Industry insiders recently pointed out that there is evidence showing that post-approval changes in the production process of Chinese generic drugs and drugs included in centralized procurement, which have undergone consistency evaluation, are widespread. These changes may affect the efficacy of the drugs but do not require a new round of consistency evaluation. It was noted that in the tenth batch of drugs included in the centralized procurement by the Chinese government’s medical insurance bureau, the score for aspirin enteric-coated tablets was as low as 3.4 points per tablet. To cut costs, companies might change excipients, resulting in a significant reduction in drug effectiveness.
On February 16, an industry insider known as Air-Moving Device published an article on the social platform BlueskySocial, stating that changes in the production process after approval are widespread among generic drugs that have undergone consistency evaluation and drugs included in centralized procurement.
By analyzing over 160,000 drug filing information from the National Medical Products Administration from January 1, 2019, to February 5, 2025, 1988 over-evaluated drug information publicly released by the Center for Drug Evaluation (CDE) of the National Medical Products Administration, and 1933 centralized procurement drug information published by the Shanghai Medical Insurance Bureau, Air-Moving Device discovered that there were significant changes in the production process post-evaluation for both generics and drugs included in the eighth batch of centralized procurement.
Further analysis revealed that among 352 types of drugs included in centralized procurement and 768 types of drugs not included, those included in centralized procurement underwent more changes in the production process that could impact the drug’s components and efficacy, around twice as much as drugs not included in the procurement.
Financial media outlet “First Financial” raised concerns about whether changes in the production process of generic drugs after consistency evaluation still meet the consistency requirements with the reference drug.
According to current regulations, after passing consistency evaluation, a generic drug can make changes to various production processes such as raw material suppliers, production techniques, and manufacturing sites without needing a new round of evaluation.
Air-Moving Device emphasized that the CDE has not disclosed detailed information regarding these changes that could impact drug efficacy, such as information about these changes, analysis of impurities in raw materials by manufacturers using new suppliers, inspections by regulatory authorities on new production sites, and whether drugs produced using new techniques have undergone in vitro bioequivalence analysis.
The majority of non-industry individuals are unaware that over-evaluated drugs and drugs included in centralized procurement may undergo production changes after evaluation.
A domestic pharmaceutical company executive told First Financial that, for instance, in the case of aspirin enteric-coated tablets, after winning a contract in centralized procurement, companies may switch to imported excipients to meet the lowest technical benchmarks while controlling costs. However, the efficacy is indeed lower than that of the original drug.
In December 2024, the Chinese government’s medical insurance bureau released the results of the tenth batch of drugs included in centralized procurement. Among them, the price of aspirin enteric-coated tablets fell as low as 3.4 points per tablet, while the lowest price for phenobarbital injection was as low as 0.22 yuan per vial.
An executive from a company that participated in the procurement of phenobarbital injection but was not selected, disclosed to the “China Business News” that their company produces the active pharmaceutical ingredient independently. Yet, the variable cost of producing one vial of phenobarbital injection reaches 0.6 yuan, with the fully loaded cost around 1 yuan when including taxes. With additional expenses like equipment depreciation and R&D amortization, it is impossible to compete at such prices.
In October 2024, the “Securities Times” reported that passing consistency evaluation is just the beginning of the generic drug market entry. After passing consistency evaluation and entering centralized procurement, some drugs often lower costs and increase profits through changes like modifying packaging and switching excipients.
A quality testing expert from a government-owned pharmaceutical quality testing institution in South China mentioned that aside from technical differences, in order to control costs, some generic drug manufacturers have different preparation processes, production equipment, and excipient sources, types, and ratios compared to the original drugs, leading to differences in taste, efficacy, and quality compared to the innovative drug.
For instance, for drugs like azithromycin, the quality standard for the generic drug concerning the reference drug is within a range, like 95% to 105% being qualified. While the reference drug may achieve 102%, domestic pharmaceutical companies might reach 97%, which is still within a reasonable range. However, as reasonable differences accumulate across multiple parameters, the gap between them can widen.
At this year’s “Two Sessions” in Shanghai, Dr. Zheng Minhua, Chief of General Surgery at Ruìjīn Hospital in Shanghai, expressed that due to the unstable quality of centralized procurement drugs and the low prices, doctors often face scenarios where “blood pressure does not decrease, anesthesia does not work, or laxatives do not function” when patients react to them. The doctors feel helpless due to the lack of choice and avenues for raising concerns.
Dr. Lu Changlin, a cardiologist at Chaoyang Hospital in Beijing and a member of the Beijing Municipal People’s Political Consultative Conference, raised concerns during this year’s conference, highlighting that doctors have commonly reported that compared to imported or original drugs, drugs obtained through centralized procurement have lower efficacy.