financial association, June 6 (reporter Lu afeng) recently, media reports said that hengrui medicine (600276.SH) received the 483 form issued by FDA, because hengrui medicine sells a large number of drugs in the United States, and the PD-1 combination therapy of hengrui medicine is being declared and listed in the United States, causing many conjectures in the market.

hengrui medicine told the reporter of the financial association that the 483 form received this time involves a preparation production site in Lianyungang area of the company, not the production site involved in the application for the combination of carrilizumab and apatinib. at present, the rectification reply and completion follow-up report have been submitted, and the company's export of preparations to the United States has not been affected.

experts in the industry are also inclined to support hengrui medicine's judgment, saying that with the end of the new crown pandemic, FDA has increased the intensity and quantity of inspections of foreign pharmaceutical enterprises in recent years. it is not an example that relevant defects have been found. after the rectification, there should be no problem. hengrui medicine's receipt of FDA483 form this time does not mean that the United States has tightened the pharmaceutical market in China, pharmaceutical products from China are urgently needed in the United States, where shortages are rife. However, for some pharmaceutical companies that sell products in the United States, it is necessary to pay more attention to quality management standards and compliance.

"The company's export of U.S. preparations is not affected"

Recently, some media reported on the Internet that "Hengrui Medicine has received the US FDA 483 form". Under the premise that the current Sino-US competition has gradually expanded to the biomedical industry and BLA, an indication for first-line treatment of advanced liver cancer in combination with apatinib, was accepted by the US FDA in July last year, the news triggered a lot of speculation in the market as soon as it was issued.

this evening, hengrui pharmaceutical responded to the above-mentioned market concerns to the reporter of the financial association, saying that the FDA inspection involved a preparation production site in Lianyungang area of the company. In response to the defects raised by the inspection, the company has submitted a rectification response and a completion tracking report, while maintaining active communication with FDA. At present, the company's preparations exported to the United States have not been affected.

"This kind of incident of receiving 483 forms is not uncommon in the industry, nor is it a very major accident." Guo Xinfeng, a senior industry expert, told Caixin that 483 forms are common documents for FDA inspections, also known as "on-site observation reports" (inspectional observation), related to the company's facilities, equipment, processes, controls, products, employee practices or records. After receiving the 483 form, the company has 15 days to respond. 483 form is not the final explanation of the violation, but it represents the company's urgent attention and resolution.

as for the relationship between the 483 form, which is generally concerned by the industry, and the application for listing of indications for first-line treatment of advanced liver cancer in the United States by karelizumab and apatinib, hengrui medicine refuted the rumor to the reporter of the financial association: "according to FDA regulations, drug production sites are managed separately according to their registered addresses. The address involved in this inspection is the site of Huanghe Road in Lianyungang, which is different from the production site involved in the combined application of carrilizumab and apatinib. The results of this examination are not related to the company's PD-1 combination therapy filing for listing in the United States."

the reporter of the financial union later inquired about the 483 form on FDA's official website and learned from it that the 483 was mainly due to technical details loopholes: insufficient details of sterility assurance management and cleaning verification evaluation; There are loopholes in the document management software and insufficient management of the destruction of discarded records. The computer system for producing individual auxiliary equipment does not meet the requirements of 21CFR Part11; Insufficient maintenance of storage air conditioning failure; Deliberately delaying inspection, however, there is no problem of data authenticity, nor does it affect the quality and safety of drugs.

"these are all minor details. now that hengrui medicine has made rectification and replied, it is expected that FDA will not impose further penalties or sanctions on hengrui medicine." Guo Xinfeng said so.

According to the 2023 Defects Summary Report published by the FDA on its website, the FDA has issued a total of 4428 483 forms between October 1, 2022 and September 30, 2023.

Case does not represent a tightening of the U.S. market. Drug gap needs to be filled

"In fact, since the end of the new crown pandemic, the US FDA has been in line with the domestic political climate and has gradually strengthened its inspection of foreign pharmaceutical companies and products, especially in China." Guo Xinfeng revealed that starting from April 2023, many overseas pharmaceutical companies have accepted a new round of FDA inspections.

according to the official website of FDA, since 2024, the number of GMP supervision and inspection for Chinese drug manufacturers has reached 52, and there are 26 "483 defects". both figures have exceeded the whole year of 2023.

in addition, at the end of November 2023, FDA issued a safety notice to consumers and medical institutions, saying that they were monitoring and evaluating whether plastic syringes produced by several Chinese syringe manufacturers were likely to have safety problems. in March and April this year, FDA further issued rectification opinions and warnings to adoption shares (301122.SZ) and kangdley (603987.SH). both enterprises said to the public that they had completed the rectification, and submit evidence to the relevant FDA agencies to prove compliance with the relevant U.S. laws.

On May 14, the White House announced that in the future, a series of products exported from China to the United States will be subject to tariffs, including syringes, needles and surgical gloves. The tariff rate on syringes and needles will be increased from 0 to 50% in 2024.

Previously, both houses of the U.S. Congress were actively promoting the "Biosafety Act". Based on the above incidents, market concerns about reducing dependence on Chinese pharmaceutical manufacturers have become a consensus in the U.S. political circles.

"Far from being so extreme." Guo Xinfeng told the Financial Associated Press that at this stage, the shortage of drugs in the United States is intensifying, especially in the field of injections and oral drugs for chronic diseases. American companies feel that their profits are meager and are unwilling to produce. Chinese companies are an important force to fill the market gap. It is impossible to be replaced, and the "Biosafety Act" and other targets are also the most cutting-edge and advanced R & D and production foundry in the pharmaceutical industry, it will not extend to the entire pharmaceutical industry chain, and the current state of the U.S. pharmaceutical industry does not support such a hard decoupling.

Guo xinfeng further proved to the reporter of the financial association that some time ago, the PD-1 varieties of junshi biology-U(688180.SH) and the CAR-T varieties of earlier legendary biology were listed in the United States, as well as the surge in sales of PD-1 varieties of baiji shenzhou-U(688235.SH) in the United States, all proved that the U.S. pharmaceutical market is open to Chinese enterprises and is worth exploring. "Therefore, for FDA to improve the inspection intensity, relevant enterprises selling products in the United States should pay more attention to relevant quality management practices and compliance."