The first in the class of drugs known as selective relaxant binding agents (SRBA), Sugammadex sodium is used to reverse anesthesia. Via 1:1 binding of rocuronium or vecuronium, it rapidly reverses any depth of neuromuscular block while avoiding cholinergic adverse effects. The generic ingredient in Merck’s Bridion®, Sugammadex reverses the effects of neuromuscular-blocking drugs that freeze vocal cords and muscles during surgery – allowing patients to be taken off breathing machines and go back to breathing on their own sooner.
Process Challenges Overcome by Neuland
Neuland has developed a robust, scalable, operationally safe process which consistently produces product as per desired yield and quality at higher volumes. The synthetic process consists of 3 steps:
- Stage 1: Prior art process involves the use of PPh3/I2 as a reagent for iodination which results in the formation of triphenylphosphine oxide as a by-product in a stoichiometric amount. The removal of the same is cumbersome. Neuland’s process involves the use of PCl5/DMF for chlorination.
- Stage 2: Prior art process involves the use of NaH/DMF for reaction with 3-Mercaptopropionic acid which is pyrophoric and hazardous. Neuland’s process involves the use of 30% NaOMe solution in DMF in this stage.
- Stage 3: Prior art process involves the use of dialysis purification which is neither feasible nor economical at an industrial scale. Neuland’s process involves preparative HPLC for purification and isolation of the final product by lyophilization.
In tech Sugammadex-Na (Stage 2), impurities at RRT 0.89 and 0.96 are very difficult to remove and attributed to Stage 1 intermediate quality. This was accomplished with purification by crystallization and achieves 85% purity as per Stage 2 specifications.
The preparative HPLC method is sensitive to many variables, including input material solubility, pH, and column performance—all of which were largely overcome with appropriate checkpoints in the process.
A process was also established to improve yield for the failed fractions unable to load into the preparative HPLC column directly.
Neuland is the first generic player to have a granted process patent for the preparation of Sugammadex Sodium in India (IN 290882/Expiry: Aug 25, 2030), USA (US 9120876/Expiry: Jan 15, 2032) and Europe (EP 2609120B1/Expiry: Aug 23, 2031).
Neuland’s API quality meets the regulatory requirements regarding any SMUI to NMT 0.089%, based on dosage value.
Early launch opportunity:
- A formulator can launch a product with Neuland’s Sugammadex API after November 2020 in the key markets India, Turkey, Canada and Brazil.
- US Market: A formulator can launch a product with Neuland’s Sugammadex API by filing ANDA with Para-IV.
- EU Market: A formulator can launch a product with Neuland’s Sugammadex API after July 24, 2023 when the product patent expires.
To discuss opportunities and find out more about launching a product with Neuland’s Sugammadex, contact Neuland Labs today.