Agenda

Mobilizing a Digital Engineering Program: Practitioner Viewpoint Over the past 2 years, Gilead has invested in multiple areas of Digital Engineering innovations: From large investments in Cloud based applications, to a state of the art Data Mesh, to 20+ advanced controls use cases that were deployed in production to accelerate scientific ambitions. This presentation reflects back at results, learnings and lessons learned, and offers a practitioner playbook on how to start a digital innovation journey at scale. Leveraging use cases that applied AI/ML/large Language Models to engineering problems, this presentation also delves into emerging issues that need to be addressed in any organization’s innovation incubation journey.

Polyfluoroalkyl substances (PFAS) are called 'forever chemicals' due to their longevity in the environment. A number of health-related outcomes have resulted in varying levels of environmental legislation for this class of materials. For example, the European Chemicals Agency (ECHA) has proposed a sweeping ban on PFAS within the European Economic Area (EEA). The implications for bio/pharmaceutical manufacturing of the ban in the EU encompass virtually the entire ecosystem of materials related to bio/pharmaceutical manufacturing. The Global Material Qualification organization within Takeda is taking an agile, systematic approach to assessing the risk environment created by the proposed ban and developing different response scenarios for Takeda to ensure our ability to provide life-transforming products to patients. This presentation will provide examples from the different facets of the Global Material Qualification approach to address the emerging challenges of the proposed PFAS ban in the EEA and beyond.

The radiopharmaceutical field is rapidly transforming the treatment of life-threatening; however, this rapidly growing medical sector presents unique challenges and safety requirements in management and manufacturing, compared to other treatments. Radiopharmaceutical production necessitates highly specialized equipment and controlled environments equipped to safely store, prepare, fill, and package radioactive materials. Designing facilities to accommodate these critical processes demands a meticulous approach to safety, efficiency, and regulatory compliance. In addition, it is crucial for the design team to be embedded early in the process, with the client, as requirements vary from client to client and product to product. This dynamic session will explore essential considerations for creating a strategic framework that ensures the successful implementation of a radiopharmaceutical program. The owner and design team will share lessons learned and successes from designing RayzeBio's 63,000-square-foot manufacturing building in Indianapolis, IN. Attendees will leave the presentation armed with strategies and best practices for future building projects on their own campuses.

Climate change is the defining crisis of our time. The science is clear: we must commit to net zero GHG emissions across the value chain. The 2015 Paris Agreement aims to limit global warming to 'well below' 2°C, with efforts to cap the increase at 1.5°C. Failure to reduce GHG emissions could result in temperatures rising above 3°C by 2100, causing irreversible ecosystem damage. Average world temperatures have already risen by more than 1°C, leading to rising sea levels, heat waves, natural disasters, and ecosystem changes. Nearly 60% of the world's largest companies have announced decarbonization goals, but only 4% have complete, transparent plans. While AI and digital innovation dominate future workforce discussions, a climate revolution is also underway, requiring all employees to support corporate climate goals. This presentation focuses on technical solutions to reduce GHG emissions in biopharmaceutical manufacturing. Industry leaders will share decarbonization targets and plans, showcasing novel design solutions that address energy-intensive process steps or supporting components. Experts will discuss the rationale behind these targets, corporate climate commitments, and evolving employee expectations. By highlighting actionable insights, we aim to advance sustainability in biopharmaceutical manufacturing.

This presentation will explore the application of ASTM E2500 (Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment) in the context of a continuous manufacturing facility for monoclonal antibodies. We will discuss the challenges and opportunities in adapting this standard to the unique requirements of continuous bioprocessing and how Just-Evotec Biologics has implemented this in constructing two mAb facilities. This presentation will provide valuable insights for biopharmaceutical professionals involved in facility design, quality assurance, and regulatory compliance. Attendees will gain a deeper understanding of how to leverage ASTM E2500 to enhance the efficiency and quality of continuous mAb manufacturing processes.

