The Vaccine Innovation Prioritisation Strategy (VIPS) represents an unprecedented three-year collaboration – known as the VIPS Alliance – between the Gavi Secretariat, World Health Organization (WHO), Bill & Melinda Gates Foundation, UNICEF and PATH. Its purpose is to develop a single integrated framework to evaluate, prioritise and drive forward vaccine product innovations. |
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Addressing immunisation barriers and achieving immunisation coverage and equity goals requires innovative approaches. Vaccine product innovations simplify logistics, increase the acceptability and safety of immunisation, minimise missed opportunities, and facilitate outreach. There is increasing recognition of the need to employ targeted solutions to extend vaccine access to communities missed by immunisation services.
The VIPS process involved in-depth research, stakeholder consultations, and development and application of a methodology capable of evaluating a variety of technologies at different stages of product development. The work required understanding countries’ needs to consider the expected financial and non-financial impacts of innovations; developing common principles across the Alliance to assess the long-term benefits of product innovations; and convening a platform of stakeholders to articulate a clear and aligned perspective on priority innovations.
Prioritising innovations in vaccine products allows VIPS to provide greater clarity to manufacturers and partners, informing and influencing investment decisions. VIPS outcomes also help to mobilise key decision-makers and funders, and chart a strategic pathway forward for the prioritised innovations.
More details can be found on the methodology, process and outcomes; scope of innovations assessed within VIPS; and VIPS Steering Committee here:
The VIPS process concluded in May 2020 with a decision to prioritise three innovations/approaches in which the Alliance will engage to advance development, policy and access:
The next step for the VIPS Alliance is to define end-to-end strategies for the three prioritised innovations, including developing clear action plans to accelerate their advancement to uptake and impact.
The VIPS Alliance’s long-term vision for microarray patches (MAPs) is to implement MAP products for priority vaccines. This will help to overcome immunisation barriers, ensuring more equitable access to and improved effectiveness of vaccines in lower-income countries and contribute to global health security.
To achieve this long-term vision, the VIPS Alliance has developed an end-to-end five-year action plan for vaccine MAPs that:
More details on the five measurable target outcomes and underlying activities identified can be found in the public summary of the VIPS Alliance Action Plan for MAPs (also linked below). The public summary is a condensed version including key background on MAPs and the list of target outcomes and activities. A longer version of the action plan is available upon request.
Controlled temperature chain (CTC) is a designation meaning that a vaccine can be used outside of the cold chain. CTC use of vaccines allows a single excursion of the vaccine into ambient temperatures not exceeding +40°C for a minimum of three days, just prior to administration.The VIPS Alliance's long-term vision for controlled temperature chain (CTC)-qualified vaccines is to enable qualification and CTC use of vaccines. It also aims to ensure that CTC-qualified vaccines will be used in countries as one of several valuable and efficient approaches to help overcome immunisation barriers, and ensure equitable access to vaccines.
In the short term, the focus of the CTC Action Plan is to:
Activities to generate evidence on CTC are already underway, with results expected in 2025. The VIPS Action Plan will be refined after the results of these studies have been assessed and published. More information on the research studies and CTC Action Plan is available upon request.
The VIPS strategy on improved vaccine heat stability is being defined and will be covered in a separate action plan.
After VIPS prioritised innovations, consultations with manufacturers and developers revealed the need for clearer guidance on priority vaccines for MAPs and CTC use. Hence, VIPS conducted an exercise to identify vaccines relevant to lower-income countries for which MAPs and CTC use would be most valuable from a programmatic perspective, as well as technically feasible.
This resulted in a priority list of 8 target vaccines for CTC use and 11 target vaccines for MAPs. The methodology and outcomes of the exercise have been validated through stakeholder and expert consultations.
For CTC use, the outcomes of this exercise will be complemented by the studies that VIPS is undertaking to measure the impact of CTC and to understand the use cases and contexts where it adds value. The CTC prioritisation may thus be revised after assessment of these results.
