1988: Back to the human world for a few years

Chapter 404: The article behind “Original Research Localization” (2)

"Any original research drug that is to be officially circulated on the market must have its prescription published!"

Lu Yingying looked at the group of people in the conference room seriously, then whispered a few words to the assistant next to her. As the assistant moved stiffly and slightly panickedly, several documents that were originally used for other purposes appeared in front of everyone.

Tugou expertly turned to the fifth page of a document and held up the molecular structure diagram to the crowd: "Leaders, take this drug as an example. This is a drug we plan to copy... It is also a very common gastric drug abroad, pantoprazole sodium injection."

"The prescription information is very clear, including 45.1 mg pantoprazole sodium, 1 mg edetate disodium, and sodium hydroxide to adjust the pH to 9.0-10.5, using a freeze-drying process."

Seeing the staff coming over, presumably wanting to take the documents over so that the leader could see the content more clearly, Tugou quickly turned to the corresponding content in the other documents and handed them over together.

"In the pharmaceutical industry, as long as you want, you can always obtain complete or relatively complete prescription information for most original research drugs circulating in the European and American markets... because these drugs generally flow into the American market first, and according to FDA regulations, all drugs to be circulated in the United States must publish their prescriptions, even the ratio and process."

"Of course, the FDA has different requirements for different types of products... For example, the prescription and ratio of all injectable products must be fully disclosed, while oral solid preparations only need to disclose the prescription and excipient names, but not the ratio;"

Perhaps it was due to the national conditions at the time, but when a fat old man heard that the FDA actually required the prescription of the original drug to be fully disclosed, he was shocked at first. Then, when he heard that oral solid preparations did not need to disclose the excipient ratio information, his eyes lit up, as if he had found some loophole.

But before he could speak, Tugou suppressed his agitation: "Of course, due to the differences between Chinese and Western medicine, the excipient prescription is not that important for oral solid drugs, so it is not important whether it is published or not... In fact, even if it is a generic drug, as long as the excipients are used within the prescribed dosage range of the IIG (excipient database) and meet the equivalent requirements of the original drug, it can still be approved by the FDA."

"The above is the FDA's regulation. In my country, as long as an original research drug is registered, its full set of registration information, including prescription, process, impurity research, analytical methods, and quality standards, can be obtained by any generic drug company. This is not a difficult task... It's just that our country's requirements in this regard are stricter than the FDA's, and the current per capita income level in China is there, so many foreign original research drugs are unwilling to enter China. We have to take this roundabout route and directly obtain the prescription information of some drugs from the FDA, and then produce related generic drugs abroad (speaking of a little-known fact, the FDA's standards for access review are actually very loose, but they are very strict in the area of ​​clinical effect monitoring and punishment.)"

The fat old man couldn't help but said, "Manager Lu, even if you know the prescription ratio, what does it matter?"

"As you said, there are quite a few original European and American drugs that have registered to enter my country in recent years. Their prescriptions, processes, impurity research, analytical methods, and quality standards have also been registered in detail...but so what?"

"In recent years, domestic generic drugs still fail to achieve the same results as others?"

“It turns out that the active ingredients in generic drugs just can’t reach the purity of the original drugs!”

"Medicines are special items that are related to the health of the general public. If, without the guidance of national documents, large-scale generic drug substitution is carried out in Dezhou, it will delay the timely treatment of the people and cause adverse effects, which will cause a big mess!"

Tugou first looked at the fat old man in surprise, then glanced at Ye Tao and found that the executive was just sitting there quietly, like a wooden sculpture.

Although he was not sure what Ye Tao meant by his silence, Tugou, who was a little angry, refuted this statement directly: "Leader, although I admit that most of the generic drugs in China today cannot achieve the same effects as the original drugs, and there are various problems in this process, but one thing is one thing. If you only use this to say that the active ingredients of generic drugs cannot reach the purity of the original drugs... then, then, then it is wrong."

She wanted to say "That's pure nonsense", but when the words came to her lips, she realized that she was not facing Yan Laoxi and Qin Xin's old friends, so she swallowed them immediately.

But the fact that the other party actually asked this question can only mean two things.

1. This fat old man is probably an important person in charge of the relevant department. He does not want to see those large and small pharmaceutical factories being divested and reorganized under the leadership of their superior authorities.

2. The fact that he could say this only shows that this fat old man has no knowledge of the pharmaceutical industry and is completely speculating based on his own imagination. This speculation is as ridiculous as commenting that rocket power should be powered by water-washed coal... Maybe even the term "active ingredient purity" was given to him by his subordinates.