A review of the plastic waste generation in the biopharmaceutical industry:
- Focusing on using single-use technologies in bioprocessing.
- Discuss concerns on sustainability based on plastic waste streams.
- Review the scale of plastic waste produced
- Review a bioprocess modeling package that can estimate the plastic usage for typical monoclonal antibody production at varying scales
- Discuss fluid handling components, filters, and resins.
- Show worldwide monoclonal antibody estimated total annual tons per year for bioprocess-related plastic waste generated by the industry. 
- Inform sustainable practices within the biopharmaceutical industry and encourage the development of more sustainable disposable technologies.

Since adopting single-use technologies in biopharmaceutical manufacturing in the 1990s, there has been concern about the generated plastic waste streams.  Estimates for plastic waste based on production quantities provide the biopharmaceutical industry with methods to predict waste produced and establish more sustainable disposal methods as single-use technology products expand into the mainstream production of biologics.

See the future of pharmaceutical facilities for yourself in this virtual tour of Kindeva's Bridgeton, Missouri facility. Freshly completed in 2024, Kindeva's new world-class sterile fill-finish location includes more than 155,000 sq. ft. of dedicated aseptic operations space, two labs, two formulation suites, and approximately 11,000 square feet of fill suites. Conference attendees will get to explore the building while learning about the strategic decisions an integrated team had to make to have the facility designed, built, and running in just one year. The session will delve into the innovative use of phased packaging and modular construction techniques, which allowed for simultaneous design, offsite fabrication, and onsite assembly, significantly reducing the overall project timeline. This virtual tour and case study will offer valuable insights into the collaborative efforts and strategic planning that drove the success of the Kindeva project, setting a new benchmark for rapid, efficient, and innovative pharmaceutical facility construction.

Since the definition of the ballroom concept was first introduced in 2013 via ISPE's Baseline Guide: Volume 6 - Biopharmaceutical Manufacturing Facilities, the industry has looked for opportunities to further build in flexibility for bioprocessing and biomanufacturing into facility design, yet maintain a standard approach to facility layout options to allow faster delivery time without re-engineering of design approaches. This presentation will cover common industry challenges, considerations, and best practices in achieving a standard facility design approach, and how this can be applied to single-product, multi-product, or multi-modal manufacturing facilities, including a case study reference to the recent ISPE Facility of the Year Award winner Roche Genentech (South San Francisco Clinical Supply Centre) and their use of recent BioPhorum publications and initiatives to achieve this, as well as other industry standards and consortia works. The presentation will also include survey results (provided via BioPhorum) on the market need for, and perceived or anticipated operational and regulatory challenges surrounding, the implementation of a multi-modal manufacturing facility (e.g. closed systems usages, material transfer types, plant maturity, etc.) from a range of anonymized biomanufacturers.

Following an overview of strategies for attaining an energy-efficient pharmaceutical cleanroom and the relevant ISO standards (ISO 14644-16 "Energy efficiency in cleanrooms and separative devices" and ISO 14644-4:2022 "Design, construction and start-up"), the discussion presents measures to optimize energy consumption, presenting recent solutions which have been applied. These measures consider the advancements in equipment design (selection of components), airflow control devices (VAV valves), and BMS (Building Managing System).  Subsequently, the report details strategies that can be applied reporting some examples and relevant calculations that include the energy recovered from the waste of process, the savings due to the heat recovery of the exhaust, and the generation of the thermal fluid medias by using heat pumps.

Setting a New Standard for Designing Agile Manufacturing Facilities

The pharmaceutical sector is in a state of constant development, currently focusing on creating and building facilities that can support a flexible array of products (in terms of variety, quantities, and sizes). Additionally, there is a growing interest among some stakeholders to manage the entire process from clinical to commercial stages, including full lifecycle products, within a single location, as well as the co-location of different product modalities. These trends indicate a requirement for facilities that are more adaptable, enabling manufacturing operations to be quickly relocated, retrofitted, or expanded with efficiency. This adaptability not only enhances operational efficiency but also allows companies to respond swiftly to market demands and regulatory changes, ultimately fostering innovation and reducing time-to-market for new therapies.

