Process Analytical Technology (PAT) is quickly becoming an integral component in the pharmaceutical manufacturing industry. Utilizing a low latency network of powerful chemometric instruments, multivariate data analysis software, process control tools and a central SQL database, PAT provides pharmaceutical and biopharmaceutical companies an edge over their competitors.
PAT and its benefits are incredible and groundbreaking. Done are the days of rigid manufacturing lines and discarded low-quality batches due to unforeseen consequences of factory automation “improvements.” Instead, PAT is a flexible system capable of keeping pace with the rapid advances in drug development and manufacture.
At the core of any PAT system is a set of Critical Process Parameters (CPPs) that are defined based on the manufacturing equipment itself, functioning as the independent variables along the production line. By monitoring physical and chemical properties, the manufacturer can also define a set of variable CPP-dependent variables known as Critical Quality Attributes (CQAs) at various stages of the process, allowing the manufacturer to better understand and control the entire process. These CPPs and CQAs are then used in conjunction with a PAT platform to create both unit-level and high-level process line models capable of predicting the precise quality of the end product. After the predictions are made, adjustments can be fed back into integrated control systems such as Siemens SIMATIC PCS7, fine-tuning the manufacturing process to further improve product quality and ensure product consistency.
PAT platforms have been developed by automation industry leaders such as Siemens, and current PAT solutions are supported by a vast number of major analyzer manufacturers such as Mettler Toledo, Thermo Scientific, Kaiser Optical Systems, and the Bruker Corp. The Siemens implementation (SIPAT) is configured to work with these manufacturers by default; however, SIPAT will integrate with nearly any analyzer, including those capable of NIR spectroscopy, NMR spectroscopy, or FBRM.
SIPAT is fully compliant with legal regulations and 21CFR11, and offers full auditing functionality. In addition, SIPAT includes a full audit trail of all changes made to all PAT objects such as methods, objects, and instrument settings. The usage of the OPC communication protocol allows for SIPAT to effectively work with nearly any automation system on the market. Using the the SIPAT Webinterface ActiveX control, the SIPAT client screen can even be embedded in the control system’s HMI. All data is stored in the central database, and is available for any standard reporting tool. SIPAT also includes a built in report generation tool, allowing for the easy presentation of results to the operator.
Non-destructive on-line or at-line testing of the product allows the manufacturer to achieve Real Time Release Testing (RTRT) that has been specifically cited by the FDA to increase economic benefit and manufacturing efficiency by lowering laboratory costs and reducing inventory. By measuring process parameters at various stages of the process, the automation system then makes real time process decisions to either accept or reject the material, thereby achieving RTRT. An FDA white paper from 2004 delves deeper into the benefits of PAT, and can be found at: http://tinyurl.com/lvdf6mk.
Recently, Panacea Technologies worked with a major pharmaceutical company to install, upgrade and expand a worldwide network of over 50 chemometric analyzers, collectors, and base stations spread out over several distinct production lines. The network implemented for this company measures process parameters such as extent of reaction, blend uniformity and tablet compression; this is one of the largest PAT systems in the world.
As modern medicine continues to advance at breakneck speed, the technology used to scale up and manufacture those advances will have to keep pace. PAT is not just evolutionary, but truly revolutionary, analogous to the advent of batch processing 20 years ago, which has now become the industry standard.
Jake Newberger is a PAT/automation engineer at Panacea Technologies Inc. He is a mechanical engineer with specialties in robotics/automatic control systems.
