List of Excipients in Branded Drug ROMIDEPSIN

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Teva Parenteral Medicines Inc	ROMIDEPSIN	romidepsin	0703-4004	.ALPHA.-TOCOPHEROL, DL-
Teva Parenteral Medicines Inc	ROMIDEPSIN	romidepsin	0703-4004	ALCOHOL
Teva Parenteral Medicines Inc	ROMIDEPSIN	romidepsin	0703-4004	POVIDONE K17
Teva Parenteral Medicines Inc	ROMIDEPSIN	romidepsin	0703-4004	PROPYLENE GLYCOL

Generic Drugs Containing ROMIDEPSIN

Company	Ingredient	NDC	Excipient
Amneal Pharmaceuticals LLC	romidepsin	70121-2250	.ALPHA.-TOCOPHEROL, DL-
Amneal Pharmaceuticals LLC	romidepsin	70121-2250	ALCOHOL
Amneal Pharmaceuticals LLC	romidepsin	70121-2250	POVIDONE K17
Amneal Pharmaceuticals LLC	romidepsin	70121-2250	PROPYLENE GLYCOL

What are the Most Frequently-Used Excipients in ROMIDEPSIN?

# Of NDCs	Excipient
1	.ALPHA.-TOCOPHEROL, DL-
1	ALCOHOL
1	POVIDONE K17
1	PROPYLENE GLYCOL

Romidepsin Excipient Strategy, Formulation Patents, Generic Entry Risk, and Commercial Opportunities

Last updated: August 27, 2026

Romidepsin is a sterile intravenous oncology product with a relatively simple excipient profile but demanding handling requirements. The commercial opportunity is concentrated in high-quality parenteral excipients, low-binding administration systems, contract manufacturing, stability optimization, and potential generic or alternative presentation development. The reference product, Istodax, uses a lyophilized powder containing romidepsin and povidone. The reconstituted product is diluted in 0.9% sodium chloride and administered by a four-hour intravenous infusion.[1]

The active pharmaceutical ingredient has orphan-oncology economics: limited patient volume, high treatment value, complex sterile manufacturing, and a market that is more suitable for specialized suppliers than for high-volume excipient businesses. The principal technical barriers are solubility, chemical stability, adsorption control, sterile lyophilization, container closure integrity, and reproducible preparation at the point of care.

What is romidepsin and how is Istodax formulated?

Romidepsin is a histone deacetylase inhibitor marketed in the United States as Istodax. It is indicated for adult patients with relapsed or refractory peripheral T-cell lymphoma after at least one prior systemic therapy.[1]

Reference product formulation

Attribute	Istodax profile
Active ingredient	Romidepsin
Dosage form	Sterile lyophilized powder for intravenous infusion
Vial strength	10 mg single-dose vial
Primary excipient identified in labeling	Povidone
Reconstitution diluent	Sterile water for injection
Final dilution	0.9% sodium chloride injection
Administration	Intravenous infusion over four hours
Route	Intravenous
Commercial implication	Sterile, low-volume oncology product requiring controlled preparation

The product is not supplied as a ready-to-infuse liquid. The healthcare provider reconstitutes the vial and transfers the solution into an intravenous infusion bag containing normal saline.[1]

The excipient strategy is therefore split into two stages:

1. A lyophilized vial containing romidepsin and povidone.
2. A hospital-prepared infusion containing romidepsin in isotonic sodium chloride.

Povidone is the key formulation excipient disclosed for the drug product. Its commercial role is likely linked to solution properties, cake structure, drug distribution during lyophilization, and reduction of formulation-related variability. The label does not establish that povidone is the sole technical driver of stability, so formulation developers should not assume that a simple povidone substitution will produce an equivalent product.

What excipients are used with romidepsin?

