The Impact of Industry 4.0 on the Pharma Industry

The future is already here, and its name is Industry 4.0. What is its affect on the pharmaceutical industry? Why is the FDA encouraging to implement it? And which pharma manufacturers have already followed the path of the future and implemented it? 

Written by Eli Pelleg, COO, and Ilana Weissberg Doron, Content Manager

Lately everyone has been talking about the fact that the world is in the midst of the 4th industrial revolution. This revolution, or Industry 4.0, has kicked in during the last few years, and it is here to stay. It has created massive hype and advancements in many fields, and is changing the way manufacturers operates.

Industry 4.0 is all about digitalization and automation of the manufacturing world. While manufacturing used to heavily rely on the human factor, industry 4.0 is based on autonomous, computerized processes. This automation theme utilizes data and analytics for improving manufacturing processes, management decision making processes and quality assurance (Industryweek.com).

Moreover, Industry 4.0 applies machine learning and IIoT (Industrial Internet of Things) to maintain the internal, autonomous, communication within the factory. It allows equipment to transfer data between them, and to be constantly connected. The machines' ability to gather and analyze data, combined with their learning ability, creates a new and exciting environment where operations can be based on better, more informed decisions (Industryweek.com).

It is only natural that the various futuristic technologies of this exciting industrial revolution, such as AI technology, Big Data, and autonomous robots, will be integrated in all industries, as they enable them to be much more in control over different processes within the factories. They allow them to be much more flexibility – and produce in less cost.

The semiconductors industry, an industry already implementing different Industry 4.0 applications in its factories for quite a long time. This adoption has yielded many advancements, and allowed a big technological leap forward in computers (i.e. size and speed), cell phones, and more. But what is the state of the pharmaceutical industry? Is it implementing the Industry 4.0 in its factories? How is this industry preparing towards the future?

This article will take look at the impacts of industry 4.0 on these two industries, specifically on a certain application of industry 4.0: “continuous manufacturing”.

Industry 4.0 in the Semiconductors Industry

We keep updating with the next big thing in cell phones, video game consoles, computers, and more. But we need to remember that the advancement of all these devices is enabled by the breakthrough of the semiconductor industry made in its manufacturing capabilities.

The semiconductors industry was one of the first industries to adopt the technologies of Industry 4.0, even before it was well recognized as today. Implementing Industry 4.0 tools like automation and robotics was the only way to deal with the market's demands for low cost, flexibility and reliability while rapid technological change was creating a fast cycle time for new products (from the development phase to the product's death – leading to a new product).

Even though the costs to implement and integrate the new technologies of Industry 4.0 were high, this important transformation allowed a giant leap ahead, turning our culture into the one we're familiar with today. Semiconductor factories, adoption of various technologies can be consolidated into one term – a smart factory, or smart manufacturing. The key characteristics of smart manufacturing in the semiconductors industry are:

• Enabling and accelerating the integrations through Industry 4.0 technologies, such as the Cloud, Big Data, Analytics, and AI (Applied Materials, 2017)
• ERP management system: monetary activity, HR, production floor work procedures, etc. The ERP managerial system provides a situation report regarding where is the order standing, how is the production performing, and more.
• Process Control: a system that supervises the parameters in the chemical process, inspecting whether the process in the machines is performing correctly.
  • This point is significant in semiconductors, as each machine functions differently. Once the operator chooses the product, the machine adjusts itself to the selected production process, according to the pre-defined process plan.
• MES (Manufacturing Execution System): MES is an electronic system that supplies information from the ERP management system level to the process control system. In case of malfunctioning, it provides management with information about the reasons the process is not performing correctly.

Fig. 1: Manufacturing network in semiconductors manufacturing (Source: Applied Materials)

In general, Semiconductors manufacturing is one of the most complicated chemical processes, entailing hundreds of process steps performed on dozens of different types of tools, from lithographic to etching, from grinding to diffusion, and more.

This entire manufacturing process is performed in a manner of continuous manufacturing – a non-stop, automated, and integrated process. Continuous manufacturing is allowed by the emergence of Industry 4.0 technologies. It relies on connectivity through the use of IIoT, Big Data, analytics, AI, automation, and more. It is monitored and managed from afar.

Although the semiconductors industry has been using continuous manufacturing for about 30 years, it started out by using batch manufacturing, which is the common practice in pharmaceutical industry as of today. So, how does the pharma industry use continuous manufacturing and Industry 4.0 and to what extant?

