Imported original research drugs are "disappearing" from public hospitals.

In 2018, the first batch of national centralized drug procurement pilots began, with 25 drugs selected, including 23 domestic drugs and 2 foreign drugs.

In November 2023, the ninth batch of centralized procurement was completed, with more than 1,600 products selected, including 1,583 domestic generic drugs and 70 imported original research drugs.

From the first to the ninth batch, domestic drugs/generic drugs increased from double to quadruple digits, while imported original research drugs only rose from single to double digits.

Public hospitals are the main body of centralized procurement.

This means that imported original research drugs that have not obtained the centralized procurement ticket will also lose a large part of the market in public hospitals.

Recently, a father narrated that when he wanted to use the imported Azithromycin—Pfizer's "Zithromax" for his 6-year-old child with a high fever in the hospital, he was told that there was "no medicine available," only domestic alternatives.

And the city where this father is located is Hangzhou, a new first-tier city with a permanent population of 12 million.

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Is this an individual phenomenon or a general existence?

Why can't imported original research drugs enter the centralized procurement on a large scale?

Is the effect of the substituted generic drugs really not good?

How can ordinary people buy imported drugs?

These issues are closely related to us.

In fact, this is not the first time that public opinion has paid attention to the "disappearance of imported drugs."

In addition to the respiratory and reproductive tract infection drug "Zithromax" that caused the topic this time, the "disappearance" of the star anti-diabetic drug "Glucophage" in public hospitals has also caused quite a discussion.

As the original research drug for treating diabetes, Metformin "Glucophage," it has been the absolute main force in the blood sugar-lowering drug market since its launch in China in 1999.

Data from the China Medical Network shows that Metformin has always ranked in the top three in sales volume among various blood sugar-lowering drugs, with a domestic Metformin market of 5.976 billion yuan in 2019.

Among them, Glucophage's market share has been maintained at around 80%.

However, by 2021, diabetic patients found that "the 'little god medicine' Glucophage that has been taken for ten years is out of stock in public hospitals, replaced by domestic Metformin at 3 yuan for 100 tablets..." This year, several imported original research drugs have also signaled their withdrawal from the Chinese market.

In January, the world's first-valued pharmaceutical company, Eli Lilly, issued a withdrawal application explanation for Strattera (Atomoxetine Capsules): Eli Lilly's product line strategic adjustment, the products currently produced by Eli Lilly's foreign factories and distributed by Eli Lilly Trading Co., Ltd. as the general agent will gradually stop supplying to the Chinese market and will ultimately terminate supply at the end of January 2024.

Strattera is a drug used to treat ADHD (Attention Deficit Hyperactivity Disorder).

In the "Expert Consensus on Early Identification, Standard Diagnosis, and Treatment of Attention Deficit Hyperactivity Disorder" published in March 2020, it was mentioned that the prevalence of ADHD among children in China is 6.26%, with about 23 million patients.

With the announcement of the "withdrawal from the network," Strattera has been "scrambled" for a while, and the E-medicine manager mentioned that some people "directly bought 100 boxes at one time," some were speculated to a high price of thousands of yuan, and some were purchased from overseas, with the price being more than three times the original price.

In addition, antihypertensive drugs "Losartan," lipid-lowering drugs "Lipitor," expectorant drugs "Mucosolvan," Ceftriaxone "Rocephin," Cefaclor sustained-release tablets "Ceclor," cough medicine "Compound Pholcodine," allergic rhinitis treatment "Enlax," and gastric inflammation and ulcer treatment "Plicam"... More and more common imported drugs have gradually faded out of people's sight in recent years.

We can't help but ask, how did these imported original research drugs disappear?

Public hospitals are difficult to enter First, it is necessary to clarify that imported original research drugs have not really "disappeared" on a large scale.

Many of them still exist in the market, but it is indeed getting harder and harder to buy imported original research drugs in public hospitals.

Behind this, there are multiple factors involved, such as centralized procurement, medical insurance payment methods, and "withdrawal from the network."

First, the access issue of centralized procurement.

The so-called centralized procurement refers to the centralized purchase of drugs by the "state" as a unit, similar to "group purchase."

The state negotiates with drug production enterprises through volume procurement and price reduction, to achieve the purpose of reducing drug prices and alleviating the burden of patients' drug costs.

The main unit is public medical institutions.

Under such rules, imported original research drugs are mostly expensive and difficult to enter.

Taking the star anti-diabetic drug Glucophage as an example, the breaking of its absolute position is due to the "centralized procurement" in 2020.

When the market price of the original research drug Glucophage fluctuates around 20 yuan/box (0.5g*20 tablets), about 1.1 yuan/0.5g, many domestic generic drug companies directly discounted the bid price of Metformin by 10%.

For example, Hydrochloride Metformin tablets have eight companies winning the bid, and the cheapest single box is only 1.29 yuan (0.25g*84 tablets), about 0.015 yuan/tablet.

