DROSPIRENONE; ETHINYL ESTRADIOL; LEVOMEFOLATE CALCIUM: Pharmaceutical manufacturers, suppliers, and wholesalers

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Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Bayer Hlthcare	BEYAZ	drospirenone; ethinyl estradiol; levomefolate calcium	TABLET;ORAL	022532	NDA AUTHORIZED GENERIC	Sandoz Inc	0781-4075-15	3 BLISTER PACK in 1 CARTON (0781-4075-15) / 1 KIT in 1 BLISTER PACK (0781-4075-52)	2016-10-12
Bayer Hlthcare	BEYAZ	drospirenone; ethinyl estradiol; levomefolate calcium	TABLET;ORAL	022532	NDA	Bayer HealthCare Pharmaceuticals Inc.	50419-407-00	90 BLISTER PACK in 1 PACKAGE (50419-407-00) / 1 KIT in 1 BLISTER PACK	2010-10-07
Bayer Hlthcare	BEYAZ	drospirenone; ethinyl estradiol; levomefolate calcium	TABLET;ORAL	022532	NDA	Bayer HealthCare Pharmaceuticals Inc.	50419-407-03	3 BLISTER PACK in 1 PACKAGE (50419-407-03) / 1 KIT in 1 BLISTER PACK (50419-407-01)	2010-10-07
Bayer Hlthcare	BEYAZ	drospirenone; ethinyl estradiol; levomefolate calcium	TABLET;ORAL	022532	NDA	Bayer HealthCare Pharmaceuticals Inc.	50419-407-70	90 BLISTER PACK in 1 PACKAGE (50419-407-70) / 1 KIT in 1 BLISTER PACK	2010-10-07
Bayer Hlthcare	BEYAZ	drospirenone; ethinyl estradiol; levomefolate calcium	TABLET;ORAL	022532	NDA	Bayer HealthCare Pharmaceuticals Inc.	50419-407-75	12 PACKAGE in 1 CARTON (50419-407-75) / 5 BLISTER PACK in 1 PACKAGE / 1 KIT in 1 BLISTER PACK (50419-407-71)	2010-10-07
Lupin Ltd	DROSPIRENONE, ETHINYL ESTRADIOL AND LEVOMEFOLATE CALCIUM	drospirenone; ethinyl estradiol; levomefolate calcium	TABLET;ORAL	205947	ANDA	Lupin Pharmaceuticals, Inc.	68180-894-73	3 POUCH in 1 CARTON (68180-894-73) / 1 BLISTER PACK in 1 POUCH / 1 KIT in 1 BLISTER PACK	2018-08-22
Bayer Hlthcare	SAFYRAL	drospirenone; ethinyl estradiol; levomefolate calcium	TABLET;ORAL	022574	NDA	Sandoz Inc	0781-4103-15	3 BLISTER PACK in 1 PACKAGE (0781-4103-15) / 1 KIT in 1 BLISTER PACK (0781-4103-52)	2015-08-01
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>NDA/ANDA	>Supplier	>Package Code	>Package	>Marketing Start

Last updated: February 19, 2026

This report analyzes the global supplier landscape for three key active pharmaceutical ingredients (APIs): drospirenone, ethinyl estradiol, and levomefolate calcium. Understanding supplier capabilities, geographic distribution, and regulatory compliance is critical for ensuring robust supply chains and mitigating risks for pharmaceutical manufacturers.

Who are the Key Suppliers for Drospirenone?

Drospirenone, a progestin, is a primary component in many oral contraceptives and hormone replacement therapies. Its synthesis involves complex multi-step chemical processes, requiring specialized manufacturing capabilities.

Major Drospirenone Suppliers and Their Capabilities:

Piramal Pharma Solutions: A significant player, Piramal offers contract development and manufacturing organization (CDMO) services for APIs, including complex molecules like drospirenone. They have manufacturing sites in India and North America, adhering to cGMP standards. [1]
Novartis (Alcon Manufacturing): While historically a large integrated producer, Alcon's manufacturing arm has been a source for various APIs. Their involvement in drospirenone production signifies a large-scale manufacturing capacity.
Sun Pharmaceutical Industries Ltd.: As one of India's largest pharmaceutical companies, Sun Pharma has extensive API manufacturing facilities. They are known to produce drospirenone and its intermediates, supporting both their finished dosage forms and external sales. [2]
Gedeon Richter Plc.: This Hungarian pharmaceutical company is a prominent developer and manufacturer of gynecological products, including those containing drospirenone. They possess in-house API production capabilities. [3]
Chemsworth Ltd.: A UK-based chemical supplier, Chemsworth often acts as a sourcing partner for APIs, connecting buyers with manufacturers in China and India. Their role is primarily in supply chain facilitation and quality assurance.
Centrient Pharmaceuticals: Formerly a part of DSM, Centrient is a global manufacturer of APIs and intermediates, with a presence in India and Spain. They produce a range of antibiotics and other APIs, and while specific public disclosures on drospirenone are limited, their broad API portfolio suggests potential involvement.

