Follitropin alfa biosimilars
Recombinant follicle-stimulating hormone for ovarian stimulation in assisted reproduction, with two EU biosimilars, none in the US, and three Indian manufacturers since 2010.
About follitropin alfa
Recombinant human follicle-stimulating hormone, a heterodimeric glycoprotein of about 30 kDa with a common alpha subunit and a specific beta subunit, four N-linked glycans, produced in Chinese hamster ovary cells. Its glycosylation and sialylation determine its half-life and biological activity.
Binds the FSH receptor on granulosa cells of the ovary, stimulating follicular growth and oestradiol production, and on Sertoli cells in men, supporting spermatogenesis. In assisted reproduction it is used to recruit and mature multiple follicles before oocyte retrieval.
Subcutaneous bioavailability about 66%, half-life about 24 to 35 hours, steady state within three to four days of daily dosing. Potency is defined in international units against a WHO standard, and filled-by-mass presentations were introduced to reduce dose variability.
75 to 450 IU daily by subcutaneous injection during controlled ovarian stimulation, adjusted to follicular response, from multi-dose pens of 300, 450 and 900 IU or single-dose vials of 75 and 150 IU.
- Anovulation in women unresponsive to clomiphene
- Controlled ovarian stimulation for assisted reproductive technology
- Severe LH and FSH deficiency in women, with lutropin alfa
- Hypogonadotropic hypogonadism in men, with hCG
Anti-FSH antibodies are rare. Comparative programmes use analytical similarity with emphasis on glycosylation, a pharmacokinetic study in pituitary-suppressed healthy women, and a comparative efficacy study in women undergoing assisted reproduction with the number of oocytes retrieved as the primary endpoint.
Gonal-f was authorised in the EU on 20 October 1995 (EMEA/H/C/000071), one of the first centrally authorised biologics, and approved by FDA in September 1997 (NDA 020378), transitioning to a biologics licence in March 2020. Teva's Ovaleap, now held by Theramex, became the first EU biosimilar in September 2013 and Finox's Bemfola, now Gedeon Richter, followed in March 2014; neither has sought US approval. India's Reliance Life Sciences was permitted in April 2010, Intas in 2013 and Cadila Healthcare in 2018.
Sources: Purple Book (S016), EMA medicines data (S017), CDSCO lists (S013, S014).
Follitropin alfa is a fertility market where biosimilars are established in Europe and absent in the United States, and where the oocyte-count endpoint gives a compact comparative study. India's three domestic manufacturers and its large assisted-reproduction sector make it a natural export product, and Bemfola is registered in the UAE, one of the few biosimilars in this register with a Gulf fertility registration.
Sources: Gonal-f 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 | Ovaleap | Theramex Ireland Limited | Sep 2013 | EMEA/H/C/002608 | Approved | S017 | |
| EMA | Bemfola | Gedeon Richter Plc. | Mar 2014 | EMEA/H/C/002615 | Approved | S017 | |
| CDSCO | Reliance Life Sciences (INN only) | Reliance Life Sciences Pvt Ltd | Apr 2010 | MF-436/10 | Approved | S014 | |
| CDSCO | Intas Biopharmaceuticals (INN only) | Intas Biopharmaceuticals Ltd | May 2013 | MF-99/2013 | Approved | S014 | |
| CDSCO | Cadila Healthcare (INN only) | Cadila Healthcare Ltd | Jan 2018 | MF-208/2017 | Approved | S014 | |
| EDE | Bemfola | Gedeon Richter Plc., Hungary | Sep 2016 | not published | Registered | S018 |
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 a follitropin alfa 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), open since 23 March 2020 when follitropin NDAs became biologics licences; no follitropin has yet been approved under it | 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 follitropin alfa programmes. Regulatory strategy consulting
Presentations and concentration
Multi-dose pens of 300 IU/0.5 mL, 450 IU/0.75 mL and 900 IU/1.5 mL, and single-dose syringes of 75 to 450 IU (Bemfola).
| Product | FDA | EMA | PMDA | HC | CDSCO | EDE |
|---|---|---|---|---|---|---|
| Ovaleap XM17 | · | see SmPC | · | · | · | · |
| Bemfola | · | see SmPC | · | · | · | 75, 150, 225, 300 and 450 IU pens |
| Reliance Life Sciences follitropin alfa | · | · | · | · | Injection | · |
| Intas follitropin alfa | · | · | · | · | Injection | · |
| Zydus follitropin alfa | · | · | · | · | Injection | · |
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 |
|---|---|---|---|---|---|---|---|
| Teva (BioGeneriX) | Ovaleap | · | ✓ | · | · | · | · |
| Finox Biotech | Bemfola | · | ✓ | · | · | · | ✓ |
| Reliance Life Sciences | Reliance Life Sciences follitropin alfa | · | · | · | · | ✓ | · |
| Intas Pharmaceuticals | Intas follitropin alfa | · | · | · | · | ✓ | · |
| Cadila Healthcare (Zydus Lifesciences) | Zydus follitropin alfa | · | · | · | · | ✓ | · |
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
Ovaleap
Bemfola
Reliance Life Sciences follitropin alfa
Intas follitropin alfa
Zydus follitropin alfa
Questions
How many follitropin alfa biosimilars has FDA approved?
None. The 351(k) pathway has been open to follitropin since March 2020, but neither EU biosimilar has sought US approval.
Which follitropin alfa biosimilars are authorised in the European Union?
Two: Ovaleap (September 2013, the first, now held by Theramex) and Bemfola (March 2014, Gedeon Richter).
Is there a follitropin alfa biosimilar approved in India?
Yes, three domestic products: Reliance Life Sciences (April 2010), Intas Biopharmaceuticals (May 2013) and Cadila Healthcare (January 2018).
Which follitropin alfa biosimilars are registered in the UAE?
Bemfola, in five strengths, registered in September 2016, alongside Gonal-f.
What comparative efficacy study do regulators accept for follitropin alfa?
A study in women undergoing controlled ovarian stimulation for assisted reproduction with the number of oocytes retrieved as the primary endpoint, supported by pharmacokinetic equivalence in pituitary-suppressed volunteers and analytical comparability of glycosylation.
Is follitropin beta a biosimilar of follitropin alfa?
No. Follitropin beta (Puregon, Follistim) is a different originator product from Organon with its own manufacturing process and INN, not a biosimilar.
Work with EvySaif on follitropin alfa
Follitropin alfa 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 follitropin alfa, 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)S014CDSCO, permissions granted in Form 46 and 46A, to 2019 Primary (regulator)S018UAE Emirates Drug Establishment, registered medical product directory Primary (regulator)S016FDA Purple Book, monthly data downloads January to August 2026 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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