1
VIPS Phase II executive summary:
Compact prefilled auto - disable devices
(CPADs)
March 2020
2
Compact prefilled auto -disable devices (CPADs)
About CPADs
? CPADs are integrated primary containers and injection devices prefilled with liquid vaccines .
They have features to prevent reuse and minimize the space required for storage and shipping.
Three CPAD subtypes have been assessed:
? Preformed CPADs: Squeezable polymer device, m anufactured ?open? and supplied sterile and ready
to fill/seal by the vaccine manufacturer.
? Blow -fill -seal (BFS) CPADs: produced, filled, and sealed in a continuous BFS process.
? Pre -assembled (with needle attached) and user -assembled configurations are possible 1.
? Other CPAD types: D esigns are in development leveraging prefilled syringe components.
Stage of development
? One preformed CPAD, Uniject TM , is commercially available .
? Uniject TM presentations of P enta , HepB and TT vaccines were WHO prequalified in 2006, 2004
and 2003 respectively. The pentavalent and tetanus toxoid products have been discontinued.
Medroxyprogesterone acetate (similar to Depo -Provera) is also commercially available in Uniject TM .
? BFS and other CPAD types are in design phases.
drugdeliverysystems.bd.com
a
Preformed CPAD (Uniject TM)
PATH
BFS CPAD ( Apiject )
INJECTO
TMb
Other CPAD ( Easyject )
a https://drugdeliverysystems.bd.com/products/prefillable -syringe -systems/vaccine -syringes/uniject -auto -disable -pre -fillable -injec tion -system ; b http://injecto.eu/easyject/
1During the Phase I VIPS review, the Steering Committee suggested de -prioritising user -assembled BFS CPAD configurations because they ha ve fewer
potential benefits than all other CPAD types, due to the greater number of components and preparation steps, and risk of prep ara tion and delivery errors and
contamination.

VIPS PHASE 2 TECHNICAL NOTE

Autodisable sharps injury protection syringes




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

Autodisable (AD) sharps -injury protection (SIP) syringe s

SECTION ONE: Vaccine compatibility and problem statements addressed by the innovations

Technology overview
AD SIP syringes are single -dose, disposable syringes with a mechanism that covers the needle after use to reduce the risk of accidental needlestick inju ry.
Summary of vaccine and innovation compatibility :
This innovation applies to all parenteral vaccines and addresses safety issues related to vaccine handling by preventing needlestick injuries and syringe re use.
The innovation is best applied to vaccines intended for routine immunization and mass campaigns (fixed dose immunizations) ,a where health care workers will be
delivering intramuscular, subcutaneous or intradermal injections b (as shown in Table 1) . For all vaccines to which the innovation applies, the comparator is delivery
of the vaccine with an autodisable needle and syringe ( AD N&S) that lacks the SIP feature. Not all vaccines are compatible with the innovations based on mode of
administration (Table 2); for example, vaccines that are delivered non -parenterally.
The problem statement which applies to each vaccine that could p otentially be addressed by AD SIPs is presented in Table 1. The key property of AD SIPs that is
relevant to the problem statement is their ability to either shield or retract the needle after administration, which could reduce the likelihood of needlestick injury and
transfer of bloodborne pathogens to patients, health care workers, and the community after vaccine administration.
The vaccines considered, or not considered for use with AD SIP syringes in this Technical Note are summarised in Table s 1 and 2 respectively.
Problem statement to be addressed:
The problem statement applying to each vaccine that could potentially be addressed by AD SIP syringes is:
? Needle -stick injuries: AD SIP syringes have a feature to reduce the risk of needle -stick injury (NSI) , as shown in Table 1 .



a World Health Organization (WHO), United Nations Children?s Fund (UNICEF), United Nations Population Fund. WHO -UNICEF -UNFPA Joint Statement* on the Use of Auto -disable Syringes in Immunization Services . WHO/V&B/99.25. Geneva: WHO; 2003. https://apps.who.int/iris/bitstream/handle/10665/63650/WHO_VB_99.25_eng.pdf?sequence=1 b WHO. WHO Guideline on the U se of Safety -Engineered Syringes for Intramuscular, Intradermal and Subcutaneous Injections in Health Care Settings . Geneva: WHO; 2016. https://apps.wh o.int/iris/bitstream/handle/10665/250144/9789241549820 -eng.pdf?sequence=1

