Insulin lispro biosimilars
The first rapid-acting insulin analogue, with two EU biosimilars, none yet under the US biosimilar pathway, and Indian supply through import permissions to Cipla and Lupin.
About insulin lispro
Recombinant human insulin analogue in which the lysine and proline at positions B28 and B29 are reversed, produced in Escherichia coli for the reference product. The reversal weakens dimer formation so the monomer is absorbed quickly after injection.
Acts at the insulin receptor exactly as human insulin, promoting glucose uptake in muscle and fat and suppressing hepatic glucose production; the modified sequence changes absorption, not receptor pharmacology.
Onset within 15 minutes of subcutaneous injection, peak effect at 30 to 90 minutes and duration of two to five hours. A 200 units/mL presentation halves the injection volume for high-dose users, and the reference product's Lyumjev formulation adds excipients that speed absorption further.
Individually titrated at mealtimes, at 100 units/mL in vials, cartridges and pre-filled pens, and 200 units/mL in pens. Biphasic lispro 25/75 and 50/50 (lispro with lispro protamine) are separate premix presentations.
- Diabetes mellitus in adults and children requiring insulin
- Continuous subcutaneous insulin infusion by pump
- Biphasic 25/75 and 50/50 premixes: type 1 and type 2 diabetes requiring mealtime and basal cover
Anti-insulin antibodies cross-react with human insulin and rarely affect control. Comparative programmes use analytical similarity, pharmacokinetic and pharmacodynamic equivalence in euglycaemic clamp studies, a comparative immunogenicity and safety study in type 1 diabetes, and device testing.
Humalog was authorised in the EU on 30 April 1996 (EMEA/H/C/000088) and approved by FDA on 14 June 1996 (NDA 020563), the first rapid-acting analogue in either market. Sanofi's Admelog reached the US in 2017 through the 505(b)(2) route, before insulins moved to the biologics framework in March 2020, so it is not a 351(k) biosimilar; in the EU the same product, Insulin lispro Sanofi, was authorised as a biosimilar in July 2017. Gan & Lee's Bysumlog followed in the EU in May 2026.
Sources: Purple Book (S016), EMA medicines data (S017), CDSCO lists (S012, S013).
Insulin lispro shows how the same product can be a biosimilar in one market and not in another: Sanofi's lispro is an EU biosimilar and a US 505(b)(2) product, and as of September 2026 no insulin lispro has been approved under 351(k). India's supply is through import permissions to Cipla (2021) and Lupin (2024) for the standard and premix presentations; no domestic manufacturing permission appears in the published lists to June 2026.
Sources: Humalog summary of product characteristics (EMA) and US prescribing information (FDA).
Approvals by year
Regulatory register
| Regulator | Brand | Holder or applicant | Approved | Application or permission | US licence | Status | Source |
|---|---|---|---|---|---|---|---|
| EMA | Insulin lispro Sanofi | Sanofi Winthrop Industrie | Jul 2017 | EMEA/H/C/004303 | Approved | S017 | |
| EMA | Bysumlog | Gan & Lee Pharmaceuticals Europe GmbH | May 2026 | EMEA/H/C/006158 | Approved | S017 | |
| CDSCO | Cipla (INN only) | Cipla Limited | Sep 2021 | IMP/BIO/21/000084 (25/75 premix, September 2021) | Approved | S012 | |
| CDSCO | Lupin (INN only) | Lupin Limited | Apr 2024 | IMP/BIO/24/000038 | Approved | S012 |
CDSCO lists permissions by firm and INN, not brand. The UAE directory does not publish registration numbers.
Regulatory pathway by market
Requirements for an insulin lispro biosimilar under the guidance in force in September 2026.
| FDA, United States | EMA, European Union | CDSCO, India | EDE, UAE | |
|---|---|---|---|---|
| Legal pathway | Section 351(k), open to insulins since 23 March 2020; no insulin lispro has yet been approved under it | Article 10(4) of Directive 2001/83/EC; centralised procedure is mandatory for biotechnology products | Guidelines on Similar Biologics (CDSCO and DBT, 2016, in force); revised draft published May 2025 | Registration through the Emirates Drug Establishment; the public directory does not distinguish biosimilars from other biologicals |
| Reference product | US-licensed reference; a non-US comparator may be used with analytical and PK bridging | EU-authorised reference; a non-EEA comparator may be used with bridging data | Product licensed in India, or if not, one licensed in an ICH country, with justification | Not stated in the public directory; registration relies on assessment by reference regulators |
| Comparative clinical study | Draft guidance (October 2025): comparative analytical assessment plus a PK similarity study and immunogenicity assessment; a comparative efficacy study is generally not needed | Reflection paper adopted March 2026: a comparative efficacy trial can be waived when analytical and PK comparability is sufficient | Comparative PK/PD study and a comparative safety and efficacy study are generally expected, followed by a post-marketing study | Assessed on the dossier accepted by the reference regulator |
| Interchangeability | A separate designation permitting pharmacy-level substitution; switching studies generally not required under the June 2024 draft | EMA and HMA statement (September 2022): EU biosimilars are interchangeable with their reference; substitution rules are set by each member state | Not defined in the guidelines | Not defined |
| Naming | INN plus a four-letter suffix | INN, identical to the reference; brand name and batch recorded for pharmacovigilance | INN with the brand name | Brand name as registered |
Sources: FDA draft guidance on comparative efficacy studies (October 2025) and interchangeability (June 2024); EMA reflection paper EMA/CHMP/BMWP/60916/2025 (March 2026) and EMA/HMA statement on interchangeability (September 2022); CDSCO Guidelines on Similar Biologics 2016 and 2025 draft (S009, S010); EDE directory (S018).
