How Analytics and Mass Spec Became the Driving Force Behind Biotherapeutic Drug Development

Biopharma discovery and development scientists are achieving new levels of structural insight into therapeutic proteins. By utilizing biopharmaceutical analytical technology and mass spectrometry, laboratories are now empowered to reveal ultra-low-level modifications and determine site-specific critical quality attributes (CQAs) and granular information—delivering more confidence when progressing candidates throughout the development pipeline, whilst ensuring drug efficacy and patient safety. This article explores the key challenges analytics and mass spectrometry solve within the biopharmaceutical industry.

In the dynamic world of biopharmaceutical discovery and development, scientists are constantly striving to advance their understanding of therapeutic proteins. Breakthroughs in biopharma analytical technology and mass spectrometry (MS) have opened new avenues for researchers, allowing them to delve deeper into the structural intricacies of biotherapeutic proteins and create new drugs.

These innovations empower laboratories to uncover ultra-low-level modifications, determine site-specific critical quality attributes (CQAs), and obtain granular information pivotal to the drug development process. This article will dive into the critical role that analytics and mass spectrometry play in addressing key challenges within the biopharmaceutical industry.

The Evolution of Mass Spectrometry in Drug Development

Traditionally, mass spectrometry was primarily associated with the early stages of drug discovery and was commonly used to assess the purity of raw materials and identify compounds of interest.

However, the pharmaceutical landscape has undergone a seismic shift in recent years and laboratories now recognize the importance of mass spectrometry throughout drug development. It is no longer confined to the initial stages but is integral to quality control and safety assessments at every step, and has become the driving force behind biotherapeutic drug development and is enhancing quality by design (QbD).

Mass spectrometry is an invaluable tool in the rapid identification and characterization of compounds and has been since its inception in the early 20th century. The technique’s high-resolution capabilities empower early-stage laboratories to analyze complex samples with unparalleled accuracy. It plays a vital role in biopharmaceutical development and manufacturing by providing detailed insights into protein structure, quality control, biosimilar development, pharmacokinetics, and process monitoring. Its high sensitivity, specificity, and ability to handle complex samples make it indispensable in the biopharmaceutical industry. As drug development techniques advance and quality control demands increase, mass spectrometry’s role in later stages of development will only increase and become more critical.

Real-Time Insights and Enhanced Quality Control

The technology behind mass spectrometry not only aids in compound identification but also offers real-time insights into the stability and degradation of pharmaceutical products throughout the drug development journey. Continuous monitoring allows laboratories to detect deviations from specifications promptly, ensuring the final product adheres to regulatory standards at all stages. This real-time monitoring capability accelerates research and development timelines, enabling laboratories to make informed decisions based on accurate data. Speed-to-market advantages are particularly crucial in addressing urgent medical needs, such as during the COVID-19 pandemic.

Mass spectrometry’s sensitivity and specificity make it a reliable method for safeguarding product integrity and upholding the reputation of drug manufacturers for biotherapeutics. The importance and value of mass spectrometry for biotherapeutic development is demonstrated by the work of the MAM Consortium, an industry-wide, nonprofit organization with the mission to advance multi-attribute method (MAMs) and other LC–MS applications in pharmaceutical and biotechnology companies for product characterization, in-process control, and GMP release and stability testing (1).

Reducing Contamination Risk and Regulatory Compliance

Mass spectrometry is well aligned to help pharmaceutical companies comply with regulatory requirements, as the technology provides robust analytical data. This data encompasses drug purity, acceptable dosage levels, and the necessary documentation required as therapies progress from research to clinical application. The inclusion of mass spectrometry at all stages of drug development significantly impacts the transition time from laboratory research to clinical applications, ensuring adherence to regulatory standards throughout the process.

Analytics and Mass Spectrometry as Biotherapeutic Game Changers

One of the remarkable achievements of biopharmaceutical analytics and mass spectrometry is their ability to uncover ultra-low-level modifications in biotherapeutic drugs. These modifications, which were previously challenging to detect, can now be identified with precision. This capability provides invaluable insights into the structural integrity and stability of therapeutic proteins, enhancing the overall quality of drug candidates.

Additionally, analytics and mass spectrometry enable researchers to pinpoint site-specific CQAs in biotherapeutic drugs. This granular information is essential for ensuring drug efficacy and patient safety. By identifying specific attributes that may impact a drug’s performance, scientists can make informed decisions and refine drug development strategies. Mass spectrometry enables another critical level of information through the process of building quality in each design step of the drug development process. Key challenges it addresses include:

• Structural Complexity: Biotherapeutic drugs are inherently complex, and understanding their intricate structures is vital for drug development. Analytics and mass spectrometry provide the tools needed to navigate this complexity, allowing scientists to unravel the nuances of these molecules.
• Quality Control & Consistency: Maintaining rigorous quality control throughout the development process is a paramount concern in biopharmaceuticals. Analytics and mass spectrometry can facilitate quality control and offer real-time insights to promptly address deviations from required specifications, allowing for greater consistency and reliability in product quality.
• Regulatory Demands: The biopharmaceutical industry operates in a highly regulated environment. Meeting regulatory demands is essential for bringing new therapies to market. Analytics and mass spectrometry aid in compliance by providing robust data and documentation required for regulatory approval.

A New Era in Biotherapeutic Drug Development

In the ever-evolving landscape of biotherapeutic drug development, analytics and mass spectrometry have emerged as the driving force behind structural insights and quality control. These technologies empower researchers to uncover ultra-low-level modifications, identify site-specific critical quality attributes, and navigate the complexities of biotherapeutic molecules. By addressing key challenges, such as structural complexity, quality control, and regulatory demands, analytics and mass spectrometry accelerate the development process while ensuring drug efficacy and patient safety. The integration of these tools into the entire drug development journey enables pharmaceutical companies to stay competitive and deliver safe and effective medications to patients more swiftly than ever before.

As the biopharmaceutical industry continues to evolve, analytics and mass spectrometry will remain indispensable, paving the way for groundbreaking discoveries and innovations in the field of biotherapeutic drug development. There is still enormous untapped potential to be realized for the implementation of mass spectrometry in biopharmaceutical development and manufacturing that will bring life changing treatments to the market faster.

Reference

(1) MAM Consortium. https://mamconsortium.org (accessed 2024-03-04).

Kelly Broster, PhD, is Senior Manager of Pharma & Biopharma Market Development and Collaborations at Thermo Fisher Scientific. E-mail: Kelly.broster@thermofisher.com