Entering ChinaAccording to the National Health Insurance Administration this afternoon (February 9):
In January this year, some experts believed that some centrally purchased drugs may have a quality risk of “blood pressure does not drop, anesthetics do not sleep, and laxatives do not diarrhea”. The relevant departments quickly sent personnel to investigate and understand the situation. A few days ago, the relevant comrades of the medical insurance and drug supervision departments who participated in the investigation were interviewed by reporters on issues of social concern.
Q: Please introduce the relevant situation of the survey, and what information did you communicate with the experts on site?
A: The investigators listened carefully to the opinions of relevant experts, as well as the heads of seven hospitals, including Ruijin Hospital, Renji Hospital, and Zhongshan Hospital, as well as medical staff from departments such as surgery, internal medicine, anesthesiology, and pharmacy. While listening to opinions, we also went deep into relevant departments to extract relevant data.
The researchers expressed to the experts the sincerity of “opening the door to centralized procurement and listening to opinions”, conscientiously accepting social supervision, introducing the specific practices of national centralized drug procurement, introducing the relevant measures to strengthen the quality supervision of centralized procurement drugs and the disposal of selected drugs found to have individual quality risks, and introducing the real-world research of selected drugs in centralized procurement carried out by more than 80 tertiary hospitals covering more than 300,000 patients.
The researchers focused on three aspects of information from the experts: one is the feeling of the efficacy and quality of drugs when using various types of centralized procurement drugs in the clinical frontline, the second is the specific situation mentioned such as “blood pressure does not drop, anesthetics do not sleep, and laxatives do not diarrhea”, and the third is the opinions and suggestions on improving the drug centralized procurement policy and strengthening drug quality supervision.
Q: What did you learn about the few statements made by the experts in the interview?
Answer: Regarding the saying that “blood pressure medication does not lower blood pressure”. There are generic drugs that reflect that “amlodipine” are not as effective as the original drugs, and the reason is personal drug 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 participated by the hospital, showing that “for patients with essential hypertension, the treatment with both the original and generic amlodipine can achieve good results, effectively reduce blood pressure levels, and the safety is comparable”. The results of this study have been published.
About the saying “anesthetics don’t sleep”. According to the clinicians of the anesthesiology department of the hospital surveyed, “the hospital has an average of more than 2,000 surgeries per month, and the usage and dosage of anesthetics before and after centralized procurement have not changed much, and various types of anesthetics such as inducers, sedatives, and muscle relaxants have not changed much.” A leader of one of the hospitals surveyed said: “There is no problem of ‘anesthetic not sleeping’ in our hospital.” After the face-to-face exchange, Ruijin Hospital quickly made a retrospective comparison of the use records of the ninth batch of the centralized anesthetic drug “Propofol Emulsion Injection”, and included laparoscopic cholecystectomy patients who received general anesthesia in the hepatobiliary surgery ward in December 2023 and December 2024. From the perspective of the whole process of anesthesia, there was no statistical difference in the average amount of anesthetic between the original drug and the generic drug in centralized procurement. Looking at the anesthesia induction period (the beginning stage of the whole process of anesthesia), the average dosage of generic drugs is 157mg, and the average dosage of original drugs is 146mg (the content of both centralized drugs and original drugs is 200mg). In the absence of “anesthetic does not sleep” and there is no difference in the total per capita dosage of propofol, the per capita dosage of generic drugs in the anesthesia induction period increased slightly, and more data analysis and judgment need to be collected.
It is stated that “laxatives for bowel preparation for endoscopy often reflect poor efficacy in clinical use”. It is understood that the laxatives used for bowel preparation are mainly compound polyethylene glycol electrolyte powder, which is a newly included variety in the tenth batch of centralized procurement, and the results of the selection have just been announced on December 30, 2024, and it is still in the preparatory stage before the implementation of the landing, which means that the relevant hospitals and medical staff have not yet used the “laxative after centralized collection”. Ruijin Hospital and several other hospitals have reported that they have not received relevant feedback from the clinical frontline on “laxatives do not laxative”. The director of the colorectal surgery department of a tertiary hospital who was surveyed said, “The two laxatives prepared for colonoscopy for many years are all domestic drugs, and there is no change, and I have never heard of the situation of ‘laxatives without laxatives’.”
