Recent breakthroughs in disease treatment, shifting global populations, and new demands for patient safety have all led to a new generation of injectable compounds. Monoclonal antibodies, multivalent vaccines, and recombinant peptides are just some of the complex, highly sensitive compounds in development today. And as drug complexity increases, so do the challenges of ensuring drug stability.
The right filling process starts with the right questions
Biologic compounds are inherently unstable and sensitive to external conditions; therefore, the development of a robust, repeatable filling process focused on maintaining stability as the compound moves through clinical development is critical. To do that, it’s important to answer some key questions:
How sensitive is the compound to the filling process? To the filtration process?
How robust without deviation from specification can I make my filling process?
Is the drug product compatible with related components like rubber stoppers and closure systems?
What materials are suitable for these components? Is pretreatment necessary?
How much silicone can the substance endure?
Once answers to these questions are established, a filling process that accounts for the many variables involved can be developed. Attention to this process in the early stages can help ensure stability will be maintained during the transition from clinical to commercial filling.
The complexity of today’s compounds influences many aspects of the filling process. The first is the filtration, which must be specifically designed for these sensitive compounds. Multistep filtration processes may have to be developed to prevent protein aggregation during pooling and to eliminate leaching of the final drug solution, for example. And recirculation of the compounded drug substance may be necessary to maintain the targeted drug concentration.
Higher dose concentrations, often desired by manufacturers looking to maximize drug efficacy or patient convenience, pose challenges in the filling process, they are often liable to dry to the surfaces of filling needles reducing filling diameters or drug yield. They also present a challenge during sterile filtration with degradation via increased protein aggregation.
Analysis is also influenced by the complicated nature of these compounds. By nature, biologics are difficult to analyze correctly and require a higher level of robustness in order to satisfy regulatory requirements. This includes stability analysis, so expertise in the testing and analysis of sensitive compounds is required. Stability tests must be performed starting at formulation development and continuing through qualification, commercial batches, and regulatory release. Ongoing stability studies to assess field shelf life must also be performed once the drug is launched to prevent any potential supply shortages. As stability testing and analysis in complex compounds is so critical, having proper stability storage space and backup systems in place is vital to the success of the analysis.
Vetter’s expertise provides stability solutions
With more than 150 experts and 15 years of experience with complex compounds, Vetter can help to find the answers you need when it comes to drug stability during the filling process. We’ve worked with compounds ranging from monoclonal antibodies to peptides to vaccines. We design each compound’s process with special attention toward maintaining drug stability, employing recirculation and other steps when necessary. Vetter’s analytical and methods transfer expertise, as well as facilities in Chicago and Ravensburg, Germany, offer the ability to provide customer-specific methods transfer. And finally, Vetter offers up to 3972 ft2 in stability storage space.
Monoclonal antibodies are antibodies made in a laboratory from identical immune cells that are clones of a single cell. They are distinct from polyclonal antibodies, which are made from different immune cells.