Pharma 4.0: What It Means and What It Offers for CGT

Executive Summary

In recent years, the pharmaceutical industry has undergone a significant transformation, driven by the adoption of advanced technologies such as automation, artificial intelligence, and data analytics.

This fourth industrial revolution, also known as Pharma 4.0, is revolutionizing the way pharmaceuticals are developed, manufactured, and delivered.

One area where Pharma 4.0 is having a particularly profound impact is in the field of cell and gene therapies (CGT). In this white paper, we’ll explore the intersection of Pharma 4.0 and CGT, highlighting the opportunities advanced technology can provide in this space.

Jump to…

• What Is Industry 4.0?
• What Is Pharma 4.0?
• The Rise of Cell and Gene Therapies
• What Solutions Does CGT Make Possible?
• What Challenges Do CGT Manufacturers Face?
• Incorporating Pharma 4.0 into CGT Workflows
• The Next Step for CGT Manufacturers
• Our Featured Thought Leader
• Closing Thoughts
• References

What Is Industry 4.0?

We learn about the Industrial Revolution as children, but as we grow up, we realize that particular revolution isn’t over.

It’s more accurate to say that we’ve undergone three separate Industrial Revolutions, each of which introduced transformative technologies which paved the way for the next.

The first Industrial Revolution took place from the late 1700s to the mid-1800s and saw the rise of steam power. The second, which ran from the late 1800s to the early 1900s, witnessed the introduction of electricity and modern manufacturing. The third, marking the rise of the computer age, began in the latter half of the 20^th century and continued through into this millennium.

Now we’re in our fourth Industrial Revolution, the age of interconnectivity, in which people, processes, and data are integrating in a comprehensive physical and digital ecosystem.

This revolution brings human effort together with automation, harnessing cloud computing, the Internet of Things (IoT), and machine learning to drive the best in production and real-time decision making. We call this new era Industry 4.0.

What Is Pharma 4.0?

As outlined by the International Society for Pharmaceutical Engineering (ISPE), Pharma 4.0 is an operating model that applies the lens of Industry 4.0 to the complex portfolio of the pharmaceutical sector.

Pharma 4.0 encompasses the entire pharma lifecycle, from research through development all the way to commercial manufacturing and delivery.

A framework designed to help companies transform their manufacturing process, Pharma 4.0 integrates technological advances into every aspect of the workflow, so every step of each iteration is instantly communicated to the next.

On the twin rails of digital maturity and data integrity by design, Pharma 4.0 reimagines resources, information systems, processes, and workplace culture with the ultimate goal of streamlining pharmaceutical operations. The result is better medical outcomes for everyone.

The Rise of Cell and Gene Therapies

In recent years, there has been a significant rise in the development and adoption of cell and gene therapies.

This is due in part to advances in genetic engineering and cell biology, as well as increased investment in research and development in this field.

Cell and gene therapies offer the potential for highly targeted and personalized treatments, and have shown promising results in early clinical trials for a range of diseases.

As a result, they are increasingly seen as a key area of innovation in medicine, with significant potential to transform the way we treat a wide range of conditions.

• Cell therapy uses new or altered cells to repair or replace damaged or diseased cells. Those cells can come directly from the patient (autologous), or from a donor (allogenic).
• Gene therapy alters genetic materials in targeted cells using a carrier to allow for the uptake of new genetic instructions. The gene alteration can be performed inside (in vivo) the patient’s body, or outside it (ex vivo).

Both cell and gene therapies have the potential to provide solutions for a wide range of diseases and conditions that were previously considered untreatable or for which there were limited treatment options.

What Solutions Does CGT Make Possible?

Cell and gene therapies have opened up new possibilities for treating diseases that were previously difficult or impossible to treat using traditional therapies.

These therapies have the potential to address the root cause of diseases at the genetic and cellular levels, offering hope for patients with a wide range of conditions.

