Pharma manufacturing is continually evolving in step with advances in technology, as companies seek to reduce costs, fully optimize resources, and streamline operations. This extends to the design and engineering of facilities. This article explores several emerging technology trends relating to facility design and engineering that significantly benefit pharma companies.
The construction and commissioning of new pharma facilities are time and cost intensive. PhRMA estimates that building a new facility can cost up to $2 billion and take anywhere from 5 to 10 years to complete. With this in mind, it’s critical every step in the commissioning and construction process is executed smoothly, efficiently, and cost-effectively so that operations are onstream and generate a return on investment as quickly as possible.
Often a significant part of that cost in terms of time and capital comes directly from facility, line, and equipment commissioning. Late-stage changes or delays to the facility or equipment design, requirements, and configurations must be minimized or ideally, eliminated completely to reduce the overall cost of facility commissioning. To solve this, pharma manufacturers can look to virtual commissioning, an approach that combines traditional and virtual development and testing using emulation. Unlike physical commissioning, virtual commissioning can commence long before any hardware is purchased or constructed. This approach enables savings of up to 40% in commission time compared to conventional commissioning, reducing risk and uncertainty, offering increased safety and agility, and reducing costs for design changes.
Simulation, emulation and digital twins
A digital twin is a virtual representation of a real-world physical entity, system, or process that is synchronized with the physical entity. The digital twin and the observable manufacturing element (OME) are typically synchronized through propagating the sensor data from the physical entity to the digital twin. Digital twins can be built of either simulations or emulations but are required to have synchronization with the OME. The frequency and fidelity of the synchronized emulations/simulations must be appropriate for the task they are designed to accomplish.
Digital twins can be built from several different commercial or open-source software packages but always include the physical element, a synchronization mechanism, and a software package used that runs the model/virtual representation (usually derived from CAE/multiphysics software). Creating a digital twin requires that elements of interest for the OME be accurately replicated in the virtual representation. For production equipment, this typically involves the definition of process or mechatronics systems, including motors, actuators, instrumentation, connected to an automation system running application specific software.
The value of implementing digital twins with production equipment is the potential to estimate the state of the physical system beyond what is immediately observable. Typical applications of this include soft-sensing, adaptive fault correction, model-predictive control, and predictive maintenance. Production equipment can fit into a larger digital twin of an entire manufacturing process to support demand driven on-time manufacturing.
In virtual commissioning applications, a digital twin may not be possible since the physical equipment may not exist. Instead, a model of the production equipment is deployed alongside the control system, so that the two can be co-developed. The control system considers the production equipment model an emulation, since the control system can interact naturally with the model through command outputs and status feedback (known as Hardware-In-the-Loop). For this technique to be successful, the production equipment model needs to accurately represent the concrete behavior of the physical system.
Emulation-based virtual commissioning leads to a valuable reduction in project risk from the perspectives of error avoidance and achieving project timelines. As scenarios and design choices can be thoroughly tested without physical equipment, engineers can test and verify various system elements including application-specific software modules, recipe configuration, failure modes and recovery, and user interface efficacy without depending on scheduled test equipment or being on-site. As a result, projects which employ virtual commissioning are often deployed with less in-person commissioning time and are generally safer for people and property.
Once the equipment is commissioned and validated, the emulation from virtual commissioning can continue its use as the digital twin synchronized to the physical equipment. Since the model is already constructed, it is immediately useful as an idealized representation of the physical system. Engineers can use this digital twin to optimize facility design, system design, production line operations, and plant and machinery requirements, among other elements.
From an IT/OT convergence angle, virtual commissioning enables the use of agile IT concepts to develop processes such as infrastructure-as-code in the OT space, the goal being to move towards the automation of code development and infrastructure configuration.
The adoption of these IT concepts will fundamentally change the workflows of OT engineers. Instead of building systems and code from scratch, as was the case with legacy distributed control systems (DCS), the process will look a lot more like an agile software development role, with engineers focusing more on maintaining the automated software systems than developing the application code and infrastructure. For end users, this could mean that the arduous tasks of installing, configuring, and patching infrastructure for control systems would become an automated workflow. For machine builders, this could result in an order processing system that sends a configuration to dynamically build automation infrastructure and application code to order based on the options selected by the customer without an engineer involved.
OEM equipment orchestration
OEM equipment forms the foundation of modern modular pharmaceutical manufacturing plants by providing the flexibility to choose and combine the best equipment solutions for specific processes. Commissioning and validating OEM equipment is generally a faster process as manufacturers receive pre-assembled, purpose-programmed units. Furthermore, OEMs typically supply equipment in a validation-ready state, making it easy to qualify the equipment for use in CGMP facilities. There is no need to rely on internal resources or third parties for equipment construction and application code development. However, challenges can arise from different connectivity standards and interfaces among various equipment vendors, making it difficult to integrate multiple pieces of equipment into a unified control system. This is where OEM equipment orchestration comes into play.
