11.06.2019 Page 1 of 22
VIPS is a Vaccine Alliance project from Gavi, World Health Organization, Bill & Melinda Gates Foundation, PATH and UNICEF
Solid -dose implants (with applicator) a

Comparator s? : Singl e dose vial (liquid ) and autodisable (AD) n eedle and syringe (N&S) ;
Single dose vial (lyophilised) + diluent + reuse prevention (RUP) reconstitution
N&S and AD N&S.

Section 1: Summary of innovation
1.1 Example s of innovation types :
Separate, compressed gas -
powered applicator: Bioneedle

Separate, spring -powered
applicator: Implavax?

Optional, separate applicator:
Micropatch TM


Image source: (1) Image source: b Image source: c
1.2. D escription of innovation:
Solid -dose implants (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 b elow the skin. After injection, the dose either dissolves immediately or is released slow ly
depending on the formulation. SDIs are also described as bioneedles (one of the SDI developers is also
called Bioneedles), pellets, bars, bio -degradable mini -implan ts, or mini -projectiles.
SDI devices have two or three components:
? The vaccine dose : This is in a solid format. Some SDIs have a central cavity of known volume filled
with liquid vaccine that is then dried. In other SDIs the vaccine and excipients are dis tributed
uniformly throughout the implant. Ideally the dose would be sufficiently thermostable to allow
storage and distribution outside the cold chain for a defined period of time.
? Vaccine dose container or cassette : In some cases, the solid vaccine dose is contained in a
cartridge or cassette for easy handling. This is expected to have a relatively small volume, possibly
similar to a single dose vial.
? An applicator or actuator : is used to propel the implant into the skin, using a spring or
compressed -gas . The applicator might be separate and re -usable, or integrated and single use. In
one device (Micropatch), manual pressure is used to deliver the implant .
a All SDIs require an applicator including separate gas - or spring -powered, or integrated applicators ? 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 mu lti- dose vial will also be conducted under Phase II for those vaccines if this innovation is prioritised. b https://www.enesipharma.com/technologies/platform/ c Nemaura presentation. Teripa ratide microneedle patch for osteoporosis, December 2018. Presented during telecon 12 February 2019.

11.06.2019 Page 1 of 17
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.

VIPS Phase I executive summary:
Prefilled dry - powder intranasal (DPIN)
devices
June 2019
Prefilled dry -powder intranasal (DPIN) devices
About Prefilled dry -powder intranasal (DPIN) devices
? A wide range of DPIN devices are being developed or are already on the market for delivering
medicines. DPIN devices fall into two basic categories based on the activation method:
? Passive devices that use mechanical energy from fingers or thumb to generate
pressure to disperse the powder;
? Active devices (breath actuated powder inhalers) that use breath flow to activate expulsion
from the container filled with the powder to enable dispersion into the nasal passageway.
? Powders would likely reach only the nare (s) to which they are administered, and it is possible to
administer doses to each nare .
? Dry powder vaccines for intranasal delivery require specialised drying methods to achieve a
formulation that is aerosolizable and of appropriate particle size for efficient delivery to the nasal
cavity.
? Various studies have demonstrated the feasibility of preparing dry powder aerosolized vaccines
using a variety of methods such as spray -drying, bubble drying (a gentle version of spray
drying), spray -freeze drying or freeze -drying methods.
Stage of development
? Most of the devices are commercially available , however their uses for vaccine delivery
are in early phase preclinical studies and early phase clinical trials.
Bespak
a
Passive device ( Unidose Bespak )
Optinose
? b
Active device
(Bi-Directional? nasal delivery
technology, Optinose ?)
aPersonal communication from Ian Anderson, Bespak , February 2015 bhttps://www.optinose.com/exhalation -delivery -systems/powder -delivery -device

11.06.2019 Page 1 of 22
VIPS is a Vaccine Alliance project from Gavi, World Health Organization, Bill & Melinda Gates Foundation, PATH and UNICEF
Prefilled dry -powder intranasal (DPIN ) device s
Comparator ? : Single dose vial (lyophilised ) + diluent + reuse prevention (RUP)
reconstitution needle and syringe (N&S) and autodisable N&S a


Section 1: Summary of innovation
1.1 Example images :
.
Unidose b Bespak

Bi-Directional? nasal delivery
technology , Optinose?


