An Introduction to MES for CGT Manufacturers

Executive Summary

In the rapidly evolving field of cell and gene therapies, manufacturing processes play a critical role in ensuring the safety and efficacy of these cutting-edge treatments. One emerging technology that has garnered significant attention in recent years is the use of manufacturing execution systems (MES) to optimize cell and gene therapy (CGT) production.

By providing real-time monitoring and control of production processes, cloud-based MES can enhance the quality and consistency of these new therapies, as well as streamline manufacturing workflows and reduce costs.

In this article, we’ll provide an in-depth introduction to MES for CGT manufacturers, exploring the underlying science behind this technology and the value it can bring to these two fields.

Jump to…

• An Overview of Cell and Gene Therapies
• Top Challenges for CGT Manufacturers
• Meet Those Needs with a Cloud-Based MES
• The Problem with Paper for CGT
• The Problem with Legacy MES for CGT
• Benefits of Cloud-Based MES for CGT
• MES: More Than Manufacturing
• Our Featured Thought Leader
• Closing Thoughts
• References

An Overview of Cell and Gene Therapies

Modern medicine continues to advance at a rapid rate, with exciting new treatments and therapies developed every day. Cell and gene therapies are two regenerative treatments at the forefront of this remarkable progress.

Cell therapy inserts new or altered cells into an area to repair or replace damaged or diseased cells. Those cells can be autologous (from the patient) or allogeneic (from a donor).

Gene therapy alters genetic material in targeted cells using a vector that enables the uptake of the new genetic instruction. The gene alteration can be performed in vivo (inside the body), or ex vivo (outside the body).

Cell and gene therapies (CGT) are overlapping disciplines. To fight specific cancers, for instance, T-cells are extracted from a patient’s blood, then genetically altered to produce chimeric antigen receptors on their surface. When re-infused into the patient, the new CAR-T cells bind to and extinguish certain cancer cells. The process is both autologous cell therapy and ex vivo gene therapy at once.

Top Challenges for CGT Manufacturers

Companies that manufacture CGT products face a unique set of needs and challenges:

1. Regulatory standards. First and foremost, they must adhere to the same Good Manufacturing Process (GMP) as every drug and treatment manufacturer, and comply with rigorous standards of purity control – a process made more difficult because the nature of the cell and gene therapy does not allow for terminal sterilization.
2. Level of detail. Most legacy drug manufacturing systems are built to be batch specific. But CGT is medicine at the individual level. It requires exceptionally detailed work on incredibly short timelines, needle-to needle and vein-to-vein.
3. Labor cost. The very nature of CGT products, involving the extraction of cells and/or the tweaking of genes, makes the process incredibly labor intensive, and thus very expensive. The batch size of each product is one: each therapy is designed for a specific individual, making them very difficult to produce at scale.
4. Precision. In addition, since the therapies involve living cells, the timing and speed of production must be incredibly precise. Monitoring and controlling every step of the complete supply chain is a complex process that both starts and finishes with the patient.
5. Traceability. Finally, given the individual nature of CGT products, traceability becomes even more important. The chain of identity (COI) ensures the correct patient gets the correct treatment. The chain of custody (COC) ensures thorough sequential documentation of the control, custody, transfer, and analysis of the product from the beginning of the manufacturing process through to the end of the treatment.

Above all, the most pressing need is to protect what’s at stake: human life. The incredibly personalized nature of these therapies leaves no room for error.

“With cell and gene therapies, you have to personalize it down to a single-person batch level. You have to label all the containers in such a way that the patients never get mixed up, because if an error does occur… chances are that patient is going to die, either from a negative immune response or from the treatment not working in cancer patients.”

— Frank Maggiore, Chief Futurist, Apprentice

To ensure patient safety, it is critical that cell and gene therapy manufacturing processes are highly precise, tightly controlled, and adhere to strict regulatory standards. Any deviation from these standards can result in severe consequences, including fatalities.

Meet Those Needs with a Cloud-Based MES

A manufacturing execution system (MES) provides a way for CGT manufacturers to proactively address key challenges such as the five listed above. That’s because an MES is able to track and document the manufacturing process from basic materials to finished products, improving efficiency and reliability while surfacing valuable data.

Flexible and scalable, an MES gives manufacturers the ability to standardize all processes digitally, making the production process faster and more accurate while ensuring compliance.

