Quality by Design (QbD)

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Quality by Design (QbD)

• Myth An expensive development tool !
• Fact A tool that makes product development and
  commercial scale manufacturing simple !
• Actually saves money !
• How ?

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Outline

• FDA initiatives for quality
• The desired state
• Quality by design (QbD) and design space (ICH Q8)
• Application of statistical tools in QbD
• Design of experiments
• Model building evaluation
• Statistical process control
• How can Innoworks assist you?

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FDAs Initiative on Quality by Design

• In a Quality-by-Design system
• The product is designed to meet patient
  requirements
• The process is designed to consistently meet
  product critical quality attributes
• The impact of formulation components and process
  parameters on product quality is understood
• Critical sources of process variability are
  identified and controlled
• The process is continually monitored and updated
  to assure consistent quality over time

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Quality by Design
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Design Space (ICH Q8)

• Definition The multidimensional combination and
  interaction of input variables (e.g., material
  attributes) and process parameters that have been
  demonstrated to provide assurance of quality
• Working within the design space is not considered
  as a change. Movement out of the design space is
  considered to be a change and would normally
  initiate a regulatory post-approval change
  process.
• Design space is proposed by the applicant and is
  subject to regulatory assessment and approval

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Current vs. QbD Approach to Pharmaceutical
Development
Current Approach QbD Approach
Quality assured by testing and inspection Quality built into product process by design, based on scientific understanding
Data intensive submission disjointed information without big picture Knowledge rich submission showing product knowledge process understanding
Specifications based on batch history Specifications based on product performance requirements
Frozen process, discouraging changes Flexible process within design space, allowing continuous improvement
Focus on reproducibility often avoiding or ignoring variation Focus on robustness understanding and controlling variation
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Pharmaceutical Development Product Lifecycle
Product Design Development
Process Design Development
Manufacturing Development
Continuous Improvement
ProductApproval
Candidate Selection
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Pharmaceutical Development Product Lifecycle
Statistical Tool
Design of Experiments (DOE)
Product Design Development Initial
Scoping Product Characterization Product
Optimization
Model Building And Evaluation
Process Design Development Initial
Scoping Process Characterization Process
Optimization Process Robustness
StatisticalProcess Control
Manufacturing Development and Continuous
Improvement Develop Control Systems Scale-up
Prediction Tracking and trending
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Design of Experiments (DOE)

• Structured, organized method for determining the
  relationship between factors affecting a process
  and the response of that process
• Application of DOEs
• Scope out initial formulation or process design
• Optimize product or process
• Determine design space, including multivariate
  relationships

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DOE Methodology

• (1) Choose experimental design
• (e.g., full factorial, d-optimal)

(2) Conduct randomized experiments
Experiment Factor A Factor B Factor C
1 - -
2 - -
3
4 -
A
B
C
(4) Create multidimensional surface
model (for optimization or control)
(3) Analyze data
www.minitab.com
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Model Building Evaluation - Examples

• Models for process development
• Kinetic models rates of reaction or degradation
• Transport models movement and mixing of mass or
  heat
• Models for manufacturing development
• Computational fluid dynamics
• Scale-up correlations
• Models for process monitoring or control
• Chemometric models
• Control models
• All models require verification through
  statistical analysis

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Model Building Evaluation - Chemometrics

• Chemometrics is the science of relating
  measurements made on a chemical system or process
  to the state of the system via application of
  mathematical or statistical methods (ICS
  definition)
• Aspects of chemometric analysis
• Empirical method
• Relates multivariate data to single or multiple
  responses
• Utilizes multiple linear regressions
• Applicable to any multivariate data
• Spectroscopic data
• Manufacturing data

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Quality by Design Statistics

• Statistical analysis has multiple roles in the
  Quality by Design approach
• Statistically designed experiments (DOEs)
• Model building evaluation
• Statistical process control
• Sampling plans

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How can Innoworks assist you?

• We can help you every step of the way in
  implementing Quality- by- Design in your work
  processes.
• Contact us drshrutibhat_at_gmail.com