Technology transfer is always challenging, even in organizations with years of experience in cGMP manufacturing, and if care is not taken to ensure meticulous planning and execution, it can be wrought with unpleasant and costly surprises. Further, a thorough understanding of the manufacturing requirements throughout the development pathway — from research, through clinical development, to commercial manufacturing — is fundamental to successful biopharmaceutical drug commercialization. Diosynth Biotechnology is dedicated to delivering products and services with the highest level of quality. It is with that in mind that the company developed standards in the form of a Standard Operating Procedure (SOP)1 to clearly define all requirements from early process development through commercial manufacturing of recombinant proteins. Diosynth has implemented this product development process SOP to help ensure that a customer's product enters the company's system at the most appropriate stage.
The process is divided into five stages that serve as guidelines to streamline process transfer and development. It is a uniform approach to cGMP manufacturing and quality operations that ensures seamless production within and between the manufacturing sites in Research Triangle Park, North Carolina and Oss, The Netherlands. This approach also helps Diosynth Biotechnology and its customers in evaluating, developing, and executing high-quality, efficient manufacturing processes by ensuring that the most appropriate program and development stage is assigned to each product. This not only saves up-front time but also helps avoid the costlier delays in redevelopment later in the clinical trajectory.While every project is unique, a formalized approach to process development allows rapid progress during preclinical and early clinical testing. To ensure that each program and product enters Diosynth's system at the optimal stage, process development and technical services specialists initially evaluate the process fundamentals, regardless of whether the product is in preclinical development or approved for the commercial market. If the process and analytical methods are robust, transfer to cGMP manufacturing areas can occur rapidly, though process and method refinement are often requested by the customer or are required to fit the customer's process into the company's facility and equipment. By gaining familiarity with the molecule and the process, process development scientists are well prepared to support further refinement and development during the development trajectory, including support of validation through small-scale modeling and experimentation.
The product development process is divided into five stages.
Stage I: Feasibility The objective of this stage is to determine whether the proposed biotechnological process can be executed.
Marketing and sales (M&S) is typically the first department to be in contact with a potential sponsor concerning a proposed program. The M&S representative records information presented by the potential sponsor and presents it to the Diosynth Biotechnology Global Portfolio Review Board. This group reviews the information and determines whether the proposed program conforms to the company business model. If this group approves the program, the process development, operations and quality/regulatory departments review the information and comments on the technical feasibility of the work proposed. A resource estimate and timeline are provided. The process development staff also evaluates, with environmental, health and safety personnel, the effect of the potential program on human safety and the environment.
During development of the Statement of Work (SOW), Diosynth forms a project team. Representatives from the quality, process development, and operations technical management departments and a program manager comprise the project team. The purpose of the project team is to ensure that the program is executed according to the SOW. The project team assembles the appropriate resources to execute the program on an as-needed basis as the program proceeds through the development process.
Stage II: Research The objective of this stage is to generate a prototype manufacturing process at a laboratory scale. The starting point for research is a cell line that produces the molecule of interest.
The duration of effort in this stage depends on the extent and suitability of a sponsor's previous work. However, each process transferred to or developed at Diosynth Biotechnology is confirmed first at an ~10-L production (fermentation or cell culture) scale in the process development laboratory. During this confirmation, significant process parameters are identified and provisional operating ranges are established or confirmed.