Given that this comes at a time when the Chemical, Manufacturing, and Control (CMC) inspection of Hangzhou Pharmaceutical has not yet taken place, the pharmaceutical industry is reacting with skepticism. HLB stated that while it is true the RLI system was officially codified last year and has been widely used recently, there is no guarantee that this regulation will apply to the CMC inspection of Hangzhou Pharmaceutical.
Possibility Raised That CMC Inspection Could Be Replaced by Written SubmissionAccording to an investigation by Pharm eDaily, the pharmaceutical and biotech premium content service of eDaily, on the 17th, it was confirmed that the CMC inspection of Hangzhou Pharmaceutical—considered a key variable in HLB’s application for approval of the new drug Riboceranib—has not yet taken place. In response, HLB stated that it cannot be definitively concluded that an on-site inspection must occur, and that there is a possibility it could be replaced by a written submission.
An HLB official said, “The U.S. Food and Drug Administration (FDA) operates the RLI (Reports in Lieu of Inspection) system, under which it reviews documents and data submitted by the manufacturer to substitute for an on-site inspection,” adding, “The fact that there have been numerous recent cases of this is a positive development.”
RLI refers to a process in which the FDA evaluates a facility based on records, reports, and data submitted by the applicant or manufacturer, rather than visiting the manufacturing site in person. However, the application of RLI is determined on a case-by-case basis and is not a procedure that can be selectively requested by the applicant or manufacturer. It is applied when the FDA determines, based on a comprehensive assessment of factors such as △the manufacturing facility’s risk level △past inspection history △the completeness of submitted data △product characteristics, that an on-site inspection can be replaced.
However, the prevailing view in the pharmaceutical industry is that it is unlikely the FDA will actually apply RLI in this case. An FDA regulatory expert stated, “Considering that the FDA has repeatedly rejected applications due to concerns about issues at Hengrui Pharmaceutical’s production facilities in China, it seems unlikely that they would now replace an on-site inspection with a review of submitted documentation.”
The fact that this review is not a simple new application but a re-review following two Complete Response Letters (CRLs) is also cited as a factor reducing the likelihood of RLI application. RLI is most likely to be applied when the condition of a facility can be sufficiently evaluated based solely on the history of previous inspections and submitted data. Given that Hengrui Pharmaceuticals already has a history of requests for additional information related to CMC inspections, the pharmaceutical industry believes the FDA has little justification to omit an on-site inspection.
HLB has consistently identified Hangseo Pharmaceutical’s CMC inspection as a key milestone in the U.S. New Drug Application (NDA) review for the combination therapy of riboceranib and camrelizumab as a first-line treatment for liver cancer. Although HLB received a CRL from the FDA, the company has emphasized that the reasons cited were related to manufacturing and quality control rather than clinical efficacy.
At an HLB shareholder meeting held last April, the schedule for the CMC inspection was a hot topic of concern among shareholders. Kim Tae-han, Executive Chairman of the HLB Group’s Bio Division, who joined the HLB Group in January of this year, also actively explained the company’s preparations regarding the CMC inspection. At the time, some shareholders expected that Chairman Kim’s加入—given his experience in global regulatory affairs—would have a positive impact on the company’s response to the CMC inspection.
HLB: “No Guarantee That RLI Will Be Applied to Hangzhou Pharmaceutical’s CMC Inspection”
HLB has maintained the position that even if a CMC inspection takes place around mid-June, it will not affect the schedule for new drug approval. HLB also cited Dextenza as an example of a drug that was approved after undergoing an inspection at the final stage of the approval review process. However, with the CMC inspection failing to materialize just over a month before the scheduled approval of its new liver cancer drug, the company raised the possibility of an RLI for the first time.
Upon news of this, HLB’s stock price, which had been on a downward trend, rebounded sharply. On the 16th, HLB’s stock price rose by over 10% at one point during the trading session and closed at 48,350 won, up 2,850 won (6.26%) from the previous day.
A pharmaceutical industry official noted, “From the company’s perspective, it may have been in a situation where it had no choice but to mention a positive possibility,” but expressed concern that “if unconfirmed possibilities are overly emphasized, it could distort investor sentiment.”
HLB also issued an additional statement via an announcement on its official blog after the market closed that day. HLB stated, “The FDA’s decision date for the new liver cancer drug is July 23 (U.S. time),” adding, “Considering the approval schedule for the new liver cancer drug, an on-site inspection should have already taken place; however, as of now, the CMC inspection of (Hangzhou Pharmaceutical’s) Camrelizumab has not been conducted.”
The company further stated, “We have not received any separate explanation or notification from the FDA regarding this matter,” adding, “It has been confirmed that Hangzhou Pharmaceutical has addressed all issues raised in last year’s CRL and submitted all relevant documentation; consequently, we have not received any additional requests for data submission from the FDA.”
The company continued, “It is true that the RLI system was officially codified last year and has been utilized frequently recently,” but added, “However, there is no guarantee that this regulation applies to the CMC inspection of Hangzhou Pharmaceutical’s camrelizumab. As various possibilities remain until the FDA’s final decision, the company is calmly awaiting the review results.”