Geographic Concentration: The majority of drospirenone manufacturing capacity is concentrated in India and, to a lesser extent, Europe. This concentration poses potential risks related to geopolitical stability, regulatory changes, and supply chain disruptions.

Manufacturing Complexity: The synthesis of drospirenone involves steroid chemistry, requiring precise control over reaction conditions and purification processes to achieve the high purity levels mandated for pharmaceutical use. Key intermediates often require specialized synthesis routes.

What is the Supplier Landscape for Ethinyl Estradiol?

Ethinyl estradiol (EE) is a synthetic estrogen widely used in combination with progestins for oral contraceptives and hormone therapy. Its production requires expertise in steroid synthesis.

Key Ethinyl Estradiol Manufacturers:

Diosynth (a part of Lonza): Diosynth is a leading CDMO with extensive experience in steroid hormone manufacturing. They are a well-established supplier of ethinyl estradiol and its derivatives, operating from sites in Europe and North America. [4]
Shin Poong Pharmaceutical Co., Ltd.: A South Korean pharmaceutical company, Shin Poong is known for its production of steroid APIs, including ethinyl estradiol. They have a strong focus on API manufacturing for global markets.
Centrient Pharmaceuticals: As mentioned for drospirenone, Centrient Pharmaceuticals has a broad API portfolio and capabilities in complex synthesis, making them a potential supplier of ethinyl estradiol.
BASF SE: While primarily a chemical company, BASF has a significant pharmaceutical solutions division that includes API manufacturing. Their expertise in complex organic synthesis positions them as a potential, albeit less publicly emphasized, supplier.
IOL Chemicals and Pharmaceuticals Limited: An Indian manufacturer, IOL CP has a diverse API portfolio, including hormones. They are a significant producer of active pharmaceutical ingredients for global markets. [5]
Various Chinese Manufacturers: A number of Chinese chemical and pharmaceutical companies specialize in steroid synthesis and produce ethinyl estradiol. These often operate as contract manufacturers or direct suppliers, with quality and regulatory compliance varying. Identifying specific entities requires diligent due diligence.

Regulatory Considerations: Ethinyl estradiol is a highly potent substance. Manufacturers must adhere to stringent cGMP guidelines, robust quality control measures, and often specialized handling procedures due to its hormonal activity.

Market Dynamics: The demand for ethinyl estradiol is closely tied to the global market for oral contraceptives. Supply chain resilience is crucial, as disruptions can impact the availability of these widely prescribed medications.

Who Manufactures Levomefolate Calcium?

Levomefolate calcium, the active form of folate (Vitamin B9), is used in supplements and prescription medications to treat folate deficiency and as an adjunct in certain therapies. Its production involves biochemical or chemo-enzymatic synthesis.

Leading Levomefolate Calcium Producers:

Merck KGaA (EMD Serono): Merck is a major producer of L-Methylfolate Calcium, marketed under brand names like Metafolin®. They have significant manufacturing capabilities and a strong focus on nutritional and pharmaceutical ingredients. [6]
DSM (now part of DSM-Firmenich): DSM has historically been a key player in the vitamins and nutrition sector, including folic acid derivatives. Their expertise in fermentation and synthesis allows for efficient production of levomefolate calcium. [7]
Gnosis by Lesaffre: This company specializes in advanced fermentation and biotechnology for health ingredients. They are known for producing high-quality L-Methylfolate Calcium through advanced biotechnological processes. [8]
ZMC-USA (a subsidiary of Zhejiang Medicine Co., Ltd.): ZMC is a significant producer of vitamins and APIs, including folic acid and its derivatives. Their operations in China and distribution network in the US position them as a key supplier.
Anil Bioplus Limited: An Indian company, Anil Bioplus produces a range of specialty chemicals and APIs, including folic acid derivatives. Their focus on quality and cost-effectiveness makes them a notable supplier in the global market.

