CONCLUSION & OUTLOOK
The success of therapeutic monoclonal antibodies throughout the years is, in part, accredited to improvements in manufacturing and formulation allowing for the development of more efficient and cost-effective mAbs. Efforts to minimize mAb heterogeneity using protein engineering and the implementation of regulatory agency guidelines to ensure reproducibility, safety and traceability, such as GMP and QbD milestones discussed herein, have shown great advances in pharmaceutical and biotechnology companies. Further improvements to process development involve the implementation of single-use strategies to reduce cost and increase flexibility of platform processes. At the current rate of growth, novel computational-based approaches will become an integral part of process development and facilitate predictions of post-translational modifications, kinetic properties and pre-formulation screening, among others.
When talking about the intended use of a therapeutic antibody, it is important to note that several factors must be considered deeply in order to make adequate decisions, ranging from choosing the RoA to the drug delivery system and appropriate formulation, and even the patient population. Tuning of PK/PD properties of a monoclonal antibody not only leads to increased safety and efficacy but may facilitate increased patient acceptability and compliance, lowering of dose or dose frequency, and ultimately lead to improved therapeutic outcomes. Consideration of the TPP in early development is an important advancement in process development, as RoA, protein modifications and mAb heterogeneity may all influence the behaviour and safety of a therapeutic mAb in humans. Early pre-formulation experiments and assessments to determine which excipients are compatible and to investigate the ideal conditions for the stability of the API, e.g. temperature, pH, etc, should be performed to improve the formulation development of a drug product.
Ultimately, the aim is to minimize potential errors and variability throughout the entire process, which could potentially hinder product quality and cause safety or efficacy concerns. While progress in the manufacturing and formulation of mAb drugs continues to be made through the advancement of high-throughput technologies and low-cost alternatives, drawbacks are nevertheless present. Compared to other drug modalities, protein pharmaceuticals tend to have higher cost of goods. Consequently, a drug product with high immunogenicity and poor bioavailability would be too costly to manufacture. Therefore, strict understanding and control of every step of the process is fundamental to the success of a therapeutic monoclonal antibody, while always keeping in mind that “the process is the product” (Kuehn, 2014).