The challenging environment of biologics product development

Jon S. Kauffman, Ph.D., Senior Vice President, Biopharma Biologics, Eurofins BioPharma Product Testing

Biologics Product development can be quite a challenging landscape to navigate, and the process has evolved over these last five post-COVID years. Principally, the progression from early phase through commercialization has accelerated by quantum leaps. Expectations have changed; the conventional 10 to 15 year timeline is now compressed as sponsors sprint to deliver lifesaving/life-changing products to patients. Therefore, it is vital for biopharmaceutical organizations to choose partners like Eurofins Biopharma Product Testing (BPT) with the agility, flexibility, capacity and experience to support their chemistry, manufacturing, and controls (CMC) and commercial release testing needs.

This acceleration has led to a more risk-based approach to method establishment and resulted in the utilization of fit-for-purpose methods to monitor critical quality attributes (CQAs) throughout the first phases of clinical activities. These methods then need to be validated rapidly and thoroughly to support crucial Process Performance Qualification (PPQ) campaigns. Expectations of regulators from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) continue to intensify, reflecting the guidance and recommendations of the International Council for Harmonization (ICH Q2 R2).

Late phase method validations have become much more complex and extensive. For example, assays for monitoring critical CQAs, such as low and high molecular weight impurities, need to be evaluated for linearity, precision, accuracy, limit of detection (LOD), and limit of quantitation (LOQ) for these species. This necessitates multiple linearity studies, including dilutional linearity, co-mixed with forced degradation material linearity and low-level linearity for each species. In addition, formulations and concentrations are sometimes only finalized entering pivotal Phase III studies, further influencing method establishment strategies and timelines.

Eurofins BPT partners with our clients through consultative discussions to develop strategies and protocols to accomplish these objectives in the most time and cost-effective manner.

Analytical equipment and software vendors also continue to develop more sensitive and powerful tools at a faster pace. There are an increasing number of antibody-drug conjugates, viral vector products, and fusion protein candidates in the pipeline. As modalities become more complex, the technology required to evaluate their CQAs and characteristics must evolve as well.

However, this can be problematic in a Good Manufacturing Practices (GMP) environment where change control must be managed. Key instrumentation platforms and software can quickly become obsolete, or their support can be discontinued. This is of concern when methods have already been filed with specific equipment and technology, and bridging studies may be needed. Therefore, method lifecycle must be carefully considered. As with method validation, Eurofins BPT interfaces with our clients and vendors to perform risk assessments on the methods, including the required instrumentation, reagents, consumables, software, etc.

The fact that multiple Contract Manufacturing Organizations (CMOs) may be utilized by the sponsor can further complicate logistics. Flexibility and capacity are key to accommodating manufacturing shifts. In some cases, sponsors prefer proximity to the manufacturing site and/or redundancy of testing laboratories.

Eurofins BPT’s harmonized network of laboratories across North America with full-service biologics capabilities in Lancaster, PA, and Columbia, MO, and capabilities in San Diego, CA, and Portage, MI, positions us well to overcome the logistical challenges that are inherent to bioprocess manufacturing and biologics product testing.

For more information visit: www.Eurofins.com/BPT or: Contact Us to submit an inquiry.