Primary container
considerations for
prequalification
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A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
Prequalification requirements
 Compliance with ISO 8362 (vials)
– Other containers
• Prefilled syringes (PFS)
• Compact prefilled auto-disable device (CPAD)
• Ampoules
 Consideration of Programmatic Suitability for
prequalification (PSPQ)
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A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
PSPQ – Mandatory characteristics
Characteristic
Anti-microbial
preservative
Applies to…
Only vaccines that:
 are in ready to use (no
reconstitution) presentation.
and
 are in multi-dose containers of
more than 2 doses per vial
Thermostability All vaccines
/ storage
Dose volume
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Value
The
vaccine
presented
for
prequalification should be adequately
preserved.
The vaccine or any component
presented for prequalification should not
require storage at less than -20°C .
Only vaccines that are:
The
vaccine
presented
for
 injectable;
prequalification should not be more than
and
1ml per dose for indicated use in
 indicated for infants and/or children aged 5 years or younger .
young children (<5 years old).
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
PSPQ – Critical characteristics (1)
Characteristic
Schedule
Applies to …
All vaccines
Process of
preparation for
administration
Thermo-stability /
storage
Oral vaccines
The vaccine presented for prequalification should be packaged in a single
component/ready to use format.
All vaccines
The vaccine presented for prequalification should not require storage below +2°C
for longer than 6 months.
Vaccine vial
monitor (VVM)
All vaccines
Proof of feasibility and intent to apply a VVM to the proposed vaccine, as defined
below:
Materials, primary
and secondary
packaging, and
injection material
Pre-filled injection
devices
All vaccines
The vaccine presented for prequalification should be packaged in materials
that can be disposed of appropriately in the field using standard procedures
(e.g., pit burning and burying, low temp incinerations, etc.).
Only vaccines that are
delivered in pre-filled
injection devices
The vaccine presented for prequalification in a prefilled injection device
should include an auto-disable (AD) feature (WHO/V&B/99.25).
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Not relevant to today's discussion
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
PSPQ – Critical characteristics (2)
Characteristic
Applies to …
Dose volume
Only injectable vaccines
The vaccine presented for prequalification
should be dosed in standardized volumes
(e.g., 0.5, 0.1, 0.05 ml) that can be easily
measured using available AD syringes .
Anti-microbial
preservative
Only vaccines that:
The vaccine presented for prequalification
should be adequately preserved.


are in ready to use (no reconstitution) 2-dose vial
presentations or
are not live attenuated, in multi-dose
presentations and require reconstitution
Antigenic stability Only vaccines that:
after reconstitution  are in multidose presentations, and
 require reconstitution of one or more components
 And are adequately preserved
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A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
The components of the vaccine must show
antigenic stability for 28 days after
reconstitution. (Appropriate testing protocol
must be chosen by the manufacturer and
will be reviewed on a case by case basis)
PSPQ – Preferred characteristics (1)
Characteristic
Applies
Value
to…
Maximum packed All vaccines  A smaller packed volume is preferred.
volume
 Where appropriate, components should be packed/shipped
together, e.g., for ready to use presentations: pre-filled AD syringe
with needle; etc.
 Packaging devices should be considered to assure components are
shipped together, e.g., vial clip.
Dose volume
Oral
 Smaller volumes and standardized volumes are preferred.
vaccines
Doses per
All vaccines  Vials with ≤10 doses per vial are preferred
primary
container, noncampaign setting
Doses per
All vaccines  Vials with ≥ 10 doses per vial are preferred.
primary
container,
campaign setting
Doses
per
All vaccines for
 Primary
ShouldVaccine
reflect logistics schedule and needs in order to minimize
A Roundtable
on Consideration
stock accumulation
at the peripheral level.
:
| Container Selection in Developing Countries
6 secondary
Primary container considerations for prequalification
container
PSPQ – Preferred characteristics (2)
Characteristic
Process of
preparation for
administration
Applies to…
All vaccines
Thermo stability / All vaccines
storage
Freeze sensitivity All vaccines
Materials,
primary and
secondary
packaging and
injection material
Secondary
packaging,
diluents and
vaccines
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All vaccines
Vaccines
requiring
reconstitution
Value
 Single component/ready to use (e.g., liquid) formats are
preferred.
 For multi-component vaccines, vaccines with a short and simple
preparation process are preferred.
 Vaccines and diluents that can be stored for extended periods at
temperatures above +8°C are preferred.
 Vaccines that are not damaged by freezing temperatures (<0°C)
are preferred.
 Materials that minimize environmental impact are preferred.

Diluents and vaccines should have the same number of doses
per secondary container.
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
Vaccine Presentation and Packaging Advisory Group
Generic Preferred Product Profile for Vaccines
Parameter
Recommendations
Single vs multicomponent vaccines
Provide Vaccines whenever possible, in “ready-to-use” presentations
that do not require the mixing of components.