Vaccine target |
---|
Tetanus-diptheria [reduced D antigen for adults/adolescents] |
Hepatitis B [birth dose] |
Human papillomavirus (HPV) |
Measles-rubella (MR) MAP |
Meningococcal A, C, W, Y (X) |
Oral cholera vaccine (OCV) |
COVID-19 |
Typhoid conjugate vaccine (TCV) |
Vaccine Target (Disease or Pathogen) | |
---|---|
Priority group 1 | Hepatitis B |
Measles-rubella (MR)/measles, mumps and rubella (MMR) | |
Human papillomavirus (HPV) | |
Rabies | |
Yellow fever | |
Influenza virus: seasonal and pandemic | |
COVID-19 | |
Priority group 2 | Group B streptococcus (GBS), S agalactiae |
Meningococcal A,C,W,Y,(X) | |
Salmonella Typhi | |
Streptococcus pneumoniae |
The VIPS Alliance’s long-term vision for barcodes implementation is to support equitable vaccine coverage in low- and middle-income countries (LMICs) by improving programme efficiency and enhancing health system digitalisation. Use of barcodes on vaccine products can:
To achieve this long-term vision, the VIPS Alliance has developed an end-to-end action plan that is a first step towards a coordinated plan to advance barcodes use among all stakeholders working on vaccine traceability to generate awareness; and ensure ownership, funding and use in countries. Further work is needed to socialise this work across relevant stakeholders.
More details on the five measurable target outcomes and underlying activities can be found in the public summary of the VIPS Alliance Roadmap for Barcodes (link below) and in supporting annex documents, including background information and findings from VIPS consultations that informed the roadmap. For more information, please contact the VIPS team at info@gavi.org, with the words “VIPS team” in the Subject line of your email.
Download: VIPS Alliance Roadmap for Barcodes Implementation on Vaccine Products in LMICS – Public Summary
Supporting documents:
1 VIPS Phase I Executive Summary Autodisable Sharps Injury Protection Syringes pdf
1 VIPS Phase I Technical Note Autodisable Sharps Injury Protection Syringes pdf
2 VIPS Phase I Executive Summary Barcodes on Primary Containers pdf
2 VIPS Phase I Technical Note Barcodes on Primary Containers pdf
3 VIPS Phase I Executive Summary Blow Fill Seal Primary Containers pdf
3 VIPS Phase I Technical Note Blow Fill Seal Primary Containers pdf
4 VIPS Phase I Executive Summary Bundling Devices pdf
4 VIPS Phase I Technical Note Bundling Devices pdf
5 VIPS Phase I Executive Summary Combined Vaccine Vial Monitor VVM and Threshold Indicators TI pdf
5 VIPS Phase I Technical Note Combined Vaccine Vial Monitor VVM and Threshold Indicators TI pdf
6 VIPS Phase I Executive Summary Compact Prefilled Auto disable Devices pdf
6 VIPS Phase I Technical Note Compact Prefilled Auto disable Devices pdf
7 VIPS Phase I Executive Summary Disposable Syringe Jet Injectors pdf
7 VIPS Phase I Technical Note Disposable Syringe Jet Injectors pdf
8 VIPS Phase I Executive summary Dry Heat Stable Formulations pdf
8 VIPS Phase I Technical Note Dry Heat Stable Formulations pdf
9 VIPS Phase I Executive summary Dual Chamber Delivery Devices pdf
9 VIPS Phase I Technical Note Dual Chamber Delivery Devices pdf
10 VIPS Phase I Executive Summary Dual Chamber Vials pdf
10 VIPS Phase I Technical Note Dual Chamber Vials pdf
11 VIPS Phase I Executive Summary Freeze Damage Resistant Liquid Formulations pdf
11 VIPS Phase I Technical Note Freeze Damage Resistant formulations pdf
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VIPS is a Vaccine Alliance project from Gavi, World Health Organization, Bill & Melinda Gates Foundation, PATH and UNICEF
Freeze damage resistant liquid formulations
Comparator : Use without innovation (i.e. current liquid formulations)
Section 1: Summary of innovation
1.1 Example images :
Image s ource : a
Image s ource : b
1.2. D escription of innovation:
? Vaccines need to be stored at their proper temperature to maintain their potency, which is
commonly at 2 -8oC.
