In January this year, some experts believed that some centralized procurement drugs may have quality risks of "blood pressure does not drop, anesthetics do not cause sleep, and laxatives do not cause diarrhea". Relevant departments quickly sent personnel to investigate and understand the situation. Recently, relevant comrades from the medical insurance and drug supervision departments who participated in the investigation accepted media interviews on issues of social concern.

Is there a quality problem on the Internet?

Regarding the saying that "antihypertensive drugs do not lower blood pressure". It is reported that the generic drugs of "amlodipine" are not as effective as the original drugs, and the reason is personal medication experience. Ruijin Hospital provided the clinical real-world research results of the comparison between the selected generic drugs and the original drugs in the centralized procurement of amlodipine besylate in which the hospital participated, showing that "for patients with primary hypertension, the use of original and generic amlodipine treatment can achieve good results, can effectively lower blood pressure levels, and is equally safe". This research result has been published publicly.

Regarding the saying that "anesthetics do not cause sleep". After face-to-face communication, Ruijin Hospital conducted a retrospective comparison of the use records of the ninth batch of centralized anesthetics "Propofol Emulsion Injection", and included patients who underwent laparoscopic cholecystectomy under general anesthesia in the hepatobiliary surgery ward in December 2023 and December 2024. From the perspective of the entire anesthesia process, there was no statistical difference in the average anesthetic dosage of original drugs and centralized generic drugs. Looking at the anesthesia induction period (the initial stage of the entire anesthesia process), the average dosage of centralized generic drugs was 157mg, and the average dosage of original drugs was 146mg (each bottle of centralized and original drugs contained 200mg).

Relevant departments stated that in the absence of "anesthesia does not sleep" and no difference in the total per capita propofol dosage, the per capita dosage of generic drugs during the anesthesia induction period increased slightly, and more data needs to be collected for analysis and judgment.

Regarding the statement that "laxatives for intestinal preparation for endoscopic examinations are often reported to have poor efficacy in clinical use." A relevant person in charge of the National Medical Insurance Administration said that it was learned that the laxatives used for intestinal preparation are mainly compound polyethylene glycol electrolyte powders. This drug is a new variety included in the tenth batch of centralized procurement. The winning results were just announced on December 30, 2024. It is still in the preparation stage before implementation. That is to say, the relevant hospitals and medical staff have not yet used the "post-centralized procurement laxatives".

At the same time, for the individual cases of adverse reactions collected clinically (both original drugs and generic drugs), the seven hospitals reported the adverse drug reactions in accordance with regulations, and the reporting channels were unobstructed. Some of the hospitals also provided further detailed reports. The adverse reactions of the generic drugs and original drugs purchased did not exceed the scope of the drug instructions and literature reports.

In general, the statements about "blood pressure does not drop, anesthetics do not sleep, and laxatives do not cause diarrhea" are mostly from others' retelling and subjective feelings. In the next step, the relevant departments will continue to pay attention. A clinical expert who was interviewed also said on the spot that "not knowing enough about the pharmaceutical industry, especially the generic drug industry, is prone to the misunderstanding that 'price equals quality' and 'price reduction will definitely reduce quality'".

Can consistency evaluation guarantee drug quality?

A relevant person in charge of the State Drug Administration responded that my country's consistency evaluation method adopts internationally recognized strict standards, and the technical requirements are in line with international standards.

Since 2015, my country has promoted the reform of the drug review and approval system, and adjusted generic drugs from the original "imitation of drugs with existing national standards" to "imitation of drugs with the same quality and efficacy as original research drugs". For generic drugs that were launched early, consistency evaluation is carried out in stages and batches according to the principle of consistency with the quality and efficacy of original research drugs.

First, strictly select reference preparations for consistency evaluation. Generally, the original research drug is selected as the reference preparation, which means that the control drug for consistency evaluation is the only one, and all generic drugs are compared with the reference preparation. Some people worry that the problem of "the first imitation is based on the original research, and the subsequent generic drugs are based on the first imitation, resulting in a decline in the imitation standard" does not exist.

Second, my country's consistency evaluation method adopts internationally recognized strict standards. my country's technical requirements for consistency evaluation of generic drugs have been aligned with international standards. We have adopted internationally accepted technical standards such as the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) to conduct technical review of generic drugs, including pharmaceutical, non-clinical, and clinical, and have adopted and implemented all ICH technical guidelines. Developed countries such as Europe and the United States also use the above technical standards to conduct reviews. Referring to the practices of European and American drug regulatory agencies, we will make the review report public on the basis of protecting the company's commercial secrets in accordance with the law.

