HLB(028300) moved a step closer to resolving the core chemistry, manufacturing and controls (CMC) issue that had blocked U.S. approval of its liver cancer drug.
The company said on the 15th that the active pharmaceutical ingredient (API) manufacturing site of China's Hansoh Pharmaceutical, cited by the U.S. Food and Drug Administration (FDA) as the reason for holding off approval of the liver cancer drug, received a final determination of "voluntary action indicated (VAI)" following a general current good manufacturing practice (cGMP) inspection.
HLB's U.S. subsidiary Elevate Therapeutics received on July 14 (local time) the FDA-issued close-out letter for the inspection of the manufacturing site from its partner Hansoh Pharmaceutical.
According to the company, the FDA concluded that the site is generally in compliance with current cGMP and classified it as VAI. The close-out letter also stated, "The VAI classification itself does not impact FDA's assessment of any pending application related to this facility."
HLB is seeking U.S. approval for a first-line hepatocellular carcinoma therapy combining its targeted anticancer drug "Rivoceranib" with Hansoh Pharmaceutical's immunotherapy "Camrelizumab." This is the third application, following 2023 and 2024.
Previously, after inspecting Hansoh Pharmaceutical's API manufacturing site, the FDA issued a Form 483. A Form 483 is a document that notifies a company of observations noted during an inspection. It does not confirm a regulatory violation but formally communicates areas the FDA deems require improvement.
This complete response letter (CRL), like the previous two, was related to Hansoh Pharmaceutical's CMC issues, but the target of the findings differed. The first two CRLs involved the finished drug product (DP) manufacturing site for the combination drug Camrelizumab. This time, however, the issue stemmed from the results of a general cGMP inspection of the Jinqiao facility that contract-manufactures the Rivoceranib API.
The FDA specified that this CRL resulted from the general cGMP inspection findings at the Jinqiao facility. As the inspection has been finally closed as VAI, Elevate plans to submit a more expedited formal inquiry, separate from a Type A meeting, to confirm the FDA's position. A Type A meeting is an official procedure for promptly consulting with the FDA when significant regulatory issues such as a refusal to approve occur.
A Form 483 was also issued for the finished drug product (DP) manufacturing site, and the observations are known to be at a level similar to those for the API site. Hansoh Pharmaceutical plans to submit a response and a corrective and preventive action (CAPA) plan to the FDA by the 24th.
A company official said, "In the previous CRL, the items requiring supplementation related to Camrelizumab were 'concluded without particular issues,' according to the FDA," and added, "With the general cGMP inspection of the API site that was the reason for this CRL also finally closed as VAI, we assess that most of the core issues that had posed problems in the new drug approval process have been resolved."
The official added, "As the CRL grounds have been effectively resolved immediately, we will work to promptly consult with the FDA so the new drug approval process can resume as soon as possible."