Heat stability
Vaccines should be stable at standard cold chain temperatures (2° to
8°C).
Maximise vaccine stability to improve effectiveness and enable higher
temperature storage
Formulate vaccines so that they will not be damaged by freezing,
where feasible
Freeze stability
Presence of preservatives
Product format
Include preservative in multi-dose vials of injectable vaccines, where
feasible, to allow safe use of opened containers in subsequent
sessions.
Provide vaccines in formats to minimise (1) number of steps and (2)
potential for error during preparation and administration
Optimal number of doses per container
Prefilled injection devices
Vaccine in prefilled injection devices syringes should have space
saving and auto-disabling features.
Multi-component vaccines
Maximum packed volume
Materials, including the primary container and delivery device
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Minimise volume and weight of secondary and tertiary packaging, as
well as the need for repackaging for in-country supply chain
distribution
.Use materials for delivery devices, primary containers and secondary
and tertiary packaging that minimize the environmental impact of
waste disposal, for resource limited systems
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
WHO maximum packaging volumes
From Vaccine Packaging Study
Feb 2012 (230-vaxpack-D4120212).docx
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A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
Multidose vials
 Multi-dose vials are commonly used in UNICEF procuring
countries and are likely to continue to be a vital part of
immunization programs
–
10 |
Trends in multi-dose vaccine vial use in UNICEF procuring countries, 2000-2011
MDVuse_UNICEFprocuringCountries_JLiu_v2_20110407.pdf
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
Distribution of presentations by vaccine type – UNICEF procured
From Vaccine
Packaging Study Feb
2012 (230-vaxpack-D4120212).docx
11 |
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
Thiomersal and multidose vials
 Removal of thiomersal and switch to single-use vials affects
manufacturing capacity, health care workload, and has cold chain and
waste management implications, with very large increases in cost
 There is a risk that some products (if alternative preservatives or no
preservatives are required to be introduced) may no longer be supported
by manufacturers
 There is a high risk of serious disruption to routine immunization
programmes and mass immunization campaigns if thiomersal-preserved
vaccines are not available
– The consequences will be a predictable and sizable increase in
mortality, for very limited environmental impact
12 |
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
Thiomersal and multidose vials
 Replacement of thiomersal with an alternative preservative
will require development of new products and their
registration in each jurisdiction of the world
 New product development will be unpredictable since:
– there are no clear alternative candidate preservatives for the
near-or mid-term
– alternative preservatives may interact with the components of
the vaccine and removal of thiomersal may impact on vaccine
performance
– lack of incentive to reformulate current low cost vaccines (TT,
DTwP, hep B)
13 |
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
Thiomersal and multidose vials
 In the long term, as an insurance policy to ensure availability of
multidose vaccines, further work should be stimulated, recognizing
- there is, currently, little or no academic or regulatory research on
alternative preservatives
- there is little or no operational research to evaluate the
relationship between the criteria for antimicrobial tests for
preservatives and the safety of multi-dose vaccines when used
with current immunization practices
- that these efforts will be difficult and may not be successful
 Investment and focused effort to identify (a) additional preservatives,
and (b) preferred product presentations /delivery systems for multi-dose
formulations with or without preservatives
14 |
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
Synflorix 2-dose presentation
 GSK proposed a 2-dose liquid unpreserved product for PQ
– a novel presentation for UN supported programmes
 Submitted before formalised PSPQ evaluation process
established
 Post introduction studies required
– No indication of increased AEFIs related to product misuse
– Some incorrect storage & waning of health worker knowledge
 Synflorix 2-dose presentation remains PQed and now
available for use in other countries
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A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
Synflorix 2-dose presentation
 Countries need to be informed of the benefits and risks of
the presentation and have the responsibility for assuring
programmatic readiness to use such a presentation.
 To be in place prior to introduction
– Enhanced training of HCWs
– Information stickers on storage fridges
 Following introduction
– Monitoring of continued good practice
– On going training
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A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
Synflorix 2-dose presentation
 WHO and UNICEF consider the two dose preservativefree presentation to introduce additional programmatic
risks for a product with a 1 dose alternative. Whilst the
benefit-risk will likely be favorable in the early postintroduction period, this may change over time. For the
longer term, presentations that reduce programmatic risk
will likely be preferred.
– Single dose, unpreserved
– Multidose, preserved
17 |
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
Summary
 PQ : evaluation of technical requirements of containers
 PQ : evaluation of programmatic requirements of
containers
 Input to development of characteristics through VPPAG,
IPAC
 Multidose vials
– A vital part of immunisation programmes
– Should contain preservative when feasible
– Supply at risk if thiomersal included in scope of mercury treaty
18 |
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification