of
substitution
 Programmatic and association based reporting
 Compulsory licenses (eg for ARVs)
 Contract penalties in procurement
7 | Medicine shortages
Who benefits from early warning systems
of stringent regulatory authorities
80
Estimated n
umber of countries
70
Access and benefit from existing early warning systems
60
50
40
30
70
48
20
38
10
0
virtually no access
very limited access
potential access to existing early warning mechanism
regular access
8 | Medicine shortages
38
Case study:
global shortage of benzathine penicillin (PenG)
 WHO quantification in 20 countries with highest syphilis burden
– 4 million doses (in 2.4 MU) for adult men and women with early stage
syphilis1 and for pregnant women with active syphilis
– 90,000 doses of 3.8 MU for infants with premature delivery due to
syphilis and infants with congenital syphilis
 Pen G and rheumatic heart disease
– Up to 20 million doses needed for acute RH disease and continuing
treatment
– figures unreliable due to poor Dx, Rx and medicine consumption data
 Global supply is insufficient with 3 producers and repeated nonavailability reports by major procurers
9 | Medicine shortages
1
Assumptions and calculations are preliminary
data from pending WHO analysis
Solutions and conclusions of the meeting on
managing and preventing global stock outs
 Global advance reporting systems for medicines at high
risk ie manufacturers report in advance
 Fast track options to manage risk of substitutions along
with communication approaches
 Harmonization of fast track regulatory reviews with
information sharing
 Forums to identify and monitor highest risk products
 Model policy and legislation to promote effective
management
10 | Medicine shortages
Solutions and conclusions of the meeting on
managing and preventing global stock outs
 Regularize pricing policy to ensure that production can
be realistically sustained
 Engage in prioritization and include models used by
industry in the discussion
 Paradigm shifts needed in supply chain, motivation to
report, and transparency
 In supply chain, development and exchange of quality
information will take major changes
– Implementation of GS1 bar coding systems as a starting point
11 | Medicine shortages
Photo: Dr Charles Senessie, SwissmedIc
Thank you to all
Thank you
12 | Medicine shortages