Interferon alfa-2b biosimilars
Recombinant interferon alfa-2b and its pegylated form for chronic hepatitis B and C and certain cancers, with Indian biosimilars since 2009 and none authorised in the United States, the European Union, Japan or Canada.
About interferon alfa-2b
Recombinant human interferon alfa-2b, a 165-amino-acid protein of about 19 kDa produced in Escherichia coli, without glycosylation. Peginterferon alfa-2b carries a single 12 kDa polyethylene glycol chain, which extends its half-life enough for once-weekly dosing.
Binds the type I interferon receptor and activates the JAK-STAT pathway, inducing antiviral proteins, enhancing antigen presentation and activating natural killer cells. Its antiviral and antiproliferative effects underlie its use in hepatitis and in cancers.
Interferon alfa-2b has a half-life of two to three hours and was given three times weekly; the pegylated form has a half-life of about 40 hours and is given once weekly with ribavirin. Both are cleared mainly by the kidney.
Peginterferon alfa-2b: 1.5 micrograms per kg once weekly with ribavirin for chronic hepatitis C, from 50 to 150 microgram lyophilised vials or pens. Interferon alfa-2b: 3 to 5 million IU three times weekly for hepatitis B, higher doses for melanoma and haematological indications.
- Chronic hepatitis C, with ribavirin (largely superseded by direct-acting antivirals)
- Chronic hepatitis B
- Hairy cell leukaemia, chronic myeloid leukaemia, multiple myeloma and follicular lymphoma
- Malignant melanoma (adjuvant)
- AIDS-related Kaposi's sarcoma
- Condylomata acuminata
Neutralising antibodies to interferon alfa develop in a proportion of patients and can reduce response, more often with some products than others. Comparative programmes would rest on analytical similarity, pharmacokinetic and pharmacodynamic equivalence using markers such as neopterin and 2',5'-oligoadenylate synthetase, and a comparative efficacy study in chronic hepatitis, a design that has become hard to run since direct-acting antivirals replaced interferon in hepatitis C.
Intron A was licensed by FDA on 4 June 1986 (BLA 103132) and PegIntron on 19 January 2001 (BLA 103949); both were centrally authorised in the EU in 2000, and both EU authorisations have since been withdrawn as the hepatitis C market moved to direct-acting antivirals. The one EU biosimilar application, Alpheon (interferon alfa-2a), was refused in 2006, and no interferon biosimilar has been filed in the United States, Japan or Canada. India permitted USV's interferon alfa-2b import in 2009, Cadila Healthcare's pegylated interferon alfa-2b in June 2011, the first pegylated interferon biosimilar anywhere, and Intas's in 2013; Cadila's product was given a restricted emergency-use indication for COVID-19 in April 2021.
Sources: Purple Book (S016), EMA medicines data (S017), CDSCO lists (S013, S014, S011); Iranian and Chinese products from company and press reports and not in the register.
Interferon alfa is a biosimilar market that arrived and left before the West engaged: India, China and Iran built products for hepatitis B and C in the 2000s and early 2010s, EMA refused the one European application, and direct-acting antivirals then removed the largest indication. The Indian permissions stand, and the pegylated product found a second life in the pandemic, but no developer has filed in a Western regulator and the page is here for completeness rather than opportunity.
Sources: PegIntron and IntronA European public assessment reports (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 | Alpheon | BioPartners GmbH | not published | EMEA/H/C/000585 | Withdrawn | S017 | |
| CDSCO | USV (INN only) | USV Ltd | Sep 2009 | Import permission | Approved | S013 | |
| CDSCO | Cadila Healthcare (INN only) | Cadila Healthcare Ltd | Jun 2011 | MF-266/11 | Approved | S014 | |
| CDSCO | Intas Biopharmaceuticals (INN only) | Intas Biopharmaceuticals Ltd | Apr 2013 | MF-89/2013 | Approved | S014 |
CDSCO lists permissions by firm and INN, not brand. PMDA's list and the UAE directory do not publish application numbers; Canadian dates are the first approval or market date recorded in the Drug Product Database.