An MES can also help manufacturers improve management of the supply chain, ensuring timely delivery of individualized CGT treatment. By integrating with other systems, an MES can manage exceptions and deviations in real time, leading to a right first-time, every-time approach.

The Problem with Paper for CGT

Many legacy drug production systems rely on a paper trail. However, paper documentation is insufficient to meet the highly complex requirements faced by CGT manufacturers.

Why? To start, paper-based systems are prone to human error. Manual data entry is time-consuming and can lead to mistakes in transcription, which can have serious consequences for patient safety. Furthermore, paper records can be lost or damaged, making it difficult to track and trace the manufacturing process, which is a critical aspect of CGT manufacturing.

An MES reduces the introduction of human errors by automatically collecting and maintaining a digital data record. Manufacturers can digitally track inventory, materials, and equipment usage in a fraction of the time it takes to comb through hundreds (if not thousands) of pages of information, drastically reducing the time and labor intensity of production. That’s especially important when it comes to already labor-intensive CGT products.

In addition, paper-based systems can make it difficult to maintain compliance with regulatory standards. CGT manufacturing is highly regulated and requires strict adherence to Good Manufacturing Practices (GMP) to ensure the safety, quality, and efficacy of the final product. Paper-based systems can make it challenging to maintain accurate and up-to-date records, which can lead to compliance issues and regulatory violations.

Last, paper cannot keep pace with the complexities of CGT manufacturing. CGT manufacturing involves a range of highly specialized activities, including cell collection and processing, gene editing, gene delivery, and quality control. Each of these activities generates a significant amount of data, which must be tracked and documented accurately. Paper-based systems can make it difficult to manage and organize this data, leading to errors, data loss, and delays in the manufacturing process.

While paper-based systems have been the traditional way of documenting manufacturing processes in many industries, they simply can’t cut it for the complexities of CGT manufacturing.

The Problem with Legacy MES for CGT

There’s a middle ground between paper and a fully cloud-based MES: legacy “paper on glass” MES systems such as Microsoft Word and Excel. 

Albeit better than paper, these legacy systems do not suffice for cell and gene therapy manufacturing because they are not designed to handle the complex, regulated, and data-intensive processes involved in manufacturing these therapies. 

Legacy MES systems lack the necessary controls and functionalities required to ensure precision, traceability, and compliance in cell and gene therapy manufacturing. MS Word, for instance, lacks key features such as real-time data capture, version control, audit trail, and secure data storage that are essential in this industry. 

In contrast, real-time cloud SaaS (Software as a Service) systems are a more viable alternative for cell and gene therapy manufacturing because they are designed to provide the necessary controls and functionalities required to ensure precision, traceability, and compliance.

Cloud-based MES can be a valuable tool for CGT manufacturers looking to improve operational efficiency, quality control, and compliance. By providing real-time information about production processes, MES can help manufacturers optimize production operations, reduce costs, and improve patient outcomes.

“If we look to other highly regulated industries such as finance, banking, general manufacturing, and mass transit systems, a cloud-first digital transformation has already proven to be of significant positive impact to cost, quality, and scale, whilst remaining compliant with regulatory requirements.

Many of the costs and scaling issues caused by the existing paper-based records in Advanced therapy medicinal products (ATMPs) could be alleviated by using integrated, cloud based, digital platforms including electronic batch manufacturing records (eBMR), manufacturing execution systems (MES), Lab Information Management Systems (LIMS), digital CoI/CoC solutions and other relevant digital systems.”

— Matt Todd, Head of Architecture, OriBiotech

Many other industries have successfully made the leap to real-time cloud technology, and are reaping the benefits in safety, speed, and accuracy. So the question isn’t “Why migrate?” The question is, “Why not sooner?”

Benefits of Cloud-Based MES for CGT

So what are the top benefits that cloud-based MES can provide for cell and gene therapy manufacturers? It boils down to three main buckets:

1. Operational efficiency. One of the key benefits of MES for CGT manufacturers is improved operational efficiency. By providing real-time data on production activities, MES can help manufacturers identify bottlenecks and inefficiencies in the manufacturing process. This information can then be used to optimize production operations, improve resource utilization, and reduce production cycle times. This can lead to lower costs, higher throughput, and increased profitability for CGT manufacturers.
2. Quality control. Another benefit of MES for CGT manufacturers is improved quality control. By tracking and monitoring production processes in real time, MES can identify potential quality issues before they become major problems. This can help manufacturers take corrective actions quickly and reduce the risk of defective products reaching patients. In addition, MES can help manufacturers track and trace product quality and identify trends or patterns that can be used to improve quality over time.
3. Real-time oversight. Finally, MES can provide CGT manufacturers with greater compliance and regulatory oversight. By providing real-time data and analytics, MES can help manufacturers ensure that they are meeting GMP requirements and regulatory standards. This can help manufacturers avoid costly compliance violations and improve patient safety.

