Tegeline ® manufacturing process was developed based on new guidance / recommendations released by the Food and Drug Administration (FDA) and European Medicine Agency (EMA) in 2009, the so-called Quality by Design (QbD) approach. This approach was introduced during conceiving, developing pharmaceutical and manufacturing processes phases to help ensure product quality. This QbD approach guarantees that the expected product quality in routine manufacturing entirely agrees with the designed product using well-controlled processes. The key concepts outlined in this guidance define a process with several steps (Figure1): – Define the Target Product Profile (TPP), summarized in the Quality Target Product Profile (QTPP). For Tegeline®, the Major Product Quality Attributes are:
1. Removal of activated coagulation factors to reduce the risk of thrombogenic adverse events.
2. Depletion of IgA to avoid immune responses in patients deficient in IgA.
3. Reduction in Anti-A and Anti-B hemagglutinins to avoid adverse events (hemolysis) in AB, A, or B blood group patients. 4. Reduction of aggregates to avoid adverse events through complement activation.
5. Reduction of potential adventitious and non-adventitious agents
– Identify the measurable characteristics of the product. – Identify the essential steps of the process and their limits. – Control strategy based on global knowledge combining process and product controls.
For Tegeline®, the five key objectives of the QTPP allowed designing the 12 purification process steps (Table1) with a specific function and impacts for each step on the final formulation (Table2). Conclusion:
LFB adopted the QbD approach to offer a high-purity product with an optimized safety profile by removing targeted undesirable proteins and other factors while meeting regulatory requirements. An additional process target was to ensure consistent batch-to-batch product quality based on explicit knowledge of the process limits and a justified control strategy.