It's a very simple truth. Regardless of how ridiculous the formula "purity of active ingredients = efficacy" is, even if it is true, if the generic drugs produced do not meet the drug content standards, they would have been shot down during factory inspections. How could they have been circulated on the market?
Yang Shidan once said that seriously discussing whether one's own views are right or wrong with a layman is undoubtedly the stupidest thing in the world. Therefore, after giving a negative answer, Tugou only said cryptically: "Well, our country has strict inspection standards for drugs leaving the factory, and after they are circulated on the market, they will also conduct random inspections on these drugs from time to time...Among them, whether the drug content of drugs within the expiration date meets the standard is one of the most important inspection standards."

After all, he was a smart man, so he naturally understood the meaning of this sentence. His face could not help but stiffen for a moment, and he glanced at Ye Tao who was sitting next to him and watching the show quietly, and hummed vaguely: "The issue of the purity of active ingredients will be discussed later... However, the generic drugs currently produced in China cannot reach the impurity research level of the original drugs. This should be beyond doubt, right?"

Classmate Tugou looked with a little surprise at this fat old man who insisted on fighting with him in an unfamiliar field, and then looked suspiciously at Ye Tao, who always had a calm face, and the other participants who had different expressions.

what's the situation?
Isn't this a project hearing? Why are they always arguing about technical viewpoints? Shouldn't they discuss more about the feasibility, economic and social accounts of the project?
Could it be possible...?
Realizing that something was wrong, Tugou immediately forced himself to calm down.

The statement that "generic drugs will never reach the impurity research level of original drugs" is strictly speaking slightly stronger than the above statement, but that's all.

A truth that is somewhat beyond the cognition of later generations is that since its establishment in 1985, China CDE (China Drug Evaluation Center, but it should be called the Drug Review Committee at this time) has far exceeded the requirements of Europe and the United States for impurity research.

Yes, you heard it right, it is far beyond!
In fact, although CDE of later generations is famous for "picking out impurities", its high requirements for research on known impurities, unknown impurities, potential impurities, degradation impurities and residual solvents are absolutely unique in the world... This makes many international pharmaceutical companies shudder.

But in fact, CDE has been working on this issue for a long time - take the ordinary interferon mentioned above as an example. If CDE had not been working on the impurity content, do you think that with the current level of domestic medical research, the imitated and improved ordinary interferon could become the recommended drug for the treatment of hepatitis C?

Objectively speaking, in the context of the times, this was out of helplessness... It is precisely because of the gap in the foundation and technology of drug research and development between China and foreign countries that the FDA does not require many detailed studies. However, under the requirements of China CDE, all studies must be done. The impurities mentioned in the original drug must be studied, and the impurities that were not considered or not fully studied in the original drug must also be studied.

This once forced domestic pharmaceutical companies to purchase large quantities of testing equipment and technical service support from America and the island countries, with each company spending millions or tens of millions each year... But there was no other way, as their own foundation was not good, and they could only force technology upgrades in this way.

Of course, it was only 1990, and the CDE's requirements for drug impurity content during review were not as stringent as they were in later generations. But even so, the trend was obvious.

Thinking of this, Tugou didn't hesitate and gave his answer directly: "The teacher said that things are in a process of continuous development and change, and as long as we persevere, they will eventually develop in a good direction."

“It is true that there is still some gap between domestic generic drugs and foreign original drugs in terms of impurity research level, but this gap is rapidly being narrowed… The Drug Review Committee has proposed a motion to introduce new standards for drug review, and among these, the content of various impurities in drugs will be an extremely important review consideration.”

After a slight pause, Tugou's tone unconsciously showed a hint of confidence: "Unlike most ordinary pharmaceutical companies, Southwest Drilling Company No. 1 has a very close cooperative relationship with Tsumura Co., Ltd. and Sankyo Co., Ltd. in the island country, and even reached a strategic cooperation in the field of authentic medicinal materials GAP planting business;"

"Although the main cooperative business is the GAP planting of authentic medicinal materials, both Tsumura Co., Ltd. and Sankyo Co., Ltd. have a very deep technical foundation and complete equipment in the research and development and production of Western medicines... Especially Sankyo Co., Ltd., the HMG-CoA reductase inhibitor they launched on the market last year has quickly become an internationally popular hyperlipidemia treatment agent with good clinical performance, and officially began to sprint towards the title of the top ten pharmaceutical companies in the island country;"

"As a leading pharmaceutical company in the island country, Sankyo Co., Ltd., which originally focused on Western medicine, naturally has a large number of original and generic drugs. As long as we are willing to invest, we can naturally obtain relatively affordable instruments and technical guidance support for a large number of drug categories."

At the end, Tugou looked at everyone sincerely and said, "Leaders, everything depends on human effort. Let's not talk about the fact that impurity content is not the most important reason why domestic generic drugs are not as effective as original drugs. Even if it is, there are increasingly strict review standards from the Drug Review Committee and related equipment and technical guidance that can be introduced from pharmaceutical companies in the island countries... We are still confident about the impurity content of future drugs."

