Written By: Pharmacally Medical News Desk
The FDA has issued a Complete Response Letter (CRL) to Regeneron Pharmaceuticals for its Eylea HD prefilled-syringe version (aflibercept 8 mg), citing manufacturing issues at a contract manufacturing facility located in Indiana. Eylea HD is a high-dose formulation of aflibercept designed to treat various retinal vascular diseases, including wet age-related macular degeneration and diabetic macular edema. Regeneron, a leading biopharmaceutical company headquartered in the United States, focuses on innovative therapies across ophthalmology and other therapeutic areas.
Detailed CRL Reason
The CRL from the FDA primarily centers on deficiencies identified at the Indiana contract manufacturing plant responsible for producing the Eylea HD prefilled syringes. The FDA’s detailed inspection report highlighted deviations from current Good Manufacturing Practices (cGMP) that could impact product quality, sterility assurance, and overall reliability of the manufacturing process. The specific concerns include:
Inadequate process controls and validation
Issues with sterility assurance and microbial contamination risk management
Insufficient oversight of contract manufacturing procedures
These findings raised significant regulatory compliance concerns, preventing approval of the current manufacturing setup for the Eylea HD prefilled syringes.
Trial Details
Eylea HD’s clinical development program included pivotal Phase 3 trials assessing the safety and efficacy of the 8 mg prefilled-syringe formulation for retinal vascular diseases. The trials met their primary endpoints, demonstrating non-inferiority or superiority in visual acuity outcomes compared to the standard 2 mg dose. These clinical data support the therapeutic benefit of the higher dose formulation for patients requiring treatment with longer dosing intervals.
FDA’s Stance on CRL
The FDA described in its CRL that while the clinical efficacy and safety data for Eylea HD are sufficient, the unresolved manufacturing quality issues at the contract facility are serious enough to withhold approval at this time. The agency emphasized its commitment to patient safety and product quality standards, stating that these manufacturing concerns must be fully addressed before the product can enter the market.
Regeneron Response on CRL
Regeneron has acknowledged the CRL and expressed its commitment to resolving the manufacturing deficiencies. In a statement, the company said, “We respect the FDA’s rigorous regulatory standards and are actively working with our contract manufacturer to remediate the identified issues expeditiously.” Regeneron reaffirmed its dedication to delivering high-quality, innovative treatments and plans to submit additional data and improvements to the FDA as soon as possible.
Novo’s Plant Indicated OAI from FDA
Novo Nordisk’s fill-finish manufacturing facility in Bloomington, Indiana, has recently drawn serious scrutiny from the FDA, receiving its most severe inspection classification, Official Action Indicated (OAI). This designation signals that the FDA found the plant to be in an unacceptable state of compliance with regulatory standards.
This facility now faces significant regulatory challenges, which could impact its clients, including Regeneron and Scholar Rock, by delaying drug approvals and complicating manufacturing supply chains. Novo Nordisk has stated that addressing these issues and restoring compliance is a priority, as it works closely with the FDA to enhance its processes and resolve the outstanding concerns.
Future Projection
The CRL will delay the commercial launch of Eylea HD prefilled syringes until Regeneron and its manufacturing partner successfully resolve the FDA’s manufacturing concerns. The company is implementing corrective actions and enhanced quality controls at the Indiana facility. Regulatory experts predict that the approval timeline could be extended by several months. This delay potentially impacts the availability of the high-dose formulation for patients who may benefit from longer dosing intervals.
Key Opinions
Dr. Leonard Schleifer, President and CEO of Regeneron Pharmaceuticals, stated, “We respect the FDA’s decision and are committed to taking all necessary measures to address the manufacturing concerns. Patient safety and product quality are our top priorities, and we are dedicated to ensuring that Eylea HD meets the highest standards for approval.”
George Yancopoulos, Regeneron’s Chief Scientific Officer and President of Research and Development, added, “Our teams are working closely with the FDA and our manufacturing partners to remediate the deficiencies swiftly and efficiently to bring this important therapy to patients who need it.”
An FDA official commented, “Maintaining rigorous manufacturing standards is essential to protect patients and ensure the effectiveness of treatments. We appreciate Regeneron’s cooperation and commitment to resolving the issues identified at their contract manufacturing site.”
References
Regeneron receives another CRL for its Eylea 8 mg, 29 October 2025, https://www.ophthalmologytimes.com/view/regeneron-receives-another-crl-for-its-eyelea-8-mg?utm_source=chatgpt.com
Regeneron reports another manufacturing-related rejection for Eylea HD but says help is on the way, fierce pharma, 28 Oct 2025, https://www.fiercepharma.com/manufacturing/regeneron-reports-another-manufacturing-related-crl-eylea-hd-says-help-way?utm_source=chatgpt.com
Novo Nordisk’s Indiana Plant Flagged by FDA for Contamination and Safety Lapses, 25 August 2025, Pharmaceutical Commerce, https://www.pharmaceuticalcommerce.com/view/novo-nordisk-indiana-plant-fda-contamination-safety-lapses
Regeneron Delays Regulatory Submission for Eylea HD Pre-Filled Syringe After CRL, 10 Oct 2025, https://eyewire.news/news/regeneron-delays-regulatory-submission-for-eylea-hd-pre-filled-syringe-after-crl?c4src=article:infinite-scroll