Quality by Design: A Brief Introduction
Bindhu M. Rayaprolu
*
Pharma Force Inc., USA
*
Corresponding author: Bindhu M. Rayaprolu, Formulation Scientist, Pharma Force, Columbus, USA,
E-mail: bindhu.rayaprolu@gmail.com
Received date: July 20, 2015; Accepted date: July 20, 2015; Published date: July 26, 2015
Copyright: © 2015 Rayaprolu BM. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Editorial
Quality by Design (QbD), a concept introduced by Dr. Joseph M.
Juran, emphasizes the design of quality into product. Quality-by-
Design is defined as “a systematic approach to pharmaceutical
development with predefined objectives”. This approach emphasizes
product and process control, based on sound science and quality risk
management. A high quality drug product, as defined by Janet
Woodcock (Director for the Center for Drug Evaluation and
Research), is a product free of contamination which can consistently
deliver the clinical performance and therapeutic effects as indicated in
the label [1]. It was recognized that the quality of product doesn’t
improve with increased testing. Following equation indicates the
factors affecting quality.
Pharmaceutical Quality=f (drug substance, excipients,
manufacturing, packaging).
QbD is a systematic approach to pharmaceutical product
development and requires a thorough understanding of the critical
factors affecting product’s quality. It demands an understanding of
product and process controls. Information included in International
Conference on Harmonization of Technical Requirements for
Registration of Pharmaceuticals for Human Use (ICH), ICH Q8,
Pharmaceutical Development, along with ICH Q9, Quality Risk
Management, and ICH Q10, Pharmaceutical Quality Systems
demonstrates how implementing quality by design ensures the quality
of product. Some of the advantages of QbD include improved product
design, reduced manufacturing issues, assessment and lowering of risk,
and improved post-approval change management [2].
A Critical Process Parameter (CPP) is a factor which has an impact
on a critical quality attribute and, hence, should be monitored to
ensure that the process produces the product with desired
quality. Critical Quality Attribute (CQA) is a physical, chemical,
biological, or microbiological property or characteristic that should be
within an appropriate limit to ensure the desired product quality [3].
Design of Experiments (DoE) and Process Analytical Technology
(PAT) are the tools that can be used in Quality by Design. ICH
guidance Q8 defines design space as “the multidimensional
combination and interaction of input variables (e.g., material
attributes) and process parameters that have been demonstrated to
provide assurance of quality”. A design space is determined at a lab
scale and is scale and equipment dependent. This needs to be
appropriately justified when using at a commercial scale [4].
For generics, few aspects of QbD include identifying and defining
the target product profile (TPP), risk assessment, and identifying the
critical quality attributes (CQA) of the product which must be
controlled to meet the quality of the product. It also includes
developing a control strategy for the manufacturing process controls
and further monitoring the process to ensure product quality. A
generic sponsor uses control strategy which includes monitoring of
input controls, process controls to ensure that the quality of the
product remains consistent when scaling up from exhibit batch to
commercial batches. The limits established for the design space must
also assist to form the basis for establishing the acceptance criteria for
process validation. In order to ensure that the established process
controls helps in achieving the product quality, process validation
needs to be demonstrated. Subsequent to the process validation,
regulatory filing shall include the acceptable ranges for all the critical
operating process monitoring plan. After the approval, the critical
quality attributes will be further monitored to ensure the performance
of the process within the defined acceptance variability. QbD thus
ensures the product quality by controlling the formulation and process
variables [2]. This approach also helps for flexible regulatory
approaches.
Quality by Design is an approach to reduce product variability and
failures which helps in achieving high quality pharmaceutical
products.
References
1. Woodcock J, Yu LX, Amidon G, Khan MA, Hoag SW, et al. (2014)
Understanding Pharmaceutical Quality by Design. The AAPS Journal 16:
771-783.
2. Lawrence X. Yu, Robert A. Lionberger, Sau Lawrence Lee, LaiMing Lee,
Andre Raw (2008) Quality by Design: Concepts for ANDAs. The AAPS
Journal, 10: 268-276.
3. Determining Criticality-Process Parameters and Quality Attributes
(2013) BioPharm International 26.
4. Rathore AS, Winkle H (2009) Quality by design for biopharmaceuticals.
Nature Biotechnology 27: 26-34.
Bindhu, J Pharmacovigilance 2015, 3:4
DOI: 10.4172/2329-6887. 1000e142
Editorial Open Access
J Pharmacovigilance
ISSN:2329-6887 JP, an open access journal
Volume 3 • Issue 4 • e142
Journal of Pharmacovigilance
J
o
u
r
n
a
l
o
f
P
h
a
r
m
a
c
o
v
i
g
i
l
a
n
c
e
ISSN: 2329-6887