At the same time, for the cases of adverse reactions collected in clinical practice (both original drugs and generic drugs), 7 hospitals reported adverse drug reactions according to regulations, and the reporting channels were unimpeded. Some of these hospitals also provided detailed reports, and the adverse reactions of generic drugs and original drugs purchased did not exceed the scope of drug instructions and literature reports.
On the whole, the statements about “blood pressure does not drop, anesthetics do not sleep, and laxatives do not diarrhea” come mostly from other people’s relays and subjective feelings. In the next step, the relevant departments will continue to pay attention. A clinical expert who was surveyed also said on the spot, “If you don’t know enough about the pharmaceutical industry, especially the generic drug industry, it is easy to have the misunderstanding that ‘price equals quality’ and ‘price reduction will definitely reduce quality’.”
Q: The society is very concerned about whether the consistency evaluation of generic drugs by the drug regulatory department is a “one-time evaluation”, can you introduce the relevant situation of the consistency evaluation?
A: Since 2015, China 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 the original drugs”. For the generic drugs that are marketed in the early stage, the consistency evaluation will be carried out in phases and batches according to the principle of consistency with the quality and efficacy of the original drugs.
First of all, the reference preparation for consistency evaluation was strictly selected. Generally, the original drug is selected as the reference preparation, that is to say, the control drug for consistency evaluation is the only one, and all generic drugs are used as the reference preparation. Some people are worried that the problem of “the first generic drug is based on the original research as a reference, and the subsequent generic drug is based on the first generic as a reference, resulting in a decline in imitation standards”.
Second, China’s consistency evaluation method adopts strict and internationally recognized standards. China’s technical requirements for the consistency evaluation of generic drugs have been in line with international standards, and international technical standards such as the International Council for the Coordination of Human Drug Registration Technology (ICH) have been adopted to carry out the technical review of generic drugs, including pharmaceutical, non-clinical, clinical, etc., and all ICH technical guidelines have been adopted and implemented. Developed countries such as Europe and the United States also use the above technical standards to carry out reviews. Referring to the practice of European and American drug regulatory agencies, the review report is made public on the basis of protecting the trade secrets of enterprises in accordance with the law.
Third, drugs continue to be strictly supervised after they have been evaluated and marketed. The drug regulatory department not only adheres to strict standards during the listing review and approval, but also adheres to strict supervision after the drug has been evaluated and marketed, requiring the enterprise to strictly follow the process production at the time of applying for consistency evaluation, and major changes must be re-approved. The review criteria for post-marketing changes are also in line with international standards, and holders are required to continuously improve and optimize drug quality in accordance with technical and regulatory considerations such as ICH Q8 (R2) drug research and 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 supervision system, not a “one-time evaluation”.
Q: Can hospitals use non-selected original drugs for centralized procurement? Have all the original drugs been withdrawn from China?
A: Some people say that the original drug will be completely withdrawn from China, but this is obviously not the case. China is one of the most important markets for innovators in the world, and it is one of the most open markets for innovators in the world. Since 2018, 212 imported drugs have been successfully negotiated, accounting for nearly 50% of the negotiated Western medicines. Even in the highly competitive centralized procurement of drugs, more than 30 original drugs have won the bid after competing with generic drugs.
From the beginning of its birth, the centralized drug procurement policy has encouraged original drugs to compete with generic drugs, and even if they are not selected, the original drugs will not be banned from use. The agreed procurement volume of centralized procurement drugs is 60%-80% of the reported demand of medical institutions, and the actual procurement volume of the hospital reaches the corresponding scale to complete the procurement agreement. Ruijin Hospital is equipped with the corresponding non-selected original drugs in addition to the centralized collection of drugs, and the materials provided by it show that “while introducing 24 centralized collection antihypertensive drugs, there are 18 corresponding original varieties of antihypertensive drugs; In terms of antibacterial drugs, 48 varieties were introduced for centralized procurement, and the corresponding 21 varieties of original drugs were retained. Among the anesthetic and muscle relaxant drugs, while 6 varieties of centralized procurement were introduced, 4 original drugs of corresponding varieties were retained.” In addition, it should be noted that not all the original drugs of the drug have been produced and sold in the domestic market, and some have never actually entered the domestic market.
Q: Can the price of centralized procurement drugs cover the cost? Has it been found that there is a quality risk in centralized procurement of drugs before? How is it handled?