Third, drugs continue to be strictly regulated after they are approved and marketed. The drug regulatory authorities not only adhere to strict standards during the review and approval of the market, but also continue to strictly regulate them after the drug is approved and marketed, requiring companies to strictly follow the process production when applying for consistency evaluation, and major changes must be re-approved. The review standards for changes after market launch are also aligned with international standards. Holders need to continuously improve and optimize drug quality in accordance with the technical and regulatory considerations of ICH Q8 (R2) drug development, ICH Q9 (R1) quality risk management, ICH Q10 drug quality system, and ICH Q12 drug life cycle management. Therefore, consistency evaluation is a complete set of quality evaluation and regulatory systems, not a "one-time evaluation".

Will it lead to the withdrawal of original research drugs from China?
A relevant person in charge of the National Medical Insurance Administration said that China is one of the most important original research drug markets in the world. In the negotiations on the national medical insurance catalog since 2018, 212 imported drugs have been successfully negotiated, accounting for nearly 50% of the negotiated Western medicines. Even in the fiercely competitive centralized procurement of drugs with volume, more than 30 original research drugs have won the bid after competing with generic drugs.

The person in charge said that the agreed procurement volume of centralized procurement drugs is 60%-80% of the reported demand of medical institutions. The actual procurement volume of the hospital reaches the corresponding scale, which means that the procurement agreement is completed. For the part outside the agreement, the medical institution can choose the brand independently and can choose to purchase non-selected original research drugs.

The data provided by Ruijin Hospital to the National Medical Insurance Administration showed that while introducing 24 centralized procurement antihypertensive drugs, the hospital retained 18 corresponding original research varieties of antihypertensive drugs; in terms of antibacterial drugs, 48 centralized procurement varieties were introduced, and 21 corresponding varieties of original research drugs were retained; in anesthetic and muscle relaxant drugs, while introducing 6 centralized procurement varieties, 4 corresponding varieties of original research drugs were retained.

In addition, it is understood that the original research drugs of some drugs have never actually entered the domestic market.

How to make the use of drugs more secure in the next step

The continuous practice since 2018 has not only clinically tested the centralized procurement policy and centralized procurement drugs, but also made the mainstream drugs used by patients in my country realize the leap from "unapproved generic drugs" to "approved generic drugs".

The relevant departments stated that they will continue to strengthen the supervision and management of drug quality. Timely disposal of drugs and companies with problems will be carried out, and regulatory information will be disclosed in accordance with the law. Continue to encourage clinical frontline doctors to make good use of the drug adverse reaction monitoring information platform and actively feedback clues to drug quality risks. Continue to encourage and support clinical medical staff and medical institutions to give full play to their professional expertise, carry forward their professional spirit, and conduct clinical research in a scientific and standardized manner. The medical insurance, drug supervision and other departments support relevant medical institutions and medical staff, especially authoritative medical institutions such as national medical centers and regional medical centers, to explore and conduct real-world research on original research drugs, generic drugs that have passed consistency evaluation, etc., to examine the efficacy of drugs on a larger scale, to indicate regulatory priorities, to promote industrial development, and to allow high-quality drugs to benefit more patients. In addition, relevant departments also stated that drug quality and safety is not only the lifeline of enterprises, but also the bottom line of regulatory authorities. For a long time, drug regulatory authorities have strictly supervised the quality of drugs, especially the quality of drugs selected in centralized procurement, and insisted on "full coverage" and "zero tolerance".

In terms of further improving the centralized procurement policy, the National Medical Insurance Administration stated that it will widely understand the daily supervision of drugs and exclude products with higher quality risks from centralized procurement. For varieties where the number of bidding companies is expected to exceed a certain scale and the competition is relatively fierce, strong competition warnings will be issued in advance to remind companies to make prudent decisions, bid scientifically, and quote rationally. Pay special attention to the lowest bid with high deviation, and ask companies to respond to relevant concerns publicly in a timely manner.

In addition, during the centralized procurement application period, bidding companies must sign a quality commitment letter and actively disclose information such as drug consistency evaluation research reports and bioequivalence test data, and previous quality supervision and inspection. After winning the bid, continue to publicly accept quality inspections by domestic and foreign drug regulatory authorities, as well as changes and approvals in production processes, raw materials, etc.

It is reported that from 2025, all drugs participating in centralized procurement must have drug traceability codes to provide support for drug quality supervision.