Self-sufficiency in drug supply chain for India means indigenous processes and platform technology to produce these important KSMs.
The Union Cabinet, headed by Prime Minister Narendra Modi, had approved on March 21 a special package for the promotion of bulk drug parks to finance common infrastructural facilities and production-linked incentive schemes for the manufacture of key starting materials (KSMs)/ drug intermediates and active pharmaceutical ingredients (APIs) in the country, in response to the medical emergency situation which might arise due to the Covid-19 lockdown for an extended period.
A list of 53 APIs/ bulk drugs was identified, half of which are based on chemical synthesis, on which CSIR-National Chemical Laboratory (CSIR-NCL) is focussing. The Indian pharmaceutical industry is the third-largest by volume but is critically dependent on imports of raw materials or KSMs, in some cases to over 80% extent, mainly from China, a note issued by CSIR -NCL said.
Drug security, self-sufficiency and continuous supply of essential medicines are the need of the hour for national security and healthy population. India has the largest number of FDA-approved manufacturing sites outside of the US, it added.
More than 27 or so bulk drugs covering different therapeutic classes such as anti-viral, retro-viral, antibiotics, anti-bacterial, anti-fungal, cardiovascular, diabetes, cholesterol-lowering, anti-cancer to simple pain killer like paracetamol, are synthesised from about 10-12 simpler building blocks or KSMs/ drug intermediates. Self-sufficiency in drug supply chain for India means indigenous processes and platform technology to produce these important KSMs.
In consultation with industry experts and from the list of essential APIs, the Organic Chemistry and Chemical Engineering scientists of CSIR-National Chemical Laboratory analysed the structures of chemical intermediates and the state of readiness employing synthetic routes which are scaleable and economical.
For 3-4 drug intermediates/ bulk chemicals, projects are already ongoing continuous flow synthesis, process optimisation and reaction engineering, an area in which CSIR-NCL has prior experience and expertise, the statement said.
The CSIR-NCL scientists have reported a novel and economical chemical synthesis of cystic fibrosis drug Ivacaftor in 2018, which is one of the highest priced drugs for patients ($300,000 per year per patient). The laboratory had recently demonstrated flow synthesis with minimal or no solvent use which will make significant economic benefit when translated for the identified molecules. Apart from cost economics, minimal chemicals, process safety, and environment friendly, the biggest advantage of multi-step continuous flow technology is that the production can be carried out on smaller scale in a distributed model at several locations, a factor which will be important in the medical emergency situation facing the country, CSIR-NCL stated.
CSIR-NCL director Prof. Ashwini Kumar Nangia is hopeful that they will be able to release the reports to the government and chemicals and pharmaceutical industry bodies soon as each laboratory scale process is ready in the next few weeks and months to be taken up for manufacturing by Indian drug companies. The capability and infrastructure for further synthesis of final APIs from the intermediate KSMs largely exists in the country.