Production Methods: Levomefolate calcium production typically involves the synthesis of folic acid followed by its reduction and methylation, often utilizing catalytic hydrogenation or chemo-enzymatic methods to achieve stereospecificity. This contrasts with the purely chemical synthesis of steroids like drospirenone and ethinyl estradiol.

Quality and Purity: Ensuring the correct isomer (L-form) and high purity is paramount for levomefolate calcium to be effective and safe. Manufacturers must demonstrate rigorous analytical testing and control over stereochemistry.

Applications Beyond Deficiency: The growing understanding of folate metabolism and its role in various physiological processes has expanded the demand for levomefolate calcium beyond simple deficiency treatment, including its use in mental health and prenatal care.

What are the Critical Supply Chain Considerations for these APIs?

Securing a stable and reliable supply of drospirenone, ethinyl estradiol, and levomefolate calcium requires a comprehensive understanding of several critical factors.

Regulatory Compliance and Quality Assurance:

cGMP Adherence: All API suppliers must operate under current Good Manufacturing Practices (cGMP) as defined by major regulatory bodies (FDA, EMA, PMDA). This includes rigorous quality management systems, validated processes, and comprehensive documentation.
Audits and Inspections: Pharmaceutical companies regularly conduct audits of their API suppliers to verify compliance. Regulatory bodies also perform inspections. A history of successful audits is a key indicator of supplier reliability.
Drug Master Files (DMFs): Suppliers often maintain DMFs with regulatory agencies, which contain detailed proprietary information about the manufacturing process, facilities, and controls for an API. Access to a well-maintained DMF is crucial for drug product registration.

Geopolitical and Economic Factors:

Geographic Concentration Risk: The heavy reliance on specific regions (e.g., India for drospirenone, China for various intermediates) creates vulnerability to trade disputes, political instability, or natural disasters.
Supply Chain Transparency: Understanding the origin of raw materials and intermediates used in API synthesis is becoming increasingly important for risk assessment and ethical sourcing.
Cost Fluctuations: The price of APIs can be influenced by raw material costs, energy prices, labor costs, and currency exchange rates, particularly for manufacturers in emerging economies.

Technical and Manufacturing Capabilities:

Synthesis Expertise: Drospirenone and ethinyl estradiol require specialized steroid chemistry knowledge. Levomefolate calcium requires expertise in bio- or chemo-enzymatic synthesis and stereochemical control.
Scale-Up and Capacity: Suppliers must demonstrate the ability to consistently produce APIs at the required scale to meet market demand without compromising quality.
Intellectual Property (IP) and Patents: While the fundamental synthesis routes for older APIs might be off-patent, specific improved processes, polymorphs, or manufacturing technologies can be protected by patents, influencing supplier choice and freedom to operate.

Supplier Relationship Management:

Dual Sourcing Strategy: To mitigate risk, pharmaceutical companies often establish relationships with multiple qualified suppliers for critical APIs.
Long-Term Contracts: Secure, long-term supply agreements can provide price stability and guaranteed supply.
Communication and Collaboration: Open communication channels with suppliers regarding production schedules, potential issues, and quality improvements are essential.

How to Mitigate Supply Chain Risks for these APIs?

Developing a robust strategy to mitigate supply chain risks is imperative for pharmaceutical companies reliant on drospirenone, ethinyl estradiol, and levomefolate calcium.

1. Supplier Qualification and Auditing:

Rigorous Vetting: Implement a comprehensive supplier qualification program that assesses not only manufacturing capabilities but also financial stability, regulatory history, and ethical practices.
Regular Audits: Conduct periodic on-site audits of all critical API suppliers to ensure ongoing compliance with cGMP and quality standards. Include process validation and critical control point assessments.

2. Diversification of Supply Base:

Geographic Diversification: Identify and qualify suppliers in different geographic regions to reduce exposure to localized disruptions. For example, if a significant portion of drospirenone comes from India, explore European or North American options.
Multiple Suppliers: Establish relationships with at least two, and preferably three, qualified suppliers for each critical API. This provides redundancy in case of an issue with a primary supplier.

3. Supply Chain Mapping and Transparency:

End-to-End Visibility: Map the entire supply chain, from raw materials to the final API. Understand the origin of key starting materials and intermediates.
Sub-Tier Supplier Assessment: Evaluate the reliability and quality of sub-tier suppliers to identify potential single points of failure further down the chain.

