DifGen Pharmaceuticals received FDA approval for fluorometholone (FML) ophthalmic suspension, 0.1%, a complex generic formulated for eye inflammation.
I’m not familiar with DifGen …
Headquartered in Miramar, Florida (as of this month), the generic pharmaceutical company specializes in developing, manufacturing, and commercializing complex formulations and pharmaceutical products.
In the last few years, the company has expanded operations via:
- Its 2023 acquisition of Aveva Drug Delivery Systems, Inc., a major developer of transdermal systems and oral dissolvable films
- With this, DifGen also acquired its first U.S. pharmaceutical manufacturing base
- The 2024 purchase (through Aveva) of an FDA-registered finished dosage manufacturing facility in Tarmarac, Florida.
- This bright new commercial manufacturing capabilities in sterile and non-sterile inhalation, ophthalmic, otic, and unit-dose formulations.
Now let’s talk generics (in general).
A generic’s status: Granted based on its formulation containing the exact same active ingredient as the brand-name drug—as well as the same strength, quality, and effectiveness.
The main difference: The pricing, with a generic's purpose being to serve as a lower-cost alternative with the same therapeutic effect as its name-brand counterpart.
- Check out the generic approval process, which requires an abbreviated new drug application (ANDA) approval by the FDA.
And what’s the difference between a generic and a complex generic?
While a simple generic is chemically identical to its branded counterpart, a complex generic is harder to develop, manufacture, or deliver than traditional generics—and involves a:
- Complex active ingredient
- Complex dosage form
- Complex route of delivery, or
- Complex drug-device combination
See here for more insights on these generics.
So what do we know about fluorometholone ophthalmic?
Generally speaking, FML ophthalmic suspension, 0.1% is a prescription-based corticosteroid formulated to topically treat steroid-responsive inflammatory conditions of the eye’s anterior segment.
In regard to its complex generic status: DifGen’s suspension is the second to be approved by the FDA, as Amneal Pharmaceuticals secured regulatory approval and commercially launched the first complex generic of FML 0.1% in January 2024.
Gotcha. And its current name-brand counterpart?
That would be FML by AbbVie (formerly Allergan), which the FDA originally approved in 1982.
Based on its prescribing information (PI): The sterile, topical anti-inflammatory agent is indicated for the treatment of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe.
What are the dosing requirements?
Per FML’s PI—which, keep in mind, mirrors that of the FML 0.1% complex generic—the following dosing is recommended after shaking the 5 mL / 10 mL bottle well:
- One drop should be instilled into the conjunctival sac 2 to 4 times daily.
- During the initial 24 to 48 hours, dosing frequency may be increased to 1 application every 4 hours
Any other notes?
The PI also emphasized that:
- Drop use shouldn’t be discontinued prematurely
- A patient should be re-evaluated if their signs and symptoms do not improve after 2 days of use:
- And if inflammation or pain persists longer than 48 hours (or becomes aggravated), patients are advised to discontinue use and consult a physician
- In chronic conditions, treatment withdrawal should be done by gradually decreasing the frequency of applications
Noted. But can contact lens wearers use the drops?
They can … however, patients wearing soft contact lenses are advised to wait at least 15 minutes after instilling the FML 0.1% drop before inserting their lenses.
Nice! Are there any contraindications to be aware of?
The drop is contraindicated in most viral diseases of the cornea and conjunctiva—including:
- Epithelial herpes simplex keratitis (dendritic keratitis)
- Vaccinia
- Varicella
Others include: Mycobacterial infection of the eye and fungal diseases of ocular structures.
How about warnings or precautions?
We’ll start with corticosteroid-associated warnings: In cases of prolonged use (such as 10+ days), intraocular pressure (IOP) may increase and result in glaucoma, bringing with it:
- Damage to the optic nerve
- Defects in visual acuity and field of vision
- Posterior subcapsular cataract formation
Prolonged use may also lead to a suppressed immune response, potentially causing an increased susceptibility for secondary ocular infections.
- See here (under Warnings) for additional potential developments (including corneal and scleral thinning).
Tell me more.
We’ll start generally with the precautions: The PI noted that FML 0.1%’s initial prescription and medication order renewal exceeding 20 mL should only be made by a physician.
- Further: These should only be permitted after a patient has been examined via a slit lamp, biomicroscopy, and (when appropriate) fluorescein staining.
And, as corneal fungal infections are typical with long-term local corticosteroid use: “Fungal invasions should be suspected in any persistent corneal ulceration.”
Let’s talk about the risk for adverse reactions (if any).
In addition to those listed under the PI’s Warnings section earlier—as well as delayed wound healing—reactions linked to local corticosteroid use may include:
- Keratitis, conjunctivitis, corneal ulcers, mydriasis, conjunctival hyperemia, loss of accommodation, and ptosis.
How about those linked specifically to FML 0.1%?
Reported adverse events have extended to: allergic reactions; foreign body sensation; erythema of the eyelid; eyelid edema and eye swelling; eye discharge; eye pain; eye pruritus; increased lacrimation; rash; taste perversion; visual disturbance (blurry vision); and visual field defects
Duly noted. So … where will this be available for purchase?
No word yet on that front … check back with DifGen for details in the near future!