Imported medicines that are difficult to buy

Economic Observer Network Reporter Zhang Ying Just entered the early autumn, mycoplasma pneumonia and other respiratory infectious diseases have entered the epidemic period one after another, and an article about the difficulty of buying imported azithromycin has detonated the field of public opinion.

The author of the article is the father of a child with mycoplasma pneumonia, and the First People's Hospital of Hangzhou, where the child was treated, could only prescribe domestic azithromycin injection, and the imported ones were out of stock, and this situation also existed in many other hospitals and community clinics he consulted.

"Zhejiang Provincial Children's Hospital only allows imported azithromycin injection to be used for hospitalized children, and only domestic ones can be used in outpatient clinics." The father told the Economic Observer that after the article was issued, it resonated with many netizens, and some parents of children chose to go to the international department of the hospital for treatment in order to use the drug, and spent 600 yuan on a registration fee to see a doctor.

According to the Economic Observer, the out-of-stock phenomenon of imported azithromycin injection is more common. According to a pediatrician at a tertiary hospital in Beijing, the drug has been out of stock since last winter.

The manufacturer of imported azithromycin injection is Pfizer, and the trade name is Xishumei. In the fifth batch of national centralized procurement carried out in June 2021, azithromycin injection from 6 domestic manufacturers including Sinopharm and CSPC was selected, and Xishumei was not selected.

In addition to imported azithromycin injection, since the launch of centralized drug procurement, many well-known imported original drugs such as Baitangping, Lipitor, Arimid, and Verred have been rumored to be out of stock.

Ma Jun, director of the Harbin Institute of Hematology and Oncology and chairman of the board of supervisors of the Chinese Society of Clinical Oncology (CSCO), told the Economic Observer that there are currently no approved generic drugs in China, which can generally be bought in hospitals or designated pharmacies.

Why it's hard to buy

Among the imported original drugs that are out of stock, the first to receive widespread attention is the star hypoglycemic drug acarbose produced by Bayer Pharmaceuticals, whose trade name is Baitang Ping.

Bai Tangping was once regarded as a typical case of imported original drugs actively embracing centralized procurement. In the second batch of national centralized procurement carried out in January 2020, Bai Tangping quoted a low price of 0.18 yuan per piece, a decrease of more than 91%. This winning bid price is even lower than the cost of production in the eyes of competitors.

Within two years of winning the bid, patients in many places found that Baitang Ping, which was available at any time, was no longer available in pharmacies, and at the same time, major hospitals were also out of stock.

According to a veteran in the pharmaceutical distribution industry, Bai Tangping's out-of-stock is because the production plans of multinational pharmaceutical companies have often been drawn up in advance, and the surge in demand brought about by centralized procurement has caused a large gap in their supply. Bayer Pharmaceuticals has told the media that within two years of implementing the centralized procurement plan, its actual supply in the selected provinces far exceeded the contracted volume.

However, more out-of-stock phenomena occur in the original drugs that have not won the bid in centralized procurement. For example, since the implementation of the third batch of national centralized procurement at the end of 2020, Roche's star product Heroda has been withdrawn from public hospitals one after another because it did not win the bid. Heroda is a basic drug for the treatment of colorectal cancer, gastric cancer and breast cancer, and in the centralized procurement, Roche Pharmaceutical quoted 24.83 yuan/tablet, much higher than the highest effective declaration price of 7.6667 yuan/tablet.

Also unsuccessful in the same batch of centralized procurement is AstraZeneca's anastrozole, whose trade name is arimidex. Anastrozole is known as a "life-saving drug" for breast cancer. In this centralized procurement, four domestic manufacturers, including Zhejiang Hisun and Hangzhou Zhongmei East China, won the bid, and AstraZeneca's Arimida was not selected.

At the beginning of 2023, Ruining will be out of stock. A patient told the Economic Observer that she had been taking the drug for a long time, the effect was good, and she was psychologically reluctant to change to domestic production, and after the stock was out of stock, she had asked her friends in United States to buy the original drug, but found that the price was too high, and finally bought the Hong Kong version of Arinide, the price was about 34 yuan/tablet, much higher than the domestic 0.9 yuan/tablet-3.5 yuan/tablet.

The patient also said that when she asked for Celelinde at the end of 2022, the doctor told her that the hospital's indicators had been used up and that she could only prescribe domestic drugs.

