[Details] Administrative Dispositions of Pharmaceutical Companies What's happening to manufacturers one after another? (Updated)

[NHK] The shortage of pharmaceutical supplies continues nationwide. It all started with a generic manufacturing problem, and then pharmaceutical companies around the world stopped working one after another. What's happening?

[Details] Administrative Dispositions of Pharmaceutical Companies What's happening to manufacturers one after another?

(Updated) May 15th, 12:02

"The drug is actually in short supply ..."

Pharmacies and medical institutions nationwide continue to have an unprecedented supply shortage of medicines.

It all started with the discovery of manufacturing fraud at a generic drug manufacturer, and over the past year or so, manufacturers in various regions have been subject to a series of dispositions for business suspension orders.

I've summarized what's happening.

(The latest information was added / updated to the article published in February)

[Details] No medicine ... From generics to original products Why (updated)

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What was the origin of it in the first place?

The origin of the series of problems was that the ingredients of the sleep-inducing agent were mixed in the therapeutic drug for fungal diseases such as water bugs manufactured by the generic = generic drug maker "Kobayashi Kako" in Fukui Prefecture, which was discovered in December 2020. It was a misconduct.

More than 240 people suffered health problems such as losing consciousness after taking the drug, and in some cases, they were injured due to an accident while driving a car.

Last February, Kobayashi Kako received a record-long 116-day business suspension order and business improvement order from Fukui Prefecture.

Even after that, manufacturing and sales did not resume, and in fact, we abandoned the restructuring of management and transferred the factory etc. to a new company established by another major generic company at the end of March.

What are the problems found in the survey?

Regarding Kobayashi Kako, it became clear that it was manufactured in a process not approved by the government.

The contamination of sleep-inducing agents was caused by mistaken for another drug container in order to perform "work to add raw materials", but this work itself was not approved by the government.

In the same way, many pharmaceutical products have been violated, such as manufacturing in a process not approved by the government or forging the results without conducting quality tests, and also keeping "double books" in preparation for the prefecture's inspection. We even created it and systematically concealed it to prevent the discovery of fraud.

At a press conference after the disposition, the president at the time revealed that he had been aware of and tolerated such illegal activities for more than 15 years.

Generic giants too

In March of last year, a little over a month after Kobayashi Kako's disposal, one of the three major domestic generic companies, Nichi-Iko, received an order to suspend operations from Toyama Prefecture.

"Nichi-Iko" has continued manufacturing for more than 10 years, which is different from the process approved by the government, such as crushing tablets that are non-conforming in the quality test and reprocessing, and not performing some pre-shipment tests. It was disposed of as it was.

After that, "Nichi-Iko" has not resumed full-scale shipments because it took time to confirm that there were no problems in the manufacturing and shipping processes of the factories subject to administrative sanctions, and it is still nationwide. It is also a major factor in the supply shortage of pharmaceutical products that follows.

In addition, the company's business performance deteriorated significantly, and on May 13, it announced that it would apply for the "Business Revitalization ADR" procedure of the national system and aim to rebuild its business with the support of trading banks.

Which manufacturer has been disposed of?

Even after the dispositions by Kobayashi Kako and Nichi-Iko, administrative dispositions have been issued one after another to pharmaceutical manufacturers in various regions.

It is the period (maximum) of business suspension with the manufacturer who received the disposition of the business suspension order in the past year or so.

* The date is the announcement date

Manufacturers who received an order to suspend operations ▼

February 9,

2021 Kobayashi Kako (Fukui) 116 days

March 3 Nichi-Iko (Toyama) 32 days

March 26 Okami Chemical Industry (Kyoto) 12 days

August 12 Hisamitsu Pharmaceutical (Saga) 8 days

September 14 North Japan Pharmaceutical (Toyama) 28 days

October 11 Choseidou Pharmaceutical (Tokushima) 31 days

November 12 Matsuda Pharmaceutical Industry (Ehime) 65 days

December 24 Nissin Pharmaceutical (Shiga) 75 days ▼

March 28,

2022 Kyowa Pharmaceutical Industry (Osaka) 33 days

(based on interviews with the Ministry of Health, Labor and Welfare and prefectures)

Disposal is received not only by generic drug manufacturers such as "Kobayashi Kako" but also by over-the-counter drug manufacturers such as "Kitanihon Pharmaceutical".

