[Edaily Reporter KIM JI-WAN ] “What you’re seeing now is the process of packaging the finished product.”

Workers were moving about beyond the window. They were wearing coveralls that covered them from head to toe, along with masks and gloves. On one side, workers were preparing packaging, while on the other, the process of harvesting and washing cultured cells was underway.

“So, is the medication for the first patient to receive treatment under the Advanced Biotechnology Act No. 1 being packaged right now?”

That was the explanation given. Among the press corps, someone remarked, “This is a historic moment.” This was the scene witnessed on the 22nd at the “V-Cell Center,” a GMP manufacturing facility operated by VigenCell. What was being prepared right before our eyes was not a mass-produced product intended for sale to the general public. It was living cells that originated from a single patient and would eventually return to that patient.

The first administration of VT-EBV-N is scheduled for this coming December. The manufacturing site unveiled that day was in the process of preparing for that first administration. Once cultured and packaged, the cells undergo quality testing and shipping procedures before being delivered to the patient. The final preparations were underway, bridging the gap between treatment plan approval and actual patient care.

VT-EBV-N consists of T cells obtained from a patient’s blood that have been stimulated to recognize the Epstein-Barr virus (EBV) antigen and proliferate. The goal is to reduce the risk of relapse by administering it to lymphoma patients who have achieved complete remission following standard treatment.

Prior to the on-site tour, Kim Hyun-woo, Manager of the Communications Team, who led the briefing, began by explaining the nature of this media visit.

“We intend to show you the facility where the actual therapeutic is manufactured without any filters.”

Shin Chang-ae, Head of the Manufacturing Team, led the tour of the manufacturing facility that day, while Executive Vice President Shin Young-bae provided additional explanations regarding production capacity and commercialization strategies.

Incoming materials and outgoing waste… even the access points were separate

The first thing that caught the eye at the entrance to the manufacturing facility was the access control system. Workers have their identities verified via fingerprint. It was explained that only trained and qualified personnel are permitted to enter the manufacturing area.

Not only people but also the routes for incoming goods were strictly designated. Items necessary for manufacturing—such as culture media and laboratory consumables—pass through designated intake facilities. They are disinfected to prevent contamination from external sources, and items requiring sterilization are processed separately.

“We manage the flow separately to ensure that waste cannot exit through the same route used for incoming raw materials.”

Team Leader Shin pointed to a separate area designated for waste disposal. This separated the path for clean supplies entering the facility from the path for used items leaving it. Successfully cultivating cells begins with controlling what is brought into—and removed from—the space where they grow.

The workers’ preparation was no simple task either. After washing their hands and changing clothes, they wore three layers of sterile garments before reaching the final work area. They also used sterile masks, hair caps, and gloves.

Unlike the reporters watching from outside the observation window, the workers inside had to handle the cells while dressed this way. Some reporters even remarked, “Isn’t this harder than being an astronaut?” Even a single hand movement—such as handling a small pipette—was accompanied by procedures to prevent contamination. Storing unused tools in designated areas served the same purpose.

Patient-specific segregation was even stricter. Manufacturing processes for different patients are never conducted simultaneously in the same workspace. Incubators are also designated for each “batch,” which is the manufacturing unit per patient. Consumables used in production are never reused for the next patient’s process.

Once work is complete, cleaning and environmental management procedures must be carried out. When moving on to the next batch, time is set aside to allow the air conditioning system to stabilize. Team Leader Shin explained that they sometimes allow about one to two hours for the indoor environment to stabilize after cleaning. It wasn’t a system where production volume could be increased simply by working faster at the workbenches as the number of patients grew.

“Training” Cancer Targets on Patient Cells… A Wait Even After Manufacturing

Viewed through the observation window, the manufacturing room resembled a well-organized laboratory rather than a massive production line. Incubators resembling refrigerators were lined up, and workers carried out their processes at their respective stations. Containers filled with a reddish liquid were also visible; this was the culture medium used to grow the cells.

There were no automatically moving conveyor belts, nor was there a scene of the same product being churned out in large quantities. The nature of autologous cell therapy—in which cells from each patient are received and handled individually—was clearly evident in the space.

The manufacturing process begins with the isolation of cells sent from the hospital. The company explained that it requests the hospital to provide raw material consisting of concentrated white blood cells. On the first day alone, the cell isolation process typically takes about six hours.

This is followed by a process designed to teach the T cells to recognize the targets they must attack. The tour guide likened this to “training.” The process involves preparing cells that present cancer-related EBV antigens and using them to repeatedly stimulate the T cells.

“So, doesn’t that mean the more ‘training’ they get, the better the results?”

The response from the manufacturing site to the reporters’ question was not straightforward. They explained that longer cultivation periods do not necessarily lead to better results. Since extended cultivation can affect cell viability, the appropriate number of stimulation cycles and duration were determined during the process development phase.

According to the company, the manufacturing process takes about 28 days. It takes about a week to prepare the antigen-presenting cells, followed by about three weeks to stimulate and cultivate the T cells. In other words, it takes nearly a month to transform a patient’s cells into cells with the required functions.

