Imagine a major game designer developing a new video game that is comprised of pitfalls and complexities so numerous and difficult that very few players reach the midpoint, let alone complete the game successfully...
And so it is in the world of biotechnology, where many companies face this scenario regularly and must do everything possible to increase the odds of successfully completing the “development game” and to reduce the risks of elimination. The risks and rewards of playing this game are high but few can afford to fail, even once.
Biotechnology projects are complex and subject to many levels of risk during the early clinical phases. Few products enter Phase III, and fewer still make it through approval and on to commercial manufacture. Furthermore, globalization and other recent developments, such as tighter quality control criteria, evolving technologies, and the increasing stringency of regulatory standards, have imposed enormous pressures on an already difficult task. The primary concern in most instances is to maximize the value of the compound in the very earliest stages of development to assist in attracting investors, provide out-licensing opportunities or in some cases, allow outright acquisition by a larger company. To such companies, little thought is given to later development or the commercialization efforts that must be applied to the compound or the myriad of interfaces between various partners that might be necessary as they move forward with a project.
Finding the right answers
In clinical development, finding answers—the right answers—is anything but simple. There are so many questions, so many unexpected challenges, and so many decisions that all need to be carefully and thoughtfully addressed because of their potential impact on the product’s success.
Successfully conducting a clinical development project means to:
Let’s take a look at a few examples of what can happen along the clinical development pathway. Finding the right solution to specific problem starts with a clear understanding of a compound’s underlying technical and scientific requirements.
Compounds are becoming more complex and that means greater demands on primary packaging. Highly sensitive drugs, including biopharmaceutical ones, require optimally designed drug-delivery systems. To the technical challenges come growing cost pressures and increasingly strict rules from regulatory agencies. Therefore, drug manufacturers need a great deal of competence when calibrating packaging with the drug product. On the one hand, it involves the compound itself and its environmental conditions (e.g., reaction with certain materials, biological specifications). On the other hand, the time factors (e.g., time-to-market) and long-term market success (e.g., product lifecycle management) are important criteria to consider.
Among other things, the following questions must be asked… and, crucially, answered:
Process development: multivalent vaccine case study
A well-defined process that helps to frame the key steps and methods that lead to a successful outcome is also crucial. Complex compounds, such as multivalent vaccines, can present especially challenging issues in the early clinical phase. In this example, a multivalent vaccine in clinical development was at risk of losing biological potency during the filling process.
Multivalent vaccines are comprised of several serotypical polysaccharide protein conjugates. Each serotypical conjugate must be prepared for filling so that the final mix of all serotypes retains its biological potency to elicit the appropriate immune response; having 8–12 different peptide antigens conjugated in the final mix while retaining the required biological potency is a major challenge.
All highly sensitive biologics, including vaccines, monoclonal antibodies, and conjugated peptides, are affected by filtration in the scale-up and filling processes. Many require multiple complex filtration processes that can include Ultra, Dia and Q-filtration steps in a single run. There are many critical variables to control: fill concentration, viscosity, and pumping pressure to name a few.
To ensure biological potency of the final conjugated mix, the process design had to include several critical steps:
In this case, a complex, multistep filtration process had to be developed to prevent protein aggregation during pooling, to eliminate leaching of any filter particles or extractable compounds in final drug solution, and to maintain targeted viscosity and concentration during scale-up. To achieve the goal, specialized teams worked together to develop a novel, customized process design that delivered a high-yield, biologically potent vaccine, which afterwards was planned for smooth scale-up from clinical to full commercial production
To meet the growing number of challenges facing the biopharmaceutical industry, outsourcing has become the critical strategic element. Outsourcing involves fundamental decisions that must be made early in drug development—when there is time to choose the right partner and develop a strong relationship. At the end of the day, the partner you choose will strongly influence how play the game. Choose wisely and everybody wins.