Ziccum presentation for DCVMN · 2021. 5. 4. · Microsoft PowerPoint - Ziccum presentation for...
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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 free 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 free
Transcript of Ziccum presentation for DCVMN · 2021. 5. 4. · Microsoft PowerPoint - Ziccum presentation for...
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
