by Stephanie Cape, Ph.D., and Chad Briscoe, Ph.D.
The 22nd annual Land O’ Lakes Bioanalytical conference was held July 12-14 2021. The meeting was focused on connecting as scientists, colleagues, and friends to share what we learned over the past year and how we will take those lessons forward to become better bioanalytical scientists. The meeting offered attendees the opportunity to come together to reflect on a year of unprecedented challenges posed by the COVID-19 pandemic and to celebrate accomplishments as example after example of scientists working together to achieve remarkable progress were shared.
The agenda and discussion quickly moved from reflection on the past to excitement for the future. It was truly a cross-disciplinary event as the field of bioanalysis has rapidly evolved beyond traditional technologies to meet the demand posed by the introduction of complex modalities. One thing remains consistent: the long-standing tradition of the Land O’ Lakes bioanalytical meeting was an open, inviting, collaborative environment where everyone is welcome, and all walk away having learned something new.
During the opening session, experts shared how they had persevered and overcome unprecedented challenges to maintain business continuity for their bioanalytical laboratories during the pandemic. Remarkably they had not only maintained standard operations, but also rapidly adapted to the new environment, building new processes and capabilities along the way.
Laboratories had to pivot quickly to develop and implement new ways of operating to accommodate workplace modifications such as social distancing and remote work. Although this created significant challenges, many of the changes resulted in additional benefits and will be incorporated as new standard practices going forward. For example, Angie Underberg of Labcorp Drug Development explained that increased use of electronic systems, electronic signatures, communication and collaboration tools, and automation have enabled traditional on-site roles to be performed remotely, thus increasing flexibility and increasing talent pools over wider geographical regions.
The collective experience of the pandemic oriented teams on a common goal. Because of the criticality of the work, barriers that previously existed were overcome and people aligned to go above and beyond to ensure success in record time. Bioanalytical laboratories played and continue to play a critical role in fighting the COVID-19 pandemic supporting not only treatment and vaccine development, but in some cases also supporting significant diagnostic testing programs.
John Smeraglia of UCB BioPharma shared his experience setting up a COVID-19 testing program within a traditionally bioanalytical laboratory. To meet the early crisis of a lack of testing resources for COVID-19 in Belgium, a consortium of laboratories with the appropriate skills and facilities were asked to assist. The presentation was a tale of organization, planning, teamwork, and dedication of committed volunteers. In the end a quality infrastructure generating thousands of highly valuable test results was delivered to meet the critical need of the general population.
Sponsors, consultants, and regulatory authorities had to adjust to a new normal where on-site audits were not practical. Stephanie Pasas-Farmer, bioanalytical expert and founder of Ariadne Software, and Nina Sahay of Charles River Laboratories, explained how they overcame the challenges of communication, document sharing and data security to perform audits in a manner that met the goals of both the auditor and the auditees. Benefits of remote audits include not having to travel and having the ability to more easily review documents pre- and post-inspection. Challenges noted are an overall longer audit process, inability to review all primary source data electronically, and less efficient overall experience. In the end, they agreed that remote audits are here to stay as they offer flexibility and complement the traditionally on-site audit program.
The lively conversation continued into the afternoon building upon the theme of advancement and shifting to what we were able to achieve analytically despite, or perhaps in some cases because of, the pandemic. Examples highlight that barriers that previously seemed insurmountable were able to be overcome as priorities came into clear focus.
Key takeaways include the following:
- As the world social distanced, it became logical that interest in decentralizing clinical trials would increase. As companies increasingly publish their results, demand for patient centric sampling solutions is accelerating.
- Matt Barfield of Roche shared that new devices and technologies have made patient centric sampling a reality that offers critical solutions especially for scenarios where a sample may not be currently possible via traditional methods (e.g., exacerbations such as asthma attack, pediatric, patient adherence). He shared an interesting case study related to Duchenne Muscular Dystrophy, for which the TassoTM device was evaluated as an alternative to venous blood sampling with the aim of understanding the stress of the patient and caregiver experience due to the different types of sampling devices. This example highlights the potential benefits of patient centric sampling devices to reduce patient burden especially for specific patient populations.
- Dana Lee of Novartis continued on this theme of reducing patient pain and burden through innovative sampling technologies as she shared an example utilizing the Seventh Sense Biosystems TAP® device. This study sought to better understand how delays in time from sample collection to processing or centrifugation can impact sample quality. It is critical that these aspects of sample collection and handling procedures are evaluated when considering patient self-collection. Another important outcome of the study was that most patients indicated that they preferred the collection using the sample device over venipuncture.
- Beth Marlowe presented not only how Quest Diagnostics has implemented SARS-CoV-2 testing in a high volume laboratory, but also assessments of the impact of self-collection. She shared that a control gene was included as part of the analysis to confirm that specimen was collected (i.e., not an air collection). Remarkably, only 0.011% of samples that were received did not have adequate sampling, thus demonstrating that self-sampling is viable and can produce largely successful sample quality.
Day 2 looked forward to what is next in the pipeline. With a focus on new technologies, the presentations gave a glimpse into the expanding suite of tools that bioanalytical chemists are increasingly employing to pursue answers.
- Morteza Razavi, SICAPA Assay Technologies, shared his experiences utilizing the SISCAPA workflow for the measurement of SARS-CoV-2 and its inflammatory effects. He demonstrated that SISCAPA can play a critical role for general screening of viral infections. The SISCAPA workflow has comparable turnaround time as standard PCR and antigen tests for SARS-CoV-2. A major advantage of the SISCAPA technology is the high accuracy of the result.