1
VIPS Phase II executive summary:
Autodisable Sharps - Injury Protection
Syringes (AD SIPs)
March 2020
2
Autodisable (AD) sharps -injury protection (SIP)
syringes
About AD SIP syringes
? AD SIP syringes are single -use, disposable syringes with a mechanism that
covers the needle after use to reduce the risk of accidental needlestick
injury .
? Mechanisms include retraction of the needle into the barrel after injection or a
needle shield .
? Some syringes have SIP features that are automatically activated, and others
require extra activation steps by the end user.
Stage of development
? AD SIP syringes are commercially available .
? A list of available World Health Organization (WHO) -prequalified AD SIP syringes
can be found in the WHO Performance, Quality, and Safety (PQS) catalogue. b
WHO
a
A VanishPoint ? retractable syringe
(Retractable Technologies, Inc.)
PATH
BD Eclipse? syringe (BD, Franklin
Lakes, NJ) with needle shield
ahttp://apps.who.int/immunisation_standards/vaccine_quality/pqs_catalogue/LinkPDF.aspx?UniqueID=f3025136 -636d -4139 -9773 -fdbf82427 6e1&TipoDoc=DataSheet&ID=0 . bWHO PQS Category E008 auto -disable syringe for fixed dose immunisation page :http://apps.who.int/immunisation_standards/vaccine_quality/pqs_catalogue/categorypage.aspx?id_cat=37 .

VIPS PHASE 2 TECHNICAL NOTE

Barcodes




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

2D Barcodes
Technology overview:
This innovation is defined as the application of 2D barcodes to vaccine primary packaging labels. They are symbols that encode information such as
vaccine product numbers, serial numbers, supplier data, batch numbers and expiry dates which can be scanned electronically us ing laser scanners
or mobile device cameras to automatically capture information.
Cu rrently, barcodes are used on secondary and tertiary packaging of vaccine s providing product identification information, expiration date and lot
number a. The use of barcodes on secondary and tertiary packaging primarily provides vaccine inventory, supply and efficiency benefits. However,
this evaluation assumes barcode placement down to the primary packaging level and t he predominant public health benefit s will be at the health
facilit y levels to improve accurate documentation of vaccine information in patient records , help reduce programmatic errors, facilitate tracking of
AEFIs and vaccine recalls, and improve timely and equitable vaccine coverage.
Radio -frequency identification (RFID) versus barcodes on primary vaccine containers:
The RFID tag is a type of labelling technology used in many different industries that can store vast amount s of information useful for inventory
control, equipment tracking, patient monitoring and providing data for electronic medical record systems. Similar t o barcodes, RFID tags can track
and trace items and link to other systems like GPS, temperature, or vaccination records. The original intention was to review both RFID tags and
barcodes on primary vaccine packaging during the VIPS phase II analysis. Howeve r, deeper evaluation of the technologies revealed that , for the
foreseeable future, RFID tags on primary vaccine packaging are not appropriate for the lower - and middle -income public sector markets that Gavi
serves .
RFID tags differ from barcodes in the pr ocess of capturing data/information as they require a dditional computer hardware and software to connect
the reader to computer systems and data repositories, by converting data captured in the form of radio signals from tags into tracking or
identificatio n information . There are different types of RFID tags (passive, semi -passive and active) that can transmit radio signals over variable
distance s, using different levels of power. As a result, RFIDs can quickly capture data in mass , whereas barcodes are des igned to be scan ned on
items one at a time in the line of sight of a laser. RFIDs are therefore particularly suited for higher levels of packaging (e.g., tertiary) for inventory
control at higher levels of health systems, for example, where all vaccine boxes on a pallet can be scanned at on ce and where the costs of the
scanning system can be spread across higher product volumes .
For the primary packaging level, RFIDs have some drawbacks in comparison to barcodes including:
? Barcodes can be read with smart phones or simple scanners, while RFID tags require more complex and expensive equipment for scanning.
barcodes are therefore much more appropriate for use at the health facility levels where they can be scanned for patient reco rdkeeping as
well as inventory purposes.
a About Two -Dimensional (2D) Vaccine Barcodes, CDC. https://www.cdc.gov/vaccines/programs/iis/2d -vaccine -barcodes/about.html

