Industry Leaders Share Strategies for Advanced Therapeutic Analytics

As the pharmaceutical industry accelerates the commercialization of complex therapies such as cell and gene treatments, RNA-based platforms, and antibody-drug conjugates, leaders are emphasizing the need for robust analytical methods. These methods must not only characterize these intricate modalities but also adapt to evolving scientific landscapes. A recent dialogue among leaders in contract development and manufacturing organizations (CDMOs), biotechs, and service providers highlighted key strategies to tackle this pressing challenge.

Regulatory Alignment as a Foundation

A critical theme in the discussions was the importance of aligning analytical development with regulatory standards. Multiple contributors pointed to the International Council for Harmonisation (ICH) guidelines Q14 and the revised Q2(R2) as cornerstones for developing effective analytical methods. Marinus Bouna, Business Development representative at Ofichem, stated, “Developing robust analytical methods for complex modalities such as antibody-oligonucleotide and antibody-peptide therapeutics is critical not only for regulatory compliance but also for ensuring smooth collaboration with outsourcing partners.”

According to Pierre Barratt, Vice President of Strategy and Program Management at Codexis, these frameworks guide method development with a science- and risk-based approach. He noted that their work is informed by case studies to ensure compliance with the latest guidelines.

Defining Quality Attributes Early

The experts unanimously agreed that defining critical quality attributes (CQAs) early in the development process is essential. Marinus explained that early identification of parameters such as conjugation ratio, linker stability, and sequence integrity allows methods to be designed for scientific reliability and cross-site transferability. Dr. Brianna Schoen, Vice President of Biotherapies Scientific Development at VITALANT, stressed the need for a comprehensive understanding of both established and emerging analytical platforms. Advanced technologies like high-resolution mass spectrometry and digital PCR can provide insights beyond traditional assays.

Orthogonal Methods for Increased Reliability

Given the complexity and heterogeneity of advanced therapeutics, reliance on a single analytical technique can pose significant risks. Jonathan Wofford, Chief Commercial Officer at Title21, emphasized the value of orthogonal methods that utilize various measurement principles to analyze the same attributes. This approach allows for independent verification of results, minimizing the potential for bias from a single method’s systematic errors.

Codexis has applied this principle to its RNA-based oligonucleotides, employing an array of techniques for identity, purity, and impurity profiling. Pierre elaborated on their multi-technique strategy, which includes LC-MS/MS for sequence fidelity and testing for residual enzymes.

Embracing Real-Time Analytics and AI

The conversation also shifted toward the integration of real-time analytics and artificial intelligence (AI) in the manufacturing process. Alexander Seyf, CEO and Co-founder of Autolomous, described a transition from traditional end-of-process testing to continuous, in-process monitoring. “We are moving away from a reliance on end-of-process testing. Instead, we use real-time, in-line analytics to monitor the manufacturing process as it happens,” he explained. This shift provides a richer dataset and allows for immediate adjustments to ensure product specifications are met.

AI and machine learning are also being harnessed to analyze extensive datasets, enabling the identification of subtle patterns that could indicate potential quality deviations before they occur.

Ensuring Transferability and Scalability

A significant challenge in outsourced development is ensuring that analytical methods are transferable across different laboratories and scalable from research to commercial manufacturing. Jonathan emphasized the necessity of designing methods that can perform consistently in Good Manufacturing Practice (GMP) settings. Applying Analytical Quality by Design principles and conducting stress tests under varying conditions can enhance confidence in reproducibility.

Marinus added that robust analytical methods must maintain performance across different laboratories and instruments, reinforcing the need for early investment in method validation.

Evolving with Scientific Advances

Leaders expressed the need for analytical strategies to evolve as scientific understanding progresses. Dr. Stella Vnook, CEO of Likarda, highlighted that novel modalities do not always align with existing pharmacopeia frameworks. “Robust doesn’t mean rigid: methods must be designed to evolve as the science does,” she said.

Brianna pointed out that delays in Biologics License Application (BLA) approvals are often linked to insufficient assay robustness and inadequate potency characterization. Addressing these challenges requires early investment in deep characterization and the development of alternative analytical options.

Integration and Collaboration

The consensus among contributors was clear: analytical strategy must be integrated with broader chemistry, manufacturing, and controls (CMC) strategies. Brianna noted that analytical strategies should be designed with regulatory expectations in mind from pre-Investigational New Drug (IND) application through to commercialization.

Codexis actively participates in the scientific community to stay updated on industry advancements. Pierre explained that ongoing education and participation in conferences such as TIDES and the RNA Leaders Congress help maintain their relevance and adaptability.

The need for analytical excellence in developing novel therapeutic modalities calls for continuous dialogue among sponsors, CDMOs, and technology providers. Upcoming events like CDMO Live Europe and Americas will provide platforms for sharing best practices and addressing emerging challenges in this dynamic field.