The requirement
Osteoarthritis in dogs is a degenerative joint disorder that leads to permanent deterioration of the cartilage, which provides cushioning for the joints. This painful condition is estimated to affect as many as 90% of dogs over five years of age in the United States1 .
The world’s leading animal health company, Zoetis, was looking for a partner to help manufacture the drug substance for Librela® (bedinvetmab), a first-in-class monoclonal antibody (mAb) used to treat this condition. Based on a long-standing relationship, Zoetis decided to partner with Syngene for this project. Zoetis signed a 10-year supply agreement with Syngene to manufacture the drug substance, leveraging Syngene’s specialist biologics manufacturing skills and facilities in its Bengaluru campus.
The challenge
- First-time-right scale-up of the drug substance from 10L to 500L
- Meeting stringent process performance parameters during scale-up
- Optimizing process conditions to consistently achieve the product quality set by the US FDA while maintaining titer
The Solution
As a first step, Syngene and Zoetis developed the process of manufacturing the drug substance for the EU. In the scale-up and manufacturing phase, the first requirement was to get the batches right the first time with seamless planning and batch execution. Syngene’s Animal Health team scaled up the process from 10L scale to 500L scale according to the veterinary international conference on harmonization (VICH) guidance documents for batch material supply. Thereafter, process performance qualification (PPQ) runs were carried out on a 500L scale for registering Librela in the EU. The product was successfully filed in the EU and approved by the EU.
As preparations for entering the US market started, the US FDA requested additional controls around the specifications for the drug substance. In response, the Syngene team, in consultation with the Zoetis team, designed and executed additional Design of Experiments studies in Ambr® 250 system and 10L bioreactors. Syngene also performed multivariate data analysis (MVDA) modeling to arrive at optimized process conditions that could consistently achieve the product quality set by the US FDA while keeping the titer unchanged.
This process was then scaled up to 500L and 2,000L for commercial manufacturing. This was followed by the production of process performance qualification (PPQ) batches. The US FDA approved the drug on May 5, 2023 based on 500L scale, and Librela was launched in the US in November 2023. Following FDA approval, Syngene embarked on commercial drug manufacturing for the US market.
Getting it right the first time
Several factors contributed to the success of the manufacturing program. Precision emerged as a key requirement involving the delivery of accurate batches from the first attempt. Another crucial step was the successful completion of a US FDA inspection of our biologics manufacturing facilities, which was completed without any 483 observations. This commitment to excellence and efficiency paved the way for an early product launch, eliminating the need for improvements mandated by the US FDA.
Conclusion
The Syngene-Zoetis partnership is going from strength to strength, rooted in the latest science and technology. With a shared commitment to operational excellence, compliance, and global quality standards, this partnership has demonstrated the power of working closely together to achieve a common goal. Despite dealing with a complex manufacturing process, the team solved problems together and delivered innovation at every turn. As a result, the EMA and US FDA approvals for Librela were achieved, and commercial supply of the drug was assured for the EU and US markets.
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