Some of the solutions that cell and gene therapies make possible include:

1. Genetic Disorders: Gene therapies have the potential to cure or treat genetic disorders, such as sickle cell anemia, by repairing or replacing faulty genes.
2. Cancer: Cell therapies, such as CAR-T cell therapy, have been shown to be effective in treating certain types of cancer by reengineering a patient's immune cells to target and destroy cancer cells.
3. Chronic Diseases: Gene therapies have the potential to cure or treat chronic diseases, such as hemophilia, by introducing functional genes into the patient's cells to correct genetic defects.
4. Orphan Diseases: Cell and gene therapies have the potential to provide treatments for rare and orphan diseases, which were often neglected by the pharmaceutical industry due to their limited patient populations.
5. Regenerative Medicine: Cell therapies have the potential to regenerate damaged tissues, such as in the case of heart disease, by introducing healthy cells into the affected area.
6. Autoimmune Diseases: Cell and gene therapies have the potential to treat autoimmune diseases, such as rheumatoid arthritis or multiple sclerosis by modulating the immune system to prevent it from attacking the body's own tissues.
7. Neurological Disorders: Cell and gene therapies have the potential to treat neurodegenerative disorders, such as Parkinson's disease, by introducing healthy cells or genes into the affected areas of the brain or by the regeneration of tissue to overcome strokes or spinal cord injuries.

These are just some of the solutions that cell and gene therapies can provide. And more are sure to emerge, as CGT is rapidly becoming an important area of focus for pharmaceutical companies, researchers, and healthcare providers around the world.

What Challenges Do CGT Manufacturers Face?

Makers of cell and gene therapies face different challenges than manufacturers of small molecule drugs.

Living cells and the fragility of genes does not allow for terminal sterilization, so purity control and compliance become even more important.

Working with biological materials also requires absolute control of the entire supply chain, one which begins and ends with the patient. The ability to track and trace chain of identity (COI) and chain of custody (COC) is vital.

“CGT is personalized medicine,” says Frank Maggiore, Chief Futurist at Apprentice. “One person gets a therapy for lymphoma, another for some other blood disorder or cancer type.” The variety and customization stumps legacy production systems. “They break down. They’re built to perform at scale, in giant batches, not a batch of one. The need greatly outstrips current capacity.”

The current methods of documentation are insufficient to meet these challenges. Bound by inflexible older technologies and tied to paper-based protocols, they can look to Pharma 4.0 for a more agile approach.

Pharma 4.0 requires the adoption of advanced technologies, like a manufacturing execution system (MES) to digitally standardize each step in every process: tracking resources; collecting data; managing exceptions and deviations in real time.

“Memory is fallible,” says Frank. “People learn things differently.” With the constant data capture and instantaneous video interaction of an MES platform like Tempo, the knowledge transfer between teams and sites remains seamless, unbroken, and secure.

This knowledge transfer, also referred to as “tech transfer,” happens at multiple points along the drug production lifecycle. Any time a drug is passed between facilities, teams, or production stages, all of the steps needed to produce it need to be transferred as well.

With cell and gene therapies in particular, the transferring of steps can be especially arduous. Due to the high number of variables involved in CGT manufacturing, the process documentation and data can quickly pile up, especially when it’s all getting transferred manually. And given the highly personalized nature of these medicines, there’s no room for error.

Incorporating Pharma 4.0 into CGT Workflows

When producing under pressure, it may seem easier to stay with the tried and true rather than adopt a new routine. After all, learning new technologies and processes takes valuable time and effort.

But it’s important to move beyond this sunk-cost fallacy. The advantages of Pharma 4.0 outweigh any hesitations, especially when it comes to CGT.

