WHO informal consultation to develop further guidance on vaccines for the UNEP-convened
Intergovernmental Negotiating Committee Meeting 4 (INC4)
4 April 2012 Geneva, Switzerland
Jodi Liu, WHO Consultant
Trends in use of multi-dose vaccine vials in UNICEF procuring countries
2 | Multi-dose vial use | 4 April 2012
Acknowledgements
WHO Headquarters: – Diana Chang Blanc
UNICEF Supply Division, Copenhagen: – Robert Matthews – Katinka Rosenbom – Jennifer Rubin – Selenge Lkhagva – Ann Ottosen
UNICEF Program Division, New York: – Maya van den Ent
3 | Multi-dose vial use | 4 April 2012
Objectives of study
Identify trends in multi-dose vial use of DTP-based, hepatitis B, and measles-containing vaccines from 2000-2011
– Review UNICEF Supply Division vaccine procurement database – Determine if there is an obvious trend of countries shifting from
larger to smaller multi-dose vials or vice versa
Assess factors that influence the use of different vial sizes, e.g. global supply and country-driven preference
4 | Multi-dose vial use | 4 April 2012
Limitations of study
Trends in UNICEF procurement are not representative of global trends. Study excludes:
– Procurement through the PAHO Revolving Fund – Countries that procure independently
Limited information on country preference – Difficult to ascertain drivers for use of a particular vaccine
presentation – An aggregate of country-driven preferences is considered here
5 | Multi-dose vial use | 4 April 2012
Assumptions
Country-driven preference: – Price, e.g. HepB: $0.2/dose for 10 dose vial vs. $0.4/dose for 1 dose – Cold chain volume requirements, e.g. DTP-HepB/Hib: 23-26 cm3/dose
for liquid 1 dose vial vs. 2.6 cm3/dose for liquid 10 dose vial – Programmatic feasibility, e.g. fully liquid preferred over liq/lyo
Source of funding is considered external, internal, or mixed – External: donors funds from outside a country – Internal: self-financing from government resources – Mixed: both external and internal funding in a given year
Annual weighted average price per dose was used to compare cost of vaccine presentations
6 | Multi-dose vial use | 4 April 2012
DTP
UNICEF procurement for 20 - 70 countries each year during 2000-2011 (70 in 2001; 20 in 2010)
WHO prequalified: 1, 10, 20 dose vials in fully liquid form
2000-2011: Overall decline in DTP procurement as the use of combination vaccines has increased; mostly procured in 10 dose vials
Country preference for 10 or 20 dose vials often flexible but 7 countries switched from 20 to 10 dose vials
7 | Multi-dose vial use | 4 April 2012
01020304050607080
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Num
ber o
f cou
ntrie
s
DTP
10 dose 20 dose
0.00
0.05
0.10
0.15
0.20
0.25
01020304050607080
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Wei
ghte
d av
g pr
ice
/ do
se (U
SD)
Num
ber o
f cou
ntrie
s
10 dose 20 dose 10 dose price 20 dose price
2006 WHO recommends universal use of Hib
Note: a single country may procure more than one vaccine presentation in a given year; thus, one country may be counted in more than one vial size category.
8 | Multi-dose vial use | 4 April 2012
DTP-HepB
UNICEF procurement for 3 - 17 countries each year during 2000-2011(17 in 2007; 3 in 2009, 2010, 2011)
– GAVI co-financing 2001-2011, but will not continue after 2011
WHO prequalified: 1, 2, 5, 10, 20 dose vials in liquid form
Mostly procured in 10 dose vials
2006-2008: Increase in use after increase in global supply 2009-2011: Decline in use with increasing uptake of pentavalent
No observed trends in use of different vial sizes
9 | Multi-dose vial use | 4 April 2012
02468
1012141618
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Num
ber o
f cou
ntrie
s
DTP-HepB
2 dose 10 dose
0.00.20.40.60.81.01.21.41.61.8
02468
1012141618
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Wei
ghte
d av
g pr
ice
/ do
se (U
SD)
Num
ber o
f cou
ntrie
s
2 dose 10 dose 2 dose price 10 dose price
2004-2005 Increase in
global supply
10 | Multi-dose vial use | 4 April 2012
DTP-Hib
UNICEF procurement for 1 - 17 countries each year during 2000-2011 (1 in 2002; 17 in 2007)
WHO prequalified: 1 and 10 dose vials in both liq and liq/lyo
Mostly procured in liquid 10 dose vials
2006: Increased uptake after universal Hib recommendation 2008-2011: Decline in overall use due to pentavalent, expected to continue to decline in future years
No clear trend in use of different vial sizes
11 | Multi-dose vial use | 4 April 2012
012345678
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Num
ber o
f cou
ntrie
s
DTP-Hib
1 dose (liq/lyo) 10 dose (liq or liq/lyo)
0.00.51.01.52.02.53.03.54.04.5
