Since Joseph Juran’s concept of Quality by Design (QbD) was first adopted by the US Food and Drug Administration (FDA), the pharmaceutical industry has been interpreting its concepts into a variety of approaches for implementation. At Alcami, our QbD approach considers evolving global regulatory guidances with a collaborative fit-for-purpose and pragmatic approach that can evolve throughout the lifecycle of the product. QbD starts from day one in modern product development, culminating in a chemistry manufacturing controls (CMC) package that maximizes every opportunity for a successful regulatory review and approval. The value of this approach is simple: design of robust processes for the consistent production of safe and effective products for our patients and long term cost savings for our partners through improved yields, reduced deviations, and efficient change management.
The QbD process for product development is intended to build quality into pharmaceuticals based on characteristics that define safety and efficacy. Critical quality attributes (CQAs) – specific physical, chemical, biological, and other properties – may impact product safety and efficacy and can be managed by identifying critical process parameters (CPPs) through the use of risk management tools and controlling them within the proven acceptable process design space.
QbD can be viewed as the process of evaluating the sum total of the development data to establish a process design space and then performing a risk assessment to establish the ability to consistently execute the process within it. This is memorialized through a series of documents to capture rationalization and outcome. These documents organize and demonstrate process knowledge and understanding. It is important to note that the QbD system is not static; it is an iterative approach that is revised as the knowledge base changes during product development. It even extends post-approval for flexibility in prior approval supplement (PAS) change management and second generation process development.
Development reports, design failure mode and effects analyses (dFMEA), process performance qualification protocols, design of experiments supported design space establishment, continued process verification protocols and reports, and quality target product profiles are examples of elements that contribute to Alcami’s approach to the establishment of a QbD filing. The expectation of regulatory bodies is that this control strategy extends all the way to a Q11 compliant establishment of regulatory starting materials for the drug substance. Our scientific teams, which span both drug substance and drug product, are experienced in developing a robust body of data while working with our partners through their development milestones. Alcami resources – development chemists, analytical scientists, formulation scientists, and project management – support each step of the product development process, including the key linkage of drug substance attributes to drug product control.
Conclusively, a well-established body of knowledge built using the principles of QbD helps ensure successful regulatory review and commercialization of a manufacturing process, resulting in consistent output of high-quality products.
Quality by Design for a pharmaceutical product can be defined as the development and design of the manufacturing process and controls around that product to robustly meet predefined product quality, safety, and efficacy specifications. This iterative system, beginning in the preclinical, R&D phase, and continuing through commmericalization, is integral to successful lifecycle management of a product. Alcami provides step-by-step support through product development and process design of both drug substance and drug product, while taking into consideration unique client requirements.