Interview with NIBRT's Noemi Dorival Garcia on the characterisation of E&L compounds

Ahead of the annual Extractables & Leachables Europe conference in Dublin this November, we spoke to Noemi Dorival Garcia, Postdoctoral Researcher at the National Institute for Bioprocessing Research and Training (NIBRT) to discuss NIBRT's case study on the characterisation of E&L compounds for single-use bioprocessing, why presenting and discussing research with the community is so important and more.

Your presentation looks at a case study of characterisation of E&L compounds for single use bioprocessing solutions; can you provide us with a brief overview of what your presentation will look into?

In biopharmaceutical manufacturing, single-use technology can offer distinct advantages over reusable, cleanable systems, which also goes hand in hand with cost benefits. The economic benefits of disposable technologies are becoming more important because biopharmaceutical manufacturers are facing increasing pressure to reduce product costs while maintaining product quality. However, despite their advantages, these plastic assemblies draw concern since they are a potential source of contamination due to extractable and leachable compounds (E&L) that result from residual polymeric fragments and different additives used in their manufacture. This attention is not only because leachables could affect the safety and efficacy of the product and consequently, putting patient health at risk, but also there is evidence that these compounds from single-use bioprocess containers have negative effects on cell viability. When in contact with the process fluid (cell culture media), these compounds might be released from the film into the media. The release of cytotoxic leachables under process conditions is particularly undesirable because these chemicals leach out in concentrations that can adversely affect growth and viability of the production cells, especially CHO cells and, as a consequence, the product titer and potentially even quality.

Given the potential for these substances to adversely affect biopharmaceutical production, this discovery clearly shows an urgent need to understand the impact of E&L not only from a patient safety standpoint but also from a biomanufacturing standpoint. This E&L approach is relatively new and although much common information could also be applied, there are also several little-known aspects about this area.

Our research is especially focused on the design and development of a specific approach for E&L studies in single-use containers for biomanufacturing process. Our idea is to develop a workflow, starting by establishing of the conditions for the E&L screening, that include the selection of model solvents, incubation and also an experimental system that is simple and efficient.

Since these cytotoxic compounds can show effects even at trace levels, it becomes necessary the development of analytical techniques to identify and quantitatively assess compounds resulting from the extraction of single-use components. Our group has developed a collection of sample treatment and analytical techniques for the determination of the whole spectrum of E&L compounds, from volatiles to high-molecular-weight non volatiles compounds, which were detected and quantified using mainly mass-spectrometry-based techniques. The analysis of leachables is especially challenging as they usually exist at trace levels within a very complex matrix, that includes solubilising agents and surfactants, which pose major chromatographic interferences and matrix effects, especially when screening for non volatiles by UHPLC–MS. We have developed extraction techniques that allow an effective clean-up of the samples, and as a consequence, an improvement in the analytical performance, with lower limits of detection, which becomes especially useful when leachables have negative effects on cells at trace levels.

We have performed a complete screening of E&Ls, mcontrol and improvement of SUTs

How important is it to evaluate and discuss results of research projects and case studies, such as your presentation, with peers and colleagues in the same industry at E&L Europe?

It is very useful and important, because, as we are working in a E&L research area that is relatively new and is not related directly with patient safety, but with CHO cell lines, any feedback from groups that are working with a similar approach becomes valuable, because there are still many aspects to improve, clarify and perhaps to correct, as well as we could know different points of view about the same subject.

As a new speaker for E&L Europe 2016, what are you most looking forward to at the conference in November? 

I really hope that my talk could be useful and contribute to improve industrial processes in order to obtain a final product with better quality and that also represents an economical benefit. I also hope this conference is enriching for me, I am eager for knowing the most important updates about E&L, as well as I hope the talks encourage the discussion among the participants, in order to obtain important conclusions at the end.

Noemi has worked at NIBRT since 2015 and is responsible for the work package related to characterisation of E&L compounds from single-use technology solutions using different analytical and new sample techniques for the extractation and clean-up of matrices related to biomanufacturing solutions.