"In fact, we believe that it is a good thing for the Drug Review Committee to raise the standards in this regard... Carrying out as much research as possible on impurities will invisibly raise the threshold for project review. This will force major pharmaceutical companies to increase their investment in scientific research in order to survive, and also allow pharmaceutical companies to snipe subsequent developers through R&D strategies, thereby rapidly increasing the intensity of industry competition and achieving survival of the fittest... There is no way. There are too many pharmaceutical companies in our country now, and it is not a good thing to have too many but not strong ones."

When the fat old man heard Tugou bringing up the Drug Review Committee, and his every word was about the will of the higher-ups, his eyelids twitched involuntarily.

To be honest, the Drug Review Committee has been gradually improving the review standards for all aspects of drugs for a long time. This is also a very important reason why most small and medium-sized pharmaceutical companies in China are having a hard time today... Where do these small and medium-sized pharmaceutical companies get so much money and technical reserves for research and development investment!

In fact, as far as he is concerned, he actually hopes to delay it for one more day until the official document is issued... Besides, even if the document is issued, there will generally be a one- to two-year buffer period from the draft to the official implementation guidelines. What he cares most about at the moment is to avoid those small and medium-sized pharmaceutical companies with weak foundations in Texas from entering the divestiture and restructuring process prematurely.

However, you can think about it, but you can't sing a different tune. The girl in front of you has brought up the Drug Review Committee, and they can indeed seek technical support from leading pharmaceutical companies in the island country such as Sankyo Co., Ltd. and Tsumura Co., Ltd. Even if the other party has no direct evidence to show that this will definitely reduce the content of various impurities in future generic drugs, you can't continue to dwell on this Schrödinger's cat problem.

The fat old man forced a smile, then seized on the obvious loophole in Tugou's words and began to ask, "Isn't the impurity content the most important reason why domestic generic drugs are not as effective as original drugs?"

"Is it true that Manager Lu believes that simply improving the level of impurity research is not enough to make up for the gap in therapeutic effects between generic drugs and original drugs?"

After a slight pause, the fat old man did not give Tugou a chance to get into the subject. He nodded in approval and said, "Yes, medicines still need to be clinically tested. Generic drugs basically do not undergo clinical trials like original drugs, so it is understandable that the efficacy is not good."

Even Ye Tao couldn't help but change his expression when he heard the fat old man almost forcibly bring up the topic of clinical trials of generic drugs.

After all, medicines are sensitive commodities that are related to physical health. Coupled with some other reasons, today's project hearing will focus on the issue of how generic drugs can improve actual efficacy.

But the problem is that clinical trials are indeed a major flaw of generic drugs. Not to mention the weak basic pharmaceutical research level in China, and whether the more than 10,000 drugs that need to be accelerated are suitable for concentrating them all together and recruiting volunteers on a large scale to launch phase III clinical trials, even if the social impact can be ignored, where is the money available for you to conduct phase III clinical trials?
These are not just one or two drugs. To mention, the number of localized generic drugs involved in the rural grassroots chain drugstore project submitted by Everbright Hua Company has reached 642!
However, if it is impossible to deduce and prove the actual therapeutic effect of generic drugs in the future, then the "correctness" of this rural grassroots chain pharmacy project based on the sale of affordable drugs will be questioned. Once any problems arise in the future, Ye Tao and other people who support the project will be punished!
The lack of clinical trials is precisely the dead end. Thinking of this, Ye Tao couldn't help but frown and looked at Tugou, the student sitting opposite him.

After all, she is just a young girl. She was busy showing off her professionalism. Now, someone took advantage of her weakness, right?

Hey ~
If I had known this, I should have called Yang Mo and asked him to come to the hearing in person.

If it was in front of Yang Mo, Director Liu would not have the courage to pursue him relentlessly. Even if he wanted to, with Yang Mo's watertight style, he would not leave him the opportunity to take advantage of the situation.

Unexpectedly, after hearing the fat old man's question, Tugou laughed and said, "Director Liu, each country has its own national conditions. If we have to benchmark against foreign countries in everything, it may be a case of forcing things to happen, which is also inconsistent with the original intention of the Drug Review Committee."

As he spoke, Tugou took a piece of paper from the assistant and handed it to the staff: "Last year, in 1989, the per capita disposable income of urban residents in my country was only 903 yuan per year... and due to the economic gap between different regions, the disposable income of urban residents in Dezhou is higher than this average, but not much higher, at about 1050 yuan per year."

"But please note that this is the disposable income level of urban residents, not the national disposable income level, let alone the per capita GDP... In the vast rural areas of Texas, even in relatively wealthy areas, it is already very good to have