That day marked the packaging of the first patient-specific cells to undergo this process. However, even after packaging is complete, the cells are not immediately sent to the hospital, as quality control testing still needs to be conducted.

Team Leader Shin explained the tests used to check for contamination, such as extrinsic viruses and mycoplasma, noting that some tests require a 28-day observation period. This is why another waiting period is necessary even after manufacturing is complete before the cells can be delivered to the patient.

The finished product is packaged in small bags. At the hospital, it is thawed according to established procedures and administered intravenously using a syringe. The storage temperature prior to shipment is -140°C or lower. The product remains frozen even during transport to the hospital.

When this reporter asked if it was possible to photograph the packaged products, staff on site explained that the survival rate of the living cells and rapid processing were critical. These were not items that could be left out for an extended period just to take a single photo.

“Once GMP is activated, it cannot be turned off”… Monitoring Continues Even at Dawn

The equipment management system observed outside the manufacturing room was like another production site. If an anomaly occurs, a text alert is sent to the person in charge. There are no exceptions, even at dawn. All alarms and corrective actions are logged.

Even during hours when no staff are on-site, the manufacturing environment and storage conditions must be continuously monitored. The company explained that it is equipped with facilities to prepare for power outages, such as emergency generators. In a facility handling living cells, the end of the workday for employees did not mean the end of monitoring.

The V-Cell Center spans approximately 1,384 square meters. It is equipped with seven cleanrooms. According to the company, approximately 10 people work in each of the manufacturing and quality control teams, and the total workforce involved in GMP operations numbers about 30.

Based on the process rooms and bioreactors currently in operation, the facility is capable of producing up to 16 batches per month. Vice President Shin stated that the company is internally reviewing a target of approximately 300 batches per year should facility utilization be increased to meet future demand. However, this is not the current production output but rather the projected scale when the equipment is fully utilized.

Maintaining the facility is just as challenging as securing it. Even when supply volumes are still low, personnel for HVAC, environmental control, and quality control are necessary.

Vice President Shin said, “Once GMP facilities are powered up, they incur enormous costs,” adding, “Once they’re turned on, they can’t be turned off.”

If operations are halted, the facility must be cleaned again, the manufacturing environment restored, and its suitability verified. The time required to resume operations also represents a cost. Vice President Shin explained that this manufacturing capability is a critical requirement even for the overseas technology transfer of autologous cell therapies. This means that the company adopting the technology must be able to perform manufacturing and quality control at the same level locally.

The process involves collecting, culturing, and testing cells from a single patient separately. The first patient’s cells, observed through the viewing window that day, embodied all of these procedures. For the approval of an advanced regenerative medicine treatment plan to translate into actual patient care, not only the clinical data presented in the materials but also the time invested in the manufacturing facility was essential.

As the tour concluded, company representatives emphasized once again:

“What we showed you today is not a simulation, but an actual manufacturing facility.”

Questions left unanswered on-site… We asked BioGenCell

The following are written responses we received separately from BioGenCell regarding manufacturing technology and the feasibility of patient-specific production. To aid the reader’s understanding, technical terms and expressions have been simplified and clarified.

―What is the most challenging aspect of the T-cell cultivation process?

“It is more difficult to selectively and intensively increase the number of T cells that recognize the EBV antigen than it is to simply increase the total number of T cells. We have established a method for combining mRNA containing antigen information, antigen-presenting cells (APCs) that display this information, and the T cells being trained in optimal proportions. Through this, we were able to mass-produce T cells that respond to the EBV antigen.”

―How do you train a patient’s T cells to recognize EBV-positive cancer cells?

“Simply put, it’s the process of teaching T cells the characteristics of the target they must attack. First, we introduce the genetic information for producing the EBV antigen in the form of mRNA into antigen-presenting cells (APCs). The APCs act as ‘teachers’ that present the target to the T cells. The goal is to enable these trained T cells to recognize and attack cancer cells expressing that specific EBV antigen.”

―Can these cells be produced for patients with weakened immune systems or those who have undergone multiple rounds of cancer treatment?

“It is possible for patients who pass the preliminary screening. In actual clinical trials, there have been successful cases of production using cells from patients who had undergone multiple rounds of cancer treatment. We do not automatically rule out production based solely on a history of cancer treatment. Since the condition of the cells varies from patient to patient, we confirm the feasibility of production through preliminary screening.”

―How long does it take from blood collection to completion? What are the manufacturing costs?

“It takes 28 days from blood collection to isolating the cells, training them, and culturing them to the required quantity. After that, another 28 days are needed for quality testing. Combined, manufacturing and quality testing take about 8 weeks. While the manufacturing costs are significant, the specific costs are trade secrets and cannot be disclosed.”

―Since the condition of the cells varies from patient to patient, how do you ensure consistent quality?

“Through years of clinical research and process development, we have established inspection criteria for each manufacturing stage and quality standards for the finished product. We monitor the manufacturing process and inspect the final product according to these standards. Skilled personnel who have been responsible for the process for a long time carry out the work, and we are minimizing variations caused by individual operators through ongoing education and training.”