If quality by design (QbD) promises a more efficient manufacturing process with more consistent product quality and increased safety, why is there reluctance among the bioprocessing industry to implement the approach?
A survey conducted at Cell Culture Engineering XIV in May, 2014 suggests that, while the industry is keen to adopt the QbD methodology, manufacturers of biopharmaceuticals are struggling to understand the expectations of the regulators.
Parker domnick hunter has put together some simple tips to consider when implementing QbD.
But first, what exactly is QbD?
QbD is the method by which the critical quality attributes (CQAs) of a biologic product are identified and an appropriate manufacturing process is defined. This is achieved by performing small-scale, often multifactorial experiments and using a risk-based approach to quality.
The knowledge obtained can be used to generate a design space for manufacturing, which will ensure consistent product quality if the process is operated within the design parameters.
The increase in flexibility that QbD should allow is derived from this ability to operate within different process parameter settings, as long as the process remains within the design space.
Now for the QbD implementation tips
- Use plausible risk assessments presented in a clear and logical manner within the submission.
- Use more than one risk assessment tool for identifying the process parameters to be studied.
- Describe the qualification of the small-scale studies within the submission to show how the control strategy predicts large-scale performance.
- Perform linkage studies using worst-case inputs to show that the unit operations will robustly deliver a quality product when operated sequentially as per the manufacturing process.
- When seeking approval for a design space, clearly communicate this to the regulator within the submission.
- Bear in mind that the design space may need to be revised during process development as greater process understanding is obtained.
- Only use terminology approved of by the regulator. For example ‘critical’ and ‘non-critical’ process parameters are accepted terms in submissions but ‘key’ is not as regulators have found a high level of inconsistency in the definition of this term between companies that have used it.
In essence, those making submissions to regulators need to make it clear how the strategy was developed and how the manufacturer is in control of product quality. Frequent and clear communications between companies and regulators is the key to successful QbD submissions.
What do you think? What element of QbD implementation does your company need greater support with? Share your experiences and insight in the comments section below.
For additional information regarding QbD implementation and how bioprocess variation can be controlled through automation, contact Parker domnick hunter Process Filtration.
Related blog posts
Read Hutchinson's full article The Potential for Implementing Quality By Design In Biomanufacturing