Giuseppe Menin: I am a manager focusing on life science and process industry automation. We cover the pharmaceutical, biotechnology, and medical devices sectors. Our core business is in life science, covering the manufacturing process, from the preparation of the active pharmaceutical ingredients through to the formulation, filling, and packaging.

An important part of my role is to keep in regular contact with customers, to understand their requirements and challenges. Based on this feedback, we try to address any issues through updating product features in our platform.

I am also involved in organisations like the International Society for Pharmaceutical Engineering (ISPE). I am a member of the Italian chapter and its international special interest group, called Pharma 4.0. These groups are working on new concepts to help improve pharma manufacturing. I report back to the company about my customers’ challenges and new trends in the industry, and then we work on innovations in our platform to support them.

While the pharma industry is one of the most innovative from a research perspective, from the manufacturing point of view, most – even the big companies – are still using a traditional approach. Their machines do their jobs well, but, from a data integration point of view, they are isolated.

Of course, the pharma industry is highly regulated and must remain compliant. Therefore, documentation is important. Data integrity is an important topic. However data integrity is often supported by a system of paper-based records on these individual machines. The operator writes on the paper, then checks the data on the machine controls, then signs the paper manually for each one. This complex operation makes errors more likely and causes problems with data integrity regulation. The MHRA in the UK, the US FDA, and the EMA are forcing pharma companies to be more compliant, which means moving from a paper-based approach to electronic batch recording.

However, within firms there is resistance to updating machines that work well, even if they are 10 or 15 years old. Changing the validation status of the machine is a nuisance. It is costly, requires new paperwork, and treats people like consultants. These factors push machinery updating plans down the priority list.

Those who receive an inspection and are found not to be compliant, though, may receive a warning letter from the FDA or other regulator. Such warning letters are publicly available to view on the internet, and can damage a company’s reputation.

For management teams, regulatory compliance is the most critical, followed by efficiency. This is especially true for the contract manufacturers producing drugs under licence.

Consider the fact that only around 30% of pharma companies today have manufacturing execution systems (MES) in place that support electronic batch record production. This leaves a lot of companies that are still using paper.

Often, it is the customer who still wants paper records. Even the big organisations, that have an MES on site, may not have moved all their processes from paper to electronic. Why? Because of problems with connectivity. Linking a big IT system to existing machines is challenging. Every machine is different and has different information and data to the next one. The first machine may be integrated successfully, but the second may have a different socket, a different language, or a different protocol. Going this last mile in integration is an issue to be overcome.

We are working to supply the latest software-integrated machines to the pharmaceutical industry. At the same time, we are also supporting customers to integrate their existing machines with IT systems using ‘middleware’. This is software that sits between the production and the automation systems, providing connectivity and local data storage to comply with GMP standards.

The main challenge is to supply and distribute the data to the important systems, like the MES or an enterprise resource planning (ERP) system, and distribute the information to the operator.

The second challenge lies in developing plug-andproduce technology for pharmaceutical manufacturers. Nowadays, if you buy a new printer and connect it via a USB cable to your laptop, the computer recognises the printer, installs the software and, in a few seconds, you can print. However, this is not the case in the industry setting. ISPE’s Pharma 4.0 group is working to achieve this same interoperability to enable a pharmaceutical company to buy a new machine and integrate it with an MES, or other systems.

Another important aspect of plug-and-produce technology is its ability to orchestrate different equipment. This is especially relevant to the biotech sector. When a biotech company produces a vaccine, for example, it uses traditional production methods in huge, pressurised tanks. Often, each piece of equipment has its own local control. A further complication is that each may have come from a different vendor. All the components are manually integrated into the process control systems computer, which orchestrates the procedures. This setup is fine until a change is needed. The system is so rigid and difficult to adapt because it must be reconfigured manually. Each vendor has to come to the company and update things, which takes time and lengthens manufacturing processes.

The idea of plug-and-produce is to find a way of creating interoperability between different vendors, providing device interfaces to easily manage different machines and change configurations. This is done using the module type package (MTP) standard defined by the international association of user companies, NAMUR, which is used in biotech process automation.

So, these are the two important challenges today: integration of existing equipment and IT systems on one side, and flexibility in production using other connectivity options, like the MTP, on the other.

Let me give you an example. Imagine that you need to produce a batch of 1,000 aspirin. Using today’s system, the production manager receives the order in the ERP system. They produce a piece of paper with details like the batch ID and product name. The operator may need to set line number one, comprising five machines, to carry out the work. This may necessitate activation of recipe number one on machine number one, recipe 23 on machine number five, and so on. All of the instructions are written on a piece of paper. The operator has to go to the first machine and type in the commands. Then they must go to the second machine and the third in turn.

In contrast, with connected solutions, the batch information and production requests go direct to the MES and the MES sends the request to the line execution system. It knows the capability of the machines and automatically sets up the recipe for each one. Of course, the operator may still need to check and modify critical, or other, settings on the machines, but all the boring input data, where errors can be made, are now automatically completed thanks to digital integration.

Then, during production, the system automatically collects critical process parameters. Let’s imagine that you have a critical parameter, like the sterilisation temperature. You can set the system to automatically monitor the temperature. If the temperature exceeds the maximum or minimum value, it sets off an alarm and automatically notifies the operator. In addition, ‘exceptions reports’ can be set that note only those specific events, not all the information. This means that the batch release time can be reduced from several days to a couple of hours.

In summary, the benefits for a regular production line are better connectivity, reduced use of paper, the ability to highlight exceptions and a faster time to market for the product.

The interoperability provided by MTP can also bring important benefits in manufacturing, by helping to speed up processes. For example, if the production manager requires more product, or if a filter needs to be replaced with one from a different supplier, these actions can be done in a few minutes, from the software point of view.

MTP allows models to be connected in a variety of configurations. Every model has a standardised interface so it can connect with the others. The system can be reconfigured for different needs, such as producing a specific product or increasing the size.

All the components meet the same standard, which means the engineer can easily reconfigure them as necessary. In addition, the process orchestration layer controls every component. The benefits of this translate to a 50% faster time to market, a reduction of 70% in engineering effort, and an increase in flexibility of 80%.

Of course, automation positively impacts people’s lives. It means they can concentrate on their day-to-day activities and not on paper processes, or repetitive operations.

IT people, for example, face difficulties when they need to create a backup of data locally in a machine. They may need to go into an area that could require them to wear protective clothing. Putting on this gear and removing it afterwards could take 30 or 40 minutes. If this operation can be performed automatically through connectivity, it saves people a lot of time and effort.

Another important aspect is the impact on process engineers involved in quality control or research and development for production. If a team member wants to see production data from six months ago, for example, digitalisation means this data are immediately available to them at their desk, via normal office automation software. They don’t need to ask the process engineer to send a backup of the data and then try to open it in different software before they can use it. Furthermore, the engineer has to make time in their schedule to carry out the request. In contrast, having the information immediately available, as we have today on Google, means staff can easily search for something.

This availability of data is definitely very important. Democratising the data means there is no longer just one person responsible for all the data who must be asked personally for access.

We are working towards ever greater connectivity, which can only bring benefits to the pharmaceutical manufacturing process and data integrity.