Insulin human biosimilars

Recombinant human insulin, identical in sequence to the pancreatic hormone: two chains of 21 and 30 amino acids linked by two disulphide bridges, about 5.8 kDa. Produced in Escherichia coli (Lilly) or Saccharomyces cerevisiae (Novo Nordisk); Indian and other manufacturers use E. coli or Pichia pastoris.

Binds the insulin receptor on muscle, fat and liver and lowers blood glucose by promoting glucose uptake and suppressing hepatic glucose output. The three presentations differ only in formulation: soluble insulin acts within 30 minutes, isophane (NPH) insulin is complexed with protamine for intermediate duration, and biphasic 30/70 combines the two.

Soluble insulin: onset in about 30 minutes, peak at two to four hours, duration up to eight hours. Isophane: onset in one to two hours, peak at four to twelve hours, duration up to 24 hours. Biphasic 30/70: a soluble peak followed by the isophane tail, given twice daily.

Individually titrated, in 40 IU/mL and 100 IU/mL vials, 3 mL cartridges and pre-filled pens. India still licenses 40 IU/mL vials alongside 100 IU/mL, a point of difference from every other market in this register.

• Type 1 diabetes mellitus
• Type 2 diabetes mellitus requiring insulin
• Diabetic ketoacidosis and hyperglycaemic emergencies (soluble insulin, intravenous)

Anti-insulin antibodies are common with all insulins and rarely clinically relevant. Where human insulin is assessed as a biosimilar, the programme rests on analytical similarity, pharmacokinetic and pharmacodynamic equivalence in euglycaemic clamp studies, and immunogenicity and safety data; in the EU the two applications assessed under the biosimilar route were refused (Solumarv, 2015) or withdrawn (Inpremzia, 2022; Rechon), and no human insulin biosimilar has been authorised.

Humulin, the first recombinant biologic of any kind, was approved by FDA on 28 October 1982 and insulins were regulated as drugs in the United States until March 2020. In the EU the originators are authorised nationally, with Insuman centrally since 1997. India's first domestic human insulins, Wockhardt's Wosulin (2003) and Biocon's Insugen (2004), predate the published CDSCO lists; the lists show Gland Pharma in 2011, Shantha in 2013, M.J. Biopharm in 2018 and a wave of new manufacturers, Epygen, Cadila Pharmaceuticals, Eris and Regenix, between 2021 and 2026, plus Biocon's Malaysian product and Lupin's imports. Canada classes Baxter's intravenous Myxredlin (2022) as a biosimilar, the only regulator in the Atlas to do so for a human insulin.

Sources: Purple Book (S016), EMA medicines data (S017), CDSCO lists (S011 to S014), Health Canada extract (S022), EDE directory (S018); Wosulin and Insugen launch years from company and press reports.

Human insulin is the largest volume biologic in India and one of the cheapest, so it is where new Indian manufacturers enter and where public procurement sets the price. Outside India and China it has almost no biosimilar market: the EU refused or saw withdrawn every application, the US never received one, and Canada's single biosimilar is a ready-to-use intravenous bag. For a developer it is a domestic and export-to-emerging-markets product, not a Western one.