Knowledge Domain

Critical Quality Attributes – a continuum of criticality

In the last article, we discussed about Quality Target Product Profile and its role in Quality by Design.In this article, we discuss Critical Quality Attributes (CQAs) which direct development and manufacturing processes so that end product meets laid down QTPP demands.
An attribute is a characteristic feature or inbuilt part of the product. Quality attributes capture important information about the products functional requirement and thus connect the functional domain (QTPP) to quantifiable physical domain (QAs).
As we know ICH Q8 defines Critical Quality Attributes as 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. If we consider that ICH Q6 defines quality as suitability for intended use it will become clear how CQAs are connected with product performance.
A product has several defining characteristics i.e. quality attributes. When we set out for development,application of the Pareto principle is extremely useful. A development plan based on this principle translates into the identification and use of a few critical quality attributes as a primary target so that most of the functional requirements are fulfilled. A subsequent refinement, as required, can then bring about product realization in terms of all identified quality attributes. The logical question is – how to define these few critical quality attributes?To answer this question, patient safety&efficacy are used as determining factors. The quality attributes, which can be harmful to the safety & efficacy of the product, are categorized as Critical Quality Attributes. One can apply prior knowledge to identify CQAs.
Few illustrative examples are given in the table below; not a comprehensive list.
Quality Attribute Is this a CQA? Justification
Appearance No Appearance is not directly linked to safety & efficacy.
Friability No Test done to ensure sturdiness to transportation, aimed at minimizing customer complaints regarding broken tablets. No direct impact on patient safety & efficacy.
Identification Yes Ensures right product is delivered. Important for patient safety.
Assay Yes Directly affects efficacy.
Impurity (levels) Yes Directly impacts patient safety.
There is widespread reservation on categorizing quality attributes as critical & non-critical. In our opinion, this is based on impression that non-critical are not important and hence can be compromised. That is not the intended idea. Every quality attribute which defines the product is important and must meet its requirements as regards product realization & release is concerned.QbD is a live process, if during development it is observed that process variables have significant impact on a non-critical attribute, it can be redefined as critical for the process and the table revised. Remember, the classification is used as a management tool for development & quality system.
In the next article, we will discuss how CQAs are used to identify Critical Process Variables (CPP&CMA).