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Process Intensification Program

By 2029, the PI program proposes to invent, design, demonstrate, and support commercialization of integrated biopharmaceutical manufacturing technology to transform drug substance (DS) and drug product (DP) manufacturing capability, enabling the following:

  • Improved control, robustness, and security of supply
  • Dramatically reduced capital and operating cost so it is much less of a barrier to the availability of capacity, innovation, or change, and supports global access to biologics medicines
  • Flexibility of facilities and equipment to supply an extremely diverse and changing portfolio of products in the face of uncertainty and changing volume demand
  • Faster product development and supply chain velocity
  • Sustainable raw materials, components, and energy use
A person in protective clothing monitors a piece of equipment in a biopharmaceutical setting

What Is Process Intensification and How Will It Benefit the Industry?

Process intensification (PI) efforts can impactfully transform Chemistry, Manufacturing, and Controls (CMC) development through end-to-end integration and technology advancement. The PI program brings together thought leaders from within the NIIMBL community to collaborate on an integrated approach to  

  • Create flexibility 
  • Improve control and security of the supply chain 
  • Foster sustainability 
  • Reduce costs 

Process Intensification Program Structure

Workstreams

The PI program is organized into workstreams focused on end-to-end control strategy, equipment flexibility, next generation technology, sustainability, and a physical test bed to evaluate and demonstrate the technologies that are developed. The elements of the program are synergistic.

Integration

Identify the technologies and methodologies necessary for the industry to reach the intermediate improvement objectives (3–5 years, second-generation) and breakthrough approaches (third-generation)

Approach
  • Design concepts for second- and third-generation factories and how innovations would have to work together to achieve the vision.
  • Conduct process, operations, and economic modeling of potential new technologies to set the appropriate ambition and show how the vision can be achieved. 
  • Scout and prioritize technology based on results of modeling and conceptual design.
Projects

Next Gen High Level Design of Facility Layout

Next-generation Factory Business & Data Mapping

Control Strategy

Explore and address the opportunities and challenges presented by integrated and continuous biomanufacturing processes, with the goal of proposing new control strategies optimized for biological processes of the future.

Approach
  • Robustness: Control strategies for next-generation continuous processes should possess improved risk profiles relative to current control strategies. While the increased interdependencies between unit operations in a continuous process may bring more complexity, they also offer new opportunities for holistic approaches to control, which in turn could lead to increased reliability.
  • Automation and digitalization: A fully connected biologics manufacturing process, in theory, should require reduced manual intervention, but requires increased adoption and greater sophistication of automation and digitalization. This workstream aims to prioritize and then investigate automation strategies that will have the greatest impact on end-to-end control strategies (Feidl et al., 2020).  
  • Integration into process development: Updated control strategies must be accompanied by updated process development methods to ensure that current process development timelines and resource requirements are equivalent or even better for integrated and continuous processes. Because such processes may require longer times between cleaning than their batch counterparts, this will require new and innovative development approaches to bioburden control. 
  • Real-time: Integrated continuous systems present more entry points for real-time or near-real-time process and product monitoring throughout the process flow (cell culture, purification, and formulation). As appropriately capable sensors are developed and tested, and accompanying control loops are designed, process control based on real-time monitoring can be implemented (Patel et al., 2018). Ultimately, this study will culminate in strategies for reduced post-hoc testing for specific attributes and potentially real-time release of drug substance and drug product.
Projects

PI – Rapid Micro: novel methods and control strategy

Sustainability

Explore how to achieve sustainable, carbon-neutral manufacturing by incorporating sustainability as a design criterion across all areas of bioprocess manufacturing, including raw material sourcing, manufacturing technology R&D, process and facility design, manufacturing operations and waste recycling; also support the development of circular economies for raw materials and consumables using an end-to-end perspective.

Approach
  • Develop decision tools and models that allow process developers to include sustainability — particularly with a goal of low or zero carbon footprint, reduced water and energy use, and reduction and recycling of raw materials
  • Establish practices based on sustainability principles for the selection of raw materials and technologies, design of process and facility, and implementation of manufacturing operations, ensuring sustainability is considered alongside cost, yield, robustness, and quality.
  • Implement a toolbox of options for recycling waste materials, including complex plastics, that supports a circular economy approach and carbon neutral bioprocessing.
Projects

PI – Sustainability Modeling

Flexibility

Explore strategies for increasing facility and equipment flexibility to address key industry problems, including improvement of demand forecasting and consolidation of products operating at different scales into the same facilities to increase utilization and thus decrease capital and operating cost.

Approach
  • Establish a unified Strategy Playbook that provides a clear understanding of enablers of flexibility and how to apply them most effectively. The playbook will include clear and concise definitions of the goals of the workstream and project roadmaps to achieve them. 
  • Build a Flexibility toolbox to act as a “living document” of available tools to achieve flexibility goals. This toolbox will include a list of prior/ongoing relevant industry initiatives that can avoid redundancies (e.g., BPOG plug-and-play, ISPE Pharma 4.0), libraries of tools (e.g., standards, equipment, components), and software programs, among others.
  • Demonstrate the flexibility solution through a series of interconnected proof-of-concept projects designed to achieve the final vision. These demonstrations are envisioned to be performed in both member institutions and the NIIMBL test bed.
Projects

PI – DNP Development & Adoption

Test Bed

Build a Test Bed at NIIMBL Headquarters in Newark, DE that will run a standard state-of-the-art platform process to produce a non-proprietary monoclonal antibody (cNISTmAb-NIIMBL).

Approach
  • Use the test bed to test new technologies in the context of the entire process and allow comparisons between technologies because they are all evaluated using the same materials.
  • Make process intermediates and drug substance available to technology developers, which will help different labs compare their results for different technologies. This will also save time in the test bed because novel technologies can be developed in labs around the country with representative process inputs and compared with expected outputs.

Progress and updates

High-level program timeline

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February 2023:

Program Participants

NIIMBL Program Leader

John Erickson, Senior Fellow

John Erickson

NIIMBL Senior Fellow

NIIMBL Scientific Program Manager

Melissa Scott, Scientific Program Manager

Melissa Scott

Scientific Project Manager

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