Seqens has just announced that it is ready for mass production of hydroxychloroquine (HC). The French group estimates that, depending on the results of numerous clinical trials, worldwide needs could require production 4 to 10 times higher than usual. Therefore, since the beginning of the crisis, Seqens’ teams have been working to supply the active ingredient and its precursors in record time.
Seqens has worked in particular on the hydroxynovaldiamine or HND chain, knowing that HC is an assembly between HND and 4,7-dichloroquinoline.
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Starting point with acetyl-butyrolactone
The group did not start from scratch, even though its experience in the field dates back to the 1990s. At that time, teams at the Lahr site in Germany had been involved in the development of acetyl-butyrolactone (AB-lactone). The latter is an important precursor. It provides access to 5-chloro-2-pentanone (chloropentanone) which is then reacted with N-(2-hydroxyethyl)-ethylamine.
The product of the reaction is finally purified by distillation before being hydrogenated under an ammonia atmosphere to obtain HND. The large capacity of hydrogenation under pressure in a specialized workshop allows this synthesis of the HND side chain under good conditions of safety, quality, and yield.
Based on the expertise developed in Lahr, the three European sites (Aramon and Limay in France, Lahr in Germany) have been mobilized and will enable the production of more than 150 tons of NDH per year. “It is the combination of our cross competences and our recognized entrepreneurial spirit that allowed such a quick location study: less than 30 days were necessary to establish the R&D prerequisites (Seqens Lab) and then to set up a complete industrial system allowing to start the first industrial productions by the end of the second quarter of 2020” explained the group.
A necessary internalization of precursors
Seqens added that it took the decision at the beginning of April to internalize the production of AB-lactone and chloropentanone. In general, these precursors are purchased in Asia, in particular in India and China, as Seqens chairman Pierre Luzeau recently explained. The COVID-19 crisis has led to border closures in producing countries and unprecedented price inflation.
It was the group’s innovation center, the Seqens’Lab in Porcheville, which successfully optimized the existing chloropentanone process, originally developed in Germany, in less than a week and adapted it to the production tools at the Bourgoin-Jallieu production site. At the same time, the development team at the English site in Middlesbrough studied the internalization of AB-lactone.
“With the example of hydrochloroquine and its precursors, Seqens is demonstrating its ability to meet a major challenge in just a few weeks. Our teams are proud to have been able to combine a wide range of technologies and expertise, to have mobilized in record time its R&D capacities and its industrial facilities – unique in the world – of specialized plants,” said the company.
The case of hydroxychloroquine is a concrete example of Seqens’ know-how, which believes it is capable of providing services and solutions for more than a hundred molecules.
For instantaneous and the widest possible availability of its offer, Seqens participates in the INOVA COVID-19 platform, a coordination platform for all the achievements of global players fighting against this infection.
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First published in INDUSTRIEPharma, a third-party contributor translated and adapted the article from the original. In case of discrepancy, the original will prevail.
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