It can be a long way from theory to implementation – but not so for CSPE (Comprehensive Scientific Process Engineering), which was launched by Optima Pharma in 2018. This process significantly shortens the delivery and commissioning times of complex turnkey systems, and numerous projects have already benefited from it.
The huge hall boasts high ceilings and is bright and much airier interior than standard assembly halls, thus offering plenty of room and so much more. At the official inauguration in June 2019 it was named “CSPE Center” – after all, “commissioning hall” wouldn’t quite have done it justice! What stands out are the two gigantic hall cranes with a span of 30 m. Less noticeable is the cable and pipe guiding system, which penetrates the entire hall floor and is indispensable for the designated use of the hall. During commissioning, pre-cycle development, and integrated FAT (iFAT), it supplies the resulting pharmaceutical lines with process heating and cooling as well as with demineralized water and compressed air. Only one third of the 3,500 m² of hall space are occupied during the first days of the 2019 summer. The first turnkey systems inaugurated with a successful iFAT are already on their way to customers.
The new hall is real proof that CSPE isn’t just a fanciful idea. Optima has invested tens of millions in the construction. Gerhard Breu, Chairman of the Optima Pharma Division, proudly explains: “Now the infrastructural conditions have been met as well. The first lines we planned, produced, and supplied according to the CSPE concept prove that it works.” That’s not least because the line commissioning including the integrated FAT for filling systems, loading units, and isolator, which can take place in the CSPE Center, is just one aspect of CSPE.
From the pre-design stage through to delivery and training, Optima Pharma draws on a variety of available features such as digital engineering, simulation, and virtual reality. The aim is to keep the period from customer inquiry to production start-up as focused and error-free as possible, and to eliminate wasted time. (Further information about CSPE can be found here).
“Our comprehensive technical-scientific approach will set new standards in the pharmaceutical plant engineering industry,” emphasizes Breu. Systems produced by means of the CSPE process are available quicker, which shortens the time-to-market of newly developed drugs. CSPE also minimizes the risks associated with large plant construction projects. The process kicks in even prior to the design stage – with a thorough analysis. Because only if potential risks based on the experience gained from comparable earlier projects are identifi ed, can they be proactively countered.
Risk minimization, from the customer's perspective, also means that Optima Pharma checks the entire system in a real test situation before delivery. The ability to merge all parts of a turnkey plant at the manufacturer, put them into operation under near real-world conditions, and carry out pre-cycle development, is unparalleled in the industry and signifi cantly shortens the final commissioning stage at the customer's site. For this purpose, isolators are transported from Optima's affiliate Metall+Plastic (M+P) in Radolfzell to the Schwaebisch Hall site.
Inan Koyuncular is process owner for the entire CSPE process. As the team leader, he coordinates the commissioning. In recent years, he witnessed during various projects how things go without integrated FAT, when the separately pre-tested plant parts are not combined until they reach the customer’s site. “A lot could happen that would slow us down,” recalls Koyuncular: “Starting with the fact that customers’ power supplies were at times unreliable. Plant specialists therefore needed several days for interface communication tests, which they usually do in just one day. And even if everything ran smoothly, Optima experts were involved in minute details concerning plant commissioning, e.g., in North America or Asia, for several days or even weeks. This meant they were absent from Schwaebisch Hall and unavailable for other projects for extended periods of time.”
Today, Koyuncular knows how to avoid these and similar hurdles in the complex process from planning to operating a plant. He has broken down the different stages of CSPE in detail – from predesign and mock-up construction through design, basic commissioning of the isolator, and construction and commissioning of the complete line to pre-cycle development and iFAT; almost every single step has been recorded. Thanks to these intensive tests, turnkey systems then master the stage leading up to media fi ll at the user’s site much faster than before.
“The challenge is that some of our teams, who in the past operated more or less independently from one another, have to work hand in hand as part of the CSPE concept,” says Koyuncular. This requires discipline and restricts certain freedoms. In the future, everyone’s tasks and the exact timeframe for their completion will be defined. As process owner, Koyuncular monitors everything and ensures that everyone involved complies with the plan. The goal is to avoid unnecessary standstills and redundant overlaps of certain activities.
Various turnkey projects are currently in one of the CSPE steps. Even if they started before the new Optima standard was adopted, they still benefit from the advantages of an integrated FAT, at least during the final stages. Methods such as digital engineering and simulation have, incidentally, been used for a long time in all Optima projects. The resulting valuable input can thus also be applied to line commissioning in these projects.
