Sterile and safe: When robots support the production of live-attenuated vaccines

The leading manufacturer of chickenpox vaccines in China, Changchun Keygen Biological Products relies on robot-based cell factory automation to produce live-attenuated vaccines in a hygienic environment with the highest efficiency. One essential process is the cultivation of the virus in special containers or “cell factories” requiring high-intensity oscillation. Robotic systems integrator Shenyang Great Elites Intelligent Equipment engineered an automated solution with no fewer than 12 Stäubli TX200 Stericlean robots.

Today, chickenpox hardly poses a threat to children or adults – thanks to a vaccine that is used worldwide and consists of live-attenuated varicella viruses. This type of vaccine encourages the body to create antibodies and memory immune cells, thus stimulating a strong, effective, long-lasting immune response. This prevents children from being infected with chickenpox and minimizes the risk of developing much more serious complications such as meningitis, pneumonia, and in the course of a lifetime, shingles (herpes zoster).

China’s biggest manufacturer of these vaccines, Changchun Keygen Biological Products (CKBP) in Changchun was established in 2003. With an annual production capacity of eight million doses of chickenpox vaccine, the company is not only supplying the domestic market but also exporting the live-attenuated varicella vaccine to various countries like South Korea and India.

A major step: From manual-assisted to automatic operation

CKBP was one of the first Chinese companies to utilize robots for vaccine production. The decision for a high level of automation was driven by the need to eliminate all potential xenobiotics, impurities, and contamination caused by personnel to the greatest extent possible and maintain a strict, sterile production environment. A high level of automation is a prerequisite for the safe production of high-quality vaccines.

Given these requirements, robotic systems integrator Shenyang Great Elites Intelligent Equipment – well familiar with the automation of critical processes in biopharmaceutical production – engineered a system that has enabled CKBP to upgrade its live-attenuated varicella vaccine production from traditional manual to automated operations.

Twelve robots in the vaccine factory

Apart from “robotizing” CKBP’s varicella vaccine production, the two companies jointly developed a mixing system, quantitative peristaltic pumps, pipeline automation systems, and other equipment. As a result, the entire facility is highly automated.

Core processes of vaccine production include cell factory passaging (including the addition of active ingredients like trypsin and a growth medium) and cell factory inoculation, where the containers filled with the liquid base substance are “fed” the varicella virus and other ingredients. After this, the containers must go through defined movements – like shaking, flipping, oscillating, and recovering – in sequence.

In the first process, cell factory passaging, four robots are involved. In the cell factory inoculation and cultivation steps, eight robots perform multiple tasks, including harvesting and cleaning the cell factories. A robotic tool change system allows for automated filling and emptying of the liquid vaccines and changing of the factories. Each robot is relatively independent and can alternately handle two stacks of cell factories. Changing the cell factories is enabled by quick change tools from the Stäubli portfolio.

Aseptic robots for sterile environments

The automation experts from Shenyang Great Elites opted for 12 identical robots in the cell and virus culturing stages – for good reasons. The six-axis Stäubli TX200 robots are available in the Stericlean version, which means they are designed for the very special environment in which they are working: critical applications in aseptic GMP Class A production areas, where these specialized robots have proven themselves thousands of times over.

The kinematics of the Stericlean six-axis machines are fully encapsulated and sealed tight, with all cabling on the inside. There are no dead spaces, only smooth surfaces on which there is no opportunity for the formation of impurities. The unique specifications of these outstanding pharmaceutical robots make them resistant to the harshest of regular sterilization, disinfection and decontamination procedures, for example with hydrogen peroxide in vaporized form (VHP). This method is used in CKBP’s vaccine production.

Precise and efficient

Apart from the high-grade hygienic requirements, there were other reasons for choosing the Stäubli TX range. Cai Yan, General Manager of CKBP explains: “The robots perform their tasks with high precision, high productivity and availability, and minimal maintenance requirements.” Robust drive systems were another important aspect, according to Cai. “The cell factories oscillate

frequently and at high speed. This requires extremely high stability of the robot arm.” Another strong point is the connectivity of the robots. Their control system is integrated with the pipeline automation system, offering fully automated vaccine production management.

In contrast to the manual operation employed previously, the robots are a great improvement with respect to the health and safety of the skilled staff. “Due to physical exhaustion, we often needed two groups of workers, and they sometimes suffered joint injuries. Now, the robots free our employees from heavy labor, and deliver the highest quality during all shifts,” said Cai.

Introducing the integrator: An expert in highly automated biopharmaceutical production

Shenyang Great Elites Intelligent Equipment is committed to providing customers with professional and intelligent solutions for biopharmaceutical production. It specializes in the biopharmaceutical industry and enables smart digital production lines. Its main products include CFAM series cell factory automation equipment, 10-layer cell factory automation workstations, intelligent cell observation equipment, and aseptic filling equipment.

Text interview with Great Elites:

Business growth in high-end biopharmaceutical production with Stäubli robots

In this short interview, Bian Tianyuan, General Manager of Great Elites Intelligent Equipment, explains how his company and Stäubli collaborate on the development and delivery of automation solutions for biopharmaceutical production.

What are, from the user´s view, the main benefits of fully automated vaccine production?

Vaccine production automation involves a high degree of technological integration. It combines numerous advanced technologies such as robotics, sensor technology, and control technology to achieve full automation from raw material processing to finished product packaging. This highly integrated technical characteristic makes vaccine production more efficient, precise, and reliable. Additionally, robots can maintain precision even during long periods of continuous production. Furthermore, vaccine production automation adheres to strict cleanliness standards. When using robots that meet high hygienic standards, we no longer need to worry about maintaining cleanliness during the production process.

Why did you select Stäubli as a robot supplier?

We have been working with Stäubli in the field of robotics for many years and have established a mutual understanding of cooperation. Stäubli’s life sciences team has accumulated deep technical knowledge and rich industry experience. Whether in early-stage technical consultation, program design, later-stage installation and debugging or maintenance, they are able to provide timely, professional support. This comprehensive service guarantee allows us to advance our work more smoothly and efficiently during the project implementation process.

What features do you particularly appreciate about the robots?

On the product side, Stäubli’s robots are renowned for their excellent stability and accuracy, and they maintain excellent performance during long-term continuous operation. At the same time, they also offer high flexibility and scalability. Their robots can be externally integrated with various devices and systems to achieve real-time detection and monitoring of the robot’s status. This integration capability makes our solutions more complete and comprehensive, and better able to meet the needs of our customers. To sum it up, we have established a long-term and lasting partnership with Stäubli. We believe that in future collaborations, Stäubli will continue to provide us with quality products and services, helping us to continuously expand the market and achieve business growth.

Do you use Stäubli robots regularly in medical and pharmaceutical applications?

Our core competence is providing customers with professional and intelligent integrated solutions for biopharmaceutical production. The main products include CFAM series cell factory automation equipment, 10-story cell factory automation workstations, intelligent cell observation equipment, sterile filling equipment, and others. We have, just to name a few applications, also collaborated with Stäubli on the Vero cell rabies vaccine transfer bottle project of Liaoning Chengda, the cell detection project of the Institute of Human Genetic Resources, and a toothbrush head packaging project for Procter & Gamble.

Thank you very much for sharing these insights!