In addition, no health hazard has been confirmed by manufacturers other than "Kobayashi Kako".

On the other hand, violations were discovered, such as using raw materials that have not been approved by the government, and not performing some quality tests and repairing necessary equipment.

Of these, "Nisshin Pharmaceutical" (Shiga), which was ordered to suspend operations for 75 days after "Kobayashi Kako" in December last year, is an active ingredient for pharmaceuticals such as nourishing tonics and cold medicines for children. In addition to reducing the amount of the drug to 1% of the amount that should be added in the smallest case, it was punished by Shiga Prefecture for being manufactured with the addition of unapproved additives.

Even "Medicine Toyama" has a big impact

Toyama Prefecture, known throughout Japan as "Toyama of Medicine," has two of the eight companies that received the business suspension order.

With about 80 pharmaceutical manufacturers and more than 100 factories, the value of pharmaceutical production per capita is the highest in Japan (2019).

Last March, when Nichi-Iko (Toyama) received an order to suspend operations from the prefecture, it had a great impact on the pharmaceutical industry in the prefecture.

In the prefecture, after the prefecture's unannounced inspection, a violation such as the use of an unapproved additive was found, and in September last year, "Kitanihon Pharmaceutical" was ordered to suspend operations. In January, a business improvement order was issued to a manufacturer that has a factory in Toyama City.

Some of the violations by both manufacturers have been committed for more than 10 years.

Furthermore, although no administrative sanctions have been issued, two manufacturers in the prefecture have begun voluntary collection of products one after another, saying that the drug was manufactured by a procedure different from the approval certificate in October and November last year.

While Toyama Prefecture has expressed a sense of crisis in this situation, "Most companies manufacture properly in accordance with laws and regulations, and it is possible that the false image that some cases apply to all pharmaceutical companies in the prefecture spreads. Very disappointing "(Toyama Prefecture Medicine Policy Division).

In order to prevent recurrence and improve quality control, we have increased the number of investigators with pharmacist qualifications by 3 from the new fiscal year, and are strengthening the system by monitoring and instructing with a system of 10 people.

Why are you getting rid of them one after another?

One of the reasons is that efforts to check for fraud, such as inspections by the government and voluntary inspections by each company, have been strengthened.

Previously, most prefectural inspections of pharmaceutical manufacturers = on-site inspections were conducted after notifying the schedule in advance.

At the press conference when Kobayashi Kako was dismissed, the person in charge of Fukui Prefecture at that time said, "Basically, I have given advance notice and conducted an investigation, but I was deceived by the forged documents. I will look at it with suspicion. "

In response to this situation, the Ministry of Health, Labor and Welfare requested prefectures in February last year to increase the number of "unannounced inspections" conducted without prior notice.

So to speak, we switched from inspections based on the "innate goodness theory" to "unannounced" inspections based on the premise that "may be cheating" and strengthened them.

In July of last year, a nationwide unannounced inspection was also conducted, and a violation of Matsuda Pharmaceutical Industry (Ehime) was discovered.

In addition, industry groups have also called for voluntary inspections by each manufacturer, and an in-house investigation revealed that Choseido Pharmaceutical Co., Ltd. (Tokushima) and Kyowa Pharmaceutical Industry Co., Ltd. (Osaka) have not received national approval. As for the violation of pharmaceuticals (Shiga), anonymous information sent to the prefecture triggered an on-site investigation of the prefecture.

(Okami Chemical Industry (Kyoto) and Hisamitsu Pharmaceutical (Saga) were discovered in an in-house survey conducted in 2020)

Are other manufacturers okay?

On March 24th, the "Japan Generic Pharmaceutical Association", which is made up of generic drug manufacturers, announced the results of self-inspections by member companies that have been underway since the problems of Kobayashi Kako and Nichi-Iko.

According to the announcement, more than 80% of the 38 member companies, 31 companies, found manufacturing procedures that are not stated in the national approval certificate.

In terms of the number of items, 1157 items, which is 15% of the total number of items to be inspected, have been reached.

The inspection was conducted by an outside expert, and no new major problems with efficacy or safety were revealed.

In the future, we will proceed with the procedure for changing the approval details according to the judgment of the national and prefectural governments.

What kind of response is in the industry?

On the other hand, the association has also proceeded with verification of cases where fraud was found.