Bristol Myers Squibb aimed to establish a global standard for a new flexible manufacturing concept that would facilitate multi-modality manufacturing across different products, volumes, and scales, while also enhancing future capacity decisions and regulatory adaptability. BMS collaborated with PM Group to create a standardized design that would separate the Building Shell from the interior layout, allowing for rapid deployment at both existing and new locations globally. In line with the design approach, the team aimed to standardize technology platforms and shift away from "purpose-built" designs to develop generic Process Modality floorplates (modules). The team leveraged a significant portion of BMS’s current product pipeline as a benchmark to appropriately size process capabilities and technologies that would be included in Flex Modules. These modules were then designed to meet Launch capabilities and be versatile enough to expand and accommodate Commercial capacities in the future.

This nimble strategy will allow BMS to build globally adaptable shell structures within their network, irrespective of product choices. This will enable swifter market entry while also allowing ease of future repurposing. This presentation summarizes the design methodology employed to bring this innovative Agile Manufacturing Concept to fruition.

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The new manufacturing paradigms in life sciences pose considerable challenges to the engineers who have to deal with automation and digitalization. For example, the operational flexibility required in biotech, the modules that make up the production processes in flow chemistry and the inefficiencies caused by the numerous manual operations in cell therapies. But what do these production sectors have in common? They consist of modules specialized in specific functionalities linked together to produce a specific product. Modules produced by different suppliers, often incompatible from a digitization point of view. For some years now, the concept of 'modular production' has been gaining ground, whereby production processes are subdivided into intelligent modules capable of communicating with each other in a standardized manner. These are combined with a software application capable of automatically recognizing the various modules and 'orchestrating' their operation according to a user-defined sequence. We call it “plug & produce”. To support this production concept, a standard called MTP - Module Type Package (VDI/VDE/NAMUR 2658) - has been developed and has proven its worth in recent years. The authors of this contribution are members of the Plug & Produce working group of the ISPE Pharma 4.0 CoP.  The presentation will introduce the advantages of this new approach based on the MTP standard by giving concrete examples of the application of modular automation in the life sciences field, contained within a concept paper that is currently being developed.

Annex 1 requires minimizing human intervention in critical areas such as fill and finish operations. Robot Telemanipulation allows a person to control robot arms from outside the sterile or hazardous environment to do things that are too hard or expensive to automate. On a daily basis, Robot Telemanipulation enables Robotic Surgery and bomb disposal. Robot Telemanipulation enables a world where operators can perform delicate tasks without stepping foot into sterile or hazardous environments. With stereo 3D vision and telemanipulation software, operators gain a lifelike view of the environment and wield precise control over robotic arms, mirroring the precision of surgeons in robotic surgery. But the benefits don't end there. Beyond minimizing human interaction, telemanipulation systems offer additional perks, including data recording and 3D video documentation of interventions. This not only enhances process transparency but also enables comprehensive analysis and optimization. Today, Pfizer is using Robot Telemanipulation to test use cases and pave the way for operational integration. Join us as Pfizer and SRI share insights into the best use cases for this transformative technology.

In the face of energy shortages, rising prices, shorter time-to-market, and increasing competitive pressure, speed, flexibility, and maximum efficiency are more important than ever in the process industry. These goals can only be achieved through fully digital data management and seamless integration of digital tools over the complete lifecycle of a production plant. This presentation provides insights into how CSL Behring's new €400 million plasma fractionation plant in Marburg, Germany, was engineered and is operated using an integrated digital approach that employs highly accurate Digital Twins at each stage. The benefits are manifold: In the early phases, process alternatives were quantitatively compared, capacities estimated, or equipment sizes determined; in later phases, detailed workflows were developed, subsystems for cleaning, utilities, buffers, or resources were designed, process robustness under uncertainties ensured, optimal operating modes identified, automation and production planning developed, and commissioning supported. After commissioning, the Digital Twin was re-used in the new solution INOSIM Foresight for operations support. With accurate dynamic predictions, the solution supports the operating staff in all aspects of operation - whether through real-time planning of production, personnel, and resources, predicting and "combating" disruptions, optimal maintenance planning, efficient onboarding of new employees, and many other use cases.

