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A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
|
1 |
Primary container
considerations for
prequalification
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
|
2 |
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)
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
|
3 |
PSPQ – Mandatory characteristics
Characteristic Applies to… Value Anti-microbial
preservative Only vaccines that:
are in ready to use (no
reconstitution) presentation.
and
are in multi-dose containers of more than 2 doses per vial
The vaccine presented for
prequalification should be adequately
preserved.
Thermostability
/ storage All vaccines The vaccine or any component
presented for prequalification should not require storage at less than -20°C .
Dose volume Only vaccines that are:
injectable;
and
indicated for infants and/or young children (<5 years old).
The vaccine presented for
prequalification should not be more than
1ml per dose for indicated use in
children aged 5 years or younger .
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
|
4 |
PSPQ – Critical characteristics (1)
Characteristic Applies to …
Schedule All vaccines Not relevant to today's discussion
Process of
preparation for
administration
Oral vaccines The vaccine presented for prequalification should be packaged in a single
component/ready to use format.
Thermo-stability /
storage
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
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.).
Pre-filled injection
devices
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).
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
|
5 |
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:
are in ready to use (no reconstitution) 2-dose vial
presentations or
are not live attenuated, in multi-dose
presentations and require reconstitution
The vaccine presented for prequalification
should be adequately preserved.
Antigenic stability
after reconstitution
Only vaccines that:
are in multidose presentations, and
require reconstitution of one or more components
And are adequately preserved
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)
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
|
6 |
PSPQ – Preferred characteristics (1)
Characteristic Applies
to…
Value
Maximum packed
volume
All vaccines A smaller packed volume is preferred.
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
vaccines
Smaller volumes and standardized volumes are preferred.
Doses per
primary
container, non-
campaign setting
All vaccines Vials with ≤10 doses per vial are preferred
Doses per
primary
container,
campaign setting
All vaccines Vials with ≥ 10 doses per vial are preferred.
Doses per
secondary
container
All vaccines Should reflect logistics schedule and needs in order to minimize
stock accumulation at the peripheral level.
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
|
7 |
PSPQ – Preferred characteristics (2)
Characteristic Applies to… Value
Process of
preparation for
administration
All vaccines 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.
Thermo stability /
storage
All vaccines Vaccines and diluents that can be stored for extended periods at
temperatures above +8°C are preferred.
Freeze sensitivity All vaccines Vaccines that are not damaged by freezing temperatures (<0°C)
are preferred.
Materials,
primary and
secondary
packaging and
injection material
All vaccines Materials that minimize environmental impact are preferred.
Secondary
packaging,
diluents and
vaccines
Vaccines
requiring
reconstitution
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
|
8 |
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
Freeze stability Formulate vaccines so that they will not be damaged by freezing,
where feasible
Presence of preservatives Include preservative in multi-dose vials of injectable vaccines, where
feasible, to allow safe use of opened containers in subsequent
sessions.
Product format 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 Minimise volume and weight of secondary and tertiary packaging, as
well as the need for repackaging for in-country supply chain
distribution
Materials, including the primary container and delivery device .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
|
9 |
WHO maximum packaging volumes
From Vaccine Packaging Study
Feb 2012 (230-vaxpack-D4-
120212).docx
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
|
10 |
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 – 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
|
11 |
Distribution of presentations by vaccine type – UNICEF procured
From Vaccine
Packaging Study Feb
2012 (230-vaxpack-D4-
120212).docx
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
|
12 |
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
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
|
13 |
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)
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
|
14 |
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
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
|
15 |
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
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
|
16 |
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
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
|
17 |
Synflorix 2-dose presentation
WHO and UNICEF consider the two dose preservative-
free 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 post-
introduction period, this may change over time. For the
longer term, presentations that reduce programmatic risk
will likely be preferred.
– Single dose, unpreserved
– Multidose, preserved
A Roundtable on Consideration for Primary Vaccine
Container Selection in Developing Countries :
Primary container considerations for prequalification
|
18 |
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