Quality by Design (QbD) is a systematic approach to pharmaceutical development outlined in the ICH regulatory guidance Q8, Q9, Q10 and Q11 as well as the more recent Q14 for analytical development. The objective of QbD is to build a harmonised approach for both technical and regulatory considerations for process and assay lifecycle management that promotes innovation and continual improvement through facilitating post-approval changes through operational and regulatory flexibility as explained in ICH Q12.
At GRA, we empower organisations to leverage QbD approaches to generate a control strategies that improves efficiency and cost-effectiveness as well as bringing regulatory flexibility. Our experts work with your teams based upon prior knowledge and data, sound science and quality risk management approaches.
QbD for Process Development
Key practices implemented by our CMC experts include:
- Quality Target Product Profile (QTPP): establishing the desired characteristics of the final product, which guides the development process
- Critical Quality Attributes (CQAs): determining key attributes that must be controlled to ensure product quality
- Risk Assessment and Management: employing tools including Failure Mode and Effects Analysis (FMEA) to identify and mitigate potential risks
- Design of Experiments (DoE): applying statistical designs through design of experiments to systematically investigate the effects of multiple factors on product quality, optimizing formulation and process parameters
- Critical Process Parameters (CPPs): identifying variables that can impact CQAs and must be monitored or controlled
- Establishing Design Space: defining the proven acceptable range (PAR) of conditions under which the product performs reliably, allowing for flexibility in manufacturing while ensuring quality
- Control Strategy: implementing the set of controls working within the process’s normal operating range (NOR) required to ensure consistent product quality throughout manufacturing
- Continuous Improvement: implementing a lifecycle approach to continually monitor and improve product and process performance.
QbD for Analytical Development
Key practices implemented by our analytical experts include:
- Defining Analytical Target Profile (ATP): Establishing the desired performance characteristics of the assay.
- Identifying Critical Quality Attributes (CQAs): Determining the key product attributes that must be analytically measured to ensure product quality.
- Designing Robust Assays: Using risk management and statistical tools systematically vary experimental parameters through DoE to develop assays that are optimal and robust. .
- Understanding Interactions: DoE reveals interactions between different assay parameters, helping to understand their combined effects on assay performance.
- Establishing Design & Control Space: DoE defines the proven acceptable ranges (PAR) of conditions under which the assay performs reliably, contributing to the overall control strategy.
Quality by Design (QbD) in Formulation Strategy:
- Optimise Formulation: By varying formulation excipient components, DoE can help streamline stable formulations with minimal compounding complexity.
- Understand Interactions: DoE reveals interactions between excipients ensuring formulations are optimal, whether stored frozen, refrigerated or at ambient temperatures.