Designing a new biological facility or planning the expansion of an existing one requires evaluation of several parameters related to product characteristics, equipment capability, and facility capacity. Decisions made at the design stages are critical to the validation plan and the ongoing operation if it is a commercial facility. Whether the facility will provide the needed future capacity is one of the critical questions requiring a credible answer. This article describes a methodology that uses currently available simulation software as a capacity planning and design tool. The PC-based simulation software described has been available for over 10 years and employees can be trained to use and develop these models. Internal and external engineering teams, operations managers, and validation and process excellence specialists have a stake in a new design, and provide inputs that are important at design stages. This is an example of a project involving all the disciplines in which alternative designs for a sterile filling suite included multiple filling equipment options, robotic cart versus fixed conveyor systems, and different lyophilization equipment (lyos). To illustrate the methodology, a model of a filling operation for a mix of liquid and lyophilized products follows. It includes formulation, filling, lyophilization, and capping in a new commercial sterile facility to meet requirements with uncertainties that are common in forecasting new products. It incorporates examples of using a model to answer "what-if" questions about design parameters and forecast scenarios.
While this is an example of one portion of the biological supply chain, this approach also applies to bulk production and packaging operations. In addition to design of a commercial operation, it also can be applied to scale up, tech transfer, and validation plan testing.
OBJECTIVES AND SCOPE OF PROJECT
The objectives of this project were to finalize the design and select equipment for a commercial facility, given forecast projections for a new product, known requirements of an existing product, and the addition of some derivative products. The facility was expected to be constructed in phases, so phasing of equipment installation and staffing ramp-up once in operation were required.
The scope of the process to be modeled included:
- Material flow through the following operations: formulation, filling lines; transport either by robotic cart or conveyor; loading the lyos; lyophilization process (freeze drying); unloading the lyos; and capping lines. For the cart option, loading and unloading are done shelf-by-shelf; therefore, accumulation tables are also needed to buffer the filling and capping lines. The conveyor option is a more continuous process and does not require the buffers for shelves.
- Cleaning and other changeover requirements between batches of material included a variety of processes including: manual cleans, clean-in-place (CIP) systems, steam-in-place (SIP) systems, vapor phase hydrogen peroxide (VHP) decontamination, glove integrity tests, and physical equipment changeovers between products and sizes. These applied to both the fixed equipment and portable vessels used in the process.
- Staffing with appropriately skilled personnel was required for cleaning and processing operations. The shift schedules for the various crews and skills in the parameters had to be evaluated.
- Activities and issues considered to be unconstrained and therefore out of scope included: availability of incoming materials and sampling; cold storage room, inspection, and packaging of completed materials; tray storage after lyophilization; and availability of portable vessels and rapid transfer port (RTP) canisters.