The commercial product uses povidone in the vial, sterile water for reconstitution, and sodium chloride injection for final dilution.[1]

Povidone

Povidone, also known as polyvinylpyrrolidone or PVP, can provide several formulation functions:

• Improves wetting and dissolution during reconstitution.
• Supports a uniform lyophilized cake.
• Acts as a polymeric stabilizer.
• Can reduce precipitation or aggregation risk in some drug systems.
• Influences viscosity, reconstitution time, and residual moisture behavior.

For romidepsin, excipient grade and molecular-weight distribution are commercially relevant. A supplier targeting this product class would need pharmaceutical-grade material with controlled residual peroxide, low bioburden, low endotoxin, consistent K-value, and documentation suitable for an injectable drug product.

Povidone can contain trace peroxide or other reactive impurities. For a complex cyclic peptide or depsipeptide with oxidation-sensitive functional groups, supplier controls may affect stability. A manufacturer evaluating alternative povidone grades should test peroxide levels, residual moisture, reconstitution performance, and long-term degradation profiles rather than relying only on compendial compliance.

Sterile water for injection

Sterile water is used to reconstitute the vial. It is not a proprietary differentiator, but it is part of the validated administration process. Water quality, container compatibility, microbial controls, and preparation time affect hospital workflow.

Sodium chloride injection

The reconstituted solution is diluted in 0.9% sodium chloride injection. The final infusion vehicle is operationally important because the product is delivered over an extended infusion period. Compatibility with bags, ports, tubing, filters, and transfer devices can create practical differentiation even when the active and excipient composition remains unchanged.

What formulation patents protect romidepsin?

Romidepsin patent protection has historically centered on the active compound, pharmaceutical compositions, therapeutic uses, and manufacturing methods. The original composition-of-matter protection is no longer the principal commercial barrier in the United States because the earliest romidepsin patents were filed more than two decades ago.

Patent categories relevant to romidepsin

Patent category	Commercial relevance
Composition of matter	Historically protected romidepsin and related depsipeptide compounds
Pharmaceutical composition	May cover romidepsin with carriers, diluents, or excipient systems
Method of treatment	May cover use in lymphoma and other cancers
Manufacturing process	Can restrict practical routes, purification, crystallization, or impurity control
Injectable formulation	May cover lyophilized compositions, concentration ranges, or stabilizer systems
Combination therapy	May cover romidepsin with other oncology agents
Device or administration	May cover infusion or delivery arrangements in limited circumstances

The most commercially important distinction is between broad expired compound protection and narrower later-filed formulation or method-of-use claims. A generic company may avoid a surviving method-of-use patent through labeling, while a formulation patent can be more difficult to avoid if it covers the only clinically practical dosage form.

For an abbreviated new drug application, the applicant would need to evaluate current Orange Book listings, patent certifications, regulatory exclusivities, and any applicable pediatric or orphan protections. The existence of an old compound patent does not by itself establish current market exclusivity.

What is the Orange Book status of romidepsin?

Istodax is an FDA-approved prescription oncology product listed in FDA drug databases. Its current commercial and patent position should be assessed through the latest FDA Orange Book entry, approved labeling, patent listing data, and regulatory notices.[1][2]

The commercial analysis should separate four issues:

1. Whether the reference product remains approved.
2. Whether the product is actively marketed.
3. Whether patents are listed against the reference product.
4. Whether any regulatory exclusivity remains active.

A drug can remain approved while experiencing reduced commercial availability or limited distribution. That distinction matters for generic launch planning, sourcing, and reference-product procurement.

Paragraph IV risk

A prospective generic applicant could use a Paragraph IV certification against any unexpired listed patent. The principal litigation risk would likely depend on:

• The number and scope of listed patents.
• Whether claims cover the active, formulation, method of treatment, or manufacturing process.
• Whether the proposed label includes patented uses.
• Whether the proposed product uses the same or different excipient system.
• Whether the reference product has a listed formulation that is difficult to design around.

