Extractables testing of polymeric single-use components used in biopharmaceutical manufacturing
The BioPhorum Extractables Workstream has made great strides in the world of extractables and is excited to announce an updated, streamlined protocol.
The protocol, Extractables Testing of Polymeric Single-use Components used in Biopharmaceutical Manufacturing, is based on an extensive scientific review and will reduce costs and focus people on the important data points
The protocol gives guidance on the suggested methods for extractables studies, including sample preparation, extraction conditions, recording test-article sampling conditions, and reporting data from the analysis of extracts. Flexibility is built-in, allowing suppliers to alter many study parameters due to restrictions based on the use of SUS, physical form factor, chemical compatibilities, etc. In these cases, the key is to provide details of what changed, why this is scientifically valid and how it meets the overall objectives of extractables testing.
The new protocol includes significant changes to the 2014 version, including:
- Removal of 5M sodium chloride and 1% Polysorbate 80 as extraction solvents, as these had low unique extraction capabilities
- Elimination of the time-point zero interval, as compounds observed at this time-point were present at higher concentrations at later time-points
- Elimination of elemental analysis of 50% Ethanol extracts.
The protocol represents the combined opinion of the biopharmaceutical manufacturers and, crucially, the supply chain. Its main achievements build on the standardization provided by the original paper and include:
- Suppliers have generated lots of high-quality data sets in the same format and using the same testing, which allowed the workstream to review the testing protocol using actual data. This review provides a fantastic resource for discussions, e.g. with regulators
- The overall quantity of testing performed is reduced by 30–50%. This makes testing more affordable, means that non-essential costs are not added to manufacturing equipment and lowers the barrier for entry to smaller suppliers and innovators
- An ‘extractables ecosystem’ has been agreed, which provides guidance on how to share data throughout the supply chain and, ultimately, to the end-user – overcoming historical challenges posed by needing three-way confidential disclosure agreements in many cases
- The protocol was developed by a combined team of biomanufacturers and suppliers. It demonstrates how expertise can come together to not only agree on what testing should be performed, but also how to share information effectively to enhance patient safety.
Sara Ullsten, R&D Section Manager at Cytiva, said the revised extractables protocol is the outcome of a close collaboration between end-users and suppliers. “By working together as one team, the test protocol could be downsized while still maintaining relevant test conditions to ensure the generation of value-adding data. The downsizing is welcomed by suppliers, as the high cost of testing was preventing the wide adoption of the original BioPhorum protocol among suppliers, especially component manufacturers.”
Using the new protocol addresses many risks – the main one being to patient safety if the final product contains impurities. But there is also a real focus on resolving inflexibility in the supply chain and reducing the significant amount of work involved in extractables/leachables testing. The protocol provides certainty on regulatory inspections and filings and applies a common industry approach, which makes it much easier to discuss and justify decisions taken on extractables testing.
The project has already made a significant impact on the industry – many biomanufacturers have been generating data sets using the original protocol and are now using the new data sets. It has also paved the way for defining user requirements and change notification practices using a collaborative model.
Ken Wong, Deputy Director at Sanofi, said that the revised protocol represents a huge improvement in many areas, “such as simplification of recommended testing, refinement of extraction requirements of broader component types, greater understanding of the risks associated with deleted test solvents, and consistency of test reports with predefined extractable data summary report templates.
“Such accomplishments were built on a strong collaborative spirit of the joint team of end-users and suppliers,” Wong added. “The highly valuable and broad sets of extractable data contributed by the suppliers were critical for our scientific analysis-driven and decision-making processes. Going forward, the supplier base will have a clearer understanding of BioPhorum’s extractable recommendations to follow in their own implementation. I’d like to take this opportunity to thank all suppliers and their representatives for their invaluable contributions.”
Until 2014, biomanufacturers and suppliers couldn’t agree on the conditions for extractables studies or what analytical methods to use. This made it almost impossible for manufacturers to perform valid leachables assessments without resorting to separate testing by each company. This was expensive across the industry, created uncertainty of the testing that regulators might request and added an extra barrier to flexibility in the supply chain. BioPhorum then published a standardized extractables protocol in 2014, which became a key element of its disposables plan to accelerate the understanding and uptake of SUS. “The extractables protocol provides a comprehensive, peer-reviewed standard approach regarding extractables testing for the pharmaceutical industry,” said Bill Scott, Scientist II at Biogen Manufacturing Science. “Before its publication, the lack of standards for testing and reporting of extractables caused a great deal of confusion and rework by both raw materials suppliers and end-users. Biogen has been one of the early adopters of the protocol and it has become the backbone of our extractables/leachables platform. The excellent track record that Biogen has enjoyed with regulatory agencies on extractables/leachables testing has, in large part, been due to our adoption of the protocol.”
|Best Practices Guide For Extractables Testing April 2020|
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