Other projects go through the process from the very beginning. One of them, for example, on behalf of LEO Pharma, a company specializing in dermatology and thrombosis, with five production sites. At its Vernouillet site in France, the company is currently investing in the production of heparin based drug and has opted for a turnkey plant from Optima Pharma. “As early as in the proposal stage, we were able to explain step-by-step to the customer what to expect from CSPE and the associated benefits,” explains Koyuncular. LEO Pharma quickly realized the underlying process expertise and understood how the typical period of time from delivery of the plant until the start of production is shortened.
In the pre-design stage, some 50 tasks are already defined. They range from the basic design of the isolator with details such as fresh air intake, through the optimization of the line layout in consideration of accessibility, etc., all the way to preliminary tests such as plug setting. Initial flow and OEE simulations facilitate the close collaboration and coordination with the customer even at this early stage.
Next a mock-up is prepared, which for the first time shows the entire system including the isolator – if only as a model. Any positioning of gloves, doors, or environmental monitoring systems (EMS), for example, will later affect the isolator load and thus the VHP cycle. Here too, customers like LEO Pharma benefit from the consistently systematic approach, which minimizes time lost.
In the meantime, LEO Pharma's turnkey plant has already gone through the engineering stage. Koyuncular’s breakdown clearly shows the customer that nothing is left to chance here. For example, detailed flow simulations or strength calculations highlight weaknesses long before the first mechanic even reaches for a wrench. The system is optimized first and foremost during this stage: through calculations based on the 3D data and simulations provided by the simulation team. If necessary, there are also second and third simulation and revision rounds. “For LEO Pharma, that wasn’t necessary. The technical engineering team had done a great job right from the outset,” says Koyuncular. In fact, however, insights obtained from simulations in comparable earlier plants were also incorporated. Koyuncular adds: “In our approach, the technical engineering and simulation teams benefit time and time again from feedback from the iFAT. This makes our models increasingly precise and reliable.” The P&ID planning and the interface concept, for example, could be finalized in no time for this project. Just as straightforward was the coordination of the security concept between Optima and M+P. Here, the fact that all plant components come from a single source has already paid off.
All parts of the new line for LEO Pharma have since been set up. After completion of the basic commissioning of the isolator at M+P in Radolfzell, the commissioning team determined that the transport and the merger with the other line components, such as the bag unpacker, Tyvek removal robot, and syringe-filling and closing machine, would take place in late September 2019 – naturally, in the CSPE Center in Schwaebisch Hall. Simulating later production conditions, the line was connected to media such as ultrapure water. Individual interface issues between the individual machines could be resolved quickly, because the necessary experts were instantly available in Schwaebisch Hall.
During commissioning, the comprehensive approach of the new method pays off once more: the quality of the basic settings for the machines are no longer dependent on the experience of the technicians. Rather, digital engineering and simulations together provide the basic parameters with high accuracy. Subsequent fine-tuning and pre-cycle development are much faster than before. The Chairman of Optima Pharma explains: “We’re seeing an essential paradigm shift here. Especially as the models are becoming more and more accurate as experiences are fed back. Simulation can even support later modifications to already delivered systems. We're switching from an experience-based model to an integral, data-driven model that leads to continuous improvement deterministically and no longer randomly,” says Breu.
After delivery to LEO Pharma, the system will be positioned in a cleanroom – unlike at Optima. “Other environmental conditions usually bring with them a certainrequalifi cation effort,” states Koyuncular, “but in the projects we have already completed, this was necessary only to a lesser extent than usual. Much of what has been qualified by us can be simply taken over, along with the relevant documentation. "This not only saves customers valuable time until the start of production, but also manpower. Anyone who has had to use expensive freelancers for requalification, for example, can now have this important task taken care of by their own employees – and thus also keep the knowledge gained in-house.
Our customers have recognized the added value it gives them. CSPE is quickly becoming a model of success – and one that is not easily duplicated!
In the future, every Optima Pharma turnkey project is set to benefit from the CSPE process including iFAT. The new hall is reserved exclusively for this purpose. “We’ve listened carefully to our customers,” says Gerhard Breu, explaining: “The requirements of minimal time-to-market, as well as the trend towards increasingly flexible and thus more complex systems have encouraged us to provide our process engineering on an entirely technical-scientific basis. In a nutshell: CSPE, Comprehensive Scientific Process Engineering.“ And it works. Breu is currently receiving a lot of positive feedback. “Our customers have recognized the added value it gives them. CSPE is quickly becoming a model of success – and one that is not easily duplicated!”