Update from the Pistoia Alliance’s Methods Hub Project
April 14, 2022: HPLC (High Performance Liquid Chromatography) is one of the most widely used separation, quantification and identification techniques in analytical laboratories today. Internally within the pharmaceutical companies, analytical methods move between departments, from discovery through clinical to quality control, etc to describe how a successful HPLC experiment should be conducted. Often, analytical methods are also shared with CROs as much work nowadays is outsourced, so it’s critical that consistent methods are used across organizations so the resulting data can be combined for analysis.
These methods often exist in a proprietary electronic format in the instrument control software that was used to create the method or are transcribed into a summary document containing selected parameters, which can lead to unnecessary variability. Often, methods are simply emailed or manually moved across departments or between collaborators with no centralized, consistent repository that scientists use to provide consistent access. This makes method transfers labor-intensive, open for human interpretation, and may lead to challenges with method reproducibility that result in costly time delays or errors. Pistoia Alliance Methods Database project manager Dr. Birthe Nielsen summarizes it well when she says that “Improved methods exchange capability from one instrument to another will create better flexibility, higher efficiency, and better reproducibility.”
The work started in 2019 when Pistoia Alliance, jointly with the Allotrope Foundation, built a data model for HPLC-UV method parameters (the ‘Methods Database’). The data model follows the FAIR data principles ensuring interoperability and reusability of method information by application of the W3C semantic stack in a standardized way using the Allotrope Framework. To demonstrate the standardized exchange of an HPLC-UV method between different Chromatography Data System (CDS) vendors and the Methods Database, a second phase of the ‘Methods Database’ project was initiated in 2021. This involved a pilot for the development of adapters to map the method information; the adapter read the acquisition parameters specified in the methods data model from the CDS and represents them in an ADF file conforming to the vendor-neutral Allotrope methods data model.
The information of a method is represented by a semantic graph structure and stored on-premises or on a virtual cloud (‘Methods Database’, ZONTAL Space) and translated into a human-readable format for the analytical scientists. This allows for a direct comparison of methods across systems, which is a critical part of the method development process and important throughout the lifecycle of method use. After a successful start, the pilot was extended to also support raw data (peaks and chromatograms) export so these data could also be exchanged and linked with the acquisition method.
The workflow is simple: the sequence sample list is prepared as usual in a LIMS/ELN/other system and submitted to the CDS via the Methods Database for execution. Any changes made to the imported method by the scientist before acquisition can be captured and recorded and can form part of a quality control system.
“HPLC method parameters are specific to both the Chromatography Data System and the HPLC Instrument Vendor and Model and have not been easily accessible in the past. This will be the first time method parameters, raw data, and results are available in an interoperable data format across a variety of software and hardware systems commonly used in the industry. The solution will increase efficiency and quality in method management and laboratory automation, and unlock the data for advanced analytics applications scientists have long been waiting for. We cannot underestimate the impact this will have for pharmaceutical companies and their partners“ – Wolfgang Colsman CEO, ZONTAL Inc.
The Pistoia Alliance Methods Database project manager Dr. Birthe Nielsen explains that “with this pilot, we are heading towards exciting capabilities, where we can carry out advanced searching, visualizing and analyses that link the method and result data together”. A Method Db member continues “As a scientist, I am excited to see this and would like to re-emphasize the importance of establishing the connection between the method used and the data collected. This will help significantly in downstream data analytics.” We can look at results across different versions of a method, find a result that has been obtained using a specific combination of method parameters, and much more, and the project group is now defining different use cases to show the functionality of the adapter.
Taking part in the PoC, the CDS adapters have been deployed in several of the analytical labs of Pistoia Alliance members. These efforts were recently summarized and presented to the Pistoia Alliance community. The next phase of the project will be to make the Methods Db an integral part of the system infrastructure in every analytical lab by extending the number of parameters within the database, eventually with the extension to other analytical techniques such as mass spectrometry and NMR. A cloud platform “Methods on Demand” will provide Methods information from different sources, including the transcription of text-based Methods to parameters automatically through Natural Language Processing.
Currently, the methods adapters have been developed to support method transfer from Agilent 1260/1290 instruments with either Empower™ CDS (Waters) or OpenLab CDS (Agilent) but the next part of the project will extend to include other instrument hardware.
About the Pistoia Alliance
The Pistoia Alliance is a global, not-for-profit members’ organization made up of life science companies, technology, and service providers, publishers, and academic groups working to lower barriers to innovation in life science and healthcare R&D. It was conceived in 2007 and incorporated in 2009 by representatives of AstraZeneca, GSK, Novartis and Pfizer who met at a conference in Pistoia, Italy. Its projects transform R&D through pre-competitive collaboration. It overcomes common R&D obstacles by identifying the root causes, developing standards and best practices, sharing pre-competitive data and knowledge, and implementing technology pilots. There are currently over 150 member companies; members collaborate on projects that generate significant value for the worldwide life sciences R&D community, using The Pistoia Alliance’s proven framework for open innovation.