Here are six ways that Pharma 4.0 can help cell and gene therapy manufacturers improve their processes:

1. Process automation. One of the key benefits of Pharma 4.0 is the ability to automate manufacturing processes, reducing the risk of errors and increasing efficiency. This is particularly important in the production of cell and gene therapies, which require highly precise and reproducible manufacturing processes.
2. Real-time monitoring. Pharma 4.0 technologies such as IoT sensors can be used to monitor the manufacturing process in real time, allowing manufacturers to identify and address issues as they occur. This can help to improve product quality and reduce the risk of batch failures.
3. Predictive maintenance. The use of advanced analytics and machine learning algorithms can help manufacturers to predict when equipment will need maintenance or repair, reducing downtime and improving efficiency.
4. Data management. Pharma 4.0 technologies can help manufacturers to manage the large amounts of data generated during the manufacturing process, allowing for better tracking of products and processes. This can help to improve quality control and facilitate compliance with regulatory requirements.
5. Supply chain optimization. Advanced analytics and machine learning can also be used to optimize the supply chain, reducing the risk of shortages or delays in the delivery of critical raw materials and components.
6. Augmented guidance. Since CGT products are targeted to a specific person, the production process is very much hands on. Advanced tech solutions can steer skilled technicians through the necessary steps with video clips, photos, and localized instructions.

Pharma 4.0 has the potential to transform the way that cell and gene therapies are manufactured, improving efficiency, reducing errors, and increasing product quality across the board.

But in order to realize the benefits, this change must truly be truly embraced at an organizational level.

By incorporating advanced technologies and digital transformation, cell and gene therapy manufacturers can position themselves for long-term success in this rapidly evolving field.

The Next Step for CGT Manufacturers

Too often, traditional manufacturing practices trying to reduce time-to-market for new products rely on paper-driven recipes and data collection models, which are too slow and cumbersome to meet the needs of modern CGT production.

CGT requires a more complex and adaptable manufacturing process than traditional small molecule drugs.

That’s where Pharma 4.0 comes in. It is the next essential step for CGT manufacturers, providing in-line and on-time control, improving business operations, production quality, and regulatory compliance.

Pharma 4.0 is not merely an IT product or solution. Instead, it is a reimagining of the entire pharmaceutical production process to add visibility, transparency, and adaptability.

A sea-change in workplace culture, Pharma 4.0’s instant communication eliminates information silos and allows for faster, more informed decision making at every level. Within a GMP-regulated cloud-based environment, data is surfaced immediately and can be made available to anyone who needs it. This allows any inconsistencies to be instantly flagged, tracked, and resolved as soon as they occur. As Frank explains it, “It cuts down on the detective work — what went wrong, and why, and where? — ensuring that it doesn’t happen again.”

That’s why we built Tempo. Our Tempo Manufacturing Cloud accelerates the drug production lifecycle from end to end. Tempo connects and orchestrates all the distributed teams and sites involved in drug production, helping them execute better on the shop floor, and optimizing their operations through enterprise-wide visibility. From preclinical benchtop to large-scale commercial manufacturing, Tempo keeps your global teams connected, empowered, and in sync.

Want to find out more about how Tempo can level up your CGT manufacturing operations? Contact us today.

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

• 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 Pharma 4.0

“With the personalization CGT requires, scalability is no longer a nice-to-have: it’s mandatory. Most legacy software systems can’t handle it. And even if they can deal with the complexity on the biologics side, traditional continuous manufacturing is not enough. That’s why Pharma 4.0 is so essential to the success of these new therapies.”

— Frank Maggiore, Chief Futurist, Apprentice

Closing Thoughts

As we wrap up this exploration of the intersection of Pharma 4.0 and cell and gene therapies, it's clear that this convergence has the potential to revolutionize healthcare.

The use of advanced technologies in CGT manufacturing processes can lead to more efficient and scalable treatments that can significantly improve patient outcomes, offering hope to those with previously untreatable diseases.

Collaboration and connection between all stakeholders is vital to build a more sustainable and innovative healthcare system that puts patients at the center. By embracing this transformative technology, we can build a brighter future for personalized medicine and offer better care to those who need it most.

References