Image source: c Image source : d

1.2. D escription of innovation:
? There are a whole range of dry powder intranasal (DPIN) devices that are being developed or
already on the market for delivering medicines.
? DPIN d evices fall into two basic categories based on the activation method used . Most of the
devices use (i) mechanical energy from fingers or thumb to generate pressure to dispers e the
powder, and others use (ii) passive or active breath flow to disperse the powder. Powders would
likely reach only the nare (s) to which they are administered, and it is possible to administer doses to
each nare. There may be some increased risk of pulmonary deposition of powders if the particle
size range includes small particles ( 5 micron).
? Powder sprayers are d evices that deliver IN dry powder sprays by c reating an internal pressure on
the compartment containing the formulation through an external mechanical force driving the
release of powder particles into the nasal passageway , they use mechanical energy to create and
internal pressure and these are know n as passive devices . Examples include the UniDose ,
DriDose TM, Fit -lizer TM .
? Breath a ctuated powder inhalers are active devices that allow the patients ? breath to activate
expulsion from the ca psule or blister containing the dry powder formulation into the nasal
passageway . An example is the Rhinocort? Turbuhaler? . The Rhinocort device uses nasal
? Single dose vials, rather than multi -dose vials (MDVs) were used for the comparator, because in most cases the innovation bein g 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 priorit ised. a A comparison against IN sprays will be required under Phase II if there is a vaccine (antigen) that is currently delivered as liquid spray in the scope of vaccines. b Universal Stabilization technologies. https://www.vitrilife.com/ c Personal communication from Ian Anderson, Bespak, February 2015 d https://www.optinose.com/exh alation -delivery -systems/powder -delivery -device

VIPS Phase I executive summary:
Radio Frequency Identification (RFID)
June 2019
Radio Frequency Identification (RFID)
About Radio Frequency Identification (RFID)
? RFID tags can be affixed to vaccine primary containers and store a wide range of information
useful for inventory control, patient monitoring and providing data for electronic medical
record systems.
? An RFID system consists of three components; ( i) a tag, (ii) a reader and (iii) the middleware ,
which is the computer hardware and software that connects the reader to computer systems by
converting data captured from tags into tracking or identification information.
? RFID tags also enable all the tags within range to be identified and every tag does not need to be
individually scanned.
There are three types of RFID tags:
? Passive tags ? which do not contain a built -in power source and cannot initiate communication
with a reader.
? Semi -passive RFID tags ? which have built -in batteries and function with a lower signal power
and act over long distances.
? Active RFID tags ? which are battery powered devices that have an active transmitter and can
communicate over greater distances.
Stage of development
? RFID tags are commercially available and are widely used as a tracking system in a variety of
industries including agriculture, food, pharmaceuticals and various healthcare practices for the
tracking of patients, medical supplies and medical equipment in hospitals.
a http://endtimestruth.com/wp -content/uploads/2014/01/RFID -chip -and -antenna -3.png b http://ww1.prweb.com/prfiles/2014/10/05/12223944/HCL%20 -%20Seal%20Tags%20Kit%20Check.jpg c https://www.abr.com/products/rfid -products/
http://endtimestruth.com
a
RFID Tag
ww1.prweb.com
b
RFID tags used for hospital medication trays
www.abr.com
c
Handheld RFID readers & scanners

12.06.2019 Page 1 of 20
VIPS is a Vaccine Alliance project fro m Gavi, World Health Organization, Bill & Melinda Gates Foundation, PATH and UNICEF

Radio Frequency Identification (RFID)
Comparator: Use without innovation (i.e. no RFID)


Section 1: Summary of innovation
1.1 Example images :
RFID tags RFID readers
RFID tag


Image source : a
RFID tags used for
hospital medication trays

Image source : b
RFID tag attached to drug

Image source : c
Handheld RFID readers &
scanners

Image source : d
Android App to
scan RFID

Image source : e




a http://endtimestruth.com/wp -content/uploads/2014/01/RFID -chip -and -antenna -3.png b http://ww1.prweb.com/prfiles/2014/10/05/12223944/HCL%20 -%20Seal%20Tags%20Kit%20Check.jpg c http://www.radiofrequency -tags.com/photo/pl13237005 - programming_printable_rfid_tags_for_identifying_medicine_bottles_to_track_prescription_drugs.jpg d https://www.abr.com/ products/rfid -products/ e https://dribbble.com/shots/1142633 -Android -App -RFID -Scan

