ready for QbD? Is the informatics sector
Sophia Ktori looks at how process analytic
technologies can make quality by design a reality
Q
uality by Design, or QbD, is a concept that aims to ensure optimum product quality by incorporating into the overall
process the precise understanding and ability to control all the parameters that may impact on each material and its processing, and on the manufacture of the final product. Te approach goes hand in hand with the application of in-line process analytical technologies (PAT) that monitor key quality attributes and process parameters in real- time, allowing for immediate adjustment and, feasibly, negating the need for the laboratory analysis of final products prior to batch release. QbD can be applied to any industry, and
both the US Food and Drug Administration (FDA) and the European Medicines Agency now have guidelines that direct companies in the pharmaceutical and biotech sectors to base their product development and regulatory submissions on QbD principles. Tis has led both R&D and manufacturing organisations to embrace new thinking and new informatics technologies. QbD impacts on both process development
and QA/QC, suggests Kjell Francois, business team manager at Siemens, and Trish Meek, director of product strategy at Termo Fisher Scientific. ‘PAT gives developers key data that can inform and help to direct changes in process parameters for scale-up, for example,’ Meek comments.
Combining real-time data with LIMS results Te same is true in pharmaceutical manufacturing and in upstream bio- production processes, such as fermentation, adds Francois. ‘Data collected in real time, which is coming out of individual PAT instrumentation, such as NIR (near infrared)
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and Raman spectroscopy, laser diffraction and the latest ultra performance liquid chromatography (UPLC) systems, can be reviewed in combination with data from the LIMS (laboratory information management system) that collates and exports results from the laboratory testing of raw materials, which isn’t carried out in real time. Tis collective information can then be interpreted with a view to choreographing automation systems to ensure optimum manufacturing or processing parameters.’
Changing roles QbD and PAT are also changing the role of the wet chemistry lab, Francois suggests. Real- time PAT will reduce the need for offline QC testing, but laboratories will still play a key role in optimising the measurement techniques and
Meek suggests. ‘Gone are the days when data from laboratory information management systems (LIMS), laboratory execution systems (LES), scientific data management systems (SDMS) and PAT, can be viewed as disparate and in separate layers. Only when you pull together data from all these systems, and in particular marry process and configuration data with that from in-line PAT analyses, can you realistically take full advantage of the tools available to interrogate and make sense of big data.’ Termo Fisher’s Sample Manager
enables raw data management of the x-y pairs that make up the mass spectroscopy, chromatography, and FT-IR data. ‘We have a web-based laboratory execution module that supports all the laboratory methods, and all that data is then rolled into a central database, along with other laboratory management tools. So now you can create dashboards and views, and real-time analyses of what is happening in your laboratory, holistically. Statistical quality control is also embedded so that you carry out trend charting and adjust your SQC limits, in real time.’
deriving the quality models and calibration curves for implementation of these in-line technologies. ‘Te responsibility of the laboratory will shiſt from product testing to an almost research-driven role that will provide the models necessary to implement the PAT.’ QbD and PAT will in addition facilitate a
shiſt from batch to continuous manufacturing, Francois continues. ‘Running a continuous production line is only feasible if you have in-line technologies that can measure and monitor critical parameters in real time. Otherwise, you are running blind at high throughput until offline analyses are carried out.’
Marrying data In-line PAT capabilities are accelerating the drive to integrate data from multiple sources,
Change in mind-set QbD and PAT have thus effectively led to a complete change in mind-set, to embrace collective multivariate analyses rather than bolting together disparate univariate analyses, Francois continues. ‘In the bio-production sector, for example, our customers are looking at integrating new types of analytical instrumentation and methodologies into their processes, and combining the data from these technologies with classic process parameters. ‘It’s opening doors for much better controlled production and, ultimately, immediate product release. Tis goal has already been realised for the manufacturing of Merck’s Januvia tablets, which are released onto the US market based entirely on in-line testing, with no QA analyses carried out in the laboratory.’ Multivariate analyses for one process
or product may also be relevant for other products or processes, and potentially can help to direct process or manufacturing
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