Aprogen Surpasses 1.5 Million Liters in Cumulative Commercial Scale Perfusion Production

Aprogen has succeeded in establishing a stable large-scale perfusion commercial production process.

On the 21st, Aprogen announced that the cumulative volume of antibody biosimilars produced through a commercial-scale large-scale perfusion (continuous perfusion culture) process, including pilot production and clinical sample production, has exceeded 1.5 million liters. The produced bulk drug substance was also successfully used to manufacture finished pharmaceutical products such as lyophilized formulations.

With this, Aprogen confirmed that it is a company capable of stably operating large-scale perfusion production processes under a strict quality control system that meets the standards of the US FDA. Until now, the industry had doubted the possibility of success in Aprogen’s attempt to commercialize production for the first time in the world using the world’s largest 2000L-class perfusion process. However, the company explained that it has completely dispelled those doubts.

The company first completed the Osong plant in 2018, equipped with two 2000L perfusion production lines and one liquid and lyophilized finished pharmaceutical production line. In 2020, it expanded the bulk drug substance and finished product lines to have four 2000L-class perfusion production lines, two liquid and lyophilized finished product lines, and one prefilled syringe finished product line. Since then, for about two years, it has continuously received consulting from more than 50 consultants from the US-based Valient company to establish a cGMP-level quality system. Through this consulting process and numerous trials and errors afterward, the company has been striving to build a stable production system.

Aprogen is the first company in Korea to pursue commercial production using the perfusion culture method, which requires advanced technology. It also introduced the ATF equipment, which separates cells and culture medium, returning cells to the bioreactor and recovering only the culture medium, to Korea for the first time in 2007. A representative pharmaceutical product commercially produced by perfusion is Johnson & Johnson’s ‘Remicade.’ Remicade is produced by operating dozens of 50L bioreactors using the perfusion method.

So far, the company has produced 42 batches at the 500L scale, considered a relatively large commercial scale in perfusion processes, 27 batches at the 1000L scale, and 21 batches at the 2000L scale, regarded as the maximum scale. It increased the scale from the relatively small 500L to the maximum 2000L possible with current technology, enhancing the completeness of its technology. The cumulative recovered culture medium volume exceeds 1.5 million liters. During this process, it also successfully completed PPQ (Process Performance Qualification) production at the 2000L scale. This means it has perfectly demonstrated the ability to stably operate the 2000L perfusion production process.

The 2000L perfusion culture line installed at Aprogen Biologics’ Osong plant can produce more than 100,000 liters of culture medium per single batch (one culture). In terms of the amount of culture medium produced, one 2000L perfusion culture line can achieve an effect equivalent to operating three traditional fed-batch (fed-batch single culture) 15,000L bioreactors simultaneously three times.

An Aprogen official said, “Over the past five years, despite difficult circumstances such as supply issues of raw materials due to COVID-19, there were many trials and errors and difficulties as we attempted the world’s first 2000L scale perfusion production.” He added, “Nevertheless, our company has succeeded in establishing a system capable of stably producing antibody drugs using the 2000L scale perfusion process.” He further stated, “This means that our company has global commercial competitiveness not only in development but also in production.”