EvySaif prepares the comparative evidence plan and the regional dossier strategy for insulin lispro programmes. Regulatory strategy consulting
Presentations and concentration
100 units/mL in vials, cartridges and pre-filled pens; 200 units/mL in pens. Premixes are 100 IU/mL suspensions at 25/75 or 50/50 lispro to lispro protamine.
| Product | FDA | EMA | CDSCO | EDE |
|---|---|---|---|---|
| Insulin lispro Sanofi SAR342434 | · | see SmPC | · | · |
| Bysumlog | · | see SmPC | · | · |
| Cipla insulin lispro | · | · | 100 IU/mL cartridge and pen; 200 U/mL pen; 25/75 and 50/50 premixes; ultra-rapid 100 U/mL (2023) | · |
| Lupin insulin lispro | · | · | 3 mL cartridge and pre-filled pen; 25/75 and 50/50 premixes | · |
Sources: Purple Book (S016), CDSCO permission lists (S011 to S014), EDE directory (S018). EU presentations are listed in each product's SmPC.
Developers by market
| Developer | Product | FDA | EMA | CDSCO | EDE |
|---|---|---|---|---|---|
| Sanofi | Insulin lispro Sanofi | · | ✓ | · | · |
| Gan & Lee Pharmaceuticals | Bysumlog | · | ✓ | · | · |
| Not stated in the CDSCO list | Cipla insulin lispro | · | · | ✓ | · |
| Not stated in the CDSCO list | Lupin insulin lispro | · | · | ✓ | · |
Entering a market where a competitor is already listed changes the evidence and pricing conversation. EvySaif's global value dossier and HTA submission work covers that side.
Products
Insulin lispro Sanofi
Bysumlog
Cipla insulin lispro
Lupin insulin lispro
Questions
How many insulin lispro biosimilars has FDA approved?
None under the 351(k) biosimilar pathway as of September 2026. Sanofi's Admelog (2017) was approved through the 505(b)(2) drug route before insulins became biologics, and Lilly's own Insulin Lispro is an authorised version of Humalog.
Which insulin lispro biosimilars are authorised in the European Union?
Two: Insulin lispro Sanofi (July 2017, the first) and Bysumlog from Gan & Lee (May 2026).
Is there an insulin lispro biosimilar approved in India?
Through import: Cipla holds permissions from 2021 for insulin lispro and the 25/75 and 50/50 premixes and, from 2023, an ultra-rapid formulation; Lupin holds permissions from April 2024 for the same three presentations. No domestic manufacturing permission appears in the published CDSCO lists.
Which insulin lispro biosimilars are registered in the UAE?
None yet in the Emirates Drug Establishment directory; Humalog, Humalog Mix and Lyumjev are registered.
Why is Admelog not counted as a biosimilar in the United States?
It was approved in December 2017 under section 505(b)(2) of the drug law, using Humalog as the listed drug, because insulins were regulated as drugs until 23 March 2020. It carries a biologics licence today but was never assessed under the biosimilar pathway.
What comparative evidence do regulators expect for insulin lispro?
Analytical comparability, pharmacokinetic and pharmacodynamic equivalence in euglycaemic clamp studies, a comparative immunogenicity and safety study in type 1 diabetes, and device testing for the pen.
Work with EvySaif on insulin lispro
Insulin lispro biosimilar landscape report
The register on this page as a delivered document: every approval, holder, presentation and pathway requirement across FDA, EMA, CDSCO and the Gulf, updated to the month, with the sources attached.
Request the landscape reportRegulatory gap assessment
For a developer deciding whether and where to file: a review of your analytical, PK and clinical package against what each regulator expects for insulin lispro, with the gaps ranked and a filing sequence recommended.
About the gap assessmentSources
S017EMA, medicines data table (medicines-output-medicines-report_en.xlsx) Primary (regulator)S012CDSCO, new drugs (r-DNA origin) approved for import and marketing, Jan 2020 to June 2026 (CT-18) Primary (regulator)S016FDA Purple Book, monthly data downloads January to August 2026 Primary (regulator)S018UAE Emirates Drug Establishment, registered medical product directory Primary (regulator)S013CDSCO, import and market permissions till 2019 (r-DNA) Primary (regulator)S009CDSCO and DBT, Guidelines on Similar Biologics 2016 Primary (regulator)S010CDSCO, Draft Guidelines on Similar Biologics 2025 Primary (regulator)
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