In the end, Glucophage was not selected and gradually withdrew from public hospitals.

The original research drug company Pfizer's "Zithromax" Azithromycin, which has attracted public opinion attention, is also the same.

Its oral products, injection products, and Azithromycin dry suspension products did not win the bid in the centralized procurement.

As a result, the original intention of centralized procurement was only to guide the drug price back to a reasonable level and reduce the burden of the public's medication, without the intention of squeezing out original research drugs.

In the end, due to the rules of centralized procurement, the high-priced original research drugs were inevitably not selected.

In addition, to ensure the completion of the "quantity," the National Medical Insurance Bureau also has a pre-condition: within a one-year cycle, hospitals participating in centralized procurement must first complete the usage of the selected varieties in centralized procurement (the hospital autonomously declares the usage), and then they can use the varieties not selected in centralized procurement.

In short, you can use other drugs, but please first complete the KPI of centralized procurement drugs, which accounts for 70%-80% of the hospital.

As a result, even if doctors want to prescribe original research drugs, the hospital's system may also pop up a prompt, telling them to be cautious.

On the other hand, when and who to use the remaining space is also a consideration of doctors and hospitals' fairness in medication and professional ethics, which is not easy to implement.

Second, the chain reaction brought by the medical insurance payment method.

Chen Hao, the director of the Center for Drug Policy and Management Research at Tongji Medical College of Huazhong University of Science and Technology and a comprehensive review expert of the National Medical Insurance Bureau, mentioned that currently, public hospitals mainly rely on medical insurance income.

For the same generic name of drugs, that is, drugs with the same drug composition, medical insurance will only pay the benchmark price of the selected variety.

The price of original research drugs is usually far higher than the benchmark price, so who will bear the excess part?

If the patient is unwilling, no one will bear it.

In addition, the current promotion of DRG (per disease group) / DIP (per disease type) payment methods also makes hospitals dare not use "expensive drugs."

The core of this payment method is to group or calculate the points of disease diagnosis and treatment, and pay for the "package" payment, that is, the total amount is fixed, "one disease, one unified price, no matter how many inspections are done and how many drugs are used in the process, the cost remains unchanged."

Data from the National Medical Insurance Bureau shows that by the end of 2023, more than 90% of the regions in the country have carried out DRG/DIP payment, and 26 provinces have achieved full coverage of all regions within the province.

Under the promotion of this payment method, using "expensive drugs" is naturally not cost-effective for hospitals.

Third, imported original research drugs that insist on not reducing prices also have the risk of "withdrawal from the network" (the pharmaceutical procurement platform built by provinces for hospitals).

Pfizer's "Zithromax" Azithromycin dry suspension is a classic example.

After being not selected in the centralized procurement at the end of last year, in April this year, it was informed by the Hebei Province Medical Device Centralized Procurement Center to withdraw from the network because "the price is higher than the Shanghai red line price."

This means that if imported original research drugs do not reduce prices, they will not only not be able to enter centralized procurement but will also completely lose the hospital as a major procurement entity, leaving only the market outside the hospital.

Under the combined factors, when an ordinary person goes to a public hospital for treatment, the probability of buying generic drugs is much higher than that of original research drugs.

For ordinary people, how much and how fast the imported original research drugs disappear is not the most important.

People are most concerned about whether the efficacy of the substituted generic drugs is good or not?

There is an endless discussion on this issue.

To this end, in June 2021, the National Medical Insurance Bureau commissioned Xuanwu Hospital of Capital Medical University to lead 29 medical institutions in 16 provinces and cities to carry out real-world research on the clinical efficacy and safety of 23 representative varieties of the second and third batches of the national organization's centralized procurement.

The results show that the clinical efficacy and safety of the selected generic drugs in centralized procurement are comparable to those of original research drugs.

On the WeChat public account of the National Medical Insurance Bureau, we can also see that it has published many articles to prove that the effect of the evaluated generic drugs is the same as that of original research drugs.

However, such results do not seem to completely dispel people's doubts.

A patient who has taken the original research drug "Gleevec" in "I Am Not a Drug God" and the "Indian divine medicine" smiled bitterly: "There are some things that you really don't know the gap between them without experiencing them.

It's like in the graphics card, the model is the same GTX1060, but the brand is the difference between Galaxy and Yingchi."

The "Survey and Analysis of Chinese Residents' Perception of Generic Drugs and Related Factors" released by the Science and Technology Development Center of the Chinese Pharmaceutical Association in 2022 also shows that among 15,046 Chinese residents, more than 60% believe that there is a gap between the "clinical efficacy" or "safety" of the evaluated generic drugs and original research drugs; among the people who have used both generic drugs and original research drugs, 49% think that the original research drugs feel better, 47% think there is no difference, and 4% think that generic drugs are better.

