New formulations, regulations, and drug sponsor demands are changing requirements for analytical test methods, development processes, and filling operations. Representatives of contract service organizations that specialize in parenteral drug development and manufacturing describe the evolving trends for the editors of Pharmaceutical Technology.
Changing expectations for CMOs/CDMOs
PharmTech: What emerging technologies or practices do drug sponsors expect your organization to provide?
Saffell-Clemmer (Baxter BioPharma Solutions): The parenteral drug pipeline has continued to shift from small molecules to complex biologics such as monoclonal antibodies and antibody drug conjugates (ADCs). As the complexity of molecules increases, drug sponsors are requesting a broader array of analytical test methods for drug product release and stability. In particular, most biologics customers are now requesting capillary electrophoresis methods such as capillary isoelectric focusing (cIEF) or imaging capillary electrophoresis (ICE), in addition to more common chromatographic methods.
Soelkner (Vetter Pharma International): Sponsors expect state-of-the-art filling lines that both enhance quality and save costs, for example, fully automatic machines to optimize yield but also reduce risk of human contamination. To meet their products’ specific needs, sponsors also demand from us high flexibility in equipment and processes. That means, for example, providing stainless steel and disposables; options in pumping and filtration systems; and the capability to handle new materials and injectable systems like polymer and pre-sterilized syringes.
PharmTech: What scientific or technical advances have positively or negatively impacted drug-development processes in this market segment?
Saffell-Clemmer (Baxter BioPharma Solutions): With more complex and frequently lyophilized biologics such as monoclonal antibodies and ADCs [antibody drug conjugates] in the pipeline, the development process has also become more complex and resource intensive. Demand for analytical services, both during the development stages and during release and stability, has increased due to the need for multiple test methods to assess drug purity and stability. Additionally, the growing pipeline of ADCs has increased demand for lyophilization formulation and process development.
Services suited to company size, needs
PharmTech: Are you seeing shifts in demand for particular types of services.
Saffell-Clemmer (Baxter BioPharma Solutions): Drug sponsors are increasingly interested in the ability to rapidly identify and characterize particles. To meet this need, our laboratories have the capability to provide stereomicroscopy, digital microscopy, [Fourier transform infrared] FTIR microscopy with comparison to libraries, and polarized light microscopy.
Soelkner (Vetter Pharma International): We’ve seen biopharmaceutical firms return to their core competencies and seek strategic partners that can complement their services. Big Pharma/Biotech are using contract manufacturers as an extension of their fill and finish network. They seek for CDMOs to provide high-quality products and long-term market supply. Smaller companies, however, often need partners to guide them through development and regulatory approval, including the creation of product documentation, so they can quickly reach the market or attract buyers.
Precision measurements to accurate filling
PharmTech: What pressing technical challenges have you seen in this market segment? What actions has your company taken to resolve the challenge? What actions does your company suggest?
Saffell-Clemmer (Baxter BioPharma Solutions): There has been increasing awareness in subvisible particles resulting from the aggregation of therapeutic proteins. The size range of interest (2-10 µm) is not monitored by current compendia methods. Baxter BioPharma Solutions has invested in particle analysis systems such as micro-flow imaging and has conducted research in the area of protein aggregation during freeze-drying in cooperation with Fluid Imaging Technologies. Characterization and monitoring of subvisible particles throughout product development should be performed for large molecules.
Soelkner (Vetter Pharma International): Accuracy on the filling line is one of the industry’s greater technical challenges. Precision is vital to product quality and patient safety. Combination products involving auto-injectors, safety features, and new primary packaging materials have to perform every time to prevent incomplete injection, glass breakage, and other failures. Continuous investment in technology and staff training helps us meet those challenges, as well as constant monitoring of the market and environment to keep up with new manufacturing regulations.
Drug security measures
PharmTech: What advances do you see in science or technology in this market segment in the next five years?
Soelkner (Vetter Pharma International): Drug counterfeiting is a serious problem facing the industry. Serialization and track-and-trace technologies are undergoing implementation worldwide over the next few years to combat counterfeiting, enhance patient safety, and enable a more secure drug supply chain. US and EU regulatory authorities, for example, have sets deadlines in 2017. In terms of process control and automation, the landscape will also continue to change as new technologies are introduced to meet ever-tighter quality requirements.