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