“Closed loop” is not a new technical feature. In fact, it was the only option to advance a complex turnkey project at an international CDMO in China when the Covid19 pandemic forced a hard lockdown. This project crossed many borders.
In November 2020, Optima Pharma received the order for a complex project in China. However, the project had to be carried out under difficult circumstances due to the outbreak of the COVID-19 pandemic. The complex project consisted of a turnkey MultiUse system with isolator and two freeze-dryers with an output of 6,000 containers/h, as well as a MultiUse R&D system with isolator.
During the pandemic, different countries had their own regulations in place to control the spread of the virus. Hendrik Hempel, Director Pharma at Optima Shanghai has been living in China for several years. He explains that life in China was relatively normal at first, as long as there were no registered infections nearby. While entry restrictions were imposed on foreigners, restaurants were still open within the designated “bubble”. In contrast, Germany implemented measures such as remote work and lockdowns to combat the virus.
In the second half of 2022, the delivery of Optima’s system components coincided with the rise of the Omicron virus variant. In Germany, most of the regulations were lifted, unlike China, where the government enforced a zero-Covid policy with a hard lockdown. The question now was how could Optima possibly install two lines in China, especially with one being a very complex system, under such circumstances? First, the single-lane R&D MultiUse system was sent upfront, since Optima Shanghai was proficient to completely set up, wire and prepare the R&D MultiUse system with an isolator for commissioning independently.
What about the larger part of the project, the four-lane MultiUse system with an output of 6,000 containers/h, isolators and two freeze-dryers? Time constraints on the customer side led to challenges on Optima’s side due to the new Covid regulations. With the sure prospect of ten or more days in quarantine, travel to China became virtually impossible. However, without the support of the German specialists, the installation of the complex line would be virtually impossible. The CDMO submitted an application for a “closed loop”, which essentially created an extended quarantine zone within the customer’s facility for the German/Chinese Optima crew to work safely.
This also allowed the Optima’s German experts to work on site, which helped expedite the project. Entry of the specialists into the country was carefully planned to avoid overlapping times and minimize quarantine phases. After a negative Covid test, free movement was permitted in the separated zones including the hotel, the company premises and the shuttle bus between the hotel and the customer. Cody Ma (Optima Shanghai), who was the responsible site manager and the interface to the customer, found out that this closed-loop regulation was strictly enforced when he brought the first German colleagues from the airport to the hotel and he had to quarantine with them.
Due to the closed-loop regulations, the installation area turned into a narrow one-way street. The question “When will each part of the line be brought in?” was crucial. A single mistake would have meant taking steps backward and complicated logistics. The team now worked in twoshifts to get back close to the original timeframe again. This involved meticulously planning. While the first shift was setting-up the filling line, the second shift worked on the isolator and had exclusively access to the filling machine to work on the isolator integration, reports Cody Ma. Special tools and testing devices always had to be available on time and at the correct location.
Optima’s on-site employees demonstrated remarkable commitment, which the customer appreciated. However, the region was hit by a large wave of infections when strict Covid regulations were unexpectedly lifted at the beginning of this year, affecting the customer’s site as well. Meanwhile work is now back to normal on site without any restrictions.Cooperation with the customer and across borders
Specific organizational processes were and are essential for the success of this international project. This means Optima Pharma Germany assumes responsibility of the project management, in close cooperation with Optima Shanghai, as well as the Optima isolator and freeze-drying experts. Project discussions with the Chinese CDMO are held between Optima Pharma Germany and Optima Shanghai, reports Hendrik Hempel. Optima Shanghai in turn reports to the German project management on the on-site progress.
According to Cody Ma, there is also close international cooperation at the customer’s site. They use virtual reality to send instructions and explanations across geographic borders from Germany to the customer’s site in China.
The deployment of the ten German employees during the closed-loop phase was also closely coordinated between Optima Shanghai and Optima Pharma in Schwäbisch Hall, ensuring a smooth and efficient process. After the German colleagues arrived on site, they immediately set-up the one-lane R&D MultiUse system.
A process engineer from Optima Shanghai supported the completion of cycle development. Cycle validation began at the end of July 2023, followed by the customer’s media fills. The large MultiUse line is also progressing well - various formats are already tested or completed. The CDMO’s employees are available to support the commissioning if necessary, such as for media connections.Another culture
It’s interesting to learn about the experiences of German employees working with their Chinese counterparts at Optima Shanghai. One of the challenges the German employees faced was figuring out how to pay for things while in China, since a payment app is necessary. Fortunately, with the help of locals, they were able to install the app and make purchases. Cody Ma also contributed to the project with his cultural knowhow. For example, the Chinese co-workers are used to a “fasterfaster” pace of work, while for German colleagues a stepbystep approach has priority.
Several major turnkey projects in China including filling machines, isolators and freeze-drying systems are already on the order books. Optima Pharma looks forward to these new projects with great confidence due to the organizational background and the great cooperation between the Chinese and German employees illustrated by this recent project.
Highly flexible MultiUse system with isolator and two freeze-dryers in China
The Chinese CDMO market is very competitive. The decision for a certain filling and capping line with an isolator and freeze-drying system requires careful consideration of price structure, quality, product yield and on-site service. In addition, the system’s configuration is very important, as it can influence the productivity and efficiency, as well as the market positioning of a CDMO.
The multinational CDMO has opted for a highly flexible MultiUse system from Optima for the Chinese market. This system will process vials (bulk and ready-to-use), pre-filled syringes and cartridges, each with a wide range of format sizes.
The turnkey system has a 100% inprocess control for all container types, up to a maximum output of 6,000 objects per hour with four-digits. CDMO customers can be sure withfunctions like priming, post-dosing and re-stoppering, that there is almost no product loss. Almost 100% of the existing drug is converted into salable product.
For CDMO customers dealing with high-priced and valuable pharmaceuticals, these system functions can quickly prove to be profitable. Pharmaceuticals with highly-active ingredients can be processed with a special isolator design and an external washing machine. The CDMO also benefits from the quick change-over time of format parts. The short decontamination cycles of the Optima isolator allows the system to be ready for production quickly. The T-shaped set-up of the freeze-dryers provides the potential for increased system uptime. If pharmaceuticals are in the freeze-dryers, vials, pre-filled syringes and cartridges can still be filled and closed during the freeze-drying process, which can sometimes take several days. The second freeze-dryer can also be actively used at the same time.
The vials closure is completed on the downstream crimping machine. The product paths of the two freeze-dryers are separated at a crucial point, so vials can be transported to the crimping machine after the stopper is placed. The stopper placement station, with a connected renester, is located before the transition to the loading station of the freezedryer. Prefilled syringes and cartridges leave the MultiUse system on this path. This extensive turnkey MultiUse system at the CDMO is supplemented by a single-lane MultiUse machine with an isolator, which is used for R&D purposes.