EyePoint Faces FDA Warning Over Manufacturing Glitches In Eye Implant Production

After encountering regulatory issues with its lead drug candidate earlier this year, EyePoint Pharmaceuticals, a company specializing in ophthalmology, has now faced another challenge with the FDA. In July, the FDA issued a warning letter to EyePoint's facility in Watertown, Massachusetts. This action followed an earlier Form 483, which the company addressed on March 7. The more severe warning letter was issued as a result of ongoing concerns.

During a February inspection, the FDA flagged several issues including batch inconsistencies and inadequate written procedures. These concerns are primarily related to Yutiq, an implant developed by EyePoint that contains the corticosteroid fluocinolone acetonide. EyePoint recently transferred certain rights to the Yutiq drug-device combination, which received U.S. approval in 2018, to Alimera Sciences in an $82.5 million transaction.

In response, EyePoint is dedicated to addressing all FDA observations with a strong focus on quality and safety. A company representative assured Fierce Pharma via email that these issues are limited to Yutiq’s manufacturing and do not impact other products in development, such as their leading candidate, Duravyu.

She said, “EyePoint has been communicating with the FDA regarding actions it has taken and is taking to address findings identified in the Warning Letter, and we have applied resources from across the company to implement corrective actions and process improvements related to the observations.”

The FDA's initial concern with EyePoint's manufacturing practices centered on the company's inability to address production inconsistencies. Inspectors criticized EyePoint for not investigating an unusually high release rate for drug cores in a specific batch of Yutiq during release testing.

Additionally, the FDA noted that EyePoint’s internal investigations did not uncover effective solutions to maintain manufacturing standards. Inspectors also highlighted issues such as "three roof leaks" that allowed moisture to enter "environmentally controlled manufacturing areas," a problem that the FDA traced back to July 2023. EyePoint informed the FDA that it planned to collaborate with the building owner to evaluate the roof's condition. However, the company failed to implement routine facility inspections to ensure that the maintenance of the space remained adequate and that it continued to be suitable for drug manufacturing, according to the FDA.

EyePoint has faced challenges with its written procedures at its Watertown facility, according to the FDA. The agency highlighted deficiencies in the performance studies of Yutiq, noting that they failed to scientifically validate blend uniformity in the final product. Furthermore, EyePoint's operations and engineering teams did not produce statistical process control charts to monitor the performance of their manufacturing processes. The FDA's warning letter pointed out that the charts generated during the inspection revealed four previously undetected adverse trends that needed investigation.

The FDA also criticized EyePoint for inadequate visual inspections during production, citing that the company’s methods lacked specific action levels for significant defects that necessitated further scrutiny. This regulatory rebuke follows EyePoint’s May announcement that its key pipeline asset, Duravyu, did not significantly improve patient scores on the Diabetic Retinopathy Severity Scale in a phase 2 PAVIA study involving non-proliferative diabetic retinopathy.

Mizuho analyst Graig Suvannavejh, Ph.D., described the trial results as a “significant disappointment” and anticipated growing concerns about Duravyu’s potential in treating diabetic macular edema and wet age-related macular degeneration (AMD). Duravyu is an intravitreal, sustained-release insert that administers the VEGFR/PDGFR tyrosine kinase inhibitor vorolanib to the eye, which EyePoint licensed from Equinox Science in early 2020. Despite these setbacks, Mizuho’s Suvannavejh expressed a more optimistic outlook for EyePoint by mid-August.