Quality by Design (QbD) is a systematic approach to development that begins with setting a predefined objective and harnessing scientific understanding and risk based principles to establish a controlled process or in pharmaceutical drug development terms, product intended to avoid loading too much dependence on an end point QC test system that rejects too many batches. The old adage of garbage in garbage out (GIGO) has never been truer. QbD seeks to avoid this by building into the infra-structure of the manufacturing process itself, assuring the safe production of drugs for the patient while simultaneously ensuring the best possible manufacturing performance and quality.
Manufacturing is getting more efficient and smarter, as process control through IT systems advance. Good quality analytical data is vital to bring products to market faster. QbD will ensure better knowledge and reduced risk minimising variation, increasing efficiency and improving productivity across the entire supply chain including contract laboratories, suppliers etc.
QbD is directly applicable to analytical methodology. By setting pre-defined goals for the method, gathering knowledge of the method to establish a design space and through experimental evaluation and assessment of multiple parameter changes (multivariate analysis) in a systematic way, optimal method performance can be achieved far more rapidly than through traditional linear trial and error, or best guess approaches. Proposed methods are carefully evaluated in a structured manner for risk evaluation, and are subject to experimental regimes within the knowledge design space to determine if pre-determined criteria are satisfied e.g. robustness and ruggedness. As a result of these experiments and approach, the method performance can be better understood and if necessary optimised. A strategy can be defined to manage risk and ensure the method performs as desired when validated and approved for use. Benefits include; better understanding of the process or method, less batch test results failures, more efficient and effective control of change and not the least an improved return on investment due to cost savings.
Tepnel Pharma Services have invested in Fusion QbD software which in conjunction with Waters® Empower™ and H-Class UPLC Systems provides an integrated solution for robust method development and optimisation, reducing turnaround times from start to finish by ca 30-50% depending on the analytical complexity required.
This approach can be used to design and develop an analytical test method approach using QbD strategy which results in a high quality robust and consistent method ready for validation very quickly when compared to a more traditional approach. Providing a more scientific and knowledge based approach, the regulators, FDA, EMA are now welcoming the use of QbD systems. The EMA have stated that,
“The European Medicines Agency (EMA) welcomes applications that include quality by design. Quality by design is an approach that aims to ensure the quality of medicines by employing statistical, analytical and risk-management methodology in the design, development and manufacturing of medicines1”.
The FDA have a similar approach, and there has been a five year joint FDA – EMA QbD Pilot programme2 since March 2011 looking at applications containing QbD elements. The programme concluded good harmonisation between the agencies and sets the scene for increased utilisation of QbD throughout the pharmaceutical industry.