PROCESS DEVELOPMENT: MULTIVALENT VACCINE CASE STUDY
A well-defined process that helps to frame the key steps to product development and methods that lead to a successful outcome
is also important. Complex compounds, such as multivalent vaccines, can present especially challenging issues in the early
clinical phase. For example, consider a multivalent vaccine in clinical development 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 key variables to control, including fill concentration, viscosity, and
To ensure biological potency of the final conjugated mix, the process design had several steps, including: constant recirculation
during final filling to avoid unwanted volatility in concentration; and specialized pump and filtration technology to optimize
bioactivity while preventing protein aggregation. (Designing an optimal pump filtration and process was equally crucial for
protecting the bioactivity of the final product).
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 a key 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 that a company chooses to work through its product
development plan will strongly influence how the game is played. Choose wisely and everybody wins.
This article is part of a new series on Basic Training for Drug Development and Manufacture, providing business and technical
guides for taking drugs from discovery to development. Send ideas and contributions to the editor at
Paul Nelles is vice-president of Vetter Development Service at Vetter Pharma-Fertigung GmbH & Co. KG
- Plan to maximize the value of the compound in its early development stages.
- Gain a clear understanding of the compound's scientific and technical requirements.
- Gather specialized teams to develop the product design; this may involve outside partners.