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
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.