VIPS Phase I executive summary:
Oral fast dissolving tablets
June 2019
Oral fast dissolving tablets
About Oral fast dissolving tablets (FDTs)
? Fast dissolving tablets are freeze dried vaccine tablets that disintegrate
rapidly in saliva.
? Oral FDTs are swallowed and rapidly disintegrate, delivering the
vaccine to the gastrointestinal tract.
Stage of development
? There are several pharmaceutical companies with drug products on
the market using a similar technology for producing oral FDTs.
? Oral FDTs are in preclinical development for vaccines such as
ETEC.
CIMA
a
PATH
ahttp://www.cimalabs.com/technology/lyoc.aspx

12.06.2019 Page 1 of 21
VIPS is a Vaccine Alliance project from Gavi, World Health Organization, Bill & Melinda Gates Foundation, PATH and UNICEF
Oral fast dissolving tablet s
Comparator s? :
? Single dose vial ( lyophilised ) + diluent + reuse prevention (RUP) reconstitution
syringe and dropper ;
? Single dose vial (liquid) and autodisable (AD) needle and syringe ( N&S )


Section 1: Summary of innovation
1.1 Examples images:



Photo source: provided by PATH
1.2. D escription of innovation:
? Fast dissolving tablets (FDTs) are freeze dried vaccine tablets that disintegrate rapidly in saliva,
requiring no/minimal fluid for oral administration. This feature allows the FDTs to be dispersed in
situ for adults or dispersed in minimal volume for administration to infants, thus eliminating any
hazards associated with choking.
? Oral FDTs are swallowed and rapidly disintegrate (not f orming a gel under the tongue like
sublingual dosage forms described in the Sublingual Dosage Form TN). This innovation is thus
delivered to the intestines and not absorbed in the mouth. This is particularly relevant for vaccines
against enteric pathogens that replicate in the gut.
? FDTs can be delivered through several routes of administration including oral, sublingual, buccal,
vaginal, or rectal. This TN will focus on FDTs for oral delivery. Referred to as oral FDTs in this
document. Sublingual FDTs, wh ich are placed under the tongue and form a gel upon contact with
saliva, will be discussed in the Sublingual Dosage Form TN.
? The small tablets are packaged in unit -dose blisters made from foil or other pharmaceutical grade
material, offering an inexpensive, scalable, and easy -to-use product presentation for live attenuated
vaccines.
? Some n ew oral enteric vaccines in development are complex vaccines with multiple components
(e.g., multiple strains, mucosal adjuvant, and antacid buffer ) that often must be packaged separately
due to cross -reactivity during testing or formulation incompatibility (1,2). With traditional
lyophilization being carried out in glass vials, this results in multiple vials and large footprint in
?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 prioritised.

VIPS Phase I executive summary:
Plastic needles (for reconstitution)
June 2019
Plastic needles (for reconstitution)
About Plastic needles (for reconstitution)
? Polymer needles designed to be capable of penetrating vial
septums could be used for reconstitution and access vaccine
products.
? These needles could be designed to be attached to a reuse
prevention (RUP) syringe or integrated into a RUP syringe itself .
Stage of development
? Plastic needles have obtained regulatory approval as medical
devices .
? At present, there are no commercially available reconstitution
syringes with plastic needles . However, there are prototypes
available and commercial products could be adapted for this purpose.
PATH
K Spike Reconsitution syringe
a Busillo E, Colton JS. Characterization of plastic hypodermic needles. J Med Device. 2009;3(4):41004.
Plastic hypodermic needle
Busillo & Colton, 2009
a

11.06.2019 Page 1 of 17
VIPS is a Vaccine Alliance project from Gavi, World Health Organization, Bill & Melinda Gates Foundation, PATH and UNICEF
P lastic needl e s (for recon stitution )
Comparator : Reuse prevention reconstitution (RUP) needle and syringe (N&S) with
metal needle


Section 1: Summary of innovation
1.1 Examples of innovation types:
Plastic hypodermic needle