Answer: The feedback from the selected enterprises that the selected price of centralized procurement drugs can cover the cost mainly due to three reasons: first, the sales volume of the selected drugs directly into the hospital is guaranteed, which greatly saves marketing costs; Second, “with volume” can form a scale effect, make full use of production capacity, reduce marginal production costs, and at the same time use large-scale procurement to improve the bargaining power of upstream suppliers and save raw material procurement costs; Third, in the large-scale and stable production environment, the enterprise carries out the automation transformation of the production line to further reduce the production cost and stabilize the quality. Therefore, the selected enterprises can make small profits but turn over quickly on the premise of ensuring quality.
Drug quality and safety is not only the lifeline of an enterprise, but also the bottom line of the regulatory authorities. For a long time, the drug regulatory department has strictly supervised the quality of drugs, especially the quality of selected drugs in centralized procurement, and adhered to “full coverage” and “zero tolerance”. Every year, the national centralized procurement of drugs is carried out two “full coverage” of the inspection of the selected enterprises and the sampling inspection of the selected varieties, which currently covers all the varieties that have been used in the national centralized procurement and more than 600 drug manufacturers involved. On the whole, China’s drug safety situation is generally stable, and the quality of drugs continues to improve.
The drug regulatory department will immediately take measures such as suspending production, import, and sales of individual products with quality risks found, whether they are original drugs or generic drugs, and will seriously deal with them and expose them to ensure the safety of drug use by the people. The medical insurance department and the drug regulatory department shall establish a normalized disposal mechanism, maintain close contact, and cancel the qualification of the drug procurement department in a timely manner in accordance with the procurement bid to ensure the safety of the public’s drug use. In the past few years, among the first 9 batches of more than 1,600 selected products that have been used, a total of 9 drugs have been disqualified due to quality risks, of which 6 are imported drugs (including 3 original drugs) and 3 are domestic drugs, and relevant enterprises have been seriously dealt with.
Q: Many real-world studies have shown that generic drugs are equivalent in efficacy and safety to original drugs, but why do some people on the Internet and around them sometimes have different feelings?
A: Generic drugs are an important part of the pharmaceutical supply. According to relevant reports, the proportion of generic drugs used in most countries in the world is relatively high, of which 90% of generic drugs are prescribed in the United States and about 80% in Japan. The individual feelings of drug efficacy reflected by the masses and experts on the Internet and around them need to be studied and elaborated through scientific methods. For example, the results of the publicly released real-world study on the efficacy of metformin hydrochloride tablets are: the compliance rate of glycosylated hemoglobin (<7%) was 78.9% in the original research group and 83.4% in the centralized procurement imitation group; The compliance rate of fasting blood glucose (<8mmol/L) was 87.6% in the original research group and 83.8% in the centralized procurement imitation group. According to the analysis of standardized statistical methods, there is no difference between the two compliance rates of the generic drug group and the original drug group. Regardless of the use of original drugs or generic drugs, about 80% of patients have blood sugar control or glycosylated hemoglobin standards, and about 20% of patients have poor efficacy, and patients need to use other treatment methods or drugs with other mechanisms of action. It is inaccurate and unscientific to select individual cases from 20% of patients with poor efficacy to “prove” that generic drugs do not respond well or that the original drug does not work well.
Scientific, fair and accurate evaluation of drug efficacy requires systematic and rigorous methods and processes, and individual cases are easier to understand and sound impactful. Still taking metformin as an example, the country uses more than 10 billion metformin tablets a year, although the glycosylated hemoglobin and fasting blood glucose compliance rates are consistent with the original research, both of which are about 80%, but it is not difficult to find out the cases of poor efficacy of generic drugs, and it is not difficult to find examples of poor efficacy of original drugs.
Q: What are the considerations for further ensuring the quality of centralized procurement of drugs?
A: The continuous practice since 2018 has not only allowed the centralized procurement policy and centralized procurement drugs to be clinically tested, but also enabled the mainstream drugs of Chinese patients to achieve a leap from “unevaluated generic drugs” to “over-evaluated generic drugs”. However, compared with the expectations of the broad masses of the people, there are still areas where our work needs to be continuously improved. For example, we can further urge the selected pharmaceutical companies to actively disclose drug quality data to the public. Another example is that we can further respond to the general concerns of society in a more down-to-earth way and effectively resolve doubts and doubts. Drug quality assurance requires long-term efforts and continuous efforts, and always maintains the spirit of “catching up with the exam” on the road. In the next step, the relevant departments will continue to make efforts from the following aspects to continue to ensure the quality of centralized procurement of drugs.