For romidepsin, the most defensible generic strategy would likely focus on a formulation that demonstrates equivalent performance without unnecessarily reproducing narrow excipient claims. A different polymer, buffer system, or lyophilization cycle could reduce formulation patent exposure, but it may increase bioequivalence and quality-risk burdens.

When does romidepsin lose exclusivity?

Romidepsin's broad small-molecule exclusivity has largely matured. The relevant loss-of-exclusivity question is now less about the original compound patent and more about remaining listed patents, regulatory status, manufacturing feasibility, and the economic attractiveness of generic entry.

Exclusivity timeline

Milestone	Date or status
Romidepsin developed as a cancer therapy	Pre-2000
FDA approval for cutaneous T-cell lymphoma	2009
FDA approval for peripheral T-cell lymphoma	2011
Orphan-drug commercial framework	Applies to approved orphan indications
Original compound-patent era	Expired or substantially matured
Current entry question	Depends on active Orange Book patents, regulatory status, and supply economics

FDA orphan-drug exclusivity generally protects the approved indication for seven years from approval, subject to statutory exceptions. It does not create perpetual protection for the molecule or prevent all uses by another sponsor.[3]

The CTCL commercial history also requires care. The current US label and active clinical positioning should be checked separately from historical approvals and withdrawn development programs. Historical approval of an indication does not automatically establish a current market opportunity.

What formulation strategies could improve romidepsin?

A development program should prioritize formulation robustness rather than excipient novelty alone.

1. Optimized lyophilized cake

A revised lyophilized formulation could target:

• Faster reconstitution.
• Lower residual moisture.
• Better cake appearance.
• Reduced vial-to-vial variability.
• Improved stability under controlled room-temperature excursions.
• Reduced dependence on a particular povidone grade.

Potential excipient classes include alternative polymeric stabilizers, sugar-based bulking agents, amino-acid stabilizers, or combinations designed for parenteral use. Each alternative creates new risks involving osmolality, cake collapse, reconstitution time, particulate generation, and container interaction.

2. Ready-to-dilute or concentrated liquid presentation

A liquid concentrate could reduce preparation steps, but it would face greater stability and packaging demands. Romidepsin developers would need to control:

• Chemical degradation during storage.
• Adsorption to glass, elastomers, bags, and tubing.
• Precipitation after dilution.
• Light sensitivity.
• Container closure compatibility.
• Sterility throughout the shelf life.

A ready-to-use presentation could have commercial value in hospitals with high oncology infusion volumes. It may also create a distinct formulation patent position if the stability profile depends on a defined excipient combination or container system.

3. Alternative infusion systems

A supplier could pursue compatibility packages involving:

• Low-sorbing infusion bags.
• Tubing with reduced drug adsorption.
• Validated transfer devices.
• Closed-system drug-transfer devices.
• Preconfigured pharmacy compounding kits.

These products may be protected more effectively through device, process, or combination claims than through conventional excipient claims. The commercial market would be smaller than the broader oncology infusion market but could support premium pricing if the system reduces waste and preparation time.

How strong is the romidepsin patent estate?

The estate is strongest where it covers a technically necessary formulation or manufacturing step that competitors cannot easily design around. It is weaker where protection depends on broad historical compound claims that have expired or where a generic applicant can use a different excipient system.

Strength assessment

Patent or IP area	Relative strength	Reason
Original compound protection	Low today	Early filing date and maturity of patent term
Standard povidone formulation	Moderate	Value depends on claim scope and current listing status
Lyophilization process	Moderate	Can create practical manufacturing barriers
Sterile manufacturing controls	Moderate to high operationally	Difficult to reproduce consistently, even without broad patent protection
Method-of-use claims	Variable	Can be avoided through labeling or indication strategy
Combination-therapy claims	Variable	Relevant only to particular regimens
Delivery-device claims	Potentially moderate	May create differentiated hospital workflow products

Patent strength is not the same as freedom to operate. Even if no broad formulation patent blocks entry, a generic sponsor still faces analytical method development, sterile process validation, reference-product access, stability studies, and limited-volume commercial economics.