The verification results announced in October last year point out that "unhealthy corporate culture" was one of the causes of the problems of "Kobayashi Kako" and "Nichi-Iko" as follows.

"A culture in which the instructions of superiors are absolute and problems cannot be raised from below." "

The

management considered employees only as management targets, not as training targets."

, A person related to the manufacturer who discovered a manufacturing problem also sent it to the NHK interview team's submission form.

Manufacturer-related person A

There are not enough human resources in the department that manages quality, but there is only an instruction to "make a number" and there is no knowledge of proper manufacturing.

Even if the site reports a problem due to poor ventilation, it will be silently killed.

Manufacturer-related person B Small and medium-

sized manufacturers cannot make capital investment, salaries are low, and human resources are not retained.

The motivation of the site was low, and there were times when the approved procedure was skipped, mistakes and accidents occurred, and it was forced to end.

Mitsuo Sawai, Chairman of the Japan Generic Pharmaceutical Association, said, "The current supply shortage has also been caused by fraudulent drugs made differently from the approval certificate. Unless the distrust of generic drugs is resolved, generics will truly contribute to medical care. I can't do it. I will work on countermeasures with a determination of immortality. "

The association plans

to strengthen measures such as

conducting regular training to raise the awareness of management

, enhancing the contact points for whistleblowing , and conducting

external audits of major manufacturing plants about once a year .

What should I do in the future?

We spoke with Professor Osamu Hirata of Kumamoto Health Science University, who was the chairman of the quality committee of the pharmaceutical industry group.

Professor Hiruta himself was an OB of the manufacturer, and focused on the fact that the percentage of manufacturers who have been found to be fraudulent for many years due to "external power" such as unannounced inspections by the government and anonymous letters to the editor is high.

Professor Hiruta

: It is natural to make medicines that patients take directly, following the procedures that have been recognized as safe, but there are more violations than I imagined and there are few manufacturers who voluntarily offered to do so. I'm discouraged.

"The morals of the questioned manager"

On top of that, Professor Hikita points out that manufacturers nationwide had a "chance to produce seaweed" six years ago.

It is a problem that Kumamoto City's pharmaceutical manufacturer "Kahemokuken" manufactured blood products etc. by a method different from the national approval and systematically concealed it, and in 2016 it was the longest business suspension for 110 days at that time. It was when I received the order.

At that time, the Ministry of Health, Labor and Welfare requested manufacturers to carry out self-inspection, and while more than 70% of manufacturers reported minor procedural delays, it is said that "more than 10 years ago" has been discovered one after another. No fraud was declared.

For these reasons, Professor Hikita points out that in response to this situation, manufacturers and the industry itself will be thoroughly rebuilt, and "whether or not we can get rid of the sea" will be the key to restoring trust in the future. ..

Professor Hiruta

: I think that the problem of the morals of the management is that he should have learned that "inappropriate manufacturing is a risk related to the survival of the company" in the blood product manufacturing problem, but he still hid it.

This time, generic manufacturers, where malicious fraud was discovered one after another, are steadily lowering the prices of drugs due to the revision of the country, so I think that there is certainly a difficult aspect in terms of management.

However, proper manufacturing can be practiced by many companies, so it should be compatible with management.

I think we must fundamentally review the organizational culture of the company and let the management take the lead in instilling an awareness of not allowing fraud in the field.

Scheduled to be broadcast in "Close-up Gendai"

"I don't have the usual medicine !? What is in the shadow of the rapid expansion of generics

Click here for Close-up Gendai program information

What is happening to the "medicines" that protect our health?

The background is that generic drug manufacturers have discovered a series of manufacturing problems.

What is the "intelligence" revealed to the interview team by the people involved in the field?

And when will the shortage be resolved?

We will approach the actual situation of unknown drug shortage by our own interview.

Request for information to the interview team

The interview team will continue to cover issues related to the manufacturing sites of pharmaceutical manufacturers.

Especially if you want to know the actual situation of the site, please send information from the following posting form (link / banner).

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(Pharmaceutical shortage coverage group Network news department Murahori et al. Toyama Broadcasting Station Shinji Hashimoto)

The following is a related article.

Please read it together.

[Details] Administrative Dispositions of Pharmaceutical Companies What's happening to manufacturers one after another? (Updated) | NHK