Accepted Manuscript
Title: Applications of quality by design (QbD) and its tools in drug delivery
Author: Lan Zhang, Shirui Mao
PII: S1818-0876(15)00247-0
DOI: http://dx.doi.org/doi: 10.1016/j.ajps.2015.11.084
Reference: AJPS 309
To appear in: Asian Journal of Pharmaceutical Sciences
Please cite this article as: Lan Zhang, Shirui Mao, Applications of quality by design (QbD) and
its tools in drug delivery, Asian Journal of Pharmaceutical Sciences (2015), http://dx.doi.org/doi:
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Applications of quality by design (QbD) and its tools in drug delivery
Lan Zhang, Shirui Mao*
Shenyang Pharmaceutical University, Shenyang 110016, China
E-mail: [email protected]
Quality by Test (QbT) was the only way to guaranteequality of drug products before FDA launching
current Good Manufacturing Practice (cGMP)[1], which is an approach without clear understanding of the
processes. In order to solve this problem, FDA generalizedQuality by Design (QbD)in the field of
pharmacy[2].Inpharmaceutical industry, QbDbrings cost-efficiency and simplicity of manufacturing process
into reality. Several tools are utilized to make QbD systemeasily applied to pharmaceutical field, namely
design of experiment (DoE), risk assessment andprocess analytical technology (PAT). QbD is based on the
thorough understanding of how materials and process parameters affecting the profile of final products. The
following parameters are defined to describe those characteristics: Quality target product profile (QTPP);
critical quality attributes (CQAs); critical material attributes (CMAs) and critical process parameters (CPPs)
[3].
The applications of DoE and PAT in pharmaceutical field are discussed in details in
thisreview.DoEcombines parameters such as CPPs, CMAs and CQAs intoQbD system, which is a reasonable
method to determine the relationship between the input and outputof a process. In addition, full factorial
design, Plackett-Burman (PB) screening design, fractional factorial statistical design, central composite–face
centered–response surface design and Box–Behnken design can be used to establish a design space (DS)for a
given process to guarantee the quality of final products.In addition to DoE, PAT is also an important tool of
QbD, by obtaining technological and material parameters on-line,it plays a role in real-time monitoring of
pharmaceutical process without interruption.In order to achieve successful PAT implementation, there
arethree-step-process(namely design, analyze and control)and four PAT toolsin the design and optimization of
drug formulations and manufacturing process, the four PAT tools are as follows: (1) multivariate tools for
design, data acquisition and analysis; (2) process analyzers; (3) process control tools; (4) continuous
improvement and knowledge management tools.In conclusion, with the assistance of DoE and PAT together
with other QbD tools, thorough understanding of pharmaceutical process can be achieved and stable quality of
products can be assured.
Keywords: Quality by Design (QbD);Critical quality attributes (CQAs);Design of experiment (DoE); Process
analytical technology (PAT)
References
[1] Food & Drug Administration. Pharmaceutical Current Good Manufacturing Practices (cGMPs) for the
Page 1 of 2
21st Century-A Risk-Based Approach. 2002.
[2] International Conference on Harmonization (ICH). Guidance for Industry: Q8 (R2) Pharmaceutical
Development, ICH Harmonised Tripartite Guideline, Step 4. 2009.
[3] Yu L X, Amidon G, et al. Understanding Pharmaceutical Quality by Design. Aaps Journal. 2014; 16:771-
83.
Fig 1. Comparison between QbT and QbD
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