? Vaccines can be exposed to multiple freeze -thaw cycles and long durations of sub -zero
temperatures along the different segments of the cold chain . For freeze -sensitive vaccines, this can
result in physical, chemical and immunological changes to the formulation, reduced potency of the
vaccine, administration of sub -optimal vaccine , local reactions to the vaccine such as st erile
abscesses, and increased wastage (if the freeze exposure is identified and the vaccine is
discarded) (1) .
? Many vaccines are freeze -sensitive, including those containing aluminium adjuvants. When
vaccines containing aluminium adjuvant are frozen, the anti gen -adjuvant particles agglomerate and
sediment which results in the irreversible loss of potency.
? Freeze damaged vaccines can be detected using the ?shake test?, but it is not always performed
given lack of training and the need for a control vaccine to c onduct the test.
? Developing novel freeze stable formulations using different excipients could prevent agglomeration
and stabilize the potency of vaccines.
? The addition of excipients such as glycerin, polyethylene glycol 300, or propylene glycol (PG) have
been demonstrated to reduce the freeze sensitivity of Hepatitis B vaccine (2) and other vaccines
contai ning aluminum adjuvant including diphtheria, tetanus and pertussis (DTP); and pentavalent
(hepatitis B, DTP, Haemophilus influenza type b) vaccines (3) .
a https://www.myelomacrowd.org/wp -content/uploads/2015/05/vials.jpg b https://www.publichealthontario.ca/en/BrowseByTopic/Infectio usDiseases/PIDAC/Pages/Infection -Prevention -and -Control -for-Clinical -Office - Practice -Multidose -Vials.aspx
12 VIPS Phase I Executive Summary Freeze Indicator on Primary Vaccine Containers pdf
12 VIPS Phase I Technical Note Freeze Indicator on Primary Containers pdf
13 VIPS Phase I Executive Summary Intradermal Devices pdf
13 VIPS Phase I Technical Note Intradermal Syringes pdf
14 VIPS Phase I Executive summary Liquid Heat Stable Formulations pdf
14 VIPS Phase I Technical Note Liquid Heat Stable Formulations pdf
15 VIPS Phase I Executive Summary Microarray Patches pdf
15 VIPS Phase I Technical Note Microarray Patches pdf
16 VIPS Phase I Executive summary Oral Fast Dissolving Tablets pdf
16 VIPS Phase I Technical Note Oral Fast Dissolving Tablets pdf
17 VIPS Phase I Executive Summary Plastic Needles For Reconstitution pdf
17 VIPS Phase I Technical Note Plastic Needles for Reconstitution pdf
18 VIPS Phase I Executive Summary Prefilled Blow Fill Seal Droppers Dispensers pdf
18_VIPS Phase I_Technical Note Prefilled Blow Fill Seal Droppers Dispensers pdf
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VIPS is a Vaccine Alliance project from Ga vi, World Health Organization, Bill & Melinda Gates Foundation, PATH and UNICEF
Prefilled polymer BFS dropper s /dispenser s
Comparator ?: Single dose vial (liquid ) and dropper/dispenser
Section 1: Summary of innovation
1.1 Example images :
PATH prototype of BFS oral squeeze
tube in a five -dose strip
Image: provided by PATH
1.2. D escription of innovation:
? Blow -fill -seal (BFS) is an aseptic filling process that is widely used to produce a variety of
pharmaceuticals in polymer primary containers. In the blow -fill -seal process, a polymer resin is
melted into a parison, which is blown into a mould , filled, and sealed, all in a continuous process
within a single piece of equipment. This is in contrast to preformed polymer primary containers, in
which the container is first produced and sterilized, and then shippe d to a different site for filling and
sealing.