Continuous Manufacturing in the Pharma Industry

The pharma industry has started implementing Industry 4.0 technologies only in recent years, and it has been using batch manufacturing for more than 50 years. However, the traditional batch process method has been proved to be a lengthy one: after each step in the process the production is typically stopped, so that the substance could be tested for quality assurance. Sometimes during these "hold times" the material may be stored in containers or even shipped to other facilities in other countries, to complete the manufacturing process (FDA, 2017). Each break increases lead time and may increase possibility of defects and error (FDA, 2016).

But the future of the pharma manufacturing is approaching. In 2016, the FDA has released a blog entry, stating that it is encouraging pharmaceutical manufacturers to transition from batch manufacturing to continuous manufacturing, due to its many advantages.

This encouragement also comes in a specific timing – today, we are entering an era of precision (personalize) medicine, "when drugs must be made with unique features and provided more quickly to patients in need." (FDA, 2016).

In order to manufacture personalized drugs, pharma factories no longer need to manufacture in big batches but in small ones, in a manner suitable to a small group of people that need a certain medicine in a certain dosage. Batch manufacturing is definitely not the solution to these needs, but the connected, smart, flexible and precise continuous manufacturing.

Fig. 2: Batch manufacturing vs. continuous manufacturing in pharma (Source: FDA, 2017)

In the pharma industry, continuous manufacturing is all about moving the substances nonstop within the same facility, thus eliminating hold times between the different steps in the process; the materials are fed through an assembly line of fully integrated components. Continuous manufacturing "saves time, reduces the likelihood for human error, and can respond more nimbly to market changes. It can run for a longer period of time, which may reduce the likelihood of drug shortages." (FDA, 2017).¹

In addition to the regulator's encouragement to move on to precise medicine, the market forces also make their impact on the pharma industry, requiring it to implement the industry 4.0 technologies and continuous manufacturing: the rising competition as generic drugs enter the market; the demand for high drug quality; prolonging the shorter drug life cycle; and the need to reduce the high costs of batch manufacturing.

Industry 4.0 and Continues Manufacturing Adoption in Pharma

So, which pharmaceutical companies have adopted the advancements that Industry 4.0 allows? True to December 2017, this is the pharma industry's continuous manufacturing adoption map:

• Johnson & Johnson's Janssen drug unit has been working on its continuous manufacturing process for five years, and won the FDA's approval to switch from batch to continuous manufacturing in 2016. This, in order to produce the HIV drug Prezista (fiercepharma.com).
• Novartis – Novartis entered a 10-year research collaboration program with the Massachusetts Institute of Technology (MIT) back in 2007 (pharmafile.com). This collaboration yielded two projects:
  1. CONTINUUS Pharmaceuticals – a center of which purpose is to lead to the creation of novel continuous flow manufacturing technologies for pharmaceuticals
  2. Technikum – Novartis has also initiated the technology transfer from CONTINUUS Pharmaceuticals to its novel continuous manufacturing unit, named the “Technikum”, located in Basel (continuuspharma.com), of which purpose is to experiment with new ideas and equipment (outsourcedpharma.com)
• Vertex – Vertex, the manufacturer of the cystic fibrosis drug, Orkambi, has been using the continuous manufacturing process since July 2015 (blogs.fda.gov)
• Eli Lilly – Eli Lilly's Ireland site achieved an important step, using an industry-first continuous process to make a compound for phase I and II clinical trials (chemistryworld.com)
• Glatt – Glatt’s continuous solid-dosage processing systems are operating at its Innovation Center in Binzen, Germany, which was inaugurated in November 2016 (pharmtech.com)
• Lonza – Lonza implemented continuous flow technology in its Highly Potent Active Pharmaceutical Ingredients (HPAPIs) manufacturing process (lonza.com)
• GSK – in 2014, GSK has initiated an Upper Providence continuous pilot plant (pharmaceuticalonline.com)
• Pfizer – on May 2017, Pfizer officially opened a modern, tablet production, continuous manufacturing plant in Freiburg (gesundheitsindustrie-bw.de). However about a month later mass manufacturing was stopped due to regulators' orders (in-pharmatechnologist.com)

Conclusion

The pharma industry is heading towards adopting more and more Industry 4.0 technologies and continuous manufacturing. With the FDA's encouragement, the pharma industry is now on the track of catching up with other industries, such as semiconductors.

In this article, we mapped the pharma companies, already in the process of implementing Industry 4.0 and continuous manufacturing. Though the above examples are of big pharmaceutical companies, today Industry 4.0 technologies are available for SMBs, are ready to be implemented in them – and allow them to become advance manufacturers.

The day in which continuous manufacturing will be a standard in the pharma industry is approaching, but pharma companies need to speed things up. Industry 4.0 is here to stay, and NOW is the time to embrace it.

^{1 Of course, during the continuous manufacturing process there might be batching, but only for monitoring and tracking purposes – and not as the base for the entire process.}