What manufacturing and IP barriers affect romidepsin?

Romidepsin is commercially more difficult to manufacture than a conventional high-volume injectable. The molecule is a complex cyclic depsipeptide and requires controlled synthesis, purification, impurity characterization, and sterile drug-product processing.

Key manufacturing barriers

• High-cost or technically demanding API production.
• Tight impurity specifications.
• Low-dose potency and content-uniformity requirements.
• Sterile filtration or aseptic processing challenges.
• Lyophilization cycle development.
• Low extractables and leachables risk.
• Adsorption to process equipment and administration components.
• Limited market scale for amortizing facility investment.

These barriers favor established oncology manufacturers and contract development and manufacturing organizations with sterile lyophilization capacity. They also create opportunities for suppliers of high-purity polymers, low-binding primary packaging, specialty stoppers, and validated infusion components.

Which companies could challenge Istodax?

Potential challengers would most likely include specialty generic injectables manufacturers, oncology-focused pharmaceutical companies, and contract manufacturers with lyophilized vial capabilities. The commercial opportunity is less attractive to large generic companies that require substantial annual volume to justify development and litigation costs.

A credible challenger would need:

• Access to romidepsin API.
• A validated sterile lyophilization process.
• A bioequivalence strategy suitable for an intravenous product.
• Reference-product characterization.
• A defensible patent certification strategy.
• Reliable supply of povidone or an alternative injectable excipient.
• A launch plan suited to a small oncology market.

Biosimilar risk is not relevant in the conventional sense because romidepsin is a chemically defined small-molecule drug, not a biologic. The main competitive threat is generic or hybrid drug entry, not biosimilar substitution.

What commercial opportunities exist for romidepsin excipients?

The most attractive opportunities are specialized and supply-chain driven.

Excipient supply

Pharmaceutical-grade povidone with tight peroxide and molecular-weight controls is the clearest direct opportunity. Suppliers can differentiate through:

• Injectable-grade documentation.
• Low-peroxide specifications.
• Consistent K-value.
• Low endotoxin and bioburden.
• Regional regulatory support.
• Dual-site manufacturing.
• Stability data in lyophilized oncology products.

Formulation development

CDMOs and formulation specialists can pursue:

• Povidone-grade optimization.
• Alternative lyophilized formulations.
• Ready-to-dilute presentations.
• Improved reconstitution systems.
• Container and tubing compatibility packages.
• Stability-indicating analytical methods.

Hospital-use products

Pharmacy compounding suppliers may develop closed-transfer or ready-to-use systems that reduce preparation complexity. The value proposition is operational: fewer manipulations, lower waste, improved dose preparation consistency, and reduced occupational exposure.

Geographic opportunities

The United States remains the most important market for branded and generic entry analysis because of FDA approval, Orange Book listings, and Paragraph IV litigation. Europe and other regulated markets may offer separate opportunities based on national reimbursement, marketing authorization status, local patent terms, and hospital procurement structures.

A regional excipient or CDMO strategy should not assume that US approval status maps directly to Europe, Japan, or emerging markets. Product availability, indication scope, and patent enforcement can differ materially by jurisdiction.

How does romidepsin compare with other HDAC inhibitors?

Romidepsin is differentiated by intravenous administration and orphan-oncology positioning. Other HDAC inhibitors may have oral dosage forms or broader development programs, which can affect adherence, manufacturing complexity, and competitive substitution.

Product	Active ingredient	Typical administration	Formulation implication
Istodax	Romidepsin	Intravenous infusion	Sterile lyophilized vial and hospital dilution
Zolinza	Vorinostat	Oral	Solid oral excipient and bioavailability strategy
Beleodaq	Belinostat	Intravenous infusion	Competing injectable oncology formulation
Exkivity-class oral oncology products	Various	Oral	Different adherence and formulation economics

Romidepsin's injectable format creates a narrower but more technically specialized excipient market. Its commercial differentiation depends less on ordinary tablet excipients and more on sterile polymers, lyophilization, packaging, and infusion compatibility.

