by Kelly Broster, Senior Manager of Pharma & Biopharma Market Development and Collaborations, Thermo Fisher Scientific
Mass spectrometry (MS) has been traditionally associated with the early stages of drug discovery, primarily for structural characterization and target identification. However, the pharmaceutical industry has recently witnessed a monumental shift in its approach to drug development. There is now an increased need to leverage mass spectrometry further downstream in development and production environments to quantify impurities and contaminants to a detection limit below what can be achieved by other techniques. Additionally, the increased complexity of biotherapeutics and their manufacturing processes can benefit from more advanced detection techniques to ensure the drug product meets all critical quality attributes. The demand for the technology is now driven not only by the need for enhanced quality control but also the urgency to expedite the delivery of life-changing therapies to patients by limiting the risk of unexpected safety issues.
Critical for compound identification
Mass spectrometry has been critical in the rapid identification and characterization of compounds during the discovery phase of research since it was first introduced in the early 20th century. Its enhanced specificity over traditional detection techniques has allowed research laboratories to analyze complex samples with confidence. As the analytical techniques used during drug development have progressed over the years, the complexity of compounds and the demand for stringent quality control measures have similarly increased. To meet these challenges, mass spectrometry has increasingly become instrumental to the later stages of the development process, playing a critical role to ensure product quality, safety, and efficacy.
One of the main benefits of utilizing mass spectrometry throughout the biopharmaceutical drug development process is to assist with structural elucidation of compounds and complexes. For example, it enables scientists to determine the sequence of a protein, identify post-translational modifications, and even characterize impurities or contaminants. This level of detail is essential for understanding how a drug candidate interacts with its target and identifies sources of potentially undesirable side effects in patients.
Real-time insights
Mass spectrometry has emerged as an indispensable tool in the QC laboratory for biopharmaceutical development. Its unrivaled sensitivity, selectivity, and quantitative capabilities make it a vital asset for identifying impurities, characterizing PTMs, and ensuring batch-to-batch consistency. This helps maintain the safety and efficacy of drugs during manufacturing and throughout their shelf life. By monitoring the purity and consistency of drug products, manufacturers can ensure their products are safe and effective for patients.
This technology helps accelerate research and development timelines, empowering labs to rapidly analyze samples and make informed decisions based on accurate data expediting the development cycle. Its sensitivity and specificity make it a reliable analytical tool for safeguarding product integrity and maintaining drug manufacturers’ reputations from start to finish. As a field continues to evolve, advancements in high-resolution mass spectrometry promise even greater precision and accuracy, solidifying its position as an essential component of biopharmaceutical QC processes.
High-resolution mass spectrometry
Modern biopharmaceutical drugs, such as monoclonal antibodies (mAbs) and antibody drug conjugates (ADCs), are tremendously complex molecules manufactured inside living cells. Characterizing and monitoring these compounds in chemistry, manufacturing and controls (CMC), and quality control environments can present a significant challenge, but the use of a high-resolution MS-based workflow offers a powerful way of overcoming these challenges.
For example, a high-resolution MS-based workflow enables comprehensive characterization and monitoring of quality attributes from research to quality control (QC). With this workflow, scientists and researchers can more easily characterize biologics. The workflow also allows potential critical quality attributes (CQAs) to be monitored throughout every stage of the drug development process, while also providing purity testing.
MAM enables highly accurate relative quantification (% difference) of post-translational and process induced modifications by comparison to a reference sample. High resolution accurate mass (HRAM) mass spectrometry (MS) delivers both the required sensitivity and specificity for increased confidence in the detection and quantification of post-translational modifications. Moreover, HRAM MS brings the capability to detect additional components in parallel; this critical additional data processing capability, called “new peak detection,” automatically detects and flags new chromatographic components in a sample once compared to a reference. This allows MAM to deliver both quantification of known differences, and the capability to flag new unknown impurities present above pre-set detection limits.
Additional benefits to a HRAM-MS workflow include:
- Reduction in cost and time, as well as fewer SOPs and instruments to maintain
- A complete solution for analytical processes run on multiple instruments across different development sites
- Workflow standardization for a global environment, which is especially crucial when preparing regulatory filings
Overall, a high-resolution MS-based workflow serves to provide significant amounts of information for biotherapeutic drugs, reducing both the number of analyses and different experiments while simultaneously increasing the product quality profile.