2. The conventional development process uses an empirical
approach that requires continuous end product testing and
inspection to determine quality. The processes that create the
end product are seen as fixed, opposed to change, and focus
only on process reproducibility. This approach ignores real-
world variability in materials and process controls. There is a
different path. It’s called Quality by Design (QbD). With QbD
you will get a proactive approach to product development,
potential to reduce FDA queries and review time, and the
scientific data to quickly get to the root cause and resolution
of any deviation
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3. Quality by Design (QbD) is a modern, scientific approach that
formalizes product design, automates manual testing, and
streamlines troubleshooting.
Definition :
The pharmaceutical Quality by Design (QbD) is a systematic
approach to development that begins with predefined
objectives and important product and process understanding
and process control, based on sound science and quality risk
management.
Quality by Design (QbD) is emerging to enhance the
assurance of safe, effective drug supply to the consumer, and
also offers promise to significantly improve manufacturing
quality performance.
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4. Defining the Product Design Goal:
In this step, you define the Quality Target Product Profile (QTPP) and
identify all the critical quality attributes (CQA) for the product
Discovering the Process Design Space:
Understanding your processes is the key to defining the design space
Understanding the Control Space:
Based on the process design space, a well-executed control space can
be defined
Targeting the Operating Space:
The operating space is the best set of parameters, determined
statistically, which enable you to accommodate any natural variability
in CPPs and CQAs .
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5. Proper implementation of QbD can potentially provide
three main benefits for development:
More efficient use of development time and costs.
Ability to meet FDA submission guidelines and
expectations.
Reduced approval times – and fewer queries – from
the FDA.
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6. Insufficient understanding of the process and its
benefits.
Organizational resistance to change.
Denial of the need (“Our process is under control”).
Competing priorities.
Lack of resources and expertise in QbD .
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8. Risk Assessment Report(s)
• Performed throughout QbD Process
• Particularly important to process development.
Quality Target Product Profile (QTPP)
• Defines the desired product characteristics and sets development goals.
Control Strategy Summary
• Defines the process, its inputs and outputs, and how it is controlled.
PPQ Report(s)
• Formal verification that the process Control Strategy has been defined
appropriately and repeatedly produces the desired results.
Continued Process Verification (CPV) Reports
• Assuring that during routine commercial production, the process remains in a
state of control (FDA); involves feedback loops into the QbD “process” where
intentional process changes and/or observed variability is assessed for risk,
characterized, re-validated, etc
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9. Necessary Elements:
• Quality characteristics: sterility, purity etc. (including
specific safety-related impurities where necessary)
• Pharmacokinetic characteristics: dissolution etc.
• Therapeutic effect
• Target patient population: neonate, adult etc., clinical
diagnosis
• Shelf life: temperature, light conditions etc.
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10. Critical Quality Attribute (ICH Q8):
“A property or characteristic that when controlled within
a defined limit, range, or distribution ensures the
desired product quality.”
• Potential CQAs are derived from the QTPP and guide
product and process development.
• CQAs are identified by quality risk management and
experimentation to determine the effect of variation on
product quality.
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11. Many CS elements are developed via risk assessments:
• CQA/CPP, Raw Material, Components, Specifications
A CS is the final outcome of process development
(“Process Design” if using FDA terminology).
A CS is not a “point-in-time” activity, but rather should
evolve as knowledge increases.
A CS is constituted of many parts, many of which are
developed/written at different points in time throughout
process development.
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12. Verification that the defined CS consistently delivers
the desired product quality
• PPQ is a significant product milestone
• Provides proof the process is well controlled
Establishes an initial baseline for future process
evaluation.
PPQ is a dynamic part of the validation concept
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13. Continuous Improvement is the last component of the
QbD Process
CPV provides the “feedback” loop in the control of our
processes
Process Monitoring and Evaluation.
Other components of Continuous Improvement include
good integration of process knowledge into change
control, deviation management, etc.
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