012345678
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Wei
ghte
d av
g pr
ice
/ do
se (U
SD)
Num
ber o
f cou
ntrie
s
1 dose (liq/lyo) 10 dose (liq or liq/lyo) 1 dose price 10 dose price
2006 WHO recommends universal use of Hib
12 | Multi-dose vial use | 4 April 2012
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
DTP-HepB/Hib Timeline
(1) GAVI begins financing liq/lyo 2 dose
(3) PQ: liq/lyo 2 dose (1 supplier) PQ: liq and liq/lyo 1 dose (2 suppliers, but initially insufficient supply)
(5) PQ: liq & liq/lyo 10 dose (1 supplier) Delisting: liq 1 and 10 dose (1 supplier) PQ: liq & liq/lyo 2 dose (1 supplier) PQ: liq & liq/lyo 1 dose (1 supplier)
(6) Delisting: liq & liq/lyo 1 dose (1 supplier) PQ: liq 1 dose (1 supplier) PQ: liq 10 dose (1 supplier)
(2) WHO universal recommendation of Hib use Global prioritisation for allocation
(4) PQ: liq 1 dose (2 suppliers) PQ: liq 10 dose (1 supplier)
13 | Multi-dose vial use | 4 April 2012
DTP-HepB/Hib
UNICEF procurement for 6 - 70 countries each year during 2000-2011 (6 in 2001, 2002, 2003; 70 in 2011)
WHO prequalified: 1, 2, 10 dose vials all in liq and liq/lyo
2001-2006: Mostly procured as liq/lyo 2 dose vials 2007-2010: Greater uptake in overall use; shift from liq/lyo 2 to fully liquid 1 dose due to increasing global supply of 1 dose vials and country-driven preference for fully liquid 2011: Shift from 1 dose to fully liquid 10 dose vials due to global supply (delisting of liquid 1 dose vial in 2010)
14 | Multi-dose vial use | 4 April 2012
0102030405060708090
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Num
ber o
f cou
ntrie
s
DTP-HepB-Hib
1 dose (liq or liq/lyo) 2 dose (liq/lyo) 10 dose (liq)
0.00.51.01.52.02.53.03.54.04.5
0102030405060708090
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Wei
ghte
d av
g pr
ice
/ do
se (U
SD)
Num
ber o
f cou
ntrie
s
1 dose (liq or liq/lyo) 2 dose (liq/lyo) 10 dose (liq)1 dose price 2 dose price 10 dose price
2006 WHO recommends universal use of Hib
15 | Multi-dose vial use | 4 April 2012
HepB
UNICEF procurement for 15 - 45 countries each year during 2000-2011 (15 in 2000; 45 in 2004)
WHO prequalified: 1, 2, 6, 10, 20 dose vials all in fully liquid form
HepB is mostly commonly procured in 10 dose vials
6 countries switched from 10 to 1 dose vials due to increasing use of DTP-HepB/Hib (1 dose vials often used for HepB birth dose)
16 | Multi-dose vial use | 4 April 2012
0
10
20
30
40
50
60
70
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Num
ber o
f cou
ntrie
s
HepB
1 dose 2 dose 6 dose 10 dose
0.0
0.2
0.4
0.6
0.8
1.0
1.2
0
10
20
30
40
50
60
70
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Wei
ghte
d av
g pr
ice
/ do
se (U
SD)
Num
ber o
f cou
ntrie
s
1 dose 2 dose 6 dose 10 dose 1 dose price 10 dose price
17 | Multi-dose vial use | 4 April 2012
Measles
UNICEF procurement for 54 -72 countries each year during 2000-2011 (72 in 2000; 54 in 2011)
WHO prequalified: 1, 2, 5, 10, 20 dose vials all in lyo form
Procured for both routine and supplementary activities
Mostly procured in 10 dose vials
No trends in vial size observed
UNICEF procurement for 1 -11 countries each year during 2000-2011 (1 in 2000; 11 in 2007)
WHO prequalified: 1, 2, 5, 10 dose vials all in lyo form
Procured for both routine and supplementary activities
Procured only in 10 dose vials
No trends observed
MR
18 | Multi-dose vial use | 4 April 2012
MMR
UNICEF procurement for 3 -14 countries each year during 2000-2011 (3 in 2000; 14 in 2010, 2011)
WHO prequalified: 1, 2, 5, 10 dose vials all in lyophilised form
Mostly procured in 1 and 10 dose vials
In the WHO European region, 5 countries switched from 10 to 1 dose vials due to country-driven preference
2009-2011: 5 dose vials procured in large quantities for a few countries
19 | Multi-dose vial use | 4 April 2012
Conclusions
The evolution of multi-dose vaccine vial use contains micro-patterns but no clear overall pattern was observed
– Shifts in national use of larger to smaller vial sizes and vice versa were observed in the UNICEF procuring countries
– The use of different multi-dose vial sizes is affected by global supply and country-driven preference, e.g. DTP supply, DTP-HepB/Hib supply and programmatic feasibility with fully liquid presentation
Despite the availability of single-dose presentations, 10 dose vials are most commonly used and there is no evidence of increasing use of 1 dose vials
Multi-dose vials are commonly used in UNICEF procuring countries and are likely to continue to be a vital part of immunization programs
20 | Multi-dose vial use | 4 April 2012
Questions?
