Extractable and leachable (E&L) compounds associated with the use of polymeric single-use systems (SUS) are important because they have the potential to directly impact on product and patient safety. The 2014 BioPhorum Extractables Protocol provided a standardized framework to conduct extractables testing and has been widely used by SUS suppliers and end-user biomanufacturers.
However, since its implementation, concerns have been raised about the testing methods proposed in the protocol and whether they increased safety or built in an unnecessary burden.
Recognizing this, BioPhorum invited suppliers to join the collaboration to accelerate the uptake of the testing. The team quickly realized that it was uniquely positioned to conduct a thorough review of a standard data set from multiple suppliers using data generated in line with the 2014 protocol. The main aim of the review was to use data to address differing opinions and positions. Fundamentally, the review addresses the question: are all six extraction solvents and all test time points value-added?
“The first version of the protocol provided a great foundation for understanding extractables under a variety of processing conditions,” said Anu Vaidya, Manufacturing Scientist at Biogen. “As we built on that foundation, an opportunity was presented for a fresh perspective on streamlining the testing process. The second version uses the same data-driven and quality-focused approach and provides new recommendations for continuous improvement.”
The review concluded that two extraction solvents (5M NaCl and 1% Polysorbate 80) and a time point (Time 0) proposed in the protocol’s testing matrix added limited value in determining a full extractables profile. This has led to these solvents and the time point being removed from the updated extractables protocol published in 2020.
Ken Wong, Deputy Director at Sanofi, summarized the impact of the review. “This momentous milestone will serve as a common expectation between suppliers and end-users, enabling the speedy evaluation and qualification of SUS for clinical and commercial vaccine productions to combat COVID-19 and other preventable diseases.”
Fundamentally, any testing that is routinely performed has a cost and provides a barrier to new products or companies innovating in the space; therefore, any testing that is performed should add value. This data set is ground-breaking as it allowed a comparison of extractables from a number of product types across several suppliers.
Four of the solvents were shown to have considerable value and detect a significant number of extractables that were not seen in other solvents. 1% Polysorbate 80 and 5M NaCl were shown not to add this value and, consequently, were removed from the protocol. In addition to reducing costs while maintaining quality, this work can be used in supporting compliance – if inspectors raise challenges as to why testing was not performed in 5M NaCl or 1% Polysorbate 80, this peer-reviewed paper provides a clear rationale. Lastly, reducing the burden of testing should allow the compliant data set to grow more rapidly, further reducing the need for leachables testing. “For far too long the industry has been stuck between heuristic interpretations of scientific principles, concerns about what regulators will require and a lack of clear supporting data,” said James Hathcock, Senior Director, Regulatory and Validation at Pall Biotech. “This excellent data review by subject matter experts in the field pushes past this monumental hurdle, allowing our industry to move forward.”