The indicator here can be understood as the proportion of centrally purchased drugs and non-centralized purchased drugs in hospital drugs. After centralized procurement, different hospitals need to purchase the required drugs according to the declared amount. The person in charge of a tertiary hospital in Zhejiang told the Economic Observer that the annual procurement volume of its hospital is 7-8 percent with reference to the actual use of the previous year, plus the measured natural growth of the year, the centralized procurement of drugs accounts for about 7 percent of the final drug consumption of the hospital, and the other 3 percent is the centralized procurement of external drugs.

He said that for patients who are intolerant to centralized procurement drugs and have poor efficacy, the authority to use original drugs outside centralized procurement will generally be appropriately opened; For original drugs with original processes, in order to facilitate the continuous treatment of patients, the manufacturer is generally not changed.

The director of a department of another tertiary hospital in Zhejiang said that the dosage of centralized procurement is a hard indicator, and imported drugs are not allowed to be used if they are not completed, and imported drugs can be used after the task is completed, but the task of centralized procurement in the second year will be determined by the total amount of the drug (domestic + imported) this year.

Not all hospitals adopt such a strategy. According to the director of the pediatric department of another tertiary hospital in Beijing, his hospital has not purchased imported azithromycin injection for a while, "If the hospital has this drug, the patient will have to prescribe it if the patient asks for it, because it and domestic azithromycin are both drugs in the medical insurance, but then the centralized procurement index may not be completed, so the hospital simply cut it off, saving the doctor trouble."

Ma Jun said that the use of imported original drugs that have a number of domestic generic drugs will help the country save medical insurance funds and reduce the medical burden of patients while the efficacy and safety are consistent and the price is cheaper.

Is the effect of generic drugs the same as imported original drugs?

In the above article, the father of the child said that the child's high fever quickly decreased after using the imported azithromycin injection, and he believed that the domestic azithromycin that had been used for three days was more likely to develop drug resistance, thus delaying the child's condition.

A pediatrician at a tertiary hospital in Beijing believes that azithromycin will be resistant regardless of whether it is imported or domestically produced, and it is impossible to judge the difference in efficacy between the two in this case.

However, since many original drugs have been withdrawn from public hospitals, many patients and their families have doubts about the consistency of efficacy and safety between generic drugs and original drugs.

According to a questionnaire survey conducted by the Science and Technology Development Center of the Chinese Pharmaceutical Association in 2022, among the 15,046 surveyed residents, 2,558 people were affected, and 49% of the patients who had used both the original drug and the generic drug said that the original drug felt better, 47% thought there was no difference, and 4% thought that the generic drug was better.

In fact, generic drugs are widely used all over the world because they are cheap. "There is nothing wrong with choosing generic drugs and biosimilars with consistent efficacy and safety, and it is a path we must take, because it is cheaper than the original drug, and the United States government also encourages the use of generic drugs." Ma Jun said.

Since 2016, China has begun to carry out the consistency evaluation of generic drugs, and generic drugs that have not undergone consistency evaluation are not allowed to be registered, and generic drugs included in centralized procurement are required to pass the consistency evaluation.

The method of consistency evaluation is to use the method of in vivo bioequivalence test in principle to evaluate whether there is a difference in the speed and degree of absorption of generic drugs and original drugs in vivo. For varieties that meet the principle of exemption from bioequivalence testing, drug manufacturers are allowed to adopt in vitro dissolution testing methods for consistency evaluation.

At the same time, the National Health Insurance Administration conducted a real-world study on some of the selected drugs in centralized procurement. For example, since June 2021, it has commissioned Xuanwu Hospital of Capital Medical University to take the lead in conducting research on 23 representative varieties of the second and third batches of national centralized procurement, and the results show that the clinical efficacy and safety of the generic drugs selected in the centralized procurement are comparable to those of the original drugs.

Zhang Lan, the leader of the research team and director of the Department of Pharmacy of Xuanwu Hospital of Capital Medical University, said that the effectiveness of any drug is probabilistic, for example, in the diabetic population, some patients will have poor efficacy when using a certain hypoglycemic drug, which will exist in both original drugs and generic drugs. "Scientific conclusions can only be drawn through controlled studies of a certain size of the population".

In the above-mentioned survey by the Science and Technology Development Center of the Chinese Pharmaceutical Association, 42.6% of people are willing to use generic drugs that have passed the consistency evaluation, and 24.5% are unwilling to use them.

Ma Jun believes that for those patients who can afford to pay and take commercial insurance to pay, they should be given the right to choose the use of drugs. "In the current DRG system, when calculating the charging level of the disease, the patient's self-payment and commercial insurance payment are added, which causes hospitals to dare not use too many high-priced drugs outside the medical insurance. However, medical insurance often cannot fully cover many serious diseases, commercial insurance is okay, and we should supplement it with commercial insurance."