FDA Rejects Valacyclovir Oral Suspension NDA Over Facility cGMP Failures

The FDA has rejected a new drug application from Hyloris Pharmaceuticals for an oral suspension formulation of valacyclovir, intended to treat infections caused by herpes simplex and varicella zoster viruses. The agency issued a complete response letter (CRL) citing manufacturing deficiencies identified during an inspection of Hyloris' third-party production facility in Greece, according to reporting from Fierce Pharma.¹

The FDA did not publicly specify the nature of the deficiencies, stating that details were communicated directly to a representative of the manufacturing facility. However, the rejection was not unexpected. Hyloris disclosed last month that the FDA had assigned the Greek plant an official action indicated (OAI) classification following inspection — the agency's most serious designation, signaling that a facility does not meet current good manufacturing practice (cGMP) standards and requires significant corrective action.^1,2

Following that OAI classification, the Greek manufacturer paused production of all products destined for the US market while continuing to supply oral dosage forms to markets outside the United States, Hyloris said in February.² The company noted that the manufacturer "has a well-established track record of pharmaceutical production and supply, serving multiple clients in regulated markets, including the US." Hyloris said it was working on a "manufacturing solution" for the product; the original FDA decision target date had been October.^1,2

In the CRL, the FDA outlined 2 additional requirements before it will approve the application: a cGMP inspection of the manufacturing site and a preapproval inspection. The agency also requested that Hyloris submit additional safety information from all clinical and nonclinical studies of valacyclovir across every indication in which the drug has been evaluated.¹

Context for Pharmacists

Valacyclovir has been available in tablet form since GSK received FDA approval for Valtrex more than 30 years ago, with the branded product subsequently approved for genital herpes and cold sores.³ Generic tablets have been on the market since 2010. An oral suspension formulation would be clinically relevant for patients who cannot swallow tablets, including pediatric patients and certain immunocompromised adults, but no FDA-approved oral suspension currently exists. Pharmacies that receive requests for this formulation must continue to rely on compounded preparations in the interim.

This CRL is part of a broader pattern of manufacturing-related rejections from the FDA. On February 27 alone, the agency issued at least 2 additional CRLs tied to manufacturing concerns: one to Ferring Pharmaceuticals for its follicle-stimulating hormone follotropin delta (Rekovelle) and one to Incyte for its PD-1 inhibitor retifanlimab-dlwr (Zynyz), linked to inspection findings at a former Catalent facility in Bloomington, Indiana—now owned by Novo Nordisk—that has been cited in multiple CRLs in recent months.¹

What to Watch

Pharmacists should monitor whether Hyloris identifies an alternative manufacturer and resubmits its NDA, and whether the FDA's scrutiny of third-party contract manufacturing sites continues to affect drug approval timelines across the industry.

REFERENCES

1. Dunleavy K. FDA fires off another manufacturing-related CRL, this one to Hyloris. FiercePharma. March 13, 2026. Accessed March 13, 2026. https://www.fiercepharma.com/pharma/fda-fires-another-manufacturing-related-crl-one-hyloris

2. Hyloris provides update on FDA review of valacyclovir for oral suspension. News release. Hyloris Pharmaceuticals. February 19, 2026. Accessed March 13, 2026. https://hyloris.com/wp-content/uploads/2026/02/Press-Release_Hyloris_Update-Valacyclovir-Oral-Solution_EN_20260219_FV.pdf

3. Valtrex [prescribing information]. GSK; June 2021. Accessed March 13, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/020487s022lbl.pdf