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Small-molecule therapeutics can also benefit from the implementation of PAT in the manufacturing process.
Ensuring consistent product quality is also a challenge for small-molecule pharmaceuticals as it is for biologics. How does process analytical technology (PAT) come into play? BioPharm International spoke to Ajay Pazhayattil, associate director, Technical Operations Process Validation, at Apotex for some insight.
BioPharm: How is process analytical testing adjusted for production scale-up?
Pazhayattil: Scale up introduces variability with raw material batches, equipment, and process parameters. Each of the input variables needs to be thoroughly understood in order to maintain the desired quality output. Factors such as PAT instrument reliability, sampling and testing frequency should be re-considered for an at-line, on-line, or in-line PAT system. The evaluation should be conducted as part of process scale-up activities in determining the control strategy for the new scaled-up process.
BioPharm: What are the major driving factors for developing more accurate process analytical tests?
Pazhayattil: Use of PAT technologies for attributes such as LOD [loss on drying], particle size distribution, and blend uniformity were developed to significantly reduce time and cost for organizations. PAT allows for better product characterization and improves product knowledge. The data can be used in continuous improvement initiatives as well as development of similar products and processes. Future advances in PAT should focus on improving the analyzer functionality and reliability.
BioPharm: What is the relevance of PAT where continuous manufacturing is integrated into the commercial manufacturing process?
Pazhayattil: With the advent of continuous manufacturing platforms in solid-dose formulation, the application of PAT analyzers has become even more crucial. During a continuous manufacturing operation, PAT signals are utilized as a feedback mechanism to optimize process controls, if required, to achieve the desired quality attributes. PAT therefore reduces the risk of failure in continuous manufacturing. PAT chemometric modeling and instrument accuracy are critical to achieve this goal.
BioPharm: What are the major challenges in updating analytical testing practices?
Pazhayattil: Adapting new technology, reliability of the PAT instrument, availability of technical skills, method development and qualification, defining acceptable measurement frequencies, incremental initial investments, and management of raw material and process changes, are few of the challenges. The prevalent uncertainty about regulatory acceptance of replacing traditional analytical methods with new PAT methods across multiple markets is one of the major deterrent factors as well.
Volume 30, Number 12
When referring to this article, please cite as F. Mirasol, “PAT From a Small-Molecule Vantage Point,” BioPharm International 30 (12) 2017.