- Federico Riccardi Sirtori of Merck presented a novel LC-MS approach for immunogenicity prediction and ADA determination based on MHC-Associated Peptide Proteomics (MAPPs) by LC-MS. The MAPP technology is best utilized in lead optimization early in drug development when there is still time to modify the antibody before going into clinical trial phases. Measuring ADA by LC-MS can lack sensitivity compared to standard LBA methods; however drug tolerance of LC-MS methods has been shown to be superior.
- Jose Estevam of Takeda shared his experience leveraging the power of mass cytometry to advance drug development. CyToF is a great tool to be used in clinical trial bioanalysis at early stages to monitor a wide range of markers in different signaling pathways of interest. Estevam demonstrated that the assays can be qualified in a manner similar to flow cytometry assays using a fit-for-purpose approach based on the context of use.
As the meeting transitioned from a new technology to new modalities focus, the speakers shared their experiences through a series of case studies. The complexity of bioanalysis is increasing as new modalities emerge and there has been a clear shift in the approach to become more strategic upfront in designing the bioanalytical plan.
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Lynne Jesaitis of BioMarin educated the attendees on the use of flow cytometry as a tool to detect neutralizing anti-drug antibodies. She described this application in a variety of matrices including blood, bone marrow, and lymph. She explained that the platform based cellular NAb assay identifies samples that specifically neutralize in vitro binding of certain enzyme replacement therapies to their cell surface receptor, the cation independent mannose-6-phosphate receptor, and their subsequent internalization and trafficking to lysosomes. Additionally, she shared a case study explaining considerations when selecting and applying flow cytometry for Nab assays.
- Bioanalytical challenges and strategies to address PK analysis of antibody drug conjugates (ADCs) were presented by Seema Kumar of EMD Serono. ADCs are complex as they are heterogenous multi-component structures. This requires additional consideration when designing the bioanalytical plan to ensure the PK can be well understood. Kumar shared that there is no single strategy that will work for all ADCs, but rather the strategy must be developed with the ADC structure, linker chemistry, target biology, and relevant PK information in mind. A case study was shared showing how orthogonal analytical platforms can be leveraged for data interpretation and integration.
- Uma Kavita of Spark Therapeutics shared an overview of the basic concepts of AAV gene therapy and bioanalytical considerations related to biodistribution (PK) studies of recombinant AAV gene therapies. She delved into detail through a case study detailing the three primary analytes, namely, transgene DNA, mRNA and protein and their relevance to various AAV GTx evaluations as an example highlighting the various aspects of method development and validation. She also provided a comparison of the two types of PCR methods used to measure AAV transgene DNA and mRNA as well as an introduction to available regulatory guidelines for PCR.
As is tradition at the annual Land O’ Lakes Bioanalytical Conference, the final session focused on the regulatory aspects of new and developing technologies. Scientists shared their perspectives and contributions to innovative solutions revealing the many collaborations across the industry focused on aligning best practices.
- Jim McNally of BioAgilytix shared that cellular therapies such as CAR T require proactive planning to ensure the assay strategy addresses the relevant questions throughout the drug development process. In the case of cell therapies, many of these assays require the use of technologies that haven’t traditionally been used in the regulated space. Pharmacokinetics analysis may have data from multiple assays to resolve (e.g., qPCR/ddPCR, Flow Cytometry). Immunogenicity assessments are also more complex than just ADA and nAb as the immune response against the holistic therapy has to be considered.
- Virginia Litwin provided an update on industry alignment of best practices for flow cytometry validation. Flow cytometry has been a critical tool in Biopharma for more than 20 years and is increasing in importance and usage in the areas of immunotherapies, immune-oncology, cell and gene therapies, and vaccines. Recently several international initiatives have been created to address the challenges associated with developing and validating robust assays for single-cell measurements as well as generating confidence and comparability of measurement results from different instrument platforms. The presentation provided an overview and update on important global standardization efforts related to the application of flow cytometry supporting novel therapies.
- Amanda Hays of BioAgilytix shared the outcomes of the AAPS Workshop focused on Harmonization of qPCR Assay Development and Validation in Regulated Bioanalytical Laboratories. This topic is of increasing importance due to the increasing application of qPCR and ddPCR technologies especially in cell and gene therapy programs. There is a lack of clear regulatory guidance for this area and therefore experts in the field have come together to discuss and harmonize best practices for validation. Practical advice to help laboratories develop aligned standard operating procedures was shared.
- An initiative being driven by the European Bioanalysis Forum (EBF) that is focused on improving data transfer processes was shared by Cecilia Arfvidsson. This initiative is a collaboration between the EBF, software developers, and instrument vendors and proposes to utilize a new vendor neutral XML file format as a compliant solution for secure file transfers between LIMS and instruments. This proposed data model would ensure data integrity, reduce time consuming quality control checks, and provide flexibility to accommodate a variety of data and instrumentation beyond LC-MS.
Overall, it was a great meeting and the presenters shared impressive progress from the past year. The stories of how bioanalytical chemists have risen to meet the challenges of the pandemic were inspiring. The examples demonstrating how bioanalytical strategies and technologies are evolving to address the needs of new modalities were exciting. And connecting with other scientists to learn together was refreshing. We hope you will join us for next year’s Land O’ Lakes meeting.