The outbreak caused a shortage of Polupi tablet.

Text: Peng Zishan, Chen Liangrong, World Web only|The text is taken from: Commonwealth Magazine

Common Wealth Magazine Interviewed the Problem of Drug Absence of Purabi Tablets in the Country During the Epidemic

The epidemic cut off the supply chain, and the drug shortage crisis in Taiwan is coming! Which patients are at risk?

New crown pneumonia has spread from China to Europe and the United States, and Taiwan’s drug shortages are also increasing. Are hospitals and pharmacies panicking and stockpiling, or is the epidemic disrupting the drug supply chain? PTU, which is used to treat hyperthyroidism, fired the first shot of lack of medicine, which also reflects the plight of Taiwan's generic medicine industry. In March, Wuhan pneumonia spread from China to Europe and the United States, disrupting Taiwan's drug supply chain. An old famous pharmaceutical factory with a history of nearly 50 years, Taiwan Genesis (referred to as Genesis), is one of the pharmaceutical factories that has encountered turbulence. PTU, which is used to treat hyperthyroidism, is one of the drug shortage items recognized by the Food and Drug Administration. In February, it was notified by the industry that there would be drug shortages. Today, entering April, the crisis has not been resolved, the shortage of drugs is still rapidly expanding, and the items are also increasing, including cardiotonics, blood pressure lowering, analgesics, diuretics, etc., are in the scope of notification. Since Genetron Health ships an average of 1 million PTU units a month, that is to say, this last barrel of PTU is only enough for half a month's shipments. Once the hospitals, channels, and Genetron Health's inventory "Porpo" are also exhausted, Genetron Health expects that it will face a stock-out crisis as soon as June.

Only the last bucket of raw materials?

Nantong Essence, a Chinese raw material supplier in Jiangsu Province, has not been shipped since the beginning of the New Year, and patients with hyperthyroidism in Taiwan are facing a drug withdrawal crisis. New crown pneumonia has spread from China to Europe and the United States, and Taiwan’s drug shortages are also increasing. Are hospitals and pharmacies panicking and stockpiling, or is the epidemic disrupting the drug supply chain? PTU, which is used to treat hyperthyroidism, fired the first shot of lack of drugs, which also reflects the plight of Taiwan's generic drug industry.

In March, COVID-19 spread from China to Europe and the United States, disrupting Taiwan's drug supply chain. Panbiotic Laboratories, a famous pharmaceutical company with a history of nearly 50 years, is one of the pharmaceutical companies that has encountered turbulence. On the fourth floor of the factory near Chengcing Lake in Kaohsiung, there is a GMP standard raw material warehouse with constant temperature and humidity maintained at more than 20 degrees C. On the shelf, a 25 kg beige paper can "Propylthiouracil" (PTU for short) is a commonly used medicine for the treatment of hyperthyroidism. This bucket of PTU, with the addition of excipients such as lactose and starch, can be made into 500,000 50-mg tablets for sale. Once the inventory of hospitals, channels, and Panbiotic are all depleted, Panbiotic Laboratories expects that it will face a stock-out crisis as soon as June.

Panbiotic Laboratories used to maintain 20 barrels of PTU inventory. Due to the impact of China's new crown pneumonia epidemic, the Chinese API manufacturer Nantong Essence in Jiangsu Province has not shipped since before the New Year, so only a lonely one is left on this shelf. barrel. PTU, which is used to treat hyperthyroidism, is one of the drug shortage items recognized by the Food and Drug Administration. In February, the industry received notification from the industry that there would be a shortage of drugs. Today, entering April, the crisis has not been resolved, the shortage of medicines is still expanding rapidly, and the items are also increasing, including cardiotonics, blood pressure lowering, analgesics, diuretics, etc., are in the scope of notification.

"Unexpectedly, Bulebi will be missing today. It used to be the least promising medicine," General Manager Cai Shen Xueying said with emotion. Since Genetron Health ships an average of 1 million PTU units a month, that is to say, this last barrel of PTU is only enough for half a month's shipments. Once the hospitals, channels, and Genetron Health's inventory "Pulepi" are all depleted, Genetron Health expects to face a stock-out crisis as soon as June. PTU has only two medical certificates in Taiwan, which are obtained by Pansheng and Nisco. Until the deadline, Niscore has not yet responded to "Tianxia"'s interview request. 

Without PTU, how serious is it for about 20,000 patients with hyperthyroidism in Taiwan?

