qbd strategy for lc method development · introduction analytical qbd steps development steps case...
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QBD STRATEGY FOR LC METHOD DEVELOPMENTMaryline Roe, Jennifer Ottoy, Jérôme Respaud
Amatsigroup SAS, Fontenilles Site, Parc de Génibrat, 31470 Fontenilles, France
www.amatsigroup.com
INTRODUCTION ANALYTICAL QBD STEPS
DEVELOPMENT STEPS
CASE STUDY
Quality by Design enables a more efficient analytical method development.
With a QbD strategy, the method will be close to its optimum and more robust in
comparison with “traditional” approach.
QbTQuality by Testing
QbDQuality by Design
OFATOne-Factor-At-A-Time
DoEDesign Of Experiments
Screening :
6 pH
4 stationary phases
2 organic solvents
3 gradients
Optimisation :
3 pH
3 column temperatures
3 initial % of organic solvent
Phase 1
Phase 2
Robustness
simulation
API + 5 impurities
FactorNumber of
levelsChoices
Stationnary
phase4
BEH C18, Kinetex C18, BEH
Shield RP18 et CSH PFP
Organic
solvent2 Methanol, Acetonitrile
Gradient time 3 4 min, 7 min, 10 min
pH 6 2, 3, 4, 5, 6, 7.5
CMP Best condition
Column Kinetex C18
Organic phase Methanol
Gradient time 4.2 min
pH 5
Kinetex C18 – Methanol – gradient : 4.2 min
FactorNumber of
levelsChoices
pH 3 4.5, 5.0, 5.5
Temperature
(°C)3 30.0, 40.0, 50.0
% initial of
methanol3 5, 10, 15
CMP Best condition
pH 4.5
Temperature (°C) 30.0
% initial of méthanol 7
Robustness zone
Robustness zone Robustness zone
Robustness zone
Equipment:
- Waters Acquity UPLC H-Class
- Waters Acquity PDA detector
- Solvent switching valve
- Waters Acquity H-Class
column manager (4 x 50 mm
columns)
Software:
- Empower 3
- Fusion QbD
Phase 1 - Screening
Phase 2 - Optimisation
Robustness simulation (for Cpk ≥ 1.33)
Available for you !
- QbD method development strategy available with Fusion® software
- QbD approach optional for your method development requirements
- To be applied during any pharmaceutical development phases (from phase I to regulatory dossier)
- Comprehensive report issued (including approach explanation, strategy applied and results obtained with Fusion®)
Automated
No peak tracking
Want to know more? [email protected]
Comparison with USP method : HPLC, run time of 50 min
Main response goal = Resolution on API and impurity peaks
run time < 6 min
Stage 3
ATP = Predefined objectives that stipulate the performance requirements for
the analytical procedure
Independent of the technique
Ideal scenario would be submission of ATP without method details
Increased regulatory flexibility and cost reduction
Stage 1
Stage 2
QbD definition (ICH Q8)A systematic approach to development that begins with predefined
objectives (= QTPP) and emphasizes product and process understanding ,
and process control, based on sound science and quality risk anagement
Definition adapted to Analytical QbDA systematic approach to development that begins with predefined
objectives (= ATP) and emphasizes data and analytical procedure
understanding , and analytical procedure control, based on sound
science and quality risk management
NO EXTRA COST & TIME
MORE EFFICIENT