Set vaccines free

Vaccines formulated as dry powders can be transported anywhere in the world, to every child in the world

With no cold chain required

Set vaccines freeSet vaccines free

Vaccines formulated as dry powders can be transported anywhere in the world, to every child in the world

With no cold chain required

Set vaccines free

Background

• LaminarPace technology developed at Inhalation Sciences AB• Micronized powder for inhalation• Early test with animal vaccines showed great temperature stability

• Technology spun-out into a newly created company: Ziccum AB• 2017

LaminarPace Process:

Spray (Air) drying process:

- Room temperature

- Gentle process

- High process yield (80-90%)

- Well defined powder size distribution (From 2 to 10 µm)

- Low energy cost

LaminarPace Process:

Counter current flow

Vibrating mesh

Particle engineering

Trehalose characteristics after spray drying:Trehalose shows a typical glass transition after spray drying

Light microscopy of spray dried trehalose

Light microscopy of Dihydrate trehalose

Before Spray drying

After Spray drying

Quality by design approach:

Process Risk analysis Design of experiement Design space definition

Characterisation spaceAcceptable space

Operating space

Humidity profile

Nebulizer

Pulse (PR)

Mesh size Life time

Frequency

Capacity

Flows

Sheath Flow

Nebulizer Flow

Filter FlowSwirl

Vacuum Pump

Velocity

FormulationRaw materials

Drying Flow

Fan capacity

Feed stockconcentration

Viscosity

Liquid Viscosity

Dry powder(Moisture Content / Glass temperature)

Post Drying

MembranesPorosity

MaterialThickness

Column dimension

PeopleMaterialsMachine

PeopleTraining

Procedure

LAPA: Critical process parameters

Vaccine potency stability

Vaccum lid

Quality target product profile and Critical QualityAttributes (Initial Design Space)

Powder: - Glass transition temperature: > 20oC above the storage temperature- Moisture content: minimize %- Size: Well defined- Yield: More than 80%

Vaccine/antigen: - Antigenicity: Limit the lost- Integrity: Keep integrity of the antigen- In-vivo study: Keep Immune responses- Stability: at 40 oC for a longer period (min 3 days CTC)

QTTP: Air dried powder of heat stable vaccine, with low moisture content, high Tg temperature. The powder contains a embedded vaccines within the sugar matrix.

Moisture content (%)

Feed Stock (%)

Production rate (%)

DOE results: Moisture (Water) content model

Air dried trehalose with different nebulizer mesh20% Feed stock (Obj x20)

Light Microscopy observation of the air dried powder:Effect of nebulizer mesh size

30 µm 30 µm

Process vaccine 20 million vials/annum

BlendingPre-blending BULK agent

LAPABuffer ions

Stabilizers

Fill

Package

TFFThawing

Frozen bulk vaccine

Storage

Fill and finish concept :

Initial air dried powder filling assesment (UsingDosator unit, air dried powder mixed with carrier)

0

2

4

6

8

10

12

1 2 3 4 5 6 7 8 9 10

mg/

plug

Sample number

Dosator system

F2 10 mg PB10

Upper limit

Lower limit

- 100+ small molecules- Peptides

- Live attenuated viruses - Inactivated viruses- VLP- Subunit/conjugate to model vaccines- (LNP)

LAPA; a new Unit operation for the Pharmaindustry

Stability assessment using thermal shift assay (TSA)of spray dried formulation containing Ovalbumin:

Stability assessment using AF4-MALSof air dried formulation containing Ovalbumin:

No aggregates of OVA after 28 days!

Standard proteins

Ovalbumin after reconstitution (after 28 days at different storage temperature)

ThanksFabrice RoseLouise Egeblad