Suppliers and packagers for rayaldee

rayaldee

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Eirgen	RAYALDEE	calcifediol	CAPSULE, EXTENDED RELEASE;ORAL	208010	NDA	OPKO Pharmaceuticals LLC	70301-1001-1	30 CAPSULE, EXTENDED RELEASE in 1 BOTTLE (70301-1001-1)	2016-10-25
Eirgen	RAYALDEE	calcifediol	CAPSULE, EXTENDED RELEASE;ORAL	208010	NDA	OPKO Pharmaceuticals LLC	70301-1001-2	60 CAPSULE, EXTENDED RELEASE in 1 BOTTLE (70301-1001-2)	2016-10-25
Eirgen	RAYALDEE	calcifediol	CAPSULE, EXTENDED RELEASE;ORAL	208010	NDA	OPKO Pharmaceuticals LLC	70301-1001-3	7 CAPSULE, EXTENDED RELEASE in 1 BOTTLE (70301-1001-3)	2016-10-25

Rayaldee Supplier Analysis

Last updated: February 19, 2026

Rayaldee, a treatment for secondary hyperparathyroidism in adult patients with stage 3 or 4 chronic kidney disease not on dialysis, relies on a specific set of suppliers for its active pharmaceutical ingredient (API) and key excipients. Understanding these supply chains is critical for assessing manufacturing risk, cost of goods, and potential for market disruption.

What is the Active Pharmaceutical Ingredient (API) for Rayaldee?

The API in Rayaldee is calcifediol. Calcifediol is a synthetic form of vitamin D, specifically 25-hydroxyvitamin D.

• Chemical Name: (3β,25R)-9,10-secocholesta-5,7,10(19)-triene-3,25-diol
• CAS Number: 16112-80-8
• Molecular Formula: C27H44O2
• Molecular Weight: 400.64 g/mol

The synthesis of calcifediol is a complex multi-step process. Key intermediates often involved in vitamin D synthesis, including those for calcifediol, can be derived from sterols such as cholesterol or plant sterols like stigmasterol or sitosterol.

Who Manufactures or Supplies Calcifediol API?

The manufacturing of calcifediol API is highly specialized due to the intricate chemical synthesis and stringent purity requirements for pharmaceutical use. Specific named suppliers for Rayaldee's calcifediol API are not always publicly disclosed by drug manufacturers like Opko Health, Inc. (the developer and marketer of Rayaldee). However, the global market for complex steroid derivatives and vitamin D analogs provides insights into the likely origins of such APIs.

Companies with demonstrated expertise in complex organic synthesis, steroid chemistry, and high-potency API manufacturing are potential candidates. These typically include:

• Specialty API Manufacturers: Firms focused on niche APIs, often with strong R&D capabilities in specific therapeutic areas or chemical classes.
• Contract Development and Manufacturing Organizations (CDMOs): Many pharmaceutical companies outsource API production to specialized CDMOs that possess the necessary technical expertise, infrastructure, and regulatory compliance.

Table 1: Potential Calcifediol API Manufacturing Landscape

Company Type	Key Capabilities	Potential Role in Calcifediol Supply
Specialty API Firms	Complex multi-step synthesis, Steroid chemistry expertise, High-purity production	Direct API manufacturing for Rayaldee
CDMOs	cGMP manufacturing, Process optimization, Scale-up, Regulatory support	Contract manufacturing of calcifediol API

Due diligence on potential calcifediol suppliers would involve assessing their:

• cGMP Compliance: Adherence to Current Good Manufacturing Practices is mandatory.
• Technical Expertise: Demonstrated experience with similar sterol derivatives and Vitamin D analogs.
• Analytical Capabilities: Robust quality control and assurance for API purity and characterization.
• Supply Chain Security: Traceability and risk mitigation strategies for raw materials and intermediates.
• Capacity and Scalability: Ability to meet commercial demand.

What Excipients are Used in Rayaldee and Who Supplies Them?

Rayaldee is formulated as a soft gelatin capsule. The excipients are therefore typically components of softgel formulations. These include:

• Fill Material: Calcifediol dissolved or suspended in a suitable carrier.
• Capsule Shell: Gelatin, plasticizer, and water.
• Colorants: For identification and branding.

While specific excipient suppliers for Rayaldee are also not always disclosed, the types of excipients used in soft gelatin capsules are common across the pharmaceutical industry.

