Jonathan speaking at the Zoetis town hall in Belgium
Osteoarthritis in dogs is a degenerative joint disorder that leads to permanent deterioration of the cartilage providing cushioning for the joints. This painful condition is estimated to affect as many as 90% of dogs over 5 years of age in the United States (1). Syngene and Zoetis have joined forces to manufacture the drug substance for Librela® (bedinvetmab), a first-in-class monoclonal antibody used to treat this condition. The product, which was initially launched in the European Union (EU), won ‘Best new companion animal product’ by IHS Markit Connect in 2021 for its transformational impact on pain relief for canines.
Building on a long-standing relationship, Zoetis and Syngene have formed a 10-year partnership to manufacture the drug substance, leveraging Syngene’s specialist biologics manufacturing skills and facilities on the Bangalore campus.
To initiate the partnership, Zoetis and Syngene developed the process to manufacture the drug substance for the EU. In the scale-up and manufacturing phase, the first requirement was to get the batches right first time with seamless planning and batch execution. Syngene 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 registration of Librela in the EU. The product was successfully filed in the EU and approved by the EU in January 2023.
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 Experiments1 studies in AMBR2 and 10L bioreactors and 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 2000L for commercial manufacturing and process performance qualification batches were produced for the launch of Librela®. It was approved by the US FDA on May 5, 2023 and Librela® was launched in the US in November. Following approval, Syngene embarked on commercial manufacturing.
1 (DOE) is a systematic, efficient method that enables scientists and engineers to study the relationship between several input variables and critical output variables.
2 The AMBR® 250 system is a high throughput, automated bioreactor system for process development with fully featured single-use 100 to 250 mL mini bioreactors.
Several factors contributed to the success of the manufacturing program: precision emerged as a key requirement involving the delivery of batches that were accurate 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.
Rooted in the latest science and technology, the Syngene/Zoetis partnership is going from strength to strength. 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. In a complex process, the team has solved problems together and delivered innovation at every turn. As a result, the US FDA and EMA approvals were achieved in record time and commercial supply of the drug substance was assured.
Teams that work well together also celebrate together and the Zoetis/Syngene team joined forces across sites in Belgium, the US and India in November 2023 to celebrate a job well done.
Zoetis leaders at Syngene, Bangalore
(1) Physical activity patterns of free living dogs diagnosed with osteoarthritis