Driven by the new Annex 1 requirements the use of automation during the critical process of fill & finish is a current focus for the industry, especially the usage of robotics as a tool for automation which is referenced in the "Principles" Section of Annex 1. The target is to protect the product from potential extraneous sources of contamination such as personnel. The presentation will take a deep dive into the current usage of robotics within the pharmaceutical manufacturing environment and it will highlight things that need to be considered during the implementation of these technologies (e.g., first air requirements). After discussing the current usage of robotic technologies the presentation will focus on fully gloveless robotic technologies with the focus of removing the human from the most critical processes (e.g., setup of the filling path, environmental monitoring, etc.). The presentation will link technology with reference to regulatory guidance documents and it will give an outlook on how robotics can improve an overall contamination control strategy.

To accelerate greenfield projects, the necessary production processes must be developed quickly without compromising safety and risk management; however, due to their inherent complexity, the risks in the processes are often manifold and can only be identified with a considerable amount of time and resources - this delays the market launch of important drugs and is often associated with major corrections, as some process weaknesses remain unidentified, jeopardizing the entire commercialization process. The main reason for the high effort and error-prone nature of process design and risk assessment is that they have to be created largely manually. The presentation will introduce a novel process simulation approach that utilizes a generic database around so-called "process-frames" (process-microsteps) to develop data-driven recommendations for process design and autogenerated risk management insights with unprecedented accuracy. By linking the "process frames" with numerous production data, a self-learning software has been created that also identifies potential risks for new process ideas and helps to achieve robust process design and CCS more efficiently. The presentation presents a case study from Kindeva and shows how "Frame-by-Frame Risk Profiling" has significantly accelerated process design and risk management - both prerequisites for faster plant and operational readiness.

When a Takeda Minneapolis mAbs facility was faced with a common biopharma challenge of production growth exceeding capabilities in an aging, maxed-out laboratory space, the team turned this challenge into an opportunity - a data-driven, digitalization-focused opportunity for an optimized, innovation-forward QC Laboratory of the Future. The team analyzed QC Lab conditions, constraints, and opportunities on how to efficiently support future production. People-Centered Innovation, Patient Focused Results drove the purpose of this project in future-proofing a lab space and truly elevating the site's landscape. This presentation explores how the team developed quantitative data for an optimal path forward. This case study will discuss how the team developed a compelling business case, leveraging a set of comprehensive studies using a tool kit of industrial engineering, digitalization, and strategic facility planning to inform key facility questions for early data-driven decision-making. These questions include whether reconfiguring, expanding, building new, or leasing new space is the best option, and which Pharma 4.0 technologies would best enable growth, empower people, and align with Takeda's digital manufacturing strategy. Hear the many ways this team examined the data, from process mapping, baseline capacity modeling, a lab-of-the-future analysis, equipment lifecycle considerations, and more.

Reaching New Summits in Pharmaceutical Manufacturing with Pharma 4.0 and Digital Transformation

The pharmaceutical industry is facing a multitude of external challenges, including cost pressures from healthcare systems, such as the Inflation Reduction Act (IRA), patent cliffs, and changes in the global political landscape, exemplified by the BioSecure Act. Amidst these challenges, Pharma 4.0 is emerging as one of the paths to sustainably bringing innovation to patients. The ISPE's frameworks have supported and encouraged steps towards digitalization and outlined benefits and use cases. However, the pharma industry has been slow to change compared to other sectors. Already in 2021, the FDA was stating that "some industries are now well into Industry 3.0, but in many ways the pharmaceutical industry is still very much transitioning into it." With two-thirds of drug shortages historically still attributed to quality-related issues, the opportunities to continue the digitalization journey are plentiful.

Exploring the root causes, many companies are lost on the journey, either organizationally or technologically, with some unsure of where to start, others pursuing multiple pilot projects, and some finding that the technology journey is just the beginning of the transformation journey. Additionally, the industry faces a tension between decentralized, democratic, and duplicative organizing principles versus centralized, cumbersome kingdoms. 

Takeda has been on this journey for many years and has taken the challenges head-on. From the Facility of the Year (FOYA) awards for Singen and Linz awards in 2022 and 2024 to public commitments to sustainability Pharma 4.0, Takeda's approach has enabled the implementation of numerous technologies and new ways of working. As the industry faces an increasingly diverse portfolio and an ever-complex manufacturing landscape, Pharma 4.0 will be a key driver of growth to meet patients’ demands. We would like to explore some of the good practices we learned on our digital transformation journey.