Suppliers and packagers for DROSPIRENONE, ETHINYL ESTRADIOL AND LEVOMEFOLATE CALCIUM

DROSPIRENONE, ETHINYL ESTRADIOL AND LEVOMEFOLATE CALCIUM

Listed suppliers include manufacturers, repackagers, relabelers, and private labeling entitities.

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Lupin	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

Drosperinone, Ethinyl Estradiol and Levomefolate Calcium suppliers: Who manufactures API, intermediates, and finished dosage forms?

Last updated: July 27, 2026

Who supplies drospirenone, ethinyl estradiol, and levomefolate calcium APIs?

Answer (high-intent): Drosperinone + ethinyl estradiol + levomefolate calcium products are typically supplied through a mixed vendor set: (1) specialized API manufacturers for drospirenone and ethinyl estradiol, (2) a folate-specialist API supplier for levomefolate calcium, and (3) contract manufacturers that package the fixed-dose combination as tablets. Supplier lists vary by market authorization, but the supply chain pattern is consistent.

API supply chain for the three actives

• Drospirenone (API)
  • Manufactured by steroid-focused API houses and specialty chemical firms with capabilities for steroid oxidation, lactonization, and purification.
  • Often sourced from multiple global GMP suppliers due to tight chemistry control and analytical requirements.
• Ethinyl estradiol (API)
  • Supplied by companies with core competence in steroid hormones and estrogen synthesis/purification under GMP.
• Levomefolate calcium (API)
  • Supplied by folate-specialist manufacturers with fermentation and chiral stabilization capability, plus strict control of oxidation state and isomer purity.

Common procurement structures

• Distributor-to-pharma model: brand and generic manufacturers buy APIs through regional distributors who qualify multiple upstream GMP sources.
• Direct API qualification: manufacturers qualify at least two suppliers for continuity, then bind orders via quality agreements and long-term supply contracts.
• CMC-driven supplier lock-in: once a tablet formulation is qualified, changes to API lot sources can trigger revalidation work, so vendors are selected early and retained.

What contract manufacturers make tablets containing drospirenone/ethinyl estradiol/levomefolate calcium?

Answer: Fixed-dose combination tablets are built by CDMOs that run tablet compression and packaging lines under GMP with combination-blend process controls. The CDMO requirement is less about the “combination” chemistry and more about:

• blend uniformity across three actives (one present at relatively low dose, levomefolate calcium),
• photostability/oxidation controls,
• humidity control for folates,
• impurity control for steroid APIs, and
• stability-indicating method capability.

Manufacturing blocks that control supplier selection

• Tablet formulation and scale-up: fixed-dose combinations require validated blend and compression parameters.
• Analytical support: stability, dissolution, assay, and impurity profiling methods are needed for regulatory filings and post-approval change management.
• Packaging: unit-dose blister packaging is commonly selected for moisture and light protection, which affects the CDMO packaging vendor list.

What intermediates and key raw materials affect supplier availability for drospirenone and ethinyl estradiol?

Answer: Upstream availability hinges on a narrow set of steroid intermediates and reagents that are controlled by route chemistry and purification capacity.

Drospirenone upstream constraints

• steroid intermediate availability
• oxidation/lactonization reagents and capacity
• chiral or stereoselective steps that limit qualified vendor count

Ethinyl estradiol upstream constraints

• estrogen precursor availability
• acetylene/ethinylation-type chemistry constraints
• estrogen purification and polymorph control during API crystallization

Levomefolate calcium upstream constraints

• chiral stabilization and controlled reduction/oxidation handling
• moisture-sensitive processing and crystallization control
• consistent folate isomer profile (including impurity spectrum control)

Which suppliers can support regulatory filings for this combination (DMF/CEP/EDQM)

Answer: For market authorization and CMC submissions, the best-aligned suppliers typically hold one or more of: DMF support, CEP documentation, or robust audit readiness aligned with EMA/FDA expectations, plus validated analytical methods.

Why this matters in supplier qualification

• you need impurity specs that match the tablet formulation process,
• you need batch-to-batch consistency evidence,
• you need change control and ability to support regulatory amendments (variations/supplements).

What generic entry risks exist if API suppliers change for drospirenone/ethinyl estradiol/levomefolate calcium?

Answer: Supplier changes can create regulatory and commercial risks via:

• impurity profile shifts,
• dissolution or bioavailability impacts if particle size, polymorph, or blending behavior changes,
• stability differences driven by hygroscopic behavior and photosensitivity.

Typical risk mitigations used by formulators

• tight incoming-API specs for assay, water content, and impurity set
• process validation bridging studies
• stability testing under the intended packaging configuration

How does supplier geography affect pricing and lead times for these APIs?

Answer: Geography drives lead times and pricing through:

• whether the supplier runs dedicated steroid/folate lines,
• whether GMP sites are near regional distribution hubs,
• whether tariff and logistics costs apply to upstream intermediates.

Commercial procurement pattern

• long-cycle APIs (steroid hormones) are ordered in advance and secured with framework agreements,
• levomefolate calcium often becomes a “stability bottleneck” due to moisture/oxidation sensitivity, so safety stock policies apply.

What does Orange Book, DMF, or reference-listed drug status imply about sourcing?

Answer: Regulatory listing status does not dictate suppliers directly, but it shapes qualification expectations. Companies building ANDAs or submitting supplements generally mirror the reference listed product’s quality target profile. That drives API supplier qualification and analytical method selection.

Key Takeaways

• This fixed-dose combination relies on a multi-supplier model: steroid APIs (drospirenone, ethinyl estradiol) are typically sourced from steroid-specialist API manufacturers; levomefolate calcium is sourced from folate-specific API producers; finished tablets are made by GMP CDMOs with formulation and packaging controls for light and moisture protection.
• Supplier qualification is CMC-driven: impurity profile, polymorph/particle behavior, and stability under packaging configuration determine whether a new API vendor is feasible.
• Lead times and risk concentrate upstream: steroid intermediates and folate-specific processing capacity limit qualified supply options, so manufacturers usually qualify at least two upstream sources.

FAQs

1. Can I source drospirenone/ethinyl estradiol/levomefolate calcium from a single API supplier?
   Typically no; the combination is usually assembled from multiple upstream GMP API sources plus a tablet CDMO.

2. What packaging is typically required to protect this combination from moisture and light?
   Blister packaging with appropriate film and desiccant strategy is commonly used to protect steroid hormones and moisture-sensitive folates.

3. How do API supplier changes impact stability testing requirements?
   They usually trigger bridging studies and stability pulls aligned to ICH schedules and packaging configuration.

4. Do CDMOs need specific analytical capabilities for triple-active contraceptive tablets?
   Yes, particularly validated methods for assay, impurities, dissolution, and stability-indicating testing across three actives.

5. What documentation is most valuable for qualifying levomefolate calcium suppliers?
   Evidence of consistent isomer profile and impurity spectrum control, plus batch records, stability data, and GMP audit readiness.

References

1. ICH Q8(R2), Q9, Q10. Pharmaceutical Development; Quality Risk Management; Pharmaceutical Quality System. International Council for Harmonisation.
2. FDA Guidance for Industry: ANDAs: Impurity Testing and Drug Substance Specifications (and related CMC guidance concepts). U.S. FDA.
3. EMA Guideline on quality of drug substances and drug products. European Medicines Agency.