Future Proofing Peptide MAM By Ensuring Scalability And Deployment
By Scott J. Berger, Sr. Manager, Waters Corporation
The development of biotherapeutics continues to accelerate with their potential to revolutionize disease treatment in areas not adequately addressed by small molecule therapeutics. However, the complexity of these macromolecules and the range of potential modification variants (attributes) creates an interesting analytical challenge for scientists tasked with their characterization and then with monitoring those attributes important to their safety and efficacy.
Liquid-chromatography-mass spectrometry (LC-MS) is a critical methodology for accurately characterizing the wide-ranging variability of biologics. This knowledge can be transformed into single multiplexed assays for monitoring attributes across development, manufacturing, and release. LC-MS-based peptide multi-attribute method (MAM) workflows, like those offered by the Waters BioAccord LC-MS System, have been gaining interest across development and commercialization organizations to accomplish this.
Flexible LC-MS workflows for peptide MAM meet the demands in all stages of modern attribute-based analysis
There is a need for robust methodology that can process a large volume of samples, typical of Quality by Design initiatives, to determine the manufacturing space to provide a biotherapeutic that achieves a target analytical profile of product attributes. The use of a targeted peptide MAM assay, combined with automated sample processing and data processing, is finding utility in biotherapeutic development. It enables rapid assessment of multiple attributes, supplementing less sensitive and less selective traditional assays and reducing longer run cycle times experienced with traditional peptide mapping methods.
In order to future-proof in this fast-changing field, development labs must have equipment and informatics platform technologies that can address changing project requirements and accelerate development cycles and do so over extended periods of time. The inherent flexibility of the MAM approach meets these expectations, with the ability to easily add or remove attributes as product knowledge increases, and quickly accommodate new molecules as pipeline priorities change.
The wide-ranging utility of LC-MS workflows for peptide MAM can also be seen in light of the industry shift to continuous manufacturing, where the attribute monitoring technique can be combined with automated sample preparation to provide high-quality data to enable upstream and downstream decisions to be made more rapidly. With the ambition of many companies to embrace more complex process monitoring technologies and adopt real-time product release, the capabilities of LC-MS based MAM analysis should fit well within these emerging efforts.
Downstream, at the more traditional quality control (QC) stage of commercial production, specifications for key and critical quality attributes (CQAs) are in place to confirm process consistency. These values need to be monitored to confirm product identity, ensure that target levels of specific attributes tied to product safety and efficacy are met, and provide additional data confirming that product purity expectations are met.
The LC-MS workflows developed for peptide MAM analysis are now capable of supporting these needs and being executed within these highly regulated environments. Combining high sensitivity and selectivity, LC-MS has the ability to monitor multiple CQAs within a single assay, potentially replacing less sensitive conventional assays. Thought leaders within the industry are now pursuing this goal, having generated proof of principle, and begun validation exercises, with some even applying the technique to drugs within their clinical pipelines.
Implementing peptide MAM LC-MS approaches in areas where high-resolution MS has not been utilized
Increased efficiency and better product knowledge are powerful drivers for labs working to deliver biologic drugs to the market. However, the adoption of LC-MS based peptide MAM workflows into late development, manufacturing, and QC needs to be achieved while continuing to meet rigorous global regulatory standards and, preferably without requiring significant personnel and organizational disruption to implement an advanced analytical technique.
As the industry moves towards adopting MAM approaches there is a clear need for an easy-to-use LC-MS system operating on a compliant-ready informatics platform that can increase the deployability and routine accessibility of the technique. By doing so, these companies should not be challenged to reinvent their organizations to make use of this LC-MS based approach, and users of varying experience levels in MS must be able to successfully leverage peptide MAM analyses on a routine basis. These dynamics become especially critical as assays begin to move from clinical towards commercial lot release, where the potential impacts of delays and OOS investigations jump significantly.
