How to develop a Risk-based manufacturing process and control strategy using Quality by Design 

Over the last years we have seen a growing interest in increasing the quality and safety of medicinal products while simultaneously reducing the cost involved in pharmaceutical development and manufacturing by implementing more structured development and manufacturing approaches. 

The regulatory acceptance of science-based approaches has created a more flexible environment for implementing existing well-established solutions known from chemical- and food engineering. One of the approaches is Quality by Design (QbD). 

Process optimization using Quality by Design  

Traditionally, the pharmaceutical and biopharmaceutical industries have not been the forerunners of innovative engineering solutions. For many decades, pharmaceutical manufacturing has been controlled by a regulatory framework centralized around testing quality into the product, also known as Quality by Testing (QbT). In contrast, other fields of processing and related manufacturing sciences have successfully implemented sophisticated technologies to increase process- and product understanding. 

The concept behind QbD is to build quality into the product and processes through a systematic scientific and risk-based approach to product and process design. A collection of tools, including Design of Experiments (DoE), Quality Risk Management (QRM) and Process Analytical Technology (PAT), contribute to organize the formulation development process and manufacturing development process. Building quality into the product and processes is done by identifying and control Critical Quality Attributes (CQAs), Critical Material Attributes (CMAs), and Critical Process Parameters (CPPs). It provides the ability to systematically design a robust formulation and manufacturing process. The combination of the aforementioned parameters/tools in the QbD approach enhances product and process knowledge and makes it possible to develop the manufacturing process simultaneously with the formulation design.   

Product and process development 

The QbD based product development begins with defining the expectations of the product in terms of quality, efficacy, and safety. These expectations are summarized in the Quality Target Product Profile (QTPP), which defines the product profile. Critical Quality Attributes (CQAs) are outlined from the Quality Target Product Profile and the CQAs’ acceptance criteria define the product quality expectations.  

The awareness of the existence of these CQA acceptance criteria enables the creation of a structured development process linking back to the CQAs and QTPP. The identification and risk assessment of Critical Material Attributes in the formulation development process and Critical Process Parameters in the manufacturing process design, and their interdependency, are the foundation for establishing a robust product, manufacturing process, and control process that ensure a product production with consistent quality.  

What are the opportunities with QbD? 

Implementing QbD in your product and process development approach will ensure predictable, efficient, and cost-effective processes with fewer interruptions, fewer product failures and increased scalability. At the same time, QbD leads to a library of advanced solutions that will enhance the benefit from QbD. The combination of a well-defined QbD manufacturing process and Process Analytical Technology (PAT) opens the possibility of moving away from conventional batch manufacturing to Continuous Manufacturing (CM).

This can improve the agility and flexibility of manufacturing, requiring less infrastructure, space, staff, and permit increasing production volume without the current obstacles related to scale-up of the manufacturing process. It will ensure a cost-effective production requiring less investment. A deeper look into the capabilities of QbD, PAT, and CM will be the natural step from here. 

Jakob Rasmussen

Jakob Rasmussen supports clients in the Pharmaceutical industry with implementation of global, harmonized quality processes and IT systems. He specializes in analyzing and optimizing processes, validation, developing quality documentation (GxP and GMP), implementing process improvements, IT and working in a GMP environment. Jakob has a strong academic background within Pharmaceutical Sciences and holds a Master of Science in Pharmaceutical Sciences.