Let's take a deeper dive. Cloud-based SaaS systems offer several benefits over legacy MES, such as: 

1. Real-time data capture. Cloud-based SaaS systems enable real-time data capture, which means that data can be entered and updated instantly, reducing the likelihood of errors and inaccuracies. 
2. Real-time collaboration. SaaS systems enable multiple stakeholders to collaborate in real-time, reducing the likelihood of communication gaps and errors. 
3. Automated version control. SaaS systems automatically track and manage different versions of documents, ensuring that the latest and most accurate information is always available. 
4. Enhanced security. SaaS systems offer secure data storage, backup, and disaster recovery capabilities, ensuring that data is protected against unauthorized access or loss. 

Overall, real-time cloud SaaS systems are a superior alternative to “paper on glass” systems such as MS Word in cell and gene therapy manufacturing, as they provide the necessary controls, functionalities, and security required to ensure precision, traceability, and compliance.

MES: More Than Manufacturing

Even before the manufacturing stage, an MES offers substantial advantages when it comes to CGT.

In the preclinical stage, the digital nature of an MES allows for rapid reiterations, essential for the kind of personalized experimentation CGT requires. Real-time feedback makes for more thorough analysis, which means a more rapid pass-through to the clinical stage.

A flexible MES allows manufacturers to tweak the clinical production process while automatically communicating design steps and logic. With built-in guardrails to prevent deviations and tracking to capture execution history, repeatable batches can instantly be shared with commercial teams. Which, in the highly customized world of CGT, is an invaluable tool.

Our Featured Thought Leader

Frank is all about future-forward approaches here at Apprentice. In fact, he’s our Chief Futurist! Read on to learn more about Frank’s perspective on the promise of cell and gene therapies.

Meet Frank Maggiore, our Chief Futurist

• Who: Frank Maggiore
• What: Chief Futurist
• When: 6 years at Apprentice
• Where: Stony Brook, NY
• Why: Frank’s a true visionary and advocate for the potential of cell and gene therapies

‍Frank’s background

Frank has worked in the pharmaceutical industry for more than 25 years. Frank’s areas of expertise include a number of fields in tech and life science, including augmented reality, artificial intelligence, and cell and gene therapies.

Frank is the inventor of Single-use Biological 3D Printing, 3D printing within sterilizable bioreactors/mixing containers, Single-use robotics, and the Variable Augmented Reality Marker.

Frank has also invented a method of “Contactless Communications” for secure cloud network computing where IoT devices can securely work with smart glasses, smartphones, or other mobile devices.

What connects all of Frank’s inventions and innovations is his core motivation: pushing technologies to the limit. Frank spends his time developing disruptive technologies, rapidly building functional prototypes, and determining how they can apply to various industries.

MEET FRANK

Frank’s take on CGT manufacturing

“Cell and gene therapies are critical to pharmaceutical manufacturing because these approaches are the underlying basis for all the new advancements headed our way. That’s what’s going to improve healthcare as a whole.”

— Frank Maggiore, Chief Futurist, Apprentice

Closing Thoughts

As the field of cell and gene therapies continues to expand, it is becoming increasingly clear that innovative manufacturing technologies such as MES will be essential to meet the growing demand for safe and effective treatments.

The success of CAR-T as a cancer treatment for certain kinds of cancers like leukemias and blood cancers, which make up around 10% of all cancers diagnosed annually and 25% of all cancers in children, are driving a massive surge in growth for cell therapy manufacturing.

The forefront of medicine is where every biopharma company wants to be. And the entire lifecycle of CGT products, from the first experimental preclinical iterations all the way through to the final commercial production, is made safer, faster, and more efficient with MES.

By staying up-to-date on the latest advances in CGT manufacturing, researchers and manufacturers alike can help to ensure that patients receive the highest-quality therapies possible. Explore what digital MES solutions can do for CGT production. Request a demo today.

References