Drug substance and finished product manufacturing facilities both receive VAI classification
Company prepares for NDA resubmission for Rivoceranib and Camrelizumab combination therapy
HLB (028300) has significantly reduced regulatory uncertainty surrounding its liver cancer drug, Rivoceranib, as it prepares to re-engage with the U.S. Food and Drug Administration (FDA). Following a successful outcome for its drug substance facility, the FDA has also concluded its inspection of the finished drug product manufacturing site with a classification of "Voluntary Action Indicated" (VAI).
HLB announced on the 6th that the FDA finalized its classification of the Current Good Manufacturing Practice (cGMP) inspection for the Rivoceranib finished product facility as VAI.
Elevar Therapeutics, HLB’s U.S. subsidiary, received the official inspection closeout letter from its partner, the Chinese pharmaceutical firm Hengrui Pharma, on the 3rd.
A VAI classification is issued when the FDA identifies certain deficiencies during an inspection but deems them minor enough to be addressed through voluntary corrective measures by the company, thus requiring no formal regulatory enforcement action. FDA inspection outcomes are categorized into No Action Indicated (NAI), Voluntary Action Indicated (VAI), and Official Action Indicated (OAI), which requires formal regulatory intervention.
Manufacturing Site Hurdles Cleared as Both Facilities Receive VAI
This result significantly lowers the manufacturing-related uncertainty that has persisted since the company received a Complete Response Letter (CRL) from the FDA in July.
Elevar is seeking FDA approval for the combination therapy of Rivoceranib and Hengrui Pharma’s immunotherapy agent, Camrelizumab, as a first-line treatment for unresectable or metastatic hepatocellular carcinoma.
In July, the FDA issued a CRL regarding the New Drug Application (NDA) for Rivoceranib. At the time, the rejection was attributed not to concerns over clinical efficacy or patient safety, but rather to cGMP issues at Hengrui Pharma’s manufacturing facilities.
While the FDA inspection of the drug substance manufacturing facility was previously concluded with a VAI, the finished drug product facility had received a "Form 483" during a separate inspection, meaning the regulatory process for manufacturing was not yet fully resolved.
A Form 483 is issued by FDA investigators when they observe conditions that may constitute violations of regulatory requirements. Hengrui Pharma has since been actively implementing corrective measures to address these findings.
With the finished drug product facility now classified as VAI, the FDA inspection process for both the drug substance and finished product facilities has been successfully concluded.
HLB Prepares for NDA Resubmission
Elevar and Hengrui Pharma are currently finalizing the documentation required for the NDA resubmission. The company plans to submit the application to the FDA as soon as the remaining work is completed.
The VAI classification is a significant milestone as it alleviates manufacturing concerns ahead of the resubmission. It is important to note that a VAI classification pertains specifically to the manufacturing site inspection and does not constitute approval of the new drug itself. Upon resubmission, the application will undergo the standard FDA filing and review process once again.
“This VAI classification is the result of Hengrui Pharma’s company-wide commitment to addressing the findings from the inspection,” an HLB representative said. “Elevar will continue to work closely with Hengrui Pharma to expedite the final preparations for the NDA resubmission and ensure a seamless response throughout the subsequent FDA review process.”
