The FDA has revised its guidance on ICH Q8, adding an annex that clarifies the original document and adds the principles of quality by design (QbD).
Guidance for Industry Critical quality attributes (CQAs), defined in the document as elements that could be affect strength, purity, release and stability, and their impact on development are covered in more detail in the revised guidance.
The US Food and Drug Administration’s (FDA) guidance states that different drug delivery methods will have varying CQAs, such as adhesion properties for transdermal patches, but raw materials such as excipients and intermediates are common factors.
Using the framework devised by the International Conference on Harmonisation (ICH) the guidance details the importance of identifying CQAs and using knowledge of them to guide product and process development. T
his list of CQAs can be revised when the formulation and manufacturing processes are in place and further monitoring as product knowledge and process understanding increase is recommended.
By monitoring these factors the guidance believes companies can evaluate how variations in ingredients and other factors will impact on the quality of the drug.
Risk assessment and process parameters
The revised guidance also covers how risk assessment tools can be used to identify and rank parameters, such as process, equipment and ingredients, based on their potential to impact product quality.
By experimenting to determine the significance of variables and potential interactions companies can trim the list of factors that it believes may impact product quality.
To illustrate this process the guidance gives an example of how a cross-functional team of experts can use an Ishikawa (fishbone) diagram to identify variables.
The diagram looks at cause and effect and in the example contains variables including granulation, drying and raw materials.By using the diagram researchers can gain an insight into how the variables might interact.
Failure mode effect analysis (FMEA) can be used to rank these variables based on “probability, severity and detectability”, with experimentation then being used to develop a control strategy.
Other topics covered in the guidance include design space, lifecycle management and quality target product profiles (QTTP). The complete document can be found here .