The recognition of generic drugs by domestic doctors is not optimistic either.

In 2022, a study published in the international academic journal Health Policy Open analyzed the common views of Chinese doctors on generic drugs.

The data shows that compared with original research drugs: 26.4% of doctors recognize the quality of generic drugs35.8% of doctors recognize the therapeutic efficacy of generic drugs, and 36.5% recognize their safety.

In terms of clinical application, 34.1% of doctors agree with the view that "generic drugs can replace the original research drugs."

The discrepancy between this overall survey result and individual micro-perceptions mainly lies in the differences in the "consistency evaluation" of collectively purchased generic drugs.

The so-called consistency evaluation, in our country, mainly depends on pharmaceutical equivalence and bioequivalence.

When the geometric mean ratio of pharmacokinetic parameters between the test preparation and the reference preparation is between 80% and 125%, it can be considered bioequivalent.

In the past, this approach was indeed the international "gold standard," but it is somewhat outdated at present.

Taking the other side of the ocean as an example, the U.S. Food and Drug Administration (FDA) released the "Guidance for Industry on Evaluation of Generic Drugs for Therapeutic Equivalence" (draft) in July 2022.

It stipulates that the scientific and regulatory basic principles for evaluating the therapeutic equivalence of prescription drugs include: pharmaceutical equivalence, bioequivalence, and the same clinical efficacy and safety under the conditions specified in the instructions.

In comparison, our consistency evaluation is mainly "theoretical" consistency, which does not necessarily mean clinical effect consistency.

Moreover, contrary to popular belief, the biggest "moat" for original research pharmaceutical companies is not the drug ingredients, but the excipients and production processes, which pharmaceutical companies do not need to disclose.

Therefore, even if generic drugs achieve the same ingredients as the original research drugs, due to the different excipients added, there may be differences in drug dissolution, bioavailability, stability, and even efficacy in the body, especially for some low-dose drugs.

The gap in process levels can also lead to different effects.

The most typical example is the cephalosporin skin test.

In China, hospitals generally require patients to undergo a skin test before using cephalosporin drugs, while imported original research drugs do not need to do so.

The reason behind this is that our country's purification process in the past could not strictly control the impurity content of the drug.

At the same time, copiers may also have speculative and shortcut-taking behaviors, ignoring the internal factors affecting the quality of drugs such as process, excipients, processes, crystal forms, and isomers, which inevitably leads to omissions.

This point is detailed in the book "The Truth About Generic Drugs."

No country in the world can design a perfect medical security system; it can only find a path suitable for its own national conditions.

China, as a populous country and a deeply aging country, faces unprecedented challenges in medical security and the pension system.

On the one hand, the number of insured people is decreasing (the total number of insured people has decreased by 29.08 million in the past two years), while the cost of residents' medical expenses is increasing by double digits, and the medical insurance fund is under pressure.

On the other hand, China's social structure still has a large number of low- and middle-income groups with relatively weak economic bearing capacity.

Taking 2020 as an example, there are 600 million people in China with an average monthly income of only 1,000 yuan.

This highlights the urgency and importance of reducing the medical burden on the public and optimizing the allocation of medical resources.

We cannot have both.

Therefore, a differentiated route is slowly unfolding: for patients pursuing "cost-effectiveness," public hospitals are still the best choice; for patients with economic bearing capacity who want to use imported original research drugs, they can choose special needs departments, international departments, high-end medical institutions that do not go through medical insurance, or public hospitals for treatment and buy medicine outside.

For ordinary people, the most convenient way to buy imported original research drugs is to go to the pharmacy with a hospital prescription.

Pharmacies belong to the out-of-hospital market, and imported original research drugs still have a certain survival space.

Last year, the author obtained imported original research drugs at a Grade III hospital in Guangzhou through a doctor's prescription and went outside to get the medicine.

There are also online platforms.

The online market of the Internet is becoming an important battlefield for foreign pharmaceutical companies.

Xinhua Health reported that after the country implemented volume procurement, more and more multinational pharmaceutical companies have started to focus on China's online market.

There are many similar cooperation cases, such as Novartis with Tencent, Boehringer Ingelheim with JD Health, Good Doctor Online, Jianke, E-Union, Ping An Good Doctor, We Doctor, Miao Doctor, AstraZeneca with Tencent, etc.

Taking JD Health as an example, the author searched for "Xishumei," "Gehuazhi," "Mushutan," and other generic drugs that were not selected for centralized procurement or "withdrawn from the network" on its WeChat mini-program, and all showed that it was possible to buy medicine with a prescription.

In this way, the out-of-hospital market is becoming another piece of the puzzle for people's freedom to use medicine.

Of course, the most ideal situation is that we can find a balance between innovation and imitation, after all, we not only have to consider whether there is medicine today, but also whether there will be medicine tomorrow.