In Taiwan, hyperthyroidism occurs in young women under 40. The male to female ratio is about 1:3. Almost 150 women per 100,000 people suffer from hyperthyroidism. However, not all first-line drugs are PTU. Wang Shunhe, the attending physician of the secretion department of the Beishi United Medical Renai Hospital, explained that in 2016, the American Thyroid Association (ATA) mentioned in the guidelines for the diagnosis and treatment of hyperthyroidism that 2-3% of people who use PTU may experience liver damage. In Taiwan's health insurance database, the proportion of liver damage is only about one in a thousand, but most doctors in Taiwan follow the recommendations of this diagnosis and treatment guide and give priority to the use of the antithyroid drug Methimazole (MMI).

However, about 5% of patients who use MMI will have allergies and rashes. In addition, studies have found that pregnant women who use MMI in the first trimester may produce neonatal scalp defects. Therefore, the diagnosis and treatment guidelines also mention that the medication in the first trimester is PTU. Mainly, patients must eat every 6 to 8 hours, and eat 3 to 9 pills 3 to 4 times a day. Even if the acute phase has passed, it is necessary to take the medicine stably for about one and a half years to ensure that the thyroid hormone value is stable and the thyroid size is normal. Taking the hospital as an example, the dosage of "Polupi" in Changhua Christian Medicine Hospital is more than 30,000 tablets per month.

Once there is no medicine available, what do these patients do?

"We may change back to MMI first. If the patient is allergic, try using antihistamines or anti-allergic drugs. I expect that most patients should be able to survive the acute phase," Wang Shunhe explained. If a small number of patients can't help it. Accept, you can also try lithium salt. This medicine, which is mostly used to treat bipolar disorder, will also have a little effect. If it still doesn't work, the last resort is to have an operation to remove a part of the thyroid gland, or take the radioactive atomic iodine 131 to destroy the thyroid gland and reduce hyperthyroidism. "These two are both destructive methods. In theory, there are no clinical medicines available, and they will only make such a choice when they are really unbearable," he said.

As the epidemic slows down in mainland China, more and more companies have announced that they will resume work. It is expected that the inventory can be used up to June's PTU. Why is there still a shortage of medicines?

Take Nantong Essence, a raw material supplier of Panbiotic, for more than 50 years of history, GMP pharmaceutical factories not only produce epilepsy drugs Phenobarbital (Phenobarbital), anticonvulsant drugs such as pyrimidinedione (Primidone) There are also traditional Chinese medicine products such as "Wang's Baochi Pills" and "Jidesheng Snake Pills". Together, "the trade volume with APEC countries has reached 20 million yuan per year." The epidemic was at the head, but Nantong Jinghua announced on February 27 that, The first batch of "Chloroquine" (Chloroquine) for the treatment of Wuhan pneumonia has been manufactured, with a daily output of 400,000 tablets, and this batch of drugs will be sent to Wuhan to fight the epidemic.

"They said they would resume work, but the operating rate may only be 30 or 40%," Cai Shenxueying explained.

In addition to the problem of personnel movement,"Last year or the year before last, many raw material factories in mainland China started to shut down. It should be a problem of environmental pollution."In addition to the epidemic disrupting the production rhythm after the resumption of work, the bigger problem is that the already tightly supplied chemical industry cannot produce enough PTU raw materials to be sent to Taiwan. The source was the explosion of the 321 Xiangshui Tianjiayi Chemical Plant in Yancheng, Jiangsu Province in March last year, which killed 78 people, injured dozens of others and shut down many small chemical plants. After the explosion of the plant producing ethylbenzene organic compounds, a large amount of toluene, dichloroethane, and methylene chloride flowed into Hanoi, and the sulfur dioxide and nitrogen oxides in the air also greatly exceeded the standard.

According to a report by Reuters, the State Council of China also decided to rectify the production and management of hazardous chemicals in Jiangsu Province at its executive meeting in November last year, and conduct special inspections on the safety of hazardous chemicals across the country. Tighter controls have led to the closure of many chemical plants, the price of the chemical industry has risen, and many raw materials have fallen into short supply. Until the end of March, Panbiotic still did not get the PTU APIs ordered at the end of last year. In addition to the epidemic disrupting the production rhythm after the resumption of work, the bigger problem is that the already tightly supplied chemical industry cannot produce enough PTU raw materials to be sent to Taiwan. Panbiotic, which could not wait for Chinese APIs, found a German supplier willing to supply after contacting API manufacturers in Japan, Germany, and India, and was waiting for a Taiwan agent to apply as an alternative drug. However, when the application can be completed, Fu Chunrong, the responsible international trade manager, has no answer yet.