1
VIPS Phase II executive summary:
Barcodes on primary containers
March 2020
2
Barcodes on primary containers
About Barcodes
? Barcodes are symbols that encode information such as product numbers, serial numbers, supplier data,
batch numbers and expiry dates which can be scanned electronically using two dimensional (2D) scanners,
laser or mobile device cameras to automatically capture information.
? Barcodes enable tracking and monitoring of vaccine products in supply chains, providing information to
manufacturers, transport providers, health facilities and other relevant parties involved in the logistics
management systems, assuming the supporting infrastructure is in place.
? 2D barcodes can hold a significant amount of information and there is a possibility to automatically import
vaccination data into patient electronic medical records (EMRs).
Stage of development
? 2D Barcodes are commercially available and are widely used on products globally across various
industries including for products used in healthcare . Many US and European vaccine suppliers provide 2D
barcodes on primary containers, though not for the Gavi/UNICEF markets.
? WHO currently recommends GS1 compliant barcodes for secondary and tertiary packaging of vaccines
containing the Global Trade Item Number (GTIN), vaccine expiry date and vaccine batch/lot number. Gavi and
UNICEF recently announced that GS1 barcoding on vaccine secondary packaging will be a requirement by
31 December 2021 to improve visibility and traceability of vaccines from manufacturer to beneficiary.
Newswire.ca
a
a https://www.newswire.ca/news -releases/sanofi -pasteur -moves -national -immunisation -strategy -forward -with -new -bar -code -technology -509575151.html
PATH
2D barcode on primary container
Barcode on secondary packaging

VIPS Phase I executive summary:
Sublingual dosage forms
June 2019
Sublingual dosage forms
About Sublingual dosage forms
? Sublingual dosage forms are tablets and thin films that are placed under the tongue and
rapidly dissolve to form a gel in a small amount of saliva.
? The gel is absorbed via the mucosal surfaces under the tongue inducing systemic
immunity, similar to an injectable vaccine, and potentially inducing robust mucosal immunity.
? In contrast to oral ingestion vaccination, sublingual dosage forms are not intended to be
swallowed or delivered to the intestinal tract.
Stage of development
? Sublingual dosage forms are in early -stage preclinical development for several vaccines including HIV Env
protein and ETEC. The mucosal adjuvant dmLT is also being evaluated.
? Some have progressed to clinical trials including a seasonal influenza vaccine combined with a novel adjuvant in a
sublingual tablet.
? Most studies of sublingual vaccines to date have not utilised optimised sublingual dosage forms that form a gel ,
which resulted in poor immune responses.
? Commercially available sublingual dosage forms are used to deliver allergy immunotherapies, low molecular weight
drugs, and therapeutic vaccines.
PATH
Gel -forming sublingual
tablet being placed under
the tongue

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VIPS is a Vaccine Alliance project from Gavi, World Health Organization, Bill & Melinda Gates Foundation, PATH and UNICEF
Sublingual dosage form s
Comparator s?:
? Single dose vial (liquid ) and dropper or spray er a;
? Single dose vial (lyophilised) + diluent + reuse prevention (RUP) reconstitution
syringe and dropper sprayer;
? Single dose vial (liquid) and autodisable (AD) needle and syringe (N&S);
? Single dose vial (lyophilised) + diluent and RUP reconstitution syringe and AD N&S.
Section 1: Summary of innovation
1.1 Examples images:


