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).