Solid/semi-solid dosage development and manufacturing
PharmTech: What emerging technologies or practices do drug sponsors expect your organization to provide?
Franco Negron: Drug sponsors expect us to provide all of the traditional technologies, along with newer technologies like hot melt extrusion, spray-drying, liquid-fill hard gelatin capsules, active coating, and continuous processing. In addition, there is increased pressure on more robust processes, more agile supply chains and lower costs.
PharmTech: What scientific or technical advances have positively or negatively impacted drug development processes in this market segment?
Franco Negron: I can’t identify any negative impacts, however newer techniques for handling insoluble or poorly soluble active ingredients, NIR in-process analyses, PAT devices, and equipment with improved containment and CIP have all enhanced manufacturing processes.
PharmTech: Are you seeing shifts in demand for particular types of services? Please describe.
Franco Negron: In the past few years, there seems to be a shift toward more complex formulations and processes, controlled-release combination products, abuse-deterent formulations, active coatings and techniques for handling insoluble compounds.
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?
Franco Negron: More complex formulations and processes require more stringent development to better understand the material characteristics, critical process parameters and quality attributes of the materials and product. Design of Experiments is one tool to help assure a quality outcome.
PharmTech: What advances do you see in science or technology in this market segment in the next five years?
Franco Negron: We will see a shift away from high volume, commodity products, to smaller more complex products targeted at niche indications. Equipment will move to smaller volume, higher containment and more flexible changeovers.
PharmTech: What regulatory changes have positively or negatively impacted drug development/manufacturing processes in this market segment?
Franco Negron: The most significant change is the focus on supply chain security. Better control of suppliers, more reliable processes and greater flexibility to meet shifting demands is increasingly important. Also, CMO’s and sponsor organizations are now jointly responsible for the integrity, safety and efficacy of their products.
PharmTech: What business trends have positively or negatively impacted drug development/manufacturing processes in this market segment?
Franco Negron: Several business trends are impacting our market segment:
PharmTech: What changes are you observing in the organization and operations of drug sponsors in this market segment?
Franco Negron: Sponsors, like the CMO’s are seeing the effects of more emphasis on supply chain security and development costs, and therefore are trending toward more outsourcing. CMO’s who focus on manufacturing and capacity utilization, are increasingly better-suited to provide products at a lower cost. Vertically integrated CMO’s, like DPx Holdings, can maximize supply chain effectiveness by providing coordinated, shorter development cycles and an array of commercial dosage forms to accommodate the specific characteristics of any API. The sponsors, in turn, are able to avoid significant investment in under-utilized capacity, particularly for the increasing diversity in capabilities.
PharmTech: How has quality by design influenced a drug sponsor’s expectations of suppliers?
Franco Negron: Quality by Design is now a normal expectation for drug product development, whether you are a drug sponsor or a CMO. Design of Experiments is routinely used as mentioned above, to understand the product and process characteristics. The challenge is to balance the amount of development work versus the cost and sometimes limited amount of API available. At the same time, there is always pressure to get products to market as quickly as possible.
PharmTech: Describe the role that quality agreements play in contract services relationships. How will FDA’s draft guidance on quality agreements affect the relationships between contract service providers and drug sponsors?
Franco Negron: Quality Agreements (QA) are an integral part of any contract service relationship, and rank equally in importance with the Supply Agreement. If completed properly, the QA identifies all sponsor and CMO responsibilities to assure the product quality and meet regulatory requirements. The FDA draft guidance just captures what the parties should have been doing already to assure product integrity on behalf of the patients.