? A wide variety of different container designs are feasible with BFS .
o For oral or intranasal vaccines, BFS containers can be designed as squeeze tube dropper or
dispenser devices for delivery of the container?s contents directly to the mouth or nostrils.
This approach is the focus of this Technical Note.
o For single -dose parenteral vaccines, BFS containers can be used similar to glass ampoules,
with the top twisted off and an AD N&S used to draw up and inject the vaccine. BFS
containers can also be designed with inset septum, similar to a glass vial. These innovation s
are reviewed in the Parenteral BFS Primary Container Technical Note.
o BFS has the potential to be used for production of compact prefilled autodisabl e devices
(CPADs), which are reviewed in the CPAD Technical Note.
? For the existing vial presentations of liquid and lyophilised vaccines, single dose vials, rather than multi -dose vials (MDVs) were used for the comparator, because in most cases, the innovation being considered is a single -dose presentation. However, when multi -dose vials are currently used by countries and would be the true comparator for countries , a comparison against the multi -dose vial will also be condu cted under Phase II if this innovation is prioritised and for antigens where multi -dose vials are used by countries.
19 VIPS Phase I Executive Summary Prefilled Dry Powder Intranasal Devices pdf
19 VIPS Phase I Technical Note Prefilled Dry Powder Intranasal Devices pdf
20 VIPS Phase I Executive summary Radio Frequency Identification RFID pdf
20 VIPS Phase I Technical Note Radio Frequency Identification RFID pdf
21 VIPS Phase I Executive Summary Reconstitution Vial Adapters pdf
21 VIPS Phase I Technical Note Reconstitution Vial Adapters pdf
22 VIPS Phase I Executive Summary Single Chamber Cartridge Injectors pdf
22 VIPS Phase I Technical Note Single Chamber Cartridge Injectors pdf
23 VIPS Phase I Executive Summary Solid Dose Implants pdf
23 VIPS Phase I Technical Note Solid Dose Implants pdf
24 VIPS Phase I Executive Summary Sublingual Dosage Forms pdf
24 VIPS Phase I Technical Note Sublingual Dosage Forms pdf
1 VIPS Phase II Executive Summary Autodisable Sharps Injury Protection AD SIPs pdf
1 VIPS Phase II Technical Note Autodisable Sharps Injury Protection Syringes pdf
2 VIPS Phase II Executive Summary Barcodes on Primary Containers pdf
2 VIPS Phase II Technical Note Barcodes on Primary Containers pdf
3 VIPS Phase II Executive Summary Combined Vaccine Vial Monitor VVM and Threshold Indicators TI pdf
3 VIPS Phase II Technical Note Combined Vaccine Vial Monitor VVM and Threshold Indicators TI pdf
4 VIPS Phase II Executive Summary Compact Prefilled Autodisable Devices pdf
4 VIPS Phase II Technical Note Compact Prefilled Auto disable Devices pdf
5 VIPS Phase II Executive Summary Dual Chamber Delivery Devices pdf
5 VIPS Phase II Technical Note Dual Chamber Delivery Devices pdf
6 VIPS Phase II Executive Summary Freeze Damage Resistant Formulations pdf
6 VIPS Phase II Technical Note Freeze Damage Resistant Formulations pdf
7 VIPS Phase II Executive Summary Heat Stable CTC Liquid formulations pdf
7 VIPS Phase II Technical Note Liquid Heat Stable CTC Formulations pdf
8 VIPS Phase II Executive Summary Microarray Patches pdf
1
VIPS Phase II executive summary:
Microarray patches (MAPs)
March 2020
2
Microarray patches (MAPs)
About MAPs
? MAPs consists of an array of micro -projections on a patch . The micro -projections are coated
with or are composed of, vaccine in a dry formulation. When a MAP is applied to the skin, the
vaccine is delivered into the dermis and/or epidermis layers.
? MAPs can be administered without an applicator , by applying pressure with fingers, or using
an integrated applicator.
