Quality by Design (QbD) – An Essential Aspect of modern drug development
by design is an essential part of the modern approach to pharmaceutical
quality. Quality by Design (QbD) is a modern, scientific approach which helps
in finalizing drug design, alignment of troubleshooting and automates manual
testing. Quality by Design (QbD) approach helps in ensuring quality by
developing a thorough understanding of the compatibility of a finished product
to all of the components and processes involved in manufacturing.
of the quality issue can be efficiently analyzed by using Quality by Design
(QbD) approach. This technique provides insights upstream throughout the
QbD requires identification of
all critical formulation attributes and process parameters as well as
determining the extent to which any variation can impact the quality of the
components of Quality by Design (QbD)
Defining the Product Design Goal b)
the Process Design Space. C) Understanding the Control Space. D). Targeting the
Some of the important tool of QbD
includes design of experiments (DOE), risk assessment and process analytical
development process involve following step:
Targeting of product profile: describes
the use, safety and efficacy of the product.
Target product quality profile: for
defining the quantitative aspects of clinical safety and efficacy during
Knowledge of prior art:
Helps in risk assessment to prioritize
knowledge gaps for further investigation.
Critical quality attributes: Design a
formulation and identify the critical quality attributes of the final product
that must be controlled to meet the target product quality profile.
Design a manufacturing process to
produce a final product having these critical quality attributes.
Identification of critical process
parameters and raw material attributes which can be used for controlling the
critical material attributes of the final product.
Establish a control strategy for the
entire process that may include input material controls, process controls and
monitors, design spaces around individual or multiple unit operations, and/or
final product tests.
Continually monitor and update the
process to assure consistent quality.
QbD beginning at the development phase requires a dedicated, disciplined, and
sustained commitment by an organizattion. Few major challenges related to QbD
design includes insufficient understanding of the process and its benefits,
organizational resistance to change, denial of the need, competing priorities
and lack of resources and expertise.
emphasis for the requirement of QbD design can be easily judged by frequent
deficiency letters citing the lack of QbD.
Pharmaceutical industries are frequently citing critical components of
QbD such as Quality target product profile (QTPP), critical quality attributes
(CQAs), critical material attributes of drug and excipients (CMAs) and critical
process parameters (CPPs).
by Design (QbD) approach can results in reduced development time and costs,
more regulatory compliance and reduction in queries from regulatory agencies.
This approach helps in the reduction of failures results during the shelf life
of the product. Quality control testing of the product may results in failure
due to non-compliance of specification or lack of robust manufacturing process.
ICH. Draft consensus guideline:
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J. Woodcock. The concept of
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P. Ganzer, J. A. Materna, M. B.
Mitchell, and L. K. Wall. Current thoughts on critical process parameters and
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M. Glodek, S. Liebowitz, R.
et al. Process robustness: A PQRI white paper.
ISPE PQLI. Draft PQLI summary update
M. N. Nasr. Implementation of
quality by design (QbD): status, challenges, and next steps. FDA Advisory
Committee for Pharmaceutical Science. Available at:
L. X. Yu. Implementation of quality-by-design:
OGD initiatives. FDA Advisory Committee for Pharmaceutical Science. Available