To date, very few filling and capping machines with isolator technology have been installed in South Korea, let alone in Asia. However, biosimilars and biopharmaceutical products are a growing market in both the country and Asia as a whole and the increasing use of isolator technology is already a clear trend within this growing market. This is only expected to continue.
Both Oh-sung Na (Aprogen Biologics, shown on p50) and Peter Kim (Optima Korea) are certain of it because Aprogen is one of the pioneers of a new development. This article deals with the background of a special isolator project, and isolator technology in South Korea in general.
Biosimilar manufacturer Aprogen is a young company founded only in 2000. Beyond its home market in South Korea, the company is already active in Japan and the US. Various biosimilars as well as self-developed biologically-based active pharmaceutical ingredients from the company, are in the process of being approved.
Isolator technology is more attractive to regulatory agencies of various countries
The company founder and owner is Dr Jaeseob Kim, who was previously a professor at the Korea Advanced Institute of Science and Technology (KAIST) in Daejeon, and is an expert in the region on pharmaceuticals.
Oh-sung Na is responsible for "Fill and Finish" at Aprogen Biologics. When asked how the decision to go with isolator technology came about in the company, he says that there are several answers to this question. "As you know, the required background environmental conditions of a cleanroom differ between Grade C and B, depending on whether an isolator or a RABS (Restricted Access Barrier Systems) is installed, respectively. This means that, in the future, we will benefit from the less demanding environmental requirement, which will give us a cost advantage."
"At the same time, VHP decontamination in the isolator leads to a higher level of safety and quality of the product. Isolator technology is also more attractive to regulatory agencies of various countries. As a result, my CEO has strongly supported and invested heavily to secure an isolator."
Local companies in South Korea are expanding into international markets
Concurrently, the question arises, why is it only now that the first companies are taking this step? Peter Kim, Director of Sales Pharma for Optima Korea, believes the reason is that South Korean companies with highly trained plant operators and responsible GMP managers were able to cover the regulatory requirements in Asia with the current technology. But now local companies in South Korea are expanding into international markets, and because of the expanded regulatory requirements this entails, it is anticipated that there will be increased use of isolator technology.
"This is becoming increasingly difficult, especially for biosimilars, due to rising regulatory expectations and the high standards of the FDA and the EMA," Kim explains. The higher initial investment in isolator technology is then expected to be offset by cost advantages in operation and, in particular, higher process reliability.
Uncharted technical territory
"Aprogen will be one of the first two companies in South Korea to use the isolator technology on a high-speed syringe system," says Oh-sung Na. He is expecting other South Korean companies to follow soon. Kim confirms that Optima Korea has already received several inquiries from other local companies.
New technology, as well as the modified processes in the company, need to be learned and mastered by the staff and there may also be concerns about this stage. Oh-sung Na gives the reasonings that the progress is still needed: "On the contrary, I believe that the complexity of creating aseptic conditions will actually be reduced. Of course, the prerequisite for this is that the employees are thoroughly trained and be familiar with the HVAC and VHP systems. The only disadvantage that could become relevant for the "Fill and Finish" manager is that there is limited flexibility if changes or options to the system are added."
In two sentences, Oh-sung Na sums up his views on the isolator technique: "First, we need to invest further to perfect the technique, which is a disadvantage. But if we look at the questions and problems around sterile processing, the isolator technology, in the end, will achieve not only process advantages, but also economic advantages."
A persuasive concept
The system is designed for a dedicated syringe system and for filling quantities from 0.5 ml to 20 ml. A pertinent question however was how could the double-packed syringe tubing be processed automatically?
For Aprogen, this question was to be one of the decisive factors for the investment decision. "The second bag sits very tightly, hence a constructive solution was important to me, because otherwise, cutting the bag could lead to more problems. Other vendors were unable to offer this. I wanted to avoid any complicated and unnecessary procedures." Two consecutive bag unpackers resolve this problem. The second debagger uses vacuum technology to align the film for cutting so that it can be removed easily and safely. The OPTIMA Tyvek Removal Robot then removes the Tyvek paper.
The technical concept provides for a ten-digit filling station with peristaltic pumps, after removing the nest from the tub. There is an automatic weight check and the Aprogen system will already be prepared for filling and sealing under vacuum as a retrofit option. Each tub will receive a data matrix code that will be controlled by an OCV (Optical Character Verification) sensor.
The modular system will work starting from the unpacking unit up to and including the insertion of the stopper under isolator. Materials can be safely fed into the aseptic area via an MTC (Material Transfer Chamber) airlock that can be decontaminated. The output is in the high-performance range, with up to 36,000 syringes per hour.
Development
Another important point for the decision to invest in Optima -as well as the special solutions for unpacking the tubs- was also the references provided. Peter Kim knows that the service capacities were also rated as an important aspect by Aprogen. At present, the project is still at an early stage. In regards to the experience so far, Oh-sung Na reported: "I developed a lot of trust over the course of the mock-up and the design review. I was also impressed by the technical knowledge and professionalism of Optima and Metall+Plastic."
During the development phase, ideas from both sides, from both Aprogen and Optima, were also discussed. 45-year-old Oh-sung Na looks back on this time positively: "The ideas put forward by Aprogen were positively received and considered by Optima. Some of them were adopted, while others were not incorporated per Optima's recommendations, all of which were clearly explained and comprehensively justified."
There are still a few months to go until FAT and SAT. But, Oh-sung Na is looking forward to it with great anticipation: "Every time I think that this line is going to be installed and run in my factory, I am thrilled and my heart starts beating faster!"