? Like solid -dose implants (SDIs), MAPS are sharps -free devices that could potentially be used
with all injected vaccines (once they have been reformulated). However, development of MAPs
is more advanced than SDIs and current MAPs do not have a separate applicator, which will
likely be needed for SDIs.
Stage of development
? Various formats of MAPs are being developed for vaccine delivery by several different developers.
? Three developers have tested influenza vaccine MAPs in phase I clinical trials , and preclinical
development is underway with other vaccines, including measles -rubella (MR) .
? MAPs for delivery of non -vaccine products, such as teriparatide (for osteoporosis) and Zolmitriptan
(migraine), have been evaluated in phase II and III trials respectively.
Vaxxas
, 15 May 2019
micronbiomedical.com
b
WHO
c
8 VIPS Phase II Technical Note Microarray Patches pdf
VIPS PHASE 2 TECHNICAL NOTE
Microarray patches
30.03.2020
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VIPS is a Vaccine Alliance project from Gavi, World Health Organization, Bill & Melinda Gates Foundation, PATH and UNICEF
Microarray patches ( MAPs )
SECTION ONE: Vaccine compatibility and problem statements addressed by the innovations
Technology overview :
MAPs consist of an array of hundreds or thousands of micro -projections on a ?patch?. The projections are coated with, or composed of, vaccine in a dry
formulation. When applied to the skin, the vaccine is delivered into the dermis and/or epidermis, which a re rich in antigen presenting cell (APCs).
Several different formats of MAPs are being developed:
? With, or without, applicators; when present, the applicator can be a separate component or integrated with the MAP. The most advanced MAPs in
development either have no applicator or an integrated applicator. Therefore, MAPs with a separate applicator are not considered in this
assessment;
? Solid micro -projections coated with vaccine;
? Micro -projections formed of vaccine plus biocompatible excipients that dissolve or biodegrade in the skin;
? Hydrogel micro -projections that swell in the skin and act as a condui t for diffusion of the active ingredient from a backing layer (primarily in development for
drug delivery).
In theory, MAPs could be used for administration of any type of vaccine, although there might be some vaccine -specific limitations: it might not be possible to
formulate some vaccines so that they remain potent during the manufacture or storage of MAPs; some vaccines (in particular th ose formulated with an adjuvant)
might have unacceptable levels of local reactogenicity when delivered into the skin; a nd in some cases, MAPs might not have the payload capacity for the vaccine
plus necessary excipients, or it might not be possible to concentrate the antigen sufficiently so that it can be loaded onto the MAP.
Summary of vaccine and innovation compatibility :
Microarray patches ( MAPs ) could potentially be used to deliver any vaccine that is currently administered by injection with needle and syringe (N&S). The
technology does have some features that might however preclude its use with some vaccines, in particular:
1. Reactogenicity: MAPs deliver vaccines to the skin rather than intramuscularly (IM) or sub -cutaneously (SC). The subsequent initial immune response
takes place near the skin surface and is more visible as local reactogenicity, than with IM or SC injections. While this administration route may offer the
potential for dose -sparing for some vaccines, reactogenicity seen with MAP delivery of some ?more -reactogenic? formulations might not be acceptable to
recipients.
The reactogenicity seen with MAP delivery of some ?more -reactogenic? vaccines might not be acceptable to recipients.
The inherent reactogenicity of any of the priority vaccines has NOT been considered in this analysis, and no vaccines have been excluded on this basis.
Reactogenicity due to inclusion of an adjuvant HAS been considered (see below).
9 VIPS Phase II Executive Summary Solid Dose Implants pdf
1
VIPS Phase II executive summary:
Solid - dose implants (SDIs)
March 2020
2
Solid -dose implants (SDIs)
About SDIs
? SDIs consist of vaccines (including antigens, adjuvants and excipients) that have been
reformulated into a solid format . This is typically shaped like a needle that is sharp and
strong enough to be implanted below the skin and the dose it contains either dissolves
immediately or is released slowly.
? In some cases, SDIs are contained in a cartridge or cassette for easy handling.