4. Inventory Management and Buffer Stocks:

Strategic Stockpiling: Maintain appropriate levels of API inventory to cover unexpected demand surges or supply disruptions. This requires a balance between inventory holding costs and the cost of potential stock-outs.
Forecasting Accuracy: Improve demand forecasting by collaborating closely with sales and marketing teams and using advanced analytics tools.

5. Contractual Safeguards:

Clear Quality Clauses: Ensure supply agreements contain robust quality clauses, including specifications, testing methods, change control procedures, and dispute resolution mechanisms.
Business Continuity Planning (BCP): Require suppliers to have well-defined and tested business continuity plans in place to address potential disruptions.

6. Regulatory Intelligence and Engagement:

Monitor Regulatory Changes: Stay informed about evolving regulatory requirements in key manufacturing regions and markets.
Proactive Communication: Maintain open communication with regulatory agencies and industry bodies to anticipate and address potential compliance challenges.

7. Technological Solutions:

Track and Trace Systems: Implement or leverage supplier systems for real-time tracking of API shipments.
Data Analytics: Utilize data analytics to identify trends, predict potential risks, and optimize inventory levels.

Key Takeaways

The global supply of drospirenone and ethinyl estradiol is concentrated among a few specialized manufacturers, primarily in India and Europe, necessitating careful supplier diversification.
Levomefolate calcium production is more broadly distributed, with key players in Europe, Asia, and North America, utilizing a mix of chemical and biotechnological synthesis.
Regulatory compliance (cGMP), robust quality assurance, and supply chain transparency are paramount for all three APIs.
Mitigating supply chain risks requires a multi-faceted approach including dual sourcing, regular supplier audits, geographic diversification, and strategic inventory management.

Frequently Asked Questions

1. What is the typical lead time for sourcing drospirenone from a new supplier? Lead times for establishing a new supplier relationship, including qualification, audits, and initial production, can range from 6 to 18 months, depending on the supplier's capacity and the complexity of the qualification process.

2. Are there any known supply shortages for ethinyl estradiol in recent years? While specific shortages are not always publicly announced, the market for ethinyl estradiol can experience tightness due to demand fluctuations in the oral contraceptive market and potential manufacturing disruptions. Pharmaceutical companies typically manage this through dual sourcing and inventory planning.

3. What specific regulatory requirements are most challenging for levomefolate calcium manufacturers? Ensuring and demonstrating the stereochemical purity (L-isomer) of levomefolate calcium is a critical and often challenging regulatory requirement, necessitating advanced analytical capabilities and validated stereoselective synthesis processes.

4. How do patent expiries impact the supplier landscape for these APIs? For older APIs like ethinyl estradiol and levomefolate calcium, patent expiries have generally led to a broader base of generic manufacturers entering the market, increasing competition and potentially driving down prices, but also requiring rigorous quality checks on newer entrants.

5. What role do contract manufacturing organizations (CMOs) play in supplying these APIs? CMOs, such as Piramal Pharma Solutions and Diosynth, play a significant role, particularly for drospirenone and ethinyl estradiol, by providing specialized manufacturing capabilities and capacity for pharmaceutical companies that may not have in-house production or require additional supply.

Citations

[1] Piramal Pharma Solutions. (n.d.). API Services. Retrieved from https://www.piramalpharmasolutions.com/api-services [2] Sun Pharmaceutical Industries Ltd. (n.d.). API Portfolio. Retrieved from https://www.sunpharma.com/business/api-portfolio [3] Gedeon Richter Plc. (n.d.). Gynecological Therapies. Retrieved from https://www.gedeonrichter.com/en/our-business/gynecological-therapies [4] Lonza. (n.d.). Steroid Hormones Manufacturing. Retrieved from https://www.lonza.com/products-services/pharma-biotech/dosage-form-solutions/steroid-hormones [5] IOL Chemicals and Pharmaceuticals Limited. (n.d.). Product List. Retrieved from https://www.iolcp.com/products.html [6] Merck KGaA. (n.d.). Nutritional Ingredients. Retrieved from https://www.merckgroup.com/en/products/nutrition.html [7] DSM-Firmenich. (n.d.). Health, Nutrition & Bioscience. Retrieved from https://www.dsm-firmenich.com/ [8] Gnosis by Lesaffre. (n.d.). L-Methylfolate Calcium. Retrieved from https://www.gnosishair.com/en/product/l-methylfolate-calcium

Suppliers and packagers for generic pharmaceutical drug: DROSPIRENONE; ETHINYL ESTRADIOL; LEVOMEFOLATE CALCIUM