First, continue to strengthen the supervision and management of drug quality. Quality is the lifeblood of medicines. The drug regulatory department will continue to benchmark against international technical standards, strictly manage technical reviews and post-marketing changes, continue to disclose review reports in accordance with laws and regulations, adhere to the full coverage inspection of selected enterprises in centralized procurement and the full coverage of sampling inspections of selected varieties, urge enterprises to continue to comply with production, timely dispose of drugs and enterprises that find problems, and disclose regulatory information in accordance with the law. At the same time, whether quality risks are found in the daily supervision of centralized procurement drugs, relevant information shall be reported to the medical insurance department in a timely manner.
Second, we should continue to encourage front-line clinical doctors to make good use of the adverse drug reaction monitoring information platform and actively feedback drug quality risk clues. Drug administration, medical insurance and other departments encourage doctors to timely and accurately discover and collect suspected adverse drug reactions, and report to the “National Adverse Drug Reaction Monitoring System” in accordance with the requirements of relevant laws and regulations. The drug regulatory department will organize evaluation, investigation and disposal in accordance with the relevant information, and will further publicize it to medical institutions and medical personnel, so as to fully protect the privacy of adverse reaction reporters and dispel concerns about voluntary reporting. At the same time, relevant people in the pharmaceutical industry and all sectors of society are also encouraged to continue to monitor the quality of drugs.
Third, we will continue to encourage and support clinical medical staff and medical institutions to give full play to their professional expertise and carry forward their professionalism, and carry out clinical research in a scientific and standardized manner. Departments such as medical insurance and drug administration support relevant medical institutions and medical personnel, especially authoritative medical institutions such as national medical centers and regional medical centers, to explore and carry out real-world research on original drugs and generic drugs that have passed consistency evaluation, investigate the efficacy of drugs on a larger scale, prompt regulatory priorities, promote industrial development, and make high-quality drugs more beneficial to more patients.
Q: How to further improve the centralized procurement policy in the next step?
A: First, strictly adhere to the standards. Continue to insist on reference preparations and high-quality generic drugs that have passed the consistency evaluation of quality and efficacy as the “threshold”. Extensive understanding of the daily supervision of drugs, and exclude products with higher quality risks from centralized procurement.
Second, refine the organization and implementation. For varieties that are expected to exceed a certain scale and the competition is fierce, early warning of strong competition will be carried out in advance, and enterprises will be reminded to make prudent decisions, bid scientifically and offer rationally. Pay close attention to the lowest quotation with a high degree of deviation, and ask enterprises to respond to relevant concerns in a timely and public manner. At the same time, we will coordinate the stability of market supply and the fairness of competition, comprehensively consider a variety of factors, continue to improve the centralized procurement policy, and better ensure the quality and supply of centralized procurement drugs with the refinement of work.
Third, the whole process should be open and transparent. During the declaration period of centralized procurement, the bidding enterprises shall sign a quality commitment letter, and take the initiative to disclose the drug consistency evaluation research report and bioequivalence test data, and the previous quality supervision and inspection information. After winning the bid, it will continue to publicly accept the quality inspection of domestic and foreign drug regulatory departments, as well as the changes and approvals of production processes, raw materials and excipients. The selected enterprises are required to disclose their contact persons to facilitate consultation and communication between medical institutions, medical personnel and relevant social parties, respond to quality concerns in a timely manner, and rectify supply problems in a timely manner. Enterprises are encouraged to organize open day activities, openly invite the media, medical staff and representatives of the public to participate, and display the production process of the selected drugs without affecting production safety, so as to enhance transparency.
Fourth, the whole chain can be traced. From 2025 onwards, all drugs participating in centralized procurement must have a drug traceability code to achieve “code procurement”. Medical insurance designated medical institutions and designated pharmacies shall, in accordance with the designated agreement, collect and upload traceability codes for the whole process of relevant drugs, and the medical insurance department will use the traceability code information as the basis for payment and implement “settlement with code”. At the same time, the medical insurance department will give full play to the data association advantages of traceability codes, resolutely curb the return and exchange of drugs, resolutely crack down on fraud and insurance fraud, and use traceability information to provide support for drug quality supervision.