? An applicator is used to propel the SDI into the skin using a spring or compressed gas.
The applicator might be separate and re -usable, or integrated and single use.
? SDIs could be regarded as an alternative to microarray patches (MAPs) as they should not
have the reactogenicity of MAPs and possibly have a higher payload. But SDIs have other
drawbacks such as the need for an applicator and being earlier in development than MAPs.
Stage of development
? SDIs are in a very early stage of development .
? No clinical studies with vaccines have been published.
Hirschberg HJHB, 2008
a
Separate, compressed gas -
powered applicator ( Bioneedle )
www.enesipharma.com
b
Separate, spring -powered
applicator ( Implavax ?)
Nemaura
presentation
c
Optional, separate applicator (Micropatch TM)
aHirschberg HJHB, van de Wijdeven GGP, Kelder AB, van den Dobbelsteen GPJM, Kersten GFA. Bioneedles as vaccine carriers. Vaccine. 2008 May 2;26(19):2389 ?97. bhttps://www.enesipharma.com/technologies/platform/cNemaura presentation. Teriparatide microneedle patch for osteoporosis, December 2018. Presented during telecon 12 February 2019.
9 VIPS Phase II Technical Note Solid Dose Implants pdf
VIPS PHASE 2 TECHNICAL NOTE
Solid -dose implants
30.03.2020
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VIPS is a Vaccine Alliance project from Gavi, World Health Organization, Bill & Melinda Gates Foundation, PATH and UNICEF
Solid dose implants (SDIs )
SECTION ONE: Vaccine compatibility and problem statements addressed by the innovations
Technology overview:
SDIs consist of vaccines (including antigens, adjuvants and excipients) that have been reformulated into a solid single -dose format, typically needle -shaped, that is
sharp and strong enough to be implanted below the skin. After injection, the dose either d issolves immediately or is released slowly depending on the formulation.
Some SDIs are contained in a cartridge or cassette for easy handling prior to administration with a n applicator to propel the SDI into the skin using a spring or
compressed gas. The applicator might be separate and re -usable, or integrated and single use.
Summary of innovation applicability to vaccines :
Solid dose implants (SDIs) could potentially be used to deliver any vaccine that is currently administered by injection with nee dle and syringe (N&S). The
technology does have some features that might however preclude its use with some vaccines , as the product is developed , in particular:
1. Adjuvants: The need to dry the vaccine for incorporation into the SDI might preclude the use of some adjuvants, including those based on aluminium salts
(such as alum).
We have assumed that manufacturing process es will be developed that are compatible with aluminium salt based adjuvants, or that it might prove to be
technically feasible to rem ove the adjuvant from the formulation of some vaccines such as HPV and HepB whilst maintain ing immunogenicity. For some
vaccines however (RTS,S and HIV) we have assumed the adjuvant will not be suitable for SDIs, nor will there be interest in re moving the adjuvant. a
2. Payload. Antigens need to be available at a sufficiently high concentration ( which might be higher than standard bulk harvests) to enable a full dose to be
loaded into a SDI .
The amount of vaccine required to be loaded onto a SDI relative to the yields of the manufacturing process has NOT been considered in this analysis, and
no vaccines have been excluded on this basis .
3. Route of delivery . SDIs will not be suitable for use wit h vaccines that are currently delivered orally.
Live -attenuated rotavirus vaccines, and E TVAX , the candidate vaccine selected as the exemplar for Enterotoxigenic E. coli (ETEC) have therefore not
been considered for use with SDI s. The candidate M.t b vaccine VPM1002 is a recombinant BCG so will need to be delivered intradermally (ID) thus SDIs will not be
suitable for administration of this vaccine.
The vaccines considered, or not considered for use with SDI s in this Technical Note are summarised in Tables 1 and 2 respectively.
a Alumimium -salt based adjuvants and saponins might be compatible with SDIs, but oil -in-water adjuvants are unlikely to be suitable. [No data provided] EnesiPharma communication, 19 November 2019.