Thanks to our cross-industry experience and our knowledge of the pharmaceutical industry and thanks to our close collaboration with the FDA,we are able to take charge of your complete PAT project, from consulting services to the implementation of a tailor-made software platform based on our own SIPAT ™ software package.
The FDA (Food & Drug Administration) recognized that significant regulatory barriers have inhibited pharmaceutical manufacturers from adopting state-of-the art manufacturing practices within the pharmaceutical industry and therefore it issued the PAT guidance in its final form in September 2004.
PAT (Process Analytical Technology) is a system for designing, analyzing and controlling manufacturing processes based on timely measurements (e.g. during processing) of critical quality and performance attributes of raw materials, in-process materials and processes with the goal of ensuring final product quality. PAT allows real time follow-up of the product quality and enhances increased process understanding.
PAT enables to manufacture Right-First-Time; this way, post-process testing will be reduced or eliminated, as the products will have been produced by a tightly controlled process designed to produce good products at the end, moreover online quality monitoring will reduce off-spec production therefore reducing production costs.
The FDA is convinced that PAT will encourage innovation in pharmaceutical manufacturing and quality assurance. FDA regulators expect that PAT will allow companies to more easily improve the manufacturing process and thereby reduce product development times.
The PAT methodology is not mandatory yet, but will most probably set the regulatory standard-reference in the pharmaceutical industry in the 21st century. Moreover one should not ignore the advantages improved process understanding could bring in (see later).
The multidisciplinary Siemens PAT implementation approach: choosing a proven path! Siemens can go further than offering the SIPAT software itself: Siemens has multi-disciplinary teams that can take charge of your complete PAT implementation:
- Firstly we support you in analyzing your process to identify additional potential for better quality control
- Secondly we develop an implementation strategy that gives you the right tools to fully control your product quality and to release your product in real-time
- And last but not least we offer you the technologies, expertise and software to help implement your PAT-solution, step by step.
SIPAT is the software solution of Siemens to support PAT implementation
Some of SIPAT's main features are:
The ultimate goal is to achieve better process insight, real-time product release, manufacturing performance improvement, quality consistency improvement and regulatory compliancy by means of online quality control.
Realizing PAT offers a high Return on Investment. Implementing SIPAT can offer the following business benefits:
Capturing process analytical data
SIPAT is able to connect with different types of analyzers to capture process analytical data. Depending on the instrument's capabilities and the instrument vendor's software capabilities, SIPAT can be used not only for data collection but also for full configuration of the instrument, including calibration and 'system suitability tests'.
Receiving/reading data & distributing data
SIPAT uses industry standard open techniques to interface with third party packages such as the process control system. If measured process parameters such as temperature, pressure or pH are used within a PAT method, SIPAT can read these through OPC. The same OPC communication can also be used to inform SIPAT about the start and finish of a batch, operation or phase. Besides online measurements from analytical instruments and the process control system, SIPAT can also use quality parameters (for example, raw material analysis results) from LIMS systems, such as SIMATIC IT Unilab, and MES systems such as SIMATIC IT Production Suite or ERP.
Manage instrument calibration and system suitability tests
Typically instruments cannot be used 'as is' without first checking the performance. Therefore SIPAT foresees workflow execution to trigger calibration or a system performance test using internal and external standards. SIPAT also keeps track of the results and stores them together with the measurements performed later on with this instrument.
SIPAT can be used for building and using models on various levels :
Analyzer model
Model based on data collected from a particular analyzer. For example, by building an analyzer model through NIR, the prediction of a certain parameters or by means of principal component analysis (PCA) or partial least squares (PLS).
Unit operation model
Model based on data collected from one particular unit operation (data from sensors, analyzers, etc). For example, combination of pH, temperature, pres-sure and dissolved oxygen and NIR data, for a bioreactor unit operation.
High Level Process/Product (line) models
This model is unique to SIPAT. It is based on data collected from the various unit operations of the complete process line, from raw materials up to the end product. Most software systems for PAT are restricted to an analyzer model or, in some cases, an additional unit operation model. SIPAT goes much further. With SIPAT you can develop a general process model, which allows to predict end-product quality parameters.
MVDA / Data mining
In the Model Builder, SIPAT gathers mea-surement data and pre-processes them. The user then starts the process of analyzing the data, building and validating models. The models are stored in the SIPAT Archive with version information and status. SIPAT is able to connect with different types of Data Mining or MVDA software packages moreover chemometrics of Umetrics are embedded in the standard SIPAT software. At runtime, SIPAT will collect data, do pre-treatment and use the model inbackground to make predictions. SIPAT can visualize and/or distribute the model results. SIPAT does not force the user to combine all predictions for a PAT Method in a single model. One method can contain multiple models and can reuse the same measurements. Models can be combined hierarchically or in parallel.
Integration to batch
The unit operation model or process model serves as a basis for the development of a control model. This model is used to perform process control actions (feed-back and feed-forward controls and corrections).
SIPAT takes care of the quality aspects of the process and makes this information available to the control system. The control system can, in turn, take care of the control and correction actions. Both systems are real-time interfaced by an OPC interface to perform feed-forward/feed-back control. SIPAT can be linked closely with the batch system enabling a tight interaction between the recipe procedures and the SIPAT methods. This synchronization allows SIPAT, for example, to give the end conditions for a specific operation (or phase).
Visualisation of data
The SIPAT Graphical User Interface (GUI) can be used interactively to gather data, set up a new PAT method or look up extra information about actual or previous production batches. All critical to quality parameters can be monitored online. Plotter parameters can be compared to the golden batch trajectory allowing Process Monitoring. This visualisation can be done using the SIPAT GUI or embedded in the existing SCADA architecture.
Feedback to the control system
To integrate PAT in the control loop, SIPAT can be configured to return predicted critical to quality parameter to the Process Control System. These can then be used by the control system for intra-batch control using traditional PID controllers or Advanced Process Control (APC) techniques. SIPAT can send prediction values and principal components online to the Control System to any OPC Server.ERP and MES systems can also be integrated as outputs. A typical example would be to inform MES or ERP about one or more Critical to Quality parameters to release a batch after a specific unit operation.
SIPAT stores all measured and calculated data during the operational execution of a PAT method together with the available batch context information. This data is available for any standard reporting tool. SIPAT has a fully elaborated and flexible reporting module which allows end users (non-IT people) to query the database. Data can be integrated seamlessly into Microsoft Office TM applications or any other statistical package.
The SIPAT Model Builder allows browsing, filtering and querying the data in ways that all required data can be used in the selected modelling software packages.
SIPAT offers full auditing functionality supporting compliance with legal regulations and 21CFR11. It includes the following main blocks of auditing functionality :
SIPAT is able to connect with different types of analyzers. It provides full instrument configuration and control (limited only by the facilities provided by the instrument manufacturer). Individual instrument capabilities are maximized using drivers for each instrument. SIPAT performs data collection and analyzer performance tests. This gives the advantage of having only one common
For more information on SIPAT, please feel free to contact us via info.sipat@siemens.com
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