Biomanufacturers' MES Manifesto Specifies Requirements

Summary

The BioPhorum “MES of the future manifesto” is a call to action from the biomanufacturing industry to manufacturing execution system (MES) vendors to understand the needs and challenges faced by biomanufacturers in the deployment, configuration and support of MES solutions in this highly regulated industry. This manifesto was created under the auspices of BioPhorum by a collaboration of manufacturing information technology (IT) experts from major biomanufacturers and technology experts from major MES vendors supporting the BioPhorum’s mission to collaborate and accelerate the biopharmaceutical industry’s rate of innovation and progress.
 
This document reinforces the fact that users understand MES requirements and have become keenly familiar with innovative technologies based on experience of those who use consumer and enterprise IT solutions. It reflects a common user-driven industry imperative for manufacturing systems to be integrated into the business enterprise to create superior efficiency.
 
The manifesto addresses the shortcomings of current MES offerings and requirements for serving future biomanufacturing technological advances. An important theme being discussed throughout all manufacturing is to capitalize on the best practices in the technology industry.

• Increasing standards providing plug-and-play integration with other systems
• Fostering a global MES knowledge GitHub-type community
• Satisfying the growing need for biomanufacturers to adopt digitally mature IT and security standards
• Addressing years of “tech debt” buildup by leveraging new technology
• Increasing product quality via automated cloud-based testing suites
• Leveraging containerized, microservices architecture to enable greater variety and tiers of licensing and pricing options.

The collaboration has been sponsored by manufacturing IT leaders representing more than 90% of the global biopharmaceutical manufacturing capability. The collaboration group was created in Q2 2021 and comprises 61 representatives from major biomanufacturers. From Q3 2021, representatives have joined the collaboration from major MES vendors, and it is intended that the publication of the manifesto will engage further MES vendors as well as provide a focus for ongoing dialogue.
 

Digitalization is essential

The biomanufacturing industry must digitalize and automate manufacturing processes and make full use of new manufacturing and digital technologies to meet new challenges meeting demand, reducing costs, and increasing manufacturing quality across current drug portfolios. In addition, new classes of biological medicines are being developed that require a radical shift in manufacturing processes.
 
Current reality: Key to this digitalization of biomanufacturing plants is the role of MES. However, current MES solutions can be expensive, slow to implement, and lack the flexibility, agility, and openness to be updated and supported efficiently. In addition, existing approaches are unsuitable for certain biomanufacturing scenarios, e.g., small-scale manufacturing plants and new biomanufacturing methods including small batch flexible production. The manifesto articulates:

• The gap between the current generation of MES solutions and the needs of the biomanufacturing industry
• A realistic and achievable vision for the MES of the future that will meet the needs of the biomanufacturing plants of the future.

The manifesto is intended to stimulate collaboration between biomanufacturers and MES solutions vendors that will outline roadmaps for future development.
 
Biomanufacturing process changes: Today, around 90% of all biological medicines are based on monoclonal antibodies and are traditionally manufactured in stainless steel bioreactors of up to 3,000-liter capacity. This is changing rapidly with the development of new drug classes and advances in manufacturing technologies.

The industry faces a substantial challenge in developing capabilities to manufacture the new modalities, therapies, and product forms. Looking to the near future, a range of these new manufacturing modalities will exist in the industry and MES solutions must evolve to be implemented across this diverse array of manufacturing scenarios. The modalities required to manufacture the widening classes of biological medicines will be combinations of the following:
 
Process types:

• Batch
• Fed-batch (partially open system)
• Semi-continuous
• Fully continuous.

Scale range:

• Single patient
• Development
• Commercial
• Industrial
• Clinical.

Containment types:

• Closed single use
• Open stainless steel
• Hybrid.

Precision medicine, for example cell and gene therapy (CGT), requires a paradigm shift in biomanufacturing. Large, or even relatively small, batch production will be replaced by unique “batch-of-one” production, based on genetic material from the patient, which will entail a significant shift in operating model; with a strong focus on logistics, chain of custody/identity, and integrating with third-party therapy centers—all at significant scale. This will drive the need to fundamentally change the architecture and approach to manufacturing systems across the business.

MES solutions will need to adopt more aspects of enterprise resource planning (ERP) platforms to provide better material identity and logistics tracking, and integration with the production operations, together with a distributed model that goes beyond traditional production cells and into the clinic. It is unlikely that current generations of MES products, focused on batch manufacturing, will be able to provide the necessary capabilities without significant customization, and emerging technologies with decentralized “mesh” approaches will need to be developed.
 