Not only PTU, but the anti-wufei quinine is next?

"The shortage of drugs has been very serious in the past three or five years." Liu Yiqing, a pharmacist in the Zhangji Materials Department who has been responsible for drug procurement for more than ten years, explained that the reason for the tight and unstable supply of drugs is that the prices of health insurance drugs have been reduced year after year, and manufacturers The profit margin has also declined. Liu Yiqing observes that from the PIC/S GMP for inspections of factories to the API GMP for the management of main components of drugs, they are all used to ensure the quality improvement of drugs, but they also increase the operating costs of pharmaceutical factories. At the same time that the price of health insurance drugs has been lowered, many pharmaceutical companies have given up pharmaceuticals, and the remaining manufacturers have used scale in exchange for profitability. "As long as a family has conditions, there will be problems with the supply."

In the process of producing Polupi, Panbiotic has also undergone a plant reconstruction upgrade from GMP to European standard PIC/S GMP. Not only compartments and air conditioners need to be changed, but the entire production line must be adjusted. But for PTU, there are only two medicine certificates in Taiwan. The health insurance prices of Prohibitor and Protech are both 1.5 yuan, and the aluminum foil or plastic foil packaging is 2 yuan each, which is cheaper than candy.

"Recently, we have received significantly more notifications than before." Zhang Yuli, director of Beirong Pharmaceutical Department and host of the domestic drug shortage notification, assessment and response plan, pointed out that most of the recent shortage notifications come from community pharmacies, but it is sporadic or sporadic. The general shortage has yet to be assessed as a whole. Part of the sporadic phenomenon comes from stockpiling in hospitals and community pharmacies. Asia’s largest healthcare group, and the largest domestic original pharmaceutical logistics market, Zuelling Pharma Group. General Manager Zhou Zhihong observed that the orders for all medicines from hospitals and pharmacies at the end of February and early March have increased over the same period last year. 70%.

Since mid-February, some people have worried that the supply of medicines will be affected by the operation of China's API factories."Therefore, some hospitals, especially those in the central part of China, have become more nervous and feel the need to increase the inventory."But Zhou Zhihong emphasized,"As long as you follow the normal order, there will be no problem with the inventory. Everyone is more worried because it is crowded out due to panic factors."In order to reduce panic drug hoarding, the Food and Drug Administration of the Ministry of Health and Welfare also announced on March 17 "Principles of drug supply management during the epidemic prevention period for severe and special infectious pneumonia", Stipulates that if the monthly order volume of hospitals, pharmacies, etc. exceeds the average monthly actual shipment volume of the previous year by more than 10%, the reasons and supporting materials must be reported to the Food and Drug Administration, and the shipments can be approved after approval. The FDA's action may be able to curb the trend of excessive drug stocking in the country, but due to problems such as resumption of work and cross-border logistics, there are more and more shortages of drugs that are in short supply, and they can only find alternatives one by one.

Looking for an alternative in Europe?

Zhang Yuli mentioned that for the shortage of PTU, pharmaceutical companies have tried to find raw materials from Europe.The problem is that the epidemic has spread around the world. It is impossible to predict when pharmaceutical factories in various countries will resume work, and Europe may not be earlier than mainland China, so continuous observation is needed. "It also regulates thyroxine, but the original German drug Eltroxin, which is used to treat hypothyroidism, is also out of stock. The reporter visited 3 community pharmacies and found that even if there is a prescription, I don’t know when I will get the medicine. The "Lanoxin", which was out of stock, was reported a few years ago. There is only one foreign original manufacturer in Taiwan. Currently, due to the factory's production schedule, it may be out of stock until the second half of the year. The Food and Drug Administration is also assisting pharmaceutical companies in discussing whether to import alternative drugs from South Korea.

With the inclusion of Hydroxychloroquine in the "Fifth Edition of the Interim Guidelines for the Clinical Management of New Coronavirus Infections", quinine drugs used in the treatment of lupus erythematosus and rheumatoid arthritis have also been out of stock. The pharmacy also launched an investigation into whether there are stockpiles. What is certain is that the past pharmaceutical supply chain is being shuffled, and the problem of lack of medicine may have just begun.

(Editor in charge: Hong Jianing)

Article taken fromCommonwealth Magazine