A more systematic approach to drug development

Quality by Design in drug developmentThere are few environments where quality control is more important than in drug manufacturing. Medicines must be safe to use and deliver a consistent clinical effect to treat the targeted disease. However, even with the most robust quality control measures, end-of-line testing cannot improve the quality of a product. For the most reliable results, quality has to be built into the design of the product from the outset. That’s why we adopt Quality by Design (QbD) principles for every one of our drug development projects.

Put simply, QbD is a more systematic approach to drug development. It all starts with a set of predefined objectives, focused on comprehensively understanding products and manufacturing processes through sound science and risk management.

Drug development according to QbD begins by specifying the Quality Target Product Profile (QTPP) – the design specifications that ensure the product is safe to use and meets the needs of patients. From this ideal description the Critical Quality Attributes (CQAs) – the measurable properties that characterize a quality product – can be identified. Once these are agreed, the impact of raw materials and manufacturing processes on these CQAs can be investigated, identifying any variability in raw material sources.

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In a design process as complex as drug development there are many factors that can impact on product CQAs. Assessing all of the material and processing parameters that could influence quality experimentally is a significant undertaking.

Risk assessments and Design of Experiment (DoE) analyses offer a more strategic and resource-efficient approach to designing quality into product workflows, and can be used to connect material and process attributes with their impact on CQAs. Approaches such as Failure Mode Effect Analysis (FMEA) can be used to evaluate Critical Process Parameters (CPPs) and Critical Material Attributes (CMAs) – the factors that will impact on CQAs and could result in product attributes falling outside of acceptable limits. Here, CPPs and CMAs can be rated based on the likelihood of failure, the severity of the impact, and the ability to be monitored.

Understanding design space

Through careful risk assessment and the use of DoE tools, the multidimensional design space where CPPs and CMAs satisfy the product CQAs can be fully mapped out. Using appropriate control measures (such as raw material specifications and process controls, supported by in-line testing using process analytical technology) CPPs and CMAs can be controlled to ensure the product’s CQAs remain within acceptable ranges.

Comprehensive understanding of the design space offers more flexibility when process changes occur that are beyond the control of developers and manufacturers. As all parameters within the design space meet CQAs, further optimizations can be made to drug products without the need for the lengthy re-approval of manufacturing processes by regulatory bodies.

Of course, the story doesn’t end there. Continued process verification strategies ensure that product batches are consistently meeting the highest standards. Combining this with information gained from other investigatory projects, processes can be improved to ensure products continue to offer the highest possible levels of quality.

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Learn how Aptuit have adopted QbD thinking throughout our drug development projects to great success, by watching our webinar series here.