Quality- by-design in pharmaceutical development - Computer-Aided Applications in Pharmaceutical Technology - page 5

pharmaceutical industry. Even though the primary intention of the ICH
Q8 document, and QbD itself, was to provide guidance on the contents of
section 3.2.P.2 (Pharmaceutical Development) for drug products defi ned
in the scope of Module 3 of the Common Technical Document (CTD), this
concept is now broadened to the whole drug product lifecycle. It is often
emphasized that the quality of a pharmaceutical product should be built
in by design rather than by testing alone. Development of the manufacturing
process should include its continuous verifi cation, meaning that rather
than one-time process validation, an alternative approach should be
employed whereby the manufacturing process performance is continuously
monitored and evaluated. The ICH Q8 guideline suggests that those
aspects of drug substances, excipients, container closure systems, and
manufacturing processes that are critical to product quality, should be
determined and control strategies justifi ed. If an adequately organized
development study is conducted, it is possible for the pharmaceutical
manufacturer to gain reduction in both post-approval submissions and
reviews/inspections by the regulatory authorities. Furthermore, real-time
quality control is recommended, leading to a reduction of end-product
release testing. Some of the tools that should be applied during the design
space appointment include experimental designs, PAT, prior knowledge,
quality risk management principles, etc. More details on quality risk
management tools are provided in the ICH Q9 guideline. QbD and quality
risk management tools are often linked to form a pharmaceutical quality
system (ICH Q10 guideline).
PAT is a system for designing, analyzing, and controlling manufacturing
through timely measurements (i.e. during processing) of critical quality
and performance attributes of raw and in-process materials and processes
with the goal of ensuring fi nal product quality. PAT brought the possibility
to evaluate and ensure the acceptable quality of in-process and/or fi nal
product based on the measured process data, allowing real-time release
of the products. The ICH Q8 annex provides examples of implementation
of QbD concepts. Elements of pharmaceutical development (QTPP,
CQAs, risk assessment tools) are defi ned in more detail. Pharmaceutical
manufacturers are encouraged to describe the design space in their
submission by using a variety of terms, for example, ranges of materials
attributes and process parameters, complex mathematical relationships,
time dependent functions, multivariate models, etc. Furthermore,
independent design spaces can be defi ned for one or more unit operations
or a single design space can be established that spans the entire
manufacturing process. In order to ensure that a product of required
quality is produced consistently, various control strategies are designed.

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