Although advancements in analytical drug substance testing are being made, the increasing diversity of the therapeutic landscape is necessitating further innovation.

The analytical testing of drug substances is a critical aspect of development and manufacturing within the bio/pharma industry. These comprehensive tests are used throughout the drug development lifecycle to ensure each product used within a therapy is safe and effective for use, and of the highest quality. To learn more about drug substance testing, Pharmaceutical Technology® spoke with Pavan Kumar Kunala, global biologics lead, Almac Sciences, and Sander Kok, PhD, director Analytical Sciences at Ardena.

The role of substance tests

PharmTech: Could you run through the role of drug substance testing for bio/pharmaceuticals and the types of tests generally used?

Kunala (Almac Sciences): The analytical methods for drug substances play a pivotal role in the journey of biologics development, from the early clinical phase to commercialization, ensuring that the product meets the highest standards of quality, safety, and efficacy for therapeutic use. Moreover, some of the drug substance [DS] methods are instrumental in testing in-process samples, providing insights into process development and ensuring that manufacturing remains consistent and robust during the early phases of product development. The characterization of the [DS], which involves understanding the critical quality attributes (CQAs) and selecting appropriate orthogonal analytical methods to assess them, is another vital application of these methods. Additionally, these methods are employed in the release and stability testing of the bulk [DS], thereby ensuring consistent quality across different batches. (See Sidebar for a link to a detailed review of drug substance test categories.)

Kok (Ardena): Typical tests in a drug substance analytical laboratory consist of in process control, release, and stability testing of DS batches. In the pre-clinical phase, analytical methods are developed, including forced degradation and robustness tests. In terms of methodologies, DS tests include at least the methods to verify identity, assay and impurities following [the] ICH [International Council for Harmonisation] Q6A guideline.

Technological advances and novel approaches

PharmTech: Have there been any technological advances or novel analytical approaches that are helping to improve efficiencies in drug substance testing?

Kok (Ardena): For many years, ultra-high pressure liquid chromatography (UHPLC) has brought the pharmaceutical analytical community additional separation power and reduced analysis time. Particularly the strong improvement in resolution compared to conventional HPLC enabled a further and detailed characterization of drug substances .