Regulatory pathway by market
Requirements for an interferon alfa-2b biosimilar under the guidance in force in September 2026.
| FDA, United States | EMA, European Union | PMDA, Japan | Health Canada | CDSCO, India | EDE, UAE | |
|---|---|---|---|---|---|---|
| Legal pathway | Section 351(k) is available; no interferon biosimilar has been filed in the United States | Article 10(4) of Directive 2001/83/EC; centralised procedure is mandatory for biotechnology products | MHLW approval on PMDA review under the Guideline for Ensuring Quality, Safety and Efficacy of Biosimilars (2009, revised 2020), with Q&A updates in 2024 and 2026 | Notice of Compliance under the Food and Drug Regulations as a biosimilar biologic drug, assessed under Health Canada's guidance on biosimilars (2016, revised 2022 and 2026) | 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 | The original biopharmaceutical approved in Japan; foreign-sourced reference accepted with bridging since the 2020 revision | Reference biologic drug authorised in Canada, or a non-Canadian version of it 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 study and, in principle, a comparative efficacy study; the May 2026 early consideration sets out when the efficacy study can be omitted, and Japanese patient data are no longer required in every case (2025) | Comparative structural and functional studies, PK and, where warranted, PD equivalence; the 2026 revision reduces the expectation of comparative efficacy trials in line with FDA and EMA | 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; prescribing by brand, with pharmacist substitution not automatic | No federal designation; substitution and mandatory switching policies are set by each province, several of which have required switching since 2019 | 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 followed by BS (biosimilar), strength, form and the company name in quotation marks, with a biosimilar number in the non-proprietary name | Non-proprietary name identical to the reference, with brand name and DIN as identifiers | 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); MHLW/PMDA biosimilar guideline and notifications (S021); Health Canada guidance on biosimilar biologic drugs.
EvySaif prepares the comparative evidence plan and the regional dossier strategy for interferon alfa-2b programmes. Regulatory strategy consulting
Presentations and concentration
Peginterferon alfa-2b: 50, 80, 100, 120 and 150 microgram lyophilised vials or pens. Interferon alfa-2b: 3, 5 and 10 million IU vials.
| Product | FDA | EMA | PMDA | HC | CDSCO | EDE |
|---|---|---|---|---|---|---|
| USV interferon alfa-2b | · | · | · | · | 3 and 5 million IU lyophilised vials | · |
| Zydus peginterferon alfa-2b | · | · | · | · | Lyophilised peginterferon alfa-2b for subcutaneous injection | · |
| Intas peginterferon alfa-2b | · | · | · | · | Pegylated interferon alfa-2b in vials and syringes | · |
| Alpheon | · | see SmPC | · | · | · | · |
Sources: Purple Book (S016), PMDA list (S020), Health Canada Drug Product Database (S022), 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 | PMDA | HC | CDSCO | EDE |
|---|---|---|---|---|---|---|---|
| Not stated in the CDSCO list | USV interferon alfa-2b | · | · | · | · | ✓ | · |
| Cadila Healthcare (Zydus Lifesciences) | Zydus peginterferon alfa-2b | · | · | · | · | ✓ | · |
| Intas Pharmaceuticals | Intas peginterferon alfa-2b | · | · | · | · | ✓ | · |
| BioPartners | Alpheon | · | withdrawn | · | · | · | · |
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
USV interferon alfa-2b
Zydus peginterferon alfa-2b
Intas peginterferon alfa-2b
Alpheon
Questions
Is there an interferon alfa biosimilar in the United States or the European Union?
No. EMA refused Alpheon, an interferon alfa-2a biosimilar, in 2006, and no interferon biosimilar has been filed with FDA.
Is there an interferon alfa-2b biosimilar in India?
Yes. CDSCO's lists show USV's interferon alfa-2b (import, 2009), Cadila Healthcare's pegylated interferon alfa-2b (June 2011, the first pegylated interferon biosimilar anywhere) and Intas's pegylated interferon alfa-2b (2013).
Which interferon alfa biosimilars are registered in the UAE?
None; Roche's Pegasys (peginterferon alfa-2a) is registered.
Why did the interferon biosimilar market not develop in the West?
Direct-acting antivirals replaced interferon in hepatitis C from 2014, the largest indication disappeared, and the originators withdrew their EU authorisations; there was no market left to enter.
What was the COVID-19 permission for pegylated interferon in India?
CDSCO granted Cadila Healthcare a restricted emergency-use indication in April 2021 for its pegylated interferon alfa-2b in moderate COVID-19, an addition to the 2011 hepatitis permission.
What comparative evidence would regulators expect for interferon alfa-2b?
Analytical comparability, pharmacokinetic and pharmacodynamic equivalence using interferon-response markers in healthy volunteers, and a comparative efficacy study in chronic hepatitis B, the indication still treated with interferon.
Work with EvySaif on interferon alfa-2b
Interferon alfa-2b 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 interferon alfa-2b, with the gaps ranked and a filing sequence recommended.
About the gap assessmentSources
S013CDSCO, import and market permissions till 2019 (r-DNA) Primary (regulator)S014CDSCO, permissions granted in Form 46 and 46A, to 2019 Primary (regulator)S017EMA, medicines data table (medicines-output-medicines-report_en.xlsx) Primary (regulator)S016FDA Purple Book, monthly data downloads January to August 2026 Primary (regulator)S018UAE Emirates Drug Establishment, registered medical product directory 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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