Continuous Manufacturing (CM) is a game changer for the manufacturing of solid oral dosage forms and many pharmaceutical companies have embarked on their journey from batch to CM over the last decade. This contribution will focus on how Merck KGaA will enable CM for clinical trial phases and commercial volume products. A small-scale but high containment, full-continuous manufacturing line with a throughput of 1 to 4 kg/h including PAT and PAT data management software (PDMS) is presented.
The key to successful product and process development, as well as later GMP manufacturing, is twin-screw granulation combined with continuous drying. Highly integrated process analytical tools controlled by an advanced PDMS as backbone is enabling the understanding of the manufacturing process as well as control of critical quality attributes with having release testing by PAT as perspective.
In addition to the control of attributes like LoD, PSD and blend uniformity, the determination of residence time distribution (RTD) by PAT plays a crucial role for process understanding, simulation of the manufacturing process as well as for the control strategy.
The ICH Q13 guideline describes scientific and regulatory considerations for development, implementation, operation, and lifecycle management of continuous manufacturing for drug substances and drug products [1]. The ICH Q14 guideline describes risk-based approaches for developing and maintaining analytical procedures for assessing the quality of drug substances and drug products and can also be applied to analytical procedures used as part of the control strategy following a risk-based approach. [2].
The presentation focusses on the implementation of PAT for the determination of relevant and accessible quality attributes and describes the advantages for the implementation of PAT in pharmaceutical industry resulting from the ICH Q13 and Q14 guidelines.
Literature: [1] ICH guideline Q13 on continuous manufacturing of drug substances and drug products, https://www.ich.org/page/quality-guidelines [2] ICH Q14 Analytical procedure development, https://www.ich.org/page/quality-guidelines
