Increasing Transparency And Confidence Through Real-Time Data Sharing
By John Chapin, Senior Automation Engineer, and John Morse, QA Lead, Strategic Growth Investments and Engineering, Lonza Biologics
Three industrial revolutions catalyzed by steam, electricity, and the computer, respectively, have occurred over the course of history and drastically changed the landscape of how goods are manufactured. The next transformation taking shape is being dubbed as Industry 4.0, which is the digitization of manufacturing utilizing data, machine learning, and artificial intelligence. Interconnectivity, real-time data sharing, and automation are used to increase transparency across an organization’s people, production line, and in the supply chain, leading to increased efficiency in manufacturing. This movement is fueled by more informed, and eventually autonomous, decision making as automation spreads throughout the business functions. A digitally connected plant is required for this transformation to occur.
The BioPhorum Operations Group recently established a Digital Plant Maturity Model (DPMM), which provides a qualitative way for manufacturers to assess where they are on their digital journey as compared to other plants in the Biopharmaceutical industry. The highest level a facility can reach is Level 5, although facilities at that level do not yet exist. Lonza’s existing goal for all new mammalian facilities is a maturity Level 3 with some elements from Level 4. This requires the application of available technologies to make the facilities run more efficiently and more autonomously. By streamlining processing and reducing the amount of resources it requires to do simple tasks, the experts in the facilities can instead focus on more complex ones. These improvements increase not only the overall control of a facility but also access to product status at any time, optimizing output and minimizing batch failure.
The Critical Role Of Electronic Batch Records In A Digital Facility
Traditionally, biopharma facilities were built as “paper plants,” relying on paper batch records and highly manual steps. The move now is toward the elimination of paper and, instead, the use of electronic batch records (eBRs) to pull information from various systems and build a fully integrated manufacturing network with a high level of digital maturity. Decisions can then be driven through the use of real-time data with the increased use of Process Analytical Technologies (PAT), exception handling with notification systems, dashboards, reports, and statistical/multi-variant analysis. Automating the transcription of data between systems also minimizes risk and moves the industry toward error-free operation.
Breaking the eBRs down to modular, reusable objects and abstracting the custom configuration will greatly reduce the tech transfer time in support of multi-product suites. With this approach, the focus is on the key and critical process parameters. There is also reduced risk because the underlying code does not require as many updates from product to product. Conversely, when it comes to moving product out of the facility, eBRs employ review and release by exception by capturing any events that require review, so they can be brought to the forefront and evaluated in real time, leading to more efficient release of product within the timeframe required to do any analytical steps afterwards. The release of the product is then no longer dependent on the review process but, instead, tied to completion of release testing.
Lonza Pharma & Biotech has designed a state-of-the-art, highly integrated and digitalized facility in Portsmouth, New Hampshire, that, among other solutions, utilize EBRs as a way to focus on transparency through real-time data sharing and improved quality of delivery. The site includes mid- and large-scale assets and leverages a hybrid approach with single-use and stainless-steel technologies. Through automation, process analytical technology (PAT), and advanced multivariate analysis, Lonza can ensure not only consistent performance but also its ability to meet the needs of a growing market by building an environment more suitable for developing products for niche indications.
Designing For The Future
The core of Lonza’s new Portsmouth facility is based off of a previous integration experience between the process control system (PCS) and the manufacturing execution system (MES), which minimizes back and forth between systems. Often implementations like these rely heavily on operators to handle the handshaking between these systems; however, by removing that burden, Lonza allows its personnel to focus on the activities where their skills and knowledge are most valuable. As a result, analysis of historical data shows the integration has greatly reduced the number of deviations per batch, creating a foundation for improving operations and reducing errors in manufacturing. From this, the facility designers were able to build and integrate the next level of systems and analytical devices, such as a laboratory information management system (LIMS) and their enterprise resource planning (ERP) system. Rather than reading the value from another system and writing it into the record, the data is automatically captured and stored in the eBR, reducing transcription errors and the need for two stage verification.
In addition to eliminating operators as the integration between systems, Lonza has added instrumentation that will allow autonomous operation of previously manual steps, such as sampling and priming. For example, Raman will be used to directly monitor and maintain glucose levels with a closed loop control scheme, eliminating the need for sampling and performing complex calculations to adjust feed rates. Another example of how automation is replacing manual operation in the new facility is the use of refractive index (RI) for protein concentration during ultrafiltration (UF). Rather than sampling and using traditional assays to determine product concentration, inline RI can be used to monitor concentration directly. Beyond the improvements to the PCS, Lonza has even deployed autonomous mobile robots to transport material from the warehouse to the suite, which allows resources previously used for these tasks to focus on more critical tasks.
Customers will maintain visibility of their processes through near real-time data access and information supplied from the eBR system post-processing. It is important to note that, while data transparency and availability can provide efficiencies in process analysis and reporting, it is critical that CDMOs responsible for multiple clients and products maintain a very high level of data protection. This is one of the biggest and most critical challenges in providing data transparency, i.e. allowing customers next to real time access to their data and only their data. The security of Lonza’s customer data is paramount.
Overall, a digital transformation of biomanufacturing offers a new path for continuous monitoring and optimization of process performance, which would ultimately lead to greater efficiency in drug production. This new era of manufacturing requires facilities to be equipped with automated tools and solutions that allow an uninterrupted flow of data in real time. With more visibility into their operations, biomanufacturers can increase flexibility, speed, and agility; without it, though, they limit their ability to advance innovation and create potential roadblocks in their race to market.