Photo source : Provided by PATH

Photo source : LTS Lohmann
1.2. D escription of innovation (1,2):
? Sublingual (under the tongue) administration allows direct absorption into the systemic circulation .
? The sublingual region under the tongue is highly vascularized, rich in blood supply , allowing for
direct absorption of the active into systemic circu lation. It also contain s numerous subsets of antigen
presenting cells ( APCs ) and plays a critical role in induction of immune response s offering a non -
invasive route for vaccine administration .
? The sublingual dosage forms reported in this TN have been developed to contain penetration
enhancers and mucoadhesive agents to assist with antigen uptake by the underlying APCs similar
to an injectable formulation (IM/SC/ID routes) . Sublingual delivery is a needle -free and simplified
alternative presentation to a parenteral vaccine.
? In addition to systemic immunity, sublingual delivery also has the potential to induce robust mucosal
immunity.
? Oral mucosal vaccination (i.e. sublingual and buccal route s) is distinct from oral ingestion
vaccination be cause the dosage form is not intended to be swallowed or delivered to the intestines.
? The sublingual route has the potential to induce mucosal immune responses in a broad range of
tissues at more distance sites compared to other mucosal routes (i.e. the r espiratory ,
gastrointestinal, or reproductive tract) (1).
? Sublingual dosage forms can be produced via different manufacturing processes such as direct
compression, melt extrusion, liquid blending or freeze drying.
? 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 commonly used by countries for specific vaccines, a comparison against the multi - dose vial will also be conducted under Phase II for those vaccines if this innovation is prioritis ed. a The dropper or sprayer comparator is expected to be delivered by the oral or intranasal route.

VIPS Phase I executive summary:
Reconstitution vial adapters
June 2019
Reconstitution vial adapters
About Reconstitution vial adapters
? Vial adapters can facilitate either:
? Vial to vial reconstitution using a reuse prevention (RUP) syringe without needle for diluent transfer
(this sub -type is assessed in the TN);
? Vial to vial reconstitution by directly connecting the two vials without the use of a syringe for diluent
transfer; or
? Reconstitution between a syringe prefilled with diluent and vaccine vial . A prefilled syringe (without a
fixed needle) containing the diluent is attached to the vaccine vial using the vial adapter as a connecting
device. The diluent is then released into the vial through the vial adapter for mixing.
? Vial adapters are manufactured in a variety of sizes , and function by fitting over the top of a vial, while
utilising a plastic spike to puncture the rubber stopper. Most designs are compatible with luer lock and
luer slip syringes for liquid transfer.
? For oral or intranasal delivery, the delivery syringe can be connected to the vial adapter to draw the dose.
? For parenteral vaccines, the vial adapter would be removed after reconstitution and an autodisable (AD)
needle and syringe (N&S) used to draw and inject the vaccine.
Stage of development
? A variety of reconstitution vial adapters are commercially available .
? ROTASIIL vaccine is supplied with a vial adapter for reconstitution and
drawing doses for oral delivery. The vaccine is a lyophilised (freeze -dried)
presentation packaged in single -dose vials alongside a diluent.
West Pharmaceutical
a
Vial adapters for reconstitution using a syringe
West Pharmaceutical
a
Vial adapters for reconstitution using a syringe
West Pharmaceutical
b
Vial adapters for direct vial to vial reconstitution
ahttps://www.westpharma.com/products/reconstitution -and -transfer -systems/vial -adapters bhttps://www.westpharma.com/products/reconstitution -and -transfer -systems/mix2vial -and -needle -free -transfer -device Chttps://www.google.com/search?q=Rotasiil+Rotavirus+Vaccine&hl=en&source=lnms&tbm=isch&sa=X&ved=0ahUKEwj -986zh -jgAhW Fa1AKHbkdCucQ _AUIDigB&biw=1920&bih=861#imgrc=8XeGpeGcrBc7W M:&spf=1551687780860
Serum Institute of India PVT. Ltd
c

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VIPS is a Vaccine Alliance project from Gavi, World Health Organization, Bill & Melinda Gates Foundation, PATH and UNICEF

Reconstitution vial adapters
Comparator ? : Use without innovation (i.e. reuse prevention reconstitution needle and
syringe (N&S) )

Section 1: Summary of innovation
1.1 Examples of innovation types:

Reconstitution vial adapters

Vial adapters
West Pharma





Mix2Vial ?
reconstitution
system
West Pharma


MixJect ? reconstitution &
delivery system
West Pharma


EZ LINK ? Duoject


Image source: a Image
source: b Image source: c Image source: d
1.2. Description of innovation:

