Quality By Design

(QbD)
Quality by Design (QbD) is a systematic approach to
pharmaceutical development that emphasizes the proactive
design and control of processes and products to ensure
quality. It is a paradigm shift from the traditional approach of
"quality control," which focused on testing and inspection
after production. QbD aims to build quality into the product
from the very beginning, leading to improved product
quality, reduced costs, and increased patient safety.

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Benefits of QbD
1 Enhanced Product Quality 2 Reduced Development Costs
QbD leads to a deeper QbD helps identify and eliminate
understanding of the critical potential problems early in the
factors influencing product quality, development process, reducing
resulting in products that are the need for costly rework and re-
consistently high-quality and meet testing.
specifications.

3 Increased Patient Safety

4 Improved Regulatory Compliance
QbD focuses on ensuring the
consistency and reliability of the QbD provides a robust framework
manufacturing process, reducing for demonstrating compliance with
the risk of product variations that regulatory requirements, making it
could impact patient safety. easier to obtain approvals and
navigate regulatory inspections.
Key Principles of QbD :-
Risk Management
QbD employs a risk-based approach to identify,
assess, and mitigate potential risks that could
impact product quality.

Design Space
QbD defines a design space, which is a
multidimensional region that encompasses all
acceptable combinations of process parameters and
material attributes that will result in a high-quality
product.
Control Strategy
QbD focuses on developing a robust control
strategy that ensures consistent product quality
within the defined design space.

Process Understanding
QbD emphasizes a thorough understanding of the product
and process, identifying the critical factors that influence
quality and ensuring their control.
 Target Product Profile (TPP):- Defines the desired characteristics
and attributes of the final product, including its intended use,
efficacy, safety, and quality attributes.

Critical Quality Attributes (CQAs):- Identifies the key quality characteristics

of the product that are essential for its efficacy, safety, and performance.

ELEMENTS
OF Critical Process Parameters (CPPs) :- Identifies the process
parameters that have the greatest impact on the CQAs and need
QUALITY to be carefully controlled during manufacturing.

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Control Strategy :- Outlines the methods and procedures used
DESIGN to monitor and control the CPPs during manufacturing to ensure
consistent product quality.

Design Space :-Defines the multidimensional region of

acceptable combinations of CPPs that will consistently produce a
high-quality product.

Risk Assessment :- Identifies and assesses potential risks that

could impact product quality, including risks related to
manufacturing, storage, and distribution.

Process Validation :- Demonstrates that the manufacturing

process consistently produces a high-quality product within the
defined design space.
Risk-based Approach
Risk Identification
Involves identifying potential risks that could impact
product quality, including risks related to manufacturing,
storage, and distribution.
Risk Assessment
Evaluates the likelihood and impact of each identified risk,
prioritizing risks based on their potential severity and
probability of occurrence.
Risk Mitigation
Develops strategies and controls to mitigate or eliminate
identified risks, reducing the likelihood of potential
problems that could impact product quality.
Risk Monitoring
Continuously monitors identified risks to ensure the
effectiveness of mitigation strategies and to identify any
emerging risks that may require further attention.
Design of Experiments (DoE)
Definition A systematic approach to planning
experiments and analyzing data to identify
the critical factors influencing product
quality and determine the optimal settings
for process parameters.

Purpose To understand the relationship between

process parameters and product quality,
optimize the manufacturing process, and
minimize variability.

Methods Various statistical methods are employed,

such as factorial designs, response surface
methodology, and mixture designs.

Benefits Increased understanding of the

process, reduced development time
and costs, improved product
quality, and increased regulatory
confidence.
Process Analytical Technology (PAT)
 Real-Time Monitoring
PAT utilises sensors and online analytical
techniques to monitor critical process parameters
in real time, providing continuous feedback on the
process and enabling early detection of deviations
from the target.
Data Analysis
PAT generates large amounts of real-time data,
which can be analyzed using statistical methods to
identify trends, patterns, and potential problems,
enabling proactive adjustments to the process.
Process Control
PAT enables real-time adjustments to process
parameters based on the collected data, ensuring
that the process remains within the defined design
space and delivering consistent product quality.
Regulatory Compliance
PAT provides a robust framework for demonstrating
process control and ensuring compliance with
regulatory requirements, strengthening the case
for product approval and reducing the risk of
Regulatory Guidance and Requirements
• Regulatory agencies worldwide have issued guidance documents and requirements
outlining their expectations for QbD implementation in pharmaceutical development.
These guidelines provide specific recommendations and expectations for each phase
of the development process, from early research to commercialization.
Agency Guidance Key
Requirements
FDA QbD Guidance for industry Risk Management, process
[2006] understanding ,control
strategy , life cycle
management

EMA Guideline on Quality Risk Risk identification ,Risk

Management [2006] assessment , Risk control,
Risk communication

ICH ICH Q8 [Pharmaceutical Principles of

Devlopment] , ICH Q9 [Risk pharmaceutical
Management] , ICH Q10 development , risk
[Pharmaceutical Quality managemnet , quality
Syringeability And injectability
 Syringes have been widely used to administer the
injectable formulations. There are tow key terms, which
define the functionality of syringes.
 Syringeability is the ease of withdrawal of a formulation
from a vial or an ampoule, a process which should be
free of clogging and foaming.Injectability is the force
required for injection. One expects an evenness of flow
which is free from clogging.
 In selecting a needle for an injection delivery system,
the key parameters considered are the :- needle gauge
and length.
 The higher the gauge number, the smaller the needle
diameter. Ten and 30G needles have outer diameters of
3.404 mm and 0.3112 mm, respectively. In general, by
increasing the gauge # and needle length, all the three
Higher the gauge Smaller the force values increased. As expected, viscous
number needle number formulations needed higher forces. However, the type
of formulation had an impact too. It is very important
for a formulator to keep in mind suchaspects in
developing a formulation and in selecting an
appropriate needle.
Syringeability and injectability are important CQAs for
parenteral drug products, ensuring the safe and effective
administration of the drug. QbD principles are applied to
design the formulation and manufacturing process to ensure
that the product meets these critical attributes. This includes
factors like viscosity, particle size, and container closure
systems, all of which are carefully considered and controlled
during development and manufacturing to ensure consistent
syringeability and injectability.
• Viscosity Measurement :- Measuring viscosity is critical for
assesing syringeability , ensuring smooth and easy injection .
• Particle size Analysis :- Analysing particle size is essential for
injectability, ensuring the drug can be injected without clogging the
needle.
• pH Control :- Maintaining the appropriate pH is crucial for both
syringeability and injectability , ensuring the drug remains safe and
stable for injection
• Reference:-