Process design is an important part of development, enabling a manufacturing process for your product that meets your exact specifications. Vetter can help create a flexible, scalable, reproducible, and efficient process.
Vetter has experience with many types of processes for drug manufacturing, including processes based on either single-use or multi-use equipment, using different pump systems (rotary piston, peristaltic, or membrane pumps) and sterile filtration types. Vetter subject matter experts will review your manufacturing process and create an agreeable design specification document. Vetter’s process design methodology is specifically developed to meet regulatory authority requirements. Based on FDA guidelines for good development practices as well as ICH Q8 Quality by Design principles, both the Critical Quality Attributes (CQAs) of the drug product and its intermediates and the associated Critical Process Parameters (CPPs) will be reviewed along with your current knowledge and accumulated data. At this stage, we will either move on to testing the implementation of the process with the use of technical batches, or we will suggest a number of studies to control the process after a quality risk assessment of the critical steps within the design space of the entire process.
These supportive studies could include:
- Mixing, pump, and filtration studies to optimize the scale-up process
- Formulation tests to determine material compatibility
- Feasibility studies for primary packaging alternatives, such as a conversion from vial to syringe and cartridge or from lyophilized vial to dual-chamber syringe
Lyophilization cycle development and optimization
We’ll work with you to develop lyophilization cycles for your drug product. This process starts during the early clinical phases, so we can optimize and fine-tune your lyophilization cycle for commercial manufacturing. Vetter’s lyophilization services include:
- Identification and verification of suitable process parameters (eg, freezing rate, shelf temperature, pressure) for freezing, primary drying, and secondary drying based on physicochemical characterizations; this allows the development of an economic freeze-drying cycle
- New lyophilization cycle development for vials, dual-chamber syringes, and cartridge syestems
- Adaptation of existing vial lyophilization cycles to dual-chamber lyophilization cycles
The aim of lyophilization cycle development is to arrive at a scalable process that is both technically and economically feasible for cGMP manufacturing. Above all, the process needs to be scalable and robust enough for the product to meet agreed-upon specifications, such as residual moisture, dissolution time, and cake appearance, with reasonable drying times. To enable the highest possible quality throughout development, we monitor the process using modern methods such as Process Analytical Technology (PAT) tools.
Process Qualification/Continued Process Verification
In Phase III leading up to commercial launch, the Vetter team will work with you on formal Process Qualification. Process Qualification determines if the process design is capable of reproducible commercial manufacturing. This includes design of the facility and qualification of the equipment and utilities, as well as the product-specific CQAs and CPPs designed and implemented in earlier phases. With Vetter’s QbD approach to process design undertaken in the earlier phases, there is far better understanding and control of parameter variability for the formal validation needed for market registration and submission. Data collected in the course of the design phase can now support formal submission.
We have both a Vetter process optimization group and a quality assurance trending group to monitor critical quality issues during manufacturing and to evaluate longer-term improvements to the process. We work with you to design a custom Continued Process Verification program with an agreed-upon set of parameters and specifications.