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Speakers’ Corner
Quality by Design and Expertise:Accelerating time to market of complex oral solid dosage forms
v
CPhI Worldwide 2017 October 24th - 26th, 2017 Frankfurt
Lucile KOWALSKI - NPI Project Manager Guy VERGNAULT - VP R&D
Speakers’ Corner
Skyepharma provides de-risked time- and cost-effective services
Time and Cost Efficiency
Early stage development Commercial & packaging
Right First Time Development
Extensive project management
Speakers’ Corner3
A ‘Right First Time’ approach creates competitive services
1. Patient-oriented, Quality by Design approach
2. Cost reduction and enhanced time-to-market
Speakers’ Corner
Quality by Design is the Gold standard
QbD Process
Material attributes (MA)
Process parameters (PP)
Quality Target Product Profile
(QTPP)
Patient :quality, safety,
efficacy
1. Quality attributes : Which ones are critical?
CQA
2. Do they have an impact on a CQA?
3. To what extent do they impact a
CQA?
Speakers’ Corner
QbD : Pros and Cons
PROS
CONS
Reduction of IPC
Process robustness
Operational flexibility
Specific skills
Raw materials
Time
Requires investment
Speakers’ Corner
Case study : To what extent do CPPs impact a CQA? (1/2)
ResponsesCase study: impact of 5 factors and their interactions on
Implementation of design of experiment
-8 -6 -4 -2 0 2 4 6 8 10 12
9.50
-0.25
-1.00
-2.25
-6.00
Final pressure
Turret speed
Pressure 2
Dose strength
Pressure 1
crushing strength
Speakers’ Corner
Case study : To what extent do CPPs impact a CQA? (2/2)
Leading science-driven development
115.0
132.0
119.5
126.5
30 Turret speed, rpm
Dose strength, mg
10
a c
Implementation of design of experiment
Crushing
strength (N)
Speakers’ Corner
QbD : Pros and Cons
PROS
CONS
Reduction of IPC
Process robustness
Operational flexibility
Specific skills
Raw materials
Time
Speakers’ Corner
QbD : Pros and Cons
PROS
CONS
Reduction of IPC
Process robustness
Operational flexibility
Time
Specific skills
Raw materials
Speakers’ Corner
QbD : Pros and Cons
PROS
CONS
Reduction of IPC
Process robustness
Operational flexibility
Time
Specific skills
Raw materials
Speakers’ Corner
QbD : Pros and Cons
PROS
CONS
Reduction of IPC
Process robustness
Operational flexibility
Raw materials
Time
Specific skills
Speakers’ Corner
Case study 2 : Do PPs have an impact on a CQA ?
20
25
30
35
40
0 200 400
Hardness (N)
Number of tablets
propeller speed : 5 %
propeller speed : 10 %
propeller speed : 20 %
propeller speed : 30 %
propeller speed : 60 %
Feeding shoe settings on hardness How improper settings of the simulator can be misleading
0
20
40
60
80
100
120
0 2 4 6 8 10 12
Time (h)
Pressure 5 kN
Pressure 13 kN
Compression pressure on disso- 500 mg of API- 0.5 day
API dissolution (%)
Competitive advantage: Quick and easy access to key information
• QbD initiation at early stage of development
• Continuous improvement of commercial product
• Rapid results using minimum amount of powder
Skyepharma special features Piezoelectric sensors Press coating module Roller compactor module
Speakers’ Corner
Conclusion #1
Time and Cost EfficiencyRight First Time
Approach
Speakers’ Corner14
1. Patient-oriented, Quality by Design approach
2. Cost reduction and enhanced time-to-market
Speakers’ Corner
Development and scale up: cost and time reductionBy straight to goal development and optimization
Setting of scale-up parameters
Formulation developmentScreening of raw materials
Compression cycle of API gradesCompression cycle of excipientsPressure/hardness relationship
RIGHT FIRST TIME
Pressure/hardness relationshipImpact of formulation on dissolutionCompression cycle
Impact of feeding shoe settingsImpact of pressure on dissolutionRejection limits determination
Impact of tooling characteristicsDetermination of compression parameters
Assessment of critical parameters
Speakers’ Corner
Development and scale up: cost and time reductionBy anticipating scale up using a compression simulator
Example #1: Press coated tablet Delayed release
0
20
40
60
80
100
0 1 2 3 4 5
AP
I dis
solu
tio
n (
%)
Time (h)
Comparison of drug delivery on Kilian industrial press and simulator
Industrial Press
Compression simulator
Speakers’ Corner
Development and scale up: cost and time reductionBy anticipating scale up using a compression simulator
Example #2: Trilayer tablet Biphasic release
Comparison of drug delivery on Hata industrial press and simulator
0
20
40
60
80
100
120
0 200 400 600 800
AP
I Dis
solu
tio
n (%
)
Time (min)
API 1 (industrial)
API 2 (industrial)
API 1 (simulator)
API 2 (simulator)
Speakers’ Corner
Step
Batch size* Time*
SimulatorIndustrial
pressSimulator
Industrial
press
Tool assembly - - 0.5 h 5 h
Setting of comp. parameters 50 g 1 kg 0.5 h 1.5 h
Production of trial batch 100 g 33 kg 1 h 2 h
Disassembly + cleaning - - 2 h 20 h
SAVINGS 70 – 95 %
*Skyepharma case study based on a monolayer tablet transfer
Development and scale up: cost and time reductionBy reducing batch size and shortening timelines
Speakers’ Corner
General Conclusion
The Right
People
The Right
Focus
Right First
Time
The Right
Technology
Come and meet our team!
Stand 41A10