Levetiracetam, an epilepsy medication used for partial onset, myoclonic or tonic-clonic seizures, was first approved for medical use in the United States in 1999. As a drug, it boasts excellent safety & therapeutic indices and high compatibility with other anti-epileptics.
Levetiracetam is now available as a generic. The global market is closing on 2,500 metric tons, and continues to experience a combined annual growth rate (CAGR) of 8-10%.
Backward Integrating SABAM
From an API manufacturer’s standpoint, intermediate costs are increasingly defining drug manufacturing market dynamics. Companies with API manufacturing capabilities, capacity & know-how are in a position to control pricing dynamics. This is the case with Levetiracetam’s intermediate, SABAM.
It’s a drug that has experienced a number of global shortages in recent years, in a number of different formats (both injectable and oral dosages).
The precursor chemicals for SABAM manufacturing are widely available around the world at affordable prices, without supply bottlenecks. In spite of this easy access to starting materials, SABAM can be tricky to manufacture – increasing its price.
Neuland manufactures about 6-8% of the world’s supply of Levetiracetam. With multiple customers, it’s one of our core products – which led to the decision to backward integrate SABAM manufacturing. Our goal is to reduce Neuland’s reliance of external suppliers and secure our supply chain to avoid disruptions. It also ensures our customers aren’t exposed to constantly-shifting market pricing and availability.
Since SABAM is the critical raw material for Levetiracetam, the production cost depends largely on the cost of SABAM. In fact, nearly 50-60% of the cost of the entire API is for SABAM.
To bring manufacturing in-house, our team performed extensive development work. In our R&D Centre, we identified and compared various routes and processes. Once a preferred route along with an economical & safe process was chosen, SABAM underwent the same tech transfer and validation processes we use for external clients.
Challenges of Manufacturing SABAM
Now, there are some challenges to manufacturing SABAM. This key intermediate of Levetiracetam is (S)-2-amino-butanamide hydrochloride (SABAM). For a cost-effective, bulk manufacturing process, we determined – after exploring all other commercial manufacturing options – that it was necessary to use the ‘cyanide route.’
The cyanide route is referred to as Strecker synthesis, and is described as a method of synthesizing amino acids by reacting an aldehyde with ammonium chloride in the presence of potassium cyanide. Given the volumes of SABAM needed, this route requires handling hazardous materials in bulk quantities.
The cyanide route is optimal, as the necessary raw materials for SABAM are abundant, available, and easy to access. In fact, one of the key synthesis chemicals is available in abundance, as a commodity chemical. This ensures stable availability, and removes dependency on other markets and external suppliers.
Implementing a Safe & Effective Bulk SABAM Process
Bulk SABAM production faces one particularly large challenge: hazardous materials handling. Due to the bulk volumes of dangerous chemicals required during manufacture (including cyanide, ammonia and other potentially hazardous materials), comprehensive controls were needed to ensure the health & safety of our team, and prevent potential environmental issues.
First and foremost, we needed to be certain we had technology in place to detect trace amounts of the hazardous chemicals in solid, liquid and the gaseous form at parts per million (ppm) levels. This informed our use of detectors, devices, and new air handling mechanisms. We planned and deployed specifically-designed control measures, coupled with continuous 24X7 monitoring.
More Opportunities for Levetiracetam
The decision to manufacture the drug’s key intermediate in-house has already attracted additional new customers for Levetiracetam. One Japanese customer, in particular, cited supply chain worries and our backward integration as decisive in their choice of Neuland as a partner. As supply chain concerns have grown in recent years, pharma companies are relying on diversified supply as a key risk management technique.
Are you interested in learning more about SABAM? Contact us today!