The pharmaceutical market for hormonal contraceptives and therapies has seen significant evolution with the introduction of combination drugs containing dienogest and estradiol valerate. These compounds, marketed under brand names such as Natazia (U.S.) and Qlaira (international), address both contraception and menstrual health[1][4][11]. This report examines the global supplier landscape for these active pharmaceutical ingredients (APIs), focusing on originator companies, generic manufacturers, patent dynamics, and regional distribution networks.
Development and Patent Landscape of Dienogest/Estradiol Valerate Combinations
Originator and Patent Holders
Bayer HealthCare Pharmaceuticals remains the dominant originator and patent holder for dienogest/estradiol valerate combinations. The company developed the quadriphasic oral contraceptive Natazia, which received U.S. FDA approval in 2010 for pregnancy prevention and later for treating heavy menstrual bleeding (HMB)[1][4][13]. Key patents protecting this formulation include:
- US8153616: Expiring in January 2028, covering the combination for contraception and dysfunctional uterine bleeding[3].
- US8071577: Expiring in May 2026, protecting the multi-phase formulation based on natural estrogens[3].
These patents ensure Bayer’s exclusivity in major markets until the late 2020s. However, expired patents (e.g., US6133251 and US6884793) have enabled generic entry in regions like Europe and Asia[3].
Key Manufacturers and Suppliers of Dienogest and Estradiol Valerate APIs
Branded Product Suppliers
As the originator, Bayer monopolizes the supply of finished products like Natazia and Qlaira. The company manufactures these drugs in-house, leveraging vertical integration from API production to distribution[5][8][10]. Natazia’s formulation includes:
- 3 mg estradiol valerate tablets (2 dark yellow tablets).
- 2 mg estradiol valerate + 2 mg dienogest tablets (5 medium red tablets).
- 2 mg estradiol valerate + 3 mg dienogest tablets (17 light yellow tablets)[7].
Bayer’s pricing strategy aligns with branded contraceptives, with U.S. pharmacy costs ranging from $86.99 to $89.99 per 28-day pack[4].
API Manufacturers for Generic Production
Post-patent expiration, generic manufacturers have entered the market, particularly for standalone dienogest and estradiol valerate APIs. Notable suppliers include:
- DQA Pharma International: A leading producer of dienogest, supplying APIs for generic contraceptives and endometriosis treatments[5][8][10].
- NewChem: Specializes in steroid hormones, including dienogest, with facilities compliant with U.S. FDA and EU GMP standards[8][10].
- Naari: India-based manufacturer exporting estradiol valerate to Southeast Asia and Africa[12][15].
- Maiden Group: Supplies dienogest to Latin American markets, including Brazil[10].
These companies typically operate under Good Manufacturing Practices (GMP) and hold certifications such as USDMF and CEP[12][14].
Regional Supply Chain Dynamics
Europe and North America
In Germany, Bayer’s headquarters, estradiol valerate exports to India and Indonesia totaled $210,538–$253,291 per shipment in 2023, indicating robust API demand[15]. The U.S. relies heavily on branded Natazia, though generic dienogest APIs from DQA Pharma International are entering the menopausal therapy segment[5][14].
Asia-Pacific
India emerges as a hub for API production, with Naari and NewChem exporting estradiol valerate to Singapore and Malaysia[12][15]. China, however, saw trial discontinuations for dienogest/estradiol valerate in 2021, delaying local generic approval[1].
Latin America
Brazil’s market features Maiden Group-supplied dienogest in combination therapies, while Chile imports finished Qlaira tablets from Germany at $184,162 per 412 kg[15].
Challenges in Sourcing Combined Formulations
Despite generic API availability, the quadriphasic regimen of Natazia/Qlaira complicates replication. The precise dosing sequence—varying estradiol valerate and dienogest concentrations across 26 active tablets—requires specialized manufacturing capabilities[7]. As of 2025, no generic equivalents for the combination exist in the U.S. or EU, though companies like Gideon Richter are developing biosimilar versions[5][8].
Regulatory and Market Considerations
Patent Expirations and Generic Entry
With Bayer’s key patent (US8153616) expiring in 2028, generic suppliers are preparing for market entry. Analysts project a 40–60% price reduction for dienogest/estradiol valerate combinations post-2028, mirroring trends observed with earlier contraceptives like Yasmin[3][14].
API Pricing Trends
- Estradiol valerate: Prices range from $106,673 to $253,291/kg, depending on purity and regional demand[12][15].
- Dienogest: Costs average $150,000–$200,000/kg, driven by synthesis complexity[14].
Conclusion
The supplier ecosystem for dienogest and estradiol valerate is bifurcated into branded (Bayer-dominated) and generic (regional API-focused) segments. While Bayer maintains control over combination therapies, generic manufacturers are expanding access to standalone APIs. Stakeholders must navigate patent cliffs, regulatory hurdles, and manufacturing complexities to capitalize on emerging opportunities in contraceptive and menstrual health markets.
References
- https://adisinsight.springer.com/drugs/800019701
- https://www.canadadrugsdirect.com/products/natazia
- https://pharsight.greyb.com/ingredient/dienogest;-estradiol-valerate-patent-expiration
- https://www.reliasmedia.com/articles/19966-estradiol-valerate-dienogest-oc-gets-nod
- https://www.pipelinepharma.com/dienogest-manufacturers/country/malta/category/generics
- https://nowpatient.com/medications/estradiol-valerate-and-estradiol-valerate-dienogest
- https://en.wikipedia.org/wiki/Dienogest
- https://www.pipelinepharma.com/dienogest-manufacturers/country/spain/category/generics
- https://pharmaoffer.com/api-excipient-supplier/estradiol-valerate-dienogest
- https://www.pipelinepharma.com/dienogest-manufacturers/country/brazil
- https://www.biospace.com/u-s-fda-approves-bayer-healthcare-pharmaceuticals-natazia-tm-a-new-oral-contraceptive-for-the-prevention-of-pregnancy
- https://www.pharmacompass.com/manufacturers-suppliers-exporters/estradiol-valerate
- https://www.managedhealthcareexecutive.com/view/fda-approves-first-oral-contraceptive-treat-heavy-menstrual-bleeding
- https://www.pharmacompass.com/manufacturers-suppliers-exporters/dienogest
- https://www.volza.com/p/estradiol-valerate/import/coo-germany/