The need for an orchestration strategy
Without a strategic approach and clear specifications, the use of OEM equipment results in fragmented islands of automation. This lack of a strategy is usually due to late collaboration with equipment vendors on the part of the end user. When automation is not considered in the initial equipment procurement process, engineers often struggle to integrate equipment or rely on engineering firms to handle the integration. This late-stage process of piecing equipment together as an afterthought can lead to limited interface capability within the plant at best. At worst, the whole process can backfire by being time-consuming and costly for no increase in digital maturity.
To solve these issues, pharma manufacturers can adopt a holistic plan for OEM equipment orchestration to automate and coordinate various components to work seamlessly together early in the facility specification and design phases. Having comprehensive standards established before any equipment is purchased allows an end user to work collaboratively with their equipment vendors, giving the OEM the opportunity to differentiate themselves on how their equipment can fit into a unified automation platform. For the end user, this simplifies cross-training and standardizes interfaces, alert systems, diagnostics, and recipe management. This reduces costs, streamlines operations, and results in faster construction, commissioning, and facility qualification.
Leveraging standardized interfaces
End users are demanding OEM equipment that comes with plug-and-produce capability to integrate with any distributed control system (DCS) or Supervisory Control and Data Acquisition (SCADA) system. This plug-and-produce capability standardizes core automation services such as equipment interfaces and recipe management, user interface screens, audit trails, and alarm management across disparate equipment. A plug-and-produce standard systematically connects all these elements and coordinates them using standardized interfaces, like the NAMUR module type package (MTP) and modern protocols, like OPC Unified Architecture (OPCUA). Integrating all these disparate platforms together brings consistency, saves time and effort on integration, and makes plug-and-produce a feasible technology for facilities of the future.
These technologies should be viewed as an augmentation to a cohesive strategy for OEM orchestration rather than replacing all the work done with collaboration between organizations and comprehensive specifications. No magic button exists to integrate equipment together seamlessly to deliver common sets of services and the end user’s constructive relationships with their equipment and technology vendors play a big part in an effective OEM orchestration strategy. Think about this situation, a plant built entirely with black box equipment with a standardized interface might be fast to integrate but would be difficult and costly for an end user to support long term due to managing numerous support contracts, disparate spare parts, and a lack of consistency in or even access to application software on the OEM equipment.
A multitude of benefits
Put simply, the orchestration of OEM equipment facilitates the work of creating a unified automation platform for a facility. This ultimately leads to a faster time to market and lower total cost of ownership for the end user. Effective orchestration enables the integration of different OEM components in a way that allows for easy customization and scalability, new equipment addition into existing systems, and seamless integration of future upgrades and expansions. Downtime and Mean Time To Repair (MTTR) are reduced through simplified troubleshooting and maintenance.
Advanced therapy medicinal products
Another emerging trend relating to facility engineering is the change of industrial automation to fit into the advanced therapy medicinal products (ATMP) space. Many of these therapies are autologous, meaning they're sourced from a person and then fed back to the same person. The production volumes for these autologous therapies are very small, often in milliliters. Existing automation systems are designed to produce at larger scales, so the concept here is to miniaturize the automation technologies to run on bench-top units or instruments. These bench-top units can then be orchestrated into a coordinated process train to make the therapy, with the process scaling out to accommodate more process trains for more individual patients.
The key to success for this strategy is going to be in the automation vendor’s willingness to scale down their technology to offer the same commercial off-the-shelf software and hardware capabilities for bench-top equipment. This will be vital to limit the amount of rework necessary for the tech transfer from the process development (PD) space to cGMP manufacturing for these advanced therapies. Collaboration with an automation vendor who has the ability to scale down and operate flexibly across these disparate trains of industrial and laboratory equipment to ensure accuracy and patient safety is crucial.
From inception to completion
Pharma companies are actively adopting technologies to enhance productivity, efficiency, and return on investment and maintain a competitive edge. Initiatives like virtual commissioning and OEM equipment orchestration are being embraced to expedite the introduction of new capacity and capabilities, as well as optimize facility operations to eventually reach an adaptive facility.
Utilizing virtual commissioning, facilities can be designed, modeled, engineered and tested before physical work begins. This approach enables the optimization of various aspects such as layout, productivity, throughput, flow and energy efficiency. The orchestration of OEM equipment automates processes and standardizes interfaces, which facilitates the work of creating a unified automation platform for a facility that will ultimately lead to a faster time to market and lower total cost of ownership for the end user.
Pharma companies that leverage the power of new technologies will be better equipped to optimize facility processes from inception to completion.