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that pharmaceutical development and manufacturing can be improved.
These facts are especially noticeable in cases of batch failures and
reworks, regulatory issues, implementation of new technologies, etc. The
current state of the pharmaceutical industry, in terms of yield and defects
(e.g. relation of quality and productivity), is not comparable to some of
the more advanced industries (e.g. the semiconductor industry). Defects
in pharmaceutical product quality can be encountered such as low
manufacturing process yield or, more dangerously, some which may
affect the therapeutic performance of the drug (or both). For some
products, waste can be as high as 50%. Furthermore, the effects of
scale-up on the fi nal product are often not understood and reasons for
manufacturing failures are not analyzed (Shah, 2009). The quality of a
pharmaceutical product can be defi ned as an acceptably low risk of
failing to achieve the desired clinical attributes of the drug (Shah, 2009).
It is recognized that reasonable product quality in the pharmaceutical
industry sometimes comes with the price of great effort and cost.
Quality-by-design (QbD) is a concept introduced by the International
Conference on Harmonization (ICH) Q8 guideline, as a systematic
approach to development, which begins with predefi ned objectives and
emphasizes product and process understanding and process control,
based on sound science and quality risk management. Predefi ned
objectives make up the quality target product profi le (QTPP), that is, the
summary of the drug product quality characteristics that ideally should
be achieved. According to the ICH Q8 guideline, QTPP is a prospective
summary of the quality characteristics of a drug product to ensure the
desired quality, taking into account safety and effi cacy of that drug
product. Through the scientifi cally based process of product development,
critical process parameters (CPPs), and critical quality attributes (CQAs)
of the product are identifi ed. CQA is a physical, chemical, biological, or
microbiological property or characteristic that should be within an
appropriate limit, range, or distribution to ensure the desired product
quality. CPP is a process parameter whose variability has an impact on a
CQA. The identifi cation of a CQA from the QTPP is based on the severity
of harm to the patient if the product falls outside the acceptable range for
that attribute. QTPP is initially defi ned, based upon properties of the
drug substance, characterization of the reference product (if it exists),
and intended patient population. It is important to emphasize that QTPP
does not necessarily need to include all of the product specifi cation tests.
A QTPP for immediate release tablets may include the following
requirements: assay, content uniformity, and dissolution should be in
accordance with the specifi cations to assure safety and effi cacy during the
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