Soft Gelatin Capsule Shell Components

The primary components of a soft gelatin capsule shell are:

• Gelatin: Derived from collagen, typically from bovine or porcine sources. Pharmaceutical-grade gelatin must meet stringent purity and quality standards.
  • Suppliers: Major global suppliers of pharmaceutical gelatin include:
    • Rousselot: A leading manufacturer of gelatin and collagen peptides.
    • PB Leiner: Part of the Tessenderlo Group, offering gelatin and collagen.
    • Nitta Gelatin: A significant player in the global gelatin market.
• Plasticizer: Compounds added to make the gelatin shell flexible and elastic. Common plasticizers include:
  • Glycerol (Glycerin)
  • Sorbitol
  • Propylene Glycol
  • Suppliers: These are commodity chemicals with numerous global suppliers. For pharmaceutical applications, USP/EP grade is required. Examples include:
    • Merck KGaA (EMD Millipore)
    • BASF SE
    • Dow Chemical Company
• Water: Purified water meeting pharmaceutical standards.

Fill Material Components

The liquid fill of Rayaldee requires a vehicle for the calcifediol. Common vehicles for softgel fills include:

• Medium-Chain Triglycerides (MCTs): Oils derived from coconut or palm kernel oil.
  • Suppliers: Pharmaceutical-grade MCTs are available from various suppliers. Examples include:
    • BASF SE
    • Croda International Plc
    • KLK OLEO
• Other Lipophilic Carriers: Such as other vegetable oils or vitamin E derivatives, depending on solubility and stability requirements.

Colorants and Opacifiers

These are used for aesthetic purposes and to protect the API from light.

• Titanium Dioxide: Used as an opacifier.
• Iron Oxides: Used as colorants.
• Suppliers: Pharmaceutical-grade colorants are specialized and must comply with regulatory requirements (e.g., FDA, EMA). Major suppliers include:
  • Sensient Technologies Corporation
  • BASF SE
  • Day Glo Color Corp. (though primarily for industrial uses, they have pharmaceutical divisions).

Table 2: Common Excipients in Rayaldee Softgel Formulation

Excipient Type	Specific Component(s) Example	Pharmaceutical Grade	Potential Supplier Categories
Capsule Shell	Gelatin	USP/EP	Rousselot, PB Leiner, Nitta Gelatin
Capsule Shell	Glycerol	USP/EP	Merck KGaA, BASF SE, Dow Chemical Company
Capsule Shell	Water	USP/EP	Pharmaceutical water purification system suppliers
Fill Vehicle	Medium-Chain Triglycerides	USP/EP	BASF SE, Croda International Plc, KLK OLEO
Colorant/Opacifier	Titanium Dioxide, Iron Oxides	USP/EP	Sensient Technologies Corporation, BASF SE, Day Glo Color Corp.

Note: The precise combination and specific suppliers for Rayaldee’s excipients are proprietary. However, the categories and leading global suppliers for these pharmaceutical-grade excipients are well-established.

What are the Regulatory Considerations for API and Excipient Sourcing?

Sourcing of both API and excipients for pharmaceutical products like Rayaldee is subject to rigorous regulatory oversight.

• API: The API manufacturer must be registered with regulatory authorities (e.g., U.S. Food and Drug Administration, European Medicines Agency). Drug master files (DMFs) are typically filed, detailing the manufacturing process, controls, and specifications. These DMFs are reviewed by regulatory agencies as part of the drug approval process. Any changes to the API supplier or manufacturing process require regulatory notification or approval.
• Excipients: While excipients may not always require a DMF, they must meet pharmacopoeial standards (e.g., United States Pharmacopeia, European Pharmacopoeia). Manufacturers of critical excipients often undergo site inspections and audits by pharmaceutical companies to ensure cGMP compliance and quality. Supply chain integrity and traceability are paramount.
• Supplier Qualification: Pharmaceutical manufacturers maintain stringent supplier qualification programs. This involves detailed audits of manufacturing facilities, quality systems, and regulatory compliance of both API and excipient suppliers.

What are the Risks Associated with the Rayaldee Supply Chain?

Potential risks in the Rayaldee supply chain include:

• Single Sourcing: If calcifediol API or a critical excipient is sourced from a single supplier, any disruption at that supplier (e.g., manufacturing issues, natural disasters, geopolitical events, insolvency) could halt Rayaldee production.
• Quality Issues: Contamination, out-of-specification results, or deviations in manufacturing processes at an API or excipient supplier can lead to batch rejection, recalls, and supply shortages.
• Regulatory Non-Compliance: If a supplier fails to maintain cGMP standards or other regulatory requirements, their products may not be usable, impacting the drug manufacturer.
• Cost Volatility: Fluctuations in the cost of raw materials for API synthesis or excipient production can impact the cost of goods for Rayaldee.
• Intellectual Property (IP): While Rayaldee's core patents may be expiring or nearing expiry, any ongoing IP disputes or restrictions related to the synthesis of calcifediol could impact the ability of multiple parties to manufacture the API.
• Geopolitical Factors: Reliance on suppliers in specific geographic regions can expose the supply chain to geopolitical instability, trade disputes, or export restrictions.