The flexibility and agility to manufacture multiple modalities and product variants will be key. Automation will drive repeatability and consistency, and reduce human exposure during manufacture, leading to efficiency, effectiveness, and sustainability benefits.
 

Biomanufacturing plant of the future

The biomanufacturing industry is facing challenges and must adapt manufacturing processes to meet a rapidly changing market for biological medicines. In the context of MES solutions, there are some key drivers for change:

• Reduce the cost to patients of biological medicines and increase market access
• Reduce cost and time to build new manufacturing plants
• Reduce cost and time to introduce new drugs to existing plants
• Increase regulatory compliance by reducing variability and demonstrating higher levels of control.

These drivers, together with advances in manufacturing and information technologies, have been brought together in the BioPhorum Biomanufacturing Technology Roadmap. The roadmap gives a 10-year view into how the developments of science, technology, and engineering will converge to drive the manufacturing of biological medicines.
 
A key part of the roadmap defines an automated biomanufacturing facility that will be created dynamically. Operationally, the facility will use real-time quality control for production capable of automatically adapting to change and deliver intelligent insights and decision support based on boundaryless information flow and self-learning.
 
Holonic components: These are “the whole and part of the whole.” What that means is equipment comes complete with automation—MES and ERP elements fully established. In effect, the MES or manufacturing ERP system for the facility is built as the components are linked together, rather than attempting to fit the equipment into an existing framework. The concept delivers significant flexibility but requires a paradigm shift in the way that “systems” are created—there is no longer a difference between the layers, simply a platform component that delivers functional capabilities. This is related to equipment that conforms to the module type package (MTP) standard, which will be a key component to help achieve:

• Real-time quality control is the logical point at which we move from parameter control (e.g., temperature) to process control (multiple parameters) to controlling the quality outputs we want to achieve. The logical conclusion of this is we have the right analytical systems in place, so external quality control is no longer necessary.
• Boundaryless information flow is integrated information securely delivered whenever and wherever it is needed, in the right context for the people or systems using that information.
• Self or machine learning focuses on prediction, based on known properties learned from the available data. It is supported by data mining, which focuses on the discovery of unknown properties of the data. The output of this process will support the ability to establish knowledge from the data.

BioPhorum background

Since its inception in 2004, BioPhorum has become the open and trusted environment where senior leaders of the biopharmaceutical industry come together to openly share and discuss the emerging trends and challenges facing their industry. Growing from an end-user group in 2008, BioPhorum now comprises more than 135 manufacturers and suppliers deploying their top 6,000 leaders and subject matter experts to work in nine focused “Phorums” spanning the biopharmaceutical value chain.
 
Communities of experts work together to articulate the industry’s technology roadmap; define supply partner practices of the future; develop and adopt best practices in biologics process development, drug substance manufacturing, and fill finish operations; address the challenges of cell and gene therapy commercialization and adoption of medical technologies; and to find common solutions to achieve industry level goals for sustainability and digitalization. In each Phorum, BioPhorum facilitators bring leaders together to create future visions, mobilize teams of experts on the opportunities, create partnerships that enable change, and provide the quickest route to implementation, so that the industry shares, learns, and builds the best solutions together.
 
The key points are:

• Current-state problem
  • While MES solutions provide considerable benefits to regulated manufacturing of biological products, current systems can be expensive, slow to implement, and lack the flexibility/agility/openness to be updated and supported efficiently.
  • Current approaches are not suitable for certain biomanufacturing scenarios, e.g., small-scale and/or low-cost manufacturing plants and for new biomanufacturing modalities such as those for CGTs.
  • The biomanufacturing industry has not created a common view on future MES requirements or support the development of new products/services from MES vendors.
• Impact on biomanufacturers
  • Deployment of MES solutions or upgrades is slow and expensive.
  • The specialist and highly technical skills required to adapt solutions adversely impact time and cost.
  • “Lite” approaches with a smaller footprint in both scale and function are not available for certain biomanufacturing situations.
  • The biomanufacturing industry’s needs are not understood or built into product roadmaps, exacerbating the problem in the long term.

The goal of the MES of the Future workstream is to create and implement a manifesto for the MES of the future that clarifies industry objectives and leads to detailed industry/MES vendor collaboration on solutions to overcome current challenges and limitations.