Q. What are your primary responsibilities as Principal Scientist at VR Analytical?
"As a Principal Scientist at VR Analytical, my primary responsibilities include overseeing extractables and leachables studies, elucidating the structure of unknown extractables utilizing high-resolution MS fragmentation data and 1D and 2D NMR techniques as needed, and taking a lead role in development of new analytical services to grow VR Analytical's technical capacity. I also represent the company in global discussions with working groups to help set best practices for extractable and leachable testing."
Q. You will be presenting research at the conference regarding designing analytical method strategies based on test article materials of construction and total organic carbon (TOC) reconciliation. Why is it important to choose an appropriate analytical method according to the material of construction?
"The industry has standardized on GC-MS/FID and LC-UV-MS as the core analytical methods to be used for the E/L analysis. However, how does one know that these standard methods are detecting the majority of the organic extractables? A significant concentration of extractables can often go undetected or underestimated unless you know your test article and apply methods based on the materials of construction (MOC). For instance, certain wetting agents for sterile filters are not detected using these standard methods. One indication that you're missing or misinterpreting the concentration of these extractables is by comparing the measurement of the TOC in the extract to the organic carbon represented by the sum of all the detected organic extractables. If you find that, for example, only half of the TOC can be reconciled then you may need to use MOC-guided methods to discover and quantitate the rest of the extractables. There is a direct link between the toxicological assessment of a complete extractables profile and patient safety. Ensuring patient safety is why we do E/L testing."
Q. Your presentation is expected to spark some discussion and debate at the conference. Why do you think there could be different mindsets regarding the use of TOC reconciliation?
"TOC is a bulk analysis of the organic chemistry present in the extract. It does not enable identification of specific extractables. And it can only be performed on extraction solutions that do not contain significant organic carbon. For this reason, it can be interpreted as an insignificant analysis since more extractables come from organic extraction solutions such as alcohols. Another potential reason against evaluating TOC reconciliation is that extractables studies are often part of a larger submission package and a poor TOC reconciliation can create a hurdle to overcome on a small budget or short timeline before submission. Overall though, we feel that TOC reconciliation is an efficient check that the correct analytical methods have been employed."
Q. What other considerations do you deem to be most important when choosing an appropriate analytical method?
"Before evaluating an extract, you should know what to expect based on your extraction solution and you test article with regards to its materials of construction and methods of manufacture. You should anticipate what chemistry you will see and how to detect it. For example, if a solvent is used during manufacturing of a test article such as with cellulose acetate and polyethersulfone membranes, you may need to include Headspace-GC-MS/FID."
Q. Do you think there is enough knowledge sharing between end-users and suppliers regarding best practice relating to E&L testing?
"I think it is improving. For example, suppliers are represented by the Bio-Process Systems Alliance and end users are participating members of the Biophorum Operations Group who are both working on establishing an extractables study best practices document. This document will be a great resource in addition to all the work done by the PQRI and USP."
Q. What are you most looking forward to about presenting your research at Extractables and Leachables USA?
"I really enjoy sharing the work we are doing at VR Analytical. First and foremost for me is doing great science, and VR Analytical has enabled and encouraged me to apply new techniques and technology to the extractables and leachables field. My background is in natural products chemistry and all of the small molecule techniques and methods are directly applicable to E & L testing."
Sarah Robinson, Principal Scientist, VR Analytical will be presenting on conference day 2, May 9. Her presentation will focus on designing analytical method strategies based on test article materials of construction and total organic carbon (TOC) reconciliation, including:
- Determining the appropriateness of an analytical strategy via TOC reconciliations
- Case studies of TOC guiding the application of additional analytical testing