Image source: (1)
K Spike Reconsitution syringe


Image source: a

1.2. Description of innovation:

? Various designs and prototypes of polymer needles have been produced and tested in terms of
functionality and comparability to metal needles (1,2) .
? Plastic needles can be designed with a luer hub for attachment to a separate syringe or can be
integrated into the syringe itself.
? Some polymer needle designs are intended to have sharpness similar to metal hypodermic needles
and could be used to puncture vial stoppers as well as to penetrate the skin for parenteral injection.
Some developers have focused on plastic needles that would be intended to be suitable only for
use for accessing a vial. Other niches for plastic needles could include veterinary, pha rmacy, or
industrial purposes. This Technical Note (TN) is focused solely on vaccine reconstitution with plastic
needles intended for vial access use , and not for injection, because of their potential safety benefits.
? At present, there are no commercially available reconstitution syringes with plastic needles.
However, there are prototypes available and commercial products that could be adapted for this
purpose.


a Courtesy of PATH, personal communication.

VIPS Phase I executive summary:
Prefilled polymer blow - fill - seal droppers /
dispensers
June 2019
Prefilled polymer blow -fill -seal (BFS) droppers /
dispensers
About prefilled polymer BFS droppers/dispensers
? Blow -fill -seal is an aseptic filling process that is widely used to produce a variety of
pharmaceuticals in polymer primary containers.
? In BFS 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 squeeze tubes, in which the container is first produced and sterilized, and then
shipped to a different site for filling and sealing.
? A BFS dropper produces metered -size droplets and could be used for small dose volume
vaccines such as oral polio vaccine (OPV) , including multidose presentations. A BFS dispenser
emits a stream of vaccine and could be used for oral vaccines such as rotavirus and cholera that
typically have a larger dose volume.
Stage of development
? BFS dispensers are currently manufactured and commercially available .
? In 2019, GlaxoSmithKline?s (GSK?s) Rotarix oral rotavirus vaccine was the first vaccine to be
WHO prequalified in a BFS container.
? Other vaccines are being evaluated for BFS dispenser presentations.
PATH
BFS squeeze tube dispensers (GSK Rotarix)

11.06.2019 Page 1 of 17
VIPS is a Vaccine Alliance project from Gavi, World Health Organization, Bill & Melinda Gates Foundation, PATH and UNICEF
Heat -stabl e /c ontrolled temperature chain (C TC )
qualified liquid formulation s
Comparator s: Use without innovation a (i.e. current liquid or lyophilised formulation)


Section 1: Summary of innovation
1.1 Example images :



1.2. D escription of innovation:
? Historically, vaccines are most commonly formulated and packaged as liquids . Liquid formulations
require simpler fill/finish and administration processes than other formulations.
? Heat stable liquid formulations (such as those inc orporating stabilizing agents) enable vaccines to
be exposed to high temperatures (e.g., a minimum of 3 days at ?40 OC) without losing their potency
and can thus be CTC qualified. b Such formulations require optimized properties (e.g. buffer, pH,
salt conce ntrations and stabilizing excipients) to prevent denaturing of proteins and reduce the
occurrence of damaging chemical reactions caused by increasing temperature.
? Heat -stabilized vaccines will differ in the length of time they can be stored in a CTC and th e
maximum temperature they can endure while remaining stable and potent, and some vaccines will
not be able to be reformulated into a heat -stable liquid.
Each vaccine will require an individual development process to identify an appropriate stabilizing
formulation. High -throughput screening method s can be used to expedite formulation optimisation
(1) .
1.3 Examples of innovations and developers:
There are currently two liquid vaccines that are thermostable and qualified for CTC use. These are:
Merck?s Gardasil? 4 (quadrivalent human papillomavirus vaccine) that is labelled to allow use at
temperat ures up to 42?C for 3 days and Shantha Biotechnics Shanchol? (oral cholera vaccine) that is
labelled to allow use at temperatures up to 40?C for 14 days .
A number of vaccine manufacturers are in the process of qualifying their existing and pipeline liquid
vaccines for CTC use.
a no comparator or equivalent existing device. b WHO. Controlled Temperature Chain publications and guidance. https://www.who.int/immunization/programmes_systems/supply_chain/ctc/en/index1.html