Implementing QbD in Sterile Manufacturing
To gain perspective on the implementation of quality by design (QbD) in sterile manufacturing, BioPharm International spoke with Wolfgang Weikmann, vice-president quality assurance at Vetter Pharma-Fertigung GmbH & Co.KG.
Weikmann: The potential critical quality attributes of a customer’s drug product in terms of aseptic processing are determined by the nature of the product and by the definition of its target product profile. Most common identified critical attributes refer to physical, chemical, and microbiological properties. We recognize sterility, bacterial endotoxin, and dose accuracy as three of the essential CQAs.
BioPharm: What are the challenges in applying QbD in sterile manufacturing?
Weikmann: In our experience, the main challenges in applying a QbD approach are due to the intensity of time, cost, and resources in the early-development stage. Another significant challenge is the high degree of expertise that must be in place to run a proper QbD approach.
Regarding timing, a much longer timetable has to be included. As for costs, the higher costs are due to the variety of additionally performed studies. And higher resource management is due to equipment, different materials as well as staff.
In summation, it is always a product-dependent balancing act between the risks and consequences on one hand, and the cost during the development stage on the other. Even if challenges as previously described appear in the early stages, the gained knowledge will likely result in an economic benefit in the long-term commercial lifecycle.
Benefits of QbD
Weikmann: The most important understanding gained by running an operation through a QbD approach versus the more traditional approach is to realize the necessary requirements of a customer´s product already in an early-development stage to accommodate the product target profile. These requirements are not limited to product quality only. They include the process performance as well as the applied systems and the environment, for example, optimized and reduced lyophilization process cycles.
Based on various studies, differing possible cases are evaluated in detail. This examination ultimately leads to a better understanding of the process variations, thus resulting in an acceptable design space. Consequently, using a QbD approach offers the possibility of gaining better process knowledge, resulting in an improved robustness of the entire process.
BioPharm: How does QbD improve quality assurance and how can it mitigate problems in manufacturing?
Weikmann: Through a greater importance given to process development activities and the resulting large number of development studies performed within a QbD approach, a better process understanding is gained. Within the risk-management approach, risks are already identified in an early stage. Consequently, risk mitigation activities can be developed, and a risk-based control strategy implemented from the very beginning of the commercial stage, forming the basis for improvement of quality assurance and quality oversight.
BioPharm: How is technology transfer improved under a QbD approach?
Weikmann: Technology transfer indeed is one area that is especially improved through a QbD approach. It leads to improved possibilities to monitor and evaluate the process. Becoming familiar with a drug product´s frame and its limits through conducting numerous tech runs of varying versions allows one to define the product´s specification in which the process is running robustly.
A day-to-day business example to showcase the improvement of tech transfer through QbD for customers is by demonstrating the lyophilization cycle development of a customer’s product. For example, by using a QbD approach with gaining the corresponding data based on numerous performed lyophilization tests, we realized a significant reduction of the lyophilization cycle for a particular customer product. This reduction resulted in saving the customer a high amount of capital, primarily within the large-scale commercial production.