? Vial adapters facilitate the reconstitution of two vaccine components from their separate primary
containers. The objective of the innovation is to eliminate the needle from the reconstitution
process, making it safer.
? Vial adapters are manufactured in a variety of sizes and used to facilitate reconstitution and/or
drawing up of a wide variety of pharmaceutical products including medicines and vaccines.
? A vial adapter functions by fitting over the top of a vial, while utilizing a plastic spike to puncture the
rubber stopper. Most designs are compatible with Luer lock and Luer slip syringes for liquid transfer.
? 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 commonly used by countries for specific vaccines, a comparison against the multi - dose vial will also be conducted under Phase II for those vaccines if this innovation is prioritis ed. a https://www.westpharma.com/products/reconstitution -and -transfer -systems/vial -adapters b https://www.westpharma.com/products/rec onstitution -and -transfer -systems/mix2vial -and -needle -free -transfer -device c https://www.westpharma.com/products/reconstitution -and -transfer -systems/mixject d http://duoject.com/wp -content/uploads/2016/01/EZLink_InformationCard.pdf

VIPS Phase I executive summary:
Single - chamber cartridge injectors
June 2019
Single -chamber cartridge injectors
About single -chamber cartridge injectors
? Vaccine delivery device that has a needle and that requires insertion of a
prefilled cartridge of vaccine product.
? Based on the design of the device, the needle could be either exposed or not
exposed.
? Some cartridge injector devices have auto -disable (AD) mechanisms and/or
sharps injury protection (SIP) needle retraction mechanisms .
Stage of development
? Currently all the single -chamber cartridge injector devices are in the design or
development phase for use with vaccines.
? There are no independent testing or user studies available on the use of the
devices in comparison to standard practice using the AD needle and syringe
(N&S), and therefore no independent information exists on ease of use, time
required to prepare and deliver, or cost and storage volume of the devices.
Pradel G et al, 2017
a
Pre -assembled device
(JUDO glass cartridge injector)
Vaccject
TM b
User -assembled devices with
integrated needle with no sharps
exposed (Vaccject TM)
a Pradel G, Leader CT, Carestia S, Manager M. JUDO A new paradigm on compact and low cost vaccine delivery devices. 2017; bhttp://duoject.com/wp -content/uploads/2016/01/Vaccject_InformationCard -1.pdf

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VIPS is a Vaccine Alliance project from Gavi, World Health Organization, Bill & Melinda Gates Foundation, PATH and UNICEF
Single -chamber cartridge injectors
Comparator : Single Dose Vial (SDV) liquid and Autodisable ( AD ) Needle and Syringe
(N&S )


Section 1: Summary of innovation
1.1 Examples of innovation types:

JUDO ? a cartridge injector prototype


Image source : (1)
Vaccject TM

Image source : a
1.2. Description of innovation:
? There is a large market for delivery devices that utilize prefilled cartridge technology, e.g., the
pen injectors that deliver drugs for chronic conditions such as diabetes and hormone
deficiencies whereby repeat injections are necessary and administered by the patient
themselves or the caregiver. Prefilled cartridges are also widely used to deliver anaesthesia for
dental applications.
? Prototypes of s ingle -chamber cartridge injectors for vaccines are single -dose presentations that
use pre -filled glass cartridges and are manually operated devices.
? The pre -filled cartridge is inserted into the delivery device that has a needle attached which is
either exposed or not exposed based on the design of the device , this is known as the user -
assembled device which is the main focus of this technical note (TN) for the assessment.
a https://www.who.int/immunization/research/meetings_workshops/PDVAC_2017_Delivery_Tech_Update_Zehrung_PATH.pdf

VIPS Phase I executive summary:
Solid - dose implants with applicator
June 2019
Solid -dose implants (SDIs) with applicator
About SDIs
? SDIs consist of vaccines (including antigens, adjuvants and excipients) that have been
reformulated into a solid format .
? A SDI 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 prior to
administration.
? 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.
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 W ijdeven 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.