Declan Lowney, Director of Stability Studies at Janssen, discussed the key differences between monoclonal antibodies and synthetics. Monoclonal antibodies (mAbs) are derived from biological systems and require highly purified and characterised analytical procedures, unlike chemically synthesized products. He also covered the analytical methods and regulatory requirements involved in ensuring their stability and quality.
Next, Lowney revealed the complexities involved in producing biopharmaceuticals, including variability arising from fermentation processes and purification methods. In contrast, chemically synthesized products have discrete manufacturing steps and alternative synthetic routes.
Analytically, mAbs require accurate and sensitive methods to ensure their quality attributes, including identity, strength, purity, and stability. Techniques such as UV absorbance, capillary electrophoresis, mass spectrometry, and particle monitoring are employed to assess these attributes and detect degradation pathways like aggregation.
Stability testing is a critical component of regulatory compliance. The testing involves evaluating how the quality of the drug substance or product changes over time under various environmental conditions. Lowney outlined some principal regulatory guidelines for stability testing. Regulatory bodies demand real-time, real-condition data, and the requirement for representative batches of commercial scale. He stressed that long-term real-time stability studies are essential for mAbs, whereas for small molecules, accelerated studies may suffice.
Furthermore, he talked about the challenges in stability study design, including the selection of representative batches, container closures, and storage conditions. Proper storage conditions are critical, especially for protein drug substances, which are often stored frozen. The glass transition temperature (Tg prime) of formulations must be considered to avoid degradation.
Additionally, he highlighted the importance of container compatibility and temperature excursions in stability studies. In summary, Lowney reiterated the extra challenges involved in stability testing for mAbs compared to small molecules, like the need for representative batch selection, complex analytical methods, and strict regulatory requirements.
