Wendy Saffell-Clemmer, Director, R&D
Mayur Valanju, Head of Sales & Marketing
Kelly Davis, Director, Regulatory Affairs
Carol Winnefeld, Contract Manager (Quality Agreements)
Parenteral Drug Development and Manufacturing
PharmTech: What emerging technologies or practices do drug sponsors expect your organization to provide?
Wendy Saffell-Clemmer: 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.
PharmTech: What scientific or technical advances have positively or negatively impacted drug development processes in this market segment?
Wendy Saffell-Clemmer: With more complex and frequently lyophilized biologics such as monoclonal antibodies and ADCs 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.
PharmTech: Are you seeing shifts in demand for particular types of services? Please describe.
Wendy Saffell-Clemmer: 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, FTIR microscopy with comparison to libraries, and polarized light microscopy.
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?
Wendy Saffell-Clemmer: 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.
PharmTech: What regulatory changes have positively or negatively impacted drug development/manufacturing processes in this market segment?
Kelly Davis: Regulatory agencies have moved towards a risk-based approach to drug development. This approach allows industry to institute product elements during the development phase based upon product knowledge of interactions with container/closure systems and the manufacturing process. The utilization of this approach requires industry to better understand the impact of container/closure and manufacturing process changes. Industry is now provided the ability to manage their products based upon scientific data vs legalistic interpretation of regulatory guidances.
PharmTech: What business trends have positively or negatively impacted drug development/ manufacturing processes in this market segment?
Mayur Valanju: The drug pipeline has continued to shift from small molecules and higher volume indications to biologics with lower volume indications. As the pipeline has shifted, so have the opportunities that are provided to contract manufacturing organizations (CMOs). As such, it is increasingly important that CMOs have the technical expertise to manage biologics within their facility. Additionally, as volumes from individual molecules have dropped, CMOs have had to adapt and implement processes to manage more molecules at one time.
PharmTech: What changes are you observing in the organization and operations of drug sponsors in this market segment?
Mayur Valanju: Several years ago, the majority of development work was being done by large pharmaceutical companies. Today, we are seeing more biotech firms and virtual companies doing the initial phases of drug development and in some cases full commercialization. Because biotech firms generally have less in-house expertise in manufacturing than large pharmaceutical companies, they rely more on the CMO to provide a broader range of services and expertise.
PharmTech: How has quality by design influenced a drug sponsor’s expectations of suppliers?
Wendy Saffell-Clemmer: Drug sponsors expect product development organizations to have an understanding of quality by design (QbD) principles and incorporate design of experiment (DoE) factorial designs into formulation development as well as design space principles in process development. BPS has developed a novel QpD approach to the definition of the primary drying stage of lyophilization, which provides a safe zone of operation bounded by equipment capability and shelf temperature. Benefits of this approach may include faster process development and better process optimization.
PharmTech: How will FDA’s draft guidance on quality agreements affect the relationships between contract service providers and drug sponsors?
Carol Winnefeld: Quality agreements are vital to ensuring consensus on the quality-related provisions between the CMO and the sponsor. The agreement should focus on the key provisions that ensure GMP compliance for the product. Prior to this guidance, there was inconsistency to sponsors’ approaches regarding what should be included. The FDA’s guidance is a good starting point for driving consistency; it will be important that the FDA and CMOS work together to refine this guidance moving forward.