21 | Multi-dose vial use | 4 April 2012
References
World Health Organization. A system for the prequalification of vaccines for UN supply. Last updated 10 November 2011. Accessed 27 March 2012. http://www.who.int/immunization_standards/vaccine_quality/pq_system/en/index.html.
World Health Organization. WHO prequalified vaccines. Last updated 19 January 2012. Accessed 5 March 2012. http://www.who.int/immunization_standards/vaccine_quality/PQ_vaccine_list_en/en/index.html.
van den Ent M, Lkhagva S, Rubin J, Hoeskstra E. Impact of rubella introduction on vaccine supplies and demand for 5-dose vial. UNICEF. 2012. Unpublished.
World Health Organization. Mumps virus vaccines. Wkly Epidemiol Rec. 2007, 7: 51-60.
World Health Organization. WHO position paper on Haemophilus influenzae type b conjugate vaccines. Wkly Epidemiol Rec. 2006, 81: 445-452.
22 | Multi-dose vial use | 4 April 2012
WHO prequalified vaccines Vaccine presentation and supplier information
Vaccine type Doses per vial
Form Current number of suppliers
Years prequalified (number of manufacturers*)
Years delisted Production comment
DTP 1 liq 1 1995, 2003 - No routine production - 1 manufacturer10 liq 2 1987, 1995, 2001, 2003 - No routine production - 2 manufacturer20 liq 1 1987, 1995, 2003 - No routine production - 2 manufacturer
DTP-HepB 1 liq 2 1998 (2), 2006 (2) 2010, 2011 Production discontinued - 1 manufacturer (2010)2 liq 1 1998 - -5 liq 1 2004 - -
10 liq 3 1998, 2004, 2006 (2) 2010 -20 liq 1 2006 - -
DTP-Hib 1 liq 1 2002, 2010 2011 -1 liq/lyo 2 2003, 2010 - -
10 liq 1 2002 - -10 liq/lyo 1 2003 - -
DTP-HepB/Hib 1 liq 3 2006 (2), 2008, 2010, 2011 2010, 2011 No production - 1 manufacturer1 liq/lyo 3 2006, 2010, 2011 - -2 liq 1 2010 - -2 liq/lyo 2 2006, 2010 - -
10 liq 1 2010 201010 liq/lyo 2 2010, 2011 - -
23 | Multi-dose vial use | 4 April 2012
WHO prequalified vaccines Vaccine presentation and supplier information (cont’d)
Vaccine type Doses per vial
Form Current number of suppliers
Years prequalified (number of manufacturers*)
Years delisted Production comment
HepB 1 liq 8 1987, 1996, 2001, 2002, 2004 (3), 2006, 2008
2011 -
2 liq 4 1996, 2002, 2004, 2008 - -6 liq 3 1996, 2002, 2008 - -
10 liq 7 1987, 1996, 2001, 2002, 2004 (2), 2006, 2008
2011 -
20 liq 3 1987, 2002, 2008 - -Measles 1 lyo 1 1987, 1993 - Production discontinued - 1 manufacturer
2 lyo 1 1993 - -5 lyo 1 1993 - -
10 lyo 4 1993, 1998, 2002, 2006, 2010
- Production discontinued - 1 manufacturer
20 lyo 1 2006 - -MR 1 lyo 1 2000 - -
2 lyo 1 2000 - -5 lyo 1 2000 - -
10 lyo 2 2000, 2004 - No production - 1 manufacturerMMR 1 lyo 4 2002, 2003, 2009, 2011 - -
2 lyo 2 2003, 2011 - -5 lyo 1 2003 - -
10 lyo 2 2002, 2003 - -
* 1 manufacturer unless otherwise specified
24 | Multi-dose vial use | 4 April 2012
0
10
20
30
40
50
60
70
80
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Num
ber o
f cou
ntrie
s
Measles
1 dose 5 dose 10 dose 20 dose
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
0
10
20
30
40
50
60
70
80
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 Wei
ghte
d av
g pr
ice
/ do
se (U
SD)
Num
ber o
f cou
ntrie
s
1 dose 5 dose 10 dose 20 dose1 dose price 5 dose price 10 dose price 20 dose price
25 | Multi-dose vial use | 4 April 2012
0
2
4
6
8
10
12
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Num
ber o
f cou
ntrie
s
MR
10 dose
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0
2
4
6
8
10
12
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Wei
ghte
d av
g pr
ice
/ do
se (U
SD)
Num
ber o
f cou
ntrie
s
10 dose 10 dose price
26 | Multi-dose vial use | 4 April 2012
0
5
10
15
20
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Num
ber o
f cou
ntrie
s
MMR
1 dose 5 dose 10 dose
0.0
1.0
2.0
3.0
4.0
5.0
6.0
0
5
10
15
20
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Wei
ghte
d av
g pr
ice
/ do
se (U
SD)
Num
ber o
f cou
ntrie
s
1 dose 5 dose 10 dose
1 dose price 5 dose price 10 dose price