How to Define CQA?
A CQA is 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. CQAs are difficult to measure directly in production. Along the upstream and downstream portions of the manufacturing process it is most common to monitor the CPPs and KPIs related to the quality attributes. The FDA’s Process Analytical Technology (PAT) framework (or similarly, the ICH Q8 R2) recommends various tools for this purpose:
- Multivariate tools for process design, data acquisition, and analysis
- Process analyzers (e.g. in-line sensors or automated at-line devices)
- Process control tools (e.g. statistical process control software)
- Continuous improvement and knowledge management tools
An appropriate combination of these tools may be applicable to a single-unit operation like a bioreactor, or to an entire manufacturing process portion like upstream or downstream. Process analyzers are a typical example of tools to measure process data. Their output is used for different scopes like univariate mechanistic modelling, process characterization or multivariate analysis such as the «golden-batch» prediction. Follow the links for an overview of the most important performance indicators and process parameters.
CQAs are specific to the application and process. According to the American Pharmaceutical Review, they can be any of the following:
- Variants of the product, such as size, charge, glycans, or oxidation
- Process-related impurities, such as host cell protein, DNA, or leachables
- Regulatory CQAs, such as composition and strength (pH, excipients, quantity/concentration, osmolality) or adventitious agents (potential viruses, bioburden, mycoplasma, endotoxin)
CQAs are especially important in regards to a quality-by-design methodology and the stages of process validation: 1) Process Design, 2) Process Validation, and 3) Continued Process Validation. Identification of CQAs typically happens during the process design stage. The goal is always to improve safety and efficacy through risk assessment and a control strategy.
White Paper: How Does PAT Apply to the Bioreactor?
Your All-Inclusive Guide to Quality Attributes, Critical Process Parameters, and Key Performance Indicators at the Bioreactor
This 20-page white paper provides a comprehensive, but accessible, overview of requirements and recommendations related to the FDA’s Process Analytical Technology (PAT) initiative for the biopharmaceutical industry.