Presented by Jordi Ruano
Jordi Ruano is Biologics Production Director at HIPRA, Girona Spain.
HIPRA is a veterinary pharmaceutical company dedicated to the research, production, and marketing of products for animal health. With headquarters located in Amer (Girona) Spain, the company is present in more than 30 countries with its own commercial subsidiaries and production plants in Europe and the United States.
Vaccines provide over 70% of the company’s sales revenues, and it produces about 20 different viruses using eight different cell lines grown in microcarrier-based adherent cell cultures. HIPRA previously had operated only stainless steel bioreactors to perform these cultures. Its multiuse bioreactor capacity comprised several bioreactors ranging from 200 L to 400 L working volumes. The company needed to rapidly expand this production capacity and faced the dilemma of installing more of the tried-and-tested stainless steel bioreactor capacity or opting instead for single-use bioreactors (with which HIPRA had no previous experience).
The company decided to purchase single-use bioreactors from Sartorius Stedim Biotech. The installation and validation of single-use bioreactors is quick because of their standardized design and the fact that no clean-in-place (CIP) or steam-in-place (SIP) validation is required. The bioreactors have a low capital cost and a small footprint, which is desirable in a space-constrained production facility. Further, BIOSTAT® STR bioreactors use the same geometries as the Sartorius stainless steel bioreactors that HIPRA was already using.
The company performed development runs in a BIOSTAT® STR 200, which has the same working volume as its existing 200 L stainless steel bioreactor, and recognized that some operating parameters would need adjusting during the transition to singleuse. Some processes required customization of the bioreactor consumables. Single-use operations require a greater number of manual operations than do stainless steel bioreactors. HIPRA recommends that companies place emphasis on operator training and apply visual indicators on component parts of consumables. Furthermore, standardization of manual operations helps to minimize the risk of manual errors.
Process data showed a high level of comparability between the single-use and multiuse bioreactors when assessed based on critical process parameters such as pH and dissolved oxygen. Product titers were equivalent when HIPRA compared batches from the two different systems. The company now has been able to manufacture all required antigens in single-use bioreactors. The team has installed a BIOSTAT® STR bioreactor with a twin controller configuration, allowing for the use of 50 and 200 L Cultibag STRs. The company also has installed two BIOSTAT® STR 500 bioreactors and plans to purchase more as its facility expands still further. The new bioreactors have been shown to have lower running costs and reduced downtime between batches compared with stainless steel bioreactors. HIPRA has successfully produced more than 200 batches of viral cultures with single-use bioreactors since 2011.