How the groundbreaking capabilities of the BioAccord LC-MS System enable LC-MS workflows for peptide MAM
Designed with the needs of the biopharma industry at the forefront, the BioAccord LC-MS System:
- Combines robustness, ease of operation, and rapid deployability
- Incorporates groundbreaking SmartMS features that bring its usability to a whole new level without compromising on data quality
- Enables use by those with wide-ranging skill levels through automated start-up and self-calibration capabilities that eliminate extensive training requirements
During operation, the ability of the system to self-diagnose issues and trigger specific alert messages based on system conditions ensures that even novice users can focus on obtaining the data with the confidence that the instrument is behaving as intended. Drawing on its SmartMS diagnostic capabilities, the BioAccord LC-MS System can communicate the need for system maintenance and walk users through the process of addressing the most common issues step-by-step with detailed instructions. Together, these game-changing capabilities pave the way for more users to unlock the benefits of LC-MS across biopharma development, and into manufacturing and QC where, historically, MS has not been routinely implemented.
A pioneering software informatics platform
We at Waters are committed to working with the biopharma industry to help deliver life-changing biotherapeutics to the market with ever-increasing speed. That’s why the BioAccord LC-MS System is driven by waters_connect. The waters_connect informatics software builds on the strong foundation created by UNIFI and decades of experience with Empower to deliver a highly usable system that can be streamlined for specific jobs. The waters_connect peptide MAM workflow walks the user through the process systematically and helps you readily collect, process, analyze, and report data with confidence in its reliability and quality.
Our customer support team further offers customized training for peptide MAM, both on-site and through remote application support. This support is reinforced by reference standards and methods that are provided for system check and system suitability analysis. By combining these features, the platform facilitates confidence and productivity by ensuring users get the most from the samples under investigation.
Two stories that illustrate the challenges and opportunities of expanding peptide MAM approaches into the world of regulated development and QC
As part of a recent Biopharm International webinar I conducted with Dr. Angelo Palmese, a scientist at Merck Serono, we heard of their efforts towards moving attribute-based analysis to the realm of QC. As part of their proof-of-concept studies, they identified sample preparation as a key element of executing an efficient, robust, and reliable MAM workflow.
In their presentation, they demonstrated a BioAccord-based peptide MAM workflow to support their DOE/QbD studies on developing an optimized sample preparation method. Results obtained from dozens of samples analyzed in this study enabled them to show that the MAM approach was a “core technology enabling QbD principles, and CQA driven development”, and that the availability of MAM on the BioAccord on GXP compliant software will streamline validation and transfer to QC.
A second talk by Dr. Stacey Helming from Regeneron at the Waters ASMS 2020 Virtual Users Meeting, highlighted their efforts to show that the MAM methodology and BioAccord-based workflow could meet their organization’s requirements towards moving attribute-based analysis into a QC function.
Their data supported moving forward with this effort, but two aspects of their presentation clearly stood out as indicators of future QC success.
- The first was in the conclusion slide that demonstrated operational returns from shifting a conventional 2-hour peptide mapping assay down to a BioAccord peptide MAM assay of 10-45 minutes. Additional efficiencies were gained by automating sample preparation for this analysis.
- The other aspect was a central theme of their presentation. All of this work, which took place over a 10 week period, was conducted by a group of summer research interns having no previous mass spectrometry experience, and limited supervision after the first few weeks.
Meeting the current and future needs of the biopharma industry
There is no doubt that the biopharmaceutical landscape will continue to evolve as new discoveries come to light. At Waters, we are committed to providing the scientific community with the tools to meet the needs of the present day and harmonize overall laboratory operations, and also future-proof their investments in instrumentation and personnel in a quickly evolving biotherapeutic market space.
The Waters BioAccord LC-MS System combines a fundamental focus on ease-of-use with the ability to deliver high-quality data as part of a streamlined compliant-ready peptide MAM workflow.
These unique capabilities are designed to meet both the current and future needs of the biopharma industry and regulatory authorities to support the full range of drug development, manufacturing, and QC for molecules that are increasing in complexity with decreased time for product development and commercialization. By facilitating the implementation of peptide MAM from early clone-screening to final lot release, new paths to innovation can be opened up to benefit the next generation of life-changing biological drugs.
Learn more about the BioAccord System