The FDA has rejected Hyloris Pharmaceuticals’ antiviral drug valacyclovir, an oral suspension for infections caused by the herpes simplex virus and the varicella-zoster virus.
In a Complete Response Letter (CRL), the FDA said it identified the issue through testing of a third-party manufacturer of gray squirrels. U.S. regulators have not identified any issues in the CRL and explained that the issues have been itemized to representatives of production facilities.
CRL was not surprising. Belgium-based Hylolith said in a release last month that the FDA assigned the Greek facility an Official Action Instruction (OAI) classification after inspection (PDF).
OAI is the most stringent of FDA’s three inspection classifications and indicates that a factory does not meet current Good Manufacturing Practice (cGMP) standards and requires significant corrective action.
“This manufacturer serves multiple customers in regulated markets, including the United States, and has an established track record in the production and supply of pharmaceutical products,” Heilolis described the factory in February. “As a result of the test results, the manufacturer temporarily suspended production of the product for the United States, but is currently manufacturing oral dosage forms for markets outside the United States.”
Gray Squirrel added in February that it was working on “manufacturing solutions” for its products. The original target date for the FDA’s decision was October.
In the CRL, the FDA stated that cGMP testing and pre-approval testing must be conducted before approving a new drug application. Additionally, the CRL specified that Hyloris needs to provide more safety information from all clinical and non-clinical studies of valacyclovir in all indications in which it has been tested.
Thirty years ago, GSK won FDA approval for Valtrex, a tablet of valacyclovir, to treat shingles and later to treat genital herpes and cold sores. It became available as a generic drug in 2010.
In 2022, the FDA rejected another gray squirrel candidate due to packaging issues (PDF). A year later, U.S. regulators approved Maxigesic IV, an intravenous post-surgical pain medication.
FDA has recently sent out several manufacturing-related CRLs, including at least two on February 27th. One of the cases was against Ferring Pharmaceuticals regarding the human recombinant follicle-stimulating hormone “Recobell.”
The other was Incyte’s PD-1 inhibitor Zynyz. The denial was over test results at a third-party fill-finish facility, a former Catalent plant in Bloomington, Indiana, now owned by Novo Nordisk. This large plant has been cited in several CRLs over the past few months.