What generic launch scenarios exist for romidepsin?

Three scenarios are commercially plausible.

Scenario 1: Delayed generic entry

A challenger delays filing or launch because the market is too small to support development, inventory, and litigation expenses. The reference product retains pricing power despite mature compound protection.

Scenario 2: Single specialized injectable entrant

One specialty manufacturer develops a generic lyophilized vial and launches with limited distribution. Pricing pressure is meaningful but may remain below the level seen in high-volume oncology injectables.

Scenario 3: Formulation-led competition

A competitor introduces a ready-to-dilute or operationally simpler presentation. The product competes on pharmacy workflow, waste reduction, and supply reliability rather than price alone.

The third scenario offers the strongest opportunity for excipient and delivery-system innovation but also carries the highest formulation-development burden.

What is the revenue exposure to generic entry?

Revenue exposure depends on the current size of the romidepsin market, treatment duration, competing regimens, reimbursement, and whether the reference sponsor continues active promotion and supply. Public sources should be used to confirm current product sales because historical peak sales, approval status, and present commercial demand are not interchangeable metrics.

For investors and suppliers, the relevant variables are:

• Annual US vial demand.
• Average dose per patient and treatment duration.
• Hospital versus specialty-pharmacy distribution.
• Number of active generic applicants.
• Reference-product availability.
• Net price after rebates and discounts.
• Manufacturing cost per vial.
• Expected launch discount.
• Probability of supply disruption.

The market can support attractive margins if supply is concentrated among few qualified manufacturers. It may not support multiple undifferentiated entrants.

Key Takeaways

• Romidepsin is supplied as a sterile lyophilized intravenous product marketed as Istodax.
• The labeled vial excipient is povidone; sterile water and 0.9% sodium chloride are used during preparation.[1]
• The main technical opportunities involve injectable-grade povidone, lyophilization, low-binding packaging, and infusion compatibility.
• Broad early compound protection has largely matured, making current Orange Book listings and later formulation or method patents more important.
• Generic entry is possible but constrained by small oncology-market size, sterile manufacturing complexity, and reference-product economics.
• Biosimilar risk is not applicable in the conventional biologic sense.
• A ready-to-dilute presentation or pharmacy-compounding system could create more commercial value than a simple excipient substitution.
• The strongest business opportunities are specialized supply, CDMO services, formulation development, and hospital-use delivery systems.

FAQs

Does romidepsin contain povidone?

Yes. The Istodax labeling identifies povidone as an inactive ingredient in the lyophilized vial.[1]

Can romidepsin be formulated as a ready-to-use liquid?

Potentially, but such a product would require extensive stability, compatibility, sterility, adsorption, and container-closure validation. The approved reference presentation is a lyophilized powder requiring reconstitution and dilution.

Is romidepsin eligible for biosimilar competition?

No. Romidepsin is a chemically defined small-molecule drug. Competition would generally proceed through generic or other abbreviated pathways rather than the biosimilar pathway.

What excipient is most commercially relevant for romidepsin?

Injectable-grade povidone is the most directly relevant excipient. Suppliers with tight peroxide, molecular-weight, endotoxin, and bioburden controls may have an advantage.

Are romidepsin method-of-use patents still commercially important?

They can be. Their impact depends on current patent term, Orange Book listing, claim scope, approved indications, and whether a generic applicant can omit the patented use from its label.

References

1. U.S. Food and Drug Administration. (2024). Istodax (romidepsin) for injection: Prescribing information. FDA.

2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.

3. U.S. Food and Drug Administration. (2024). Orphan drug designation and exclusivity. FDA.