ICH guideline Q8(R2) – Pharmaceutical development

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This guideline suggests looking into the quality of drug product during development stage itself. It says that Quality should be built into the product design rather than testing into products1 during the initial stages of development, all the variables that may likely effect the production or manufacturing process should be completely studied. Those critical variables that are found to be affecting the quality of product must be properly controlled and monitored during the process. In order to ensure safe, effective and quality drug products, the concepts and tools of design of experiments and design space needs to be adopted into pharmaceutical development. A systematic approach has been proposed for adopting the quality by design and quality risk management in this guideline.

The first step is to define the quality target product profile which includes dosage form, strength, delivery system as well as container closure system and various quality criteria like purity, stability, and drug release has to be listed. These attributes depends on the type of dosage form and its desired objectives. For example, sterility in parenterals1, adhesion in transdermal patches1, and disintegration time in case of orally disintegrating tablets are the critical quality attributes. There may be more than one critical quality attribute like hardness and disintegration time in ODTs. They can be prioritized and the typical process and formulation or process parameters that affect those attributes have to be listed.

Next step is risk management which deals with various types of input parameters like quality of raw materials, type of equipment, various formulation and process variables that may have impact on quality attributes. Various mathematical tools, design of experiments and mathematical models are helpful in achieving better process understanding and establishing a relationship between the affect of variables on critical quality attributes. This relationship can be represented by design space using various contour plots. A graphical plot of the relationship or effect of different variables on a response is the contour graph. Design space is "Multidimensional combination and interaction of input variables and process parameters that have been demonstrated to provide assurance of quality."1 It is preferred to work within the design space to provide quality. Within the design space, changes in any variable or parameter will not significantly affect the response.


1. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Qua... accessed on 27/2/2011.


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