Translating small-molecule development to complex generics and biosimilars

Key Learning Outcomes

• Understand the differences between analytical and CMC aspects across four drug categories: small molecules, complex generics, biologics, and biosimilars, and why strategies for characterisation, comparability, and quality control grow increasingly complex as molecular complexity rises.
• Learn what makes complex generics like low molecular weight heparin and glatiramer acetate analytically challenging, why simple small molecule methods are inadequate, and how the diversity of reference listed drugs must be mapped across multiple batches and manufacturing attributes to support a generic claim.
• Discover how the approximately 300 million possible molecular combinations in a monoclonal antibody necessitate extensive multi-attribute characterisation of the reference product, covering primary structure, higher-order structure, post-translational modifications, aggregation, and degradation pathways before meaningful biosimilarity can be evaluated.
• Explore the concept of fingerprint-like similarity in biosimilar development, demonstrating it through orthogonal analytical methods across large datasets of reference product lots, and how the level of physicochemical similarity directly influences the scope of clinical and non-clinical testing required.

Event Overview

This session by Dr. Joseph Glajch adopts a structured analytical and CMC perspective on the entire range of drug complexity, from simple small molecules to complex generics, biologics, and biosimilars. It demonstrates how the same fundamental quality assurance goals demand increasingly sophisticated strategies as molecular complexity rises.

The presentation begins by highlighting the straightforward nature of small molecule generics: single molecular entities created through chemical synthesis, where comparing brand to generic requires only a few batches and standard HPLC, GC, and compendial techniques. This foundation then shows what changes when complexity increases. Complex generics, exemplified by low molecular weight heparin, which demands around 50 characterisation methods, are mixtures of related molecular species, where no single analytical technique suffices, and the entire reference listed drug spectrum must be mapped to determine what “the same active ingredient” truly means.

For monoclonal antibodies, the challenge is of a completely different scale. With around 300 million potential molecular combinations caused by post-translational modifications alone, characterising the reference product is already a significant analytical effort. The session covers the detailed method set required, from backbone characterisation and higher-order structure analysis to glycosylation profiling, aggregation measurement, and terminal variant quantification, as well as the statistical difficulties of working with non-normally distributed data across large, multi-regional reference product lot datasets.

The idea of fingerprint-like similarity is then introduced as the strategic framework for biosimilar development: the more thoroughly a biosimilar candidate can be demonstrated to match the reference product at the physicochemical and functional levels, the less residual uncertainty remains for clinical programmes to resolve. Real-world examples from a 45-lot reference product characterisation exercise, covering US and EU lots over multiple years, show how lot diversity is mapped, how target ranges are set, and how different data types — from binary qualitative tests to continuous quantitative distributions — require different analytical and statistical approaches.

Who Should Attend?

Scientists, quality professionals, and regulatory specialists working on generics, complex generics, biosimilars, or biologic drug development seeking a comprehensive understanding of how CMC and analytical strategy must evolve with increasing molecular complexity.

• Analytical Scientists and CMC Chemists across small molecule and biologic programmes
• Biosimilar Development and Characterisation Scientists
• Quality Control and Quality Assurance Professionals
• Regulatory Affairs and CMC Submission Specialists
• Formulation and Process Development Scientists working on complex generics or biologics
• Statisticians supporting reference product characterisation and comparability programmes
• R&D and Technical Operations Managers overseeing analytical and CMC functions

Unlock Additional Educational Resources

Register today for Joe’s presentation and gain access to exclusive bonus content, such as the insightful panel discussion on “CMC: A Developmental Approach to Ensure Drug Quality – from Small-Molecule Drugs to Biotherapeutics”.

Brought to you by: