Industry Leaders Tackle Challenges in Analytical Development for Novel Therapies

As the pharmaceutical industry pushes forward with the commercialization of innovative treatments such as cell and gene therapies, RNA platforms, and antibody-drug conjugates, a pressing challenge has emerged: developing analytical methods that can effectively characterize these increasingly complex modalities. Industry leaders from various sectors, including contract development and manufacturing organizations (CDMOs), biotechs, and service providers, have shared insights into their strategies for overcoming these hurdles.

Regulatory Alignment and Robust Development

A consensus among experts highlights that successful analytical development begins with alignment to regulatory frameworks, particularly the ICH Q14 guideline on analytical procedure development and the revised Q2(R2) on analytical validation. Marinus Bouna, Business Development professional at Ofichem, emphasized, “Developing robust analytical methods for complex modalities is critical not only for regulatory compliance but also for ensuring smooth collaboration with outsourcing partners.”

The emphasis on a science- and risk-based approach in method development has become paramount. Pierre Barratt, Vice President of Strategy & Program Management at Codexis, noted the importance of grounding method development in these frameworks: “The framework is anchored in ICH Q14 and Q2(R2) and informed by case studies to ensure compliance with the latest guidelines.”

While regulatory compliance provides necessary structure, experts stressed that it is not a guarantee of analytical success for novel modalities.

Defining Quality Attributes Early

Defining critical quality attributes (CQAs) early in development is essential, according to industry leaders. This proactive approach is especially important for sponsors collaborating with outsourcing partners. Bouna pointed out that establishing parameters such as conjugation ratio, linker stability, and sequence integrity at the outset allows for methods designed with both scientific reliability and cross-site transferability in mind.

Dr. Brianna Schoen, Vice President of Biotherapies Scientific Development at VITALANT, underscored the need for a profound understanding of both established and emerging analytical platforms. She stated, “Beyond traditional assays for identity, purity, and potency, advanced technologies such as high-resolution mass spectrometry and digital PCR offer critical insights.”

Orthogonal Approaches for Complex Analytics

Given the heterogeneity of advanced therapeutics, relying solely on single analytical techniques poses significant risks. Leaders recommend employing orthogonal approaches, which utilize different measurement principles to analyze the same attributes for independent verification.

Jonathan Wofford, Chief Commercial Officer at Title21, explained, “Methods should use different measurement principles to analyze the same element, providing independent verification and minimizing bias.” Codexis applies this principle in its analytical processes, integrating various techniques to ensure reliability and robustness while minimizing artifacts.

Real-Time Analytics and Artificial Intelligence

A notable trend involves shifting from traditional end-of-process testing to continuous, real-time monitoring facilitated by advanced sensors and artificial intelligence (AI). Alexander Seyf, CEO and Co-founder of Autolomous, highlighted this shift: “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.”

This approach not only enhances data quality but also enables immediate adjustments, ensuring the final product meets specifications. Seyf further noted that AI can analyze large datasets, revealing patterns and correlations that might be overlooked by human analysts.

Ensuring Transferability and Scalability

A critical aspect of outsourced development is ensuring that analytical methods are transferable between laboratories and scalable from research through commercial manufacturing. Wofford stressed that “analytical methods must perform consistently across different laboratories and instruments.” Applying Analytical Quality by Design principles and performing stress testing under varied conditions can enhance reproducibility and robustness.

Bouna reiterated that maintaining this consistency is vital for reliable outcomes, particularly as processes evolve.

Dynamic Analytical Strategies

Industry leaders advocate for a flexible approach to analytical strategy, viewing it as a dynamic capability that must evolve throughout a product’s lifecycle. Dr. Stella Vnook, CEO of Likarda, articulated this perspective: “Robust doesn’t mean rigid: methods must be designed to evolve as the science does.”

Schoen emphasized that analytical development should be informed by both successes and failures in clinical progression to create resilient strategies. She noted that delays in Biologics License Application (BLA) approvals often stem from insufficient assay robustness and inadequate potency characterization.

Integration from the Start

A common thread throughout the discussions is that analytical strategy must align with broader chemistry, manufacturing, and controls (CMC) strategies, especially for novel modalities. Schoen urged that “analytical strategies must be designed with regulatory expectations in mind from pre-Investigational New Drug (IND) through commercialization.”

Codexis stays current by actively participating in scientific discussions and forums, such as CDMO Live Europe and Americas, which includes workshops focused on CMC and analytical strategies. These events provide platforms for manufacturers and sponsors to share best practices and address challenges in this rapidly evolving field.

As the pharmaceutical landscape continues to evolve, the emphasis on robust and adaptable analytical strategies will be crucial for the successful development and commercialization of novel therapeutic modalities.