Key Takeaways

• Rayaldee’s active pharmaceutical ingredient is calcifediol, a complex synthetic vitamin D analog.
• The synthesis of calcifediol is specialized, pointing to niche API manufacturers or CDMOs with expertise in sterol chemistry.
• Rayaldee is formulated as a soft gelatin capsule, utilizing common pharmaceutical excipients like gelatin, plasticizers (glycerol), and lipid-based carriers (MCTs).
• Leading global suppliers for pharmaceutical-grade gelatin, plasticizers, and lipid carriers are readily identifiable, though specific Rayaldee excipient suppliers are proprietary.
• The supply chain for both API and excipients is heavily regulated, requiring cGMP compliance and robust quality systems.
• Potential supply chain risks include single-sourcing, quality control failures, regulatory non-compliance, and cost volatility.

FAQs

1. How is calcifediol API typically manufactured? Calcifediol API is manufactured through a multi-step chemical synthesis process. This often begins with a sterol precursor, which undergoes a series of controlled chemical reactions, including hydroxylation and oxidation steps, to yield the final calcifediol molecule. The process requires strict control over reaction conditions and rigorous purification to meet pharmaceutical standards.

2. Are there generic versions of Rayaldee available, and how does this affect API sourcing? As of the current analysis, the availability of generic versions of Rayaldee is limited. The development of generic drugs necessitates obtaining a bioequivalent formulation and often requires sourcing the same or equivalent API from an approved supplier. The market entry of generics would increase demand for calcifediol API and potentially introduce new suppliers or CDMOs into the supply chain.

3. What is the role of a Contract Development and Manufacturing Organization (CDMO) in supplying Rayaldee's components? CDMOs play a crucial role by offering specialized manufacturing services. For Rayaldee, a CDMO could be responsible for manufacturing the calcifediol API, performing the drug product formulation, or encapsulating the softgels. Their expertise in cGMP manufacturing, process scale-up, and regulatory affairs allows pharmaceutical companies to outsource complex production steps.

4. How does the origin of raw materials for excipients impact pharmaceutical supply chains? The origin of raw materials for excipients, such as the bovine or porcine sources for gelatin or the plant sources for MCTs, can impact supply chains due to religious, ethical, or geopolitical considerations. Manufacturers must ensure their raw material sources are consistently available, compliant with relevant regulations (e.g., BSE/TSE regulations), and do not present undue supply chain risks.

5. What steps does a pharmaceutical company take to ensure the quality of its suppliers? Pharmaceutical companies employ a comprehensive supplier qualification process. This includes conducting thorough audits of potential suppliers' manufacturing facilities, quality management systems, and regulatory compliance records. Ongoing supplier performance is monitored through regular reviews, site visits, and testing of incoming materials. Critical suppliers may also be required to meet specific contractual obligations regarding quality and supply continuity.

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Citations

[1] Opko Health, Inc. (n.d.). Rayaldee® (Calcifediol) Extended Release Capsules. Retrieved from [Developer's official product information or corporate website - specific URL not provided as it can change, but can be found via search] [2] U.S. Food & Drug Administration. (n.d.). Drug Master Files. Retrieved from FDA.gov [3] United States Pharmacopeia. (n.d.). Pharmacopeial Forum. Retrieved from USP.org [4] European Medicines Agency. (n.d.). Information for manufacturers. Retrieved from EMA.europa.eu [5] Rousselot. (n.d.). Pharmaceutical Gelatin. Retrieved from Rousselot.com [6] PB Leiner. (n.d.). Gelatin & Collagen Peptides. Retrieved from PBL.com [7] Nitta Gelatin Inc. (n.d.). About Us. Retrieved from NittaGelatin.com [8] BASF SE. (n.d.). Medium-Chain Triglycerides. Retrieved from BASF.com [9] Croda International Plc. (n.d.). Specialty Excipients. Retrieved from Croda.com [10] Sensient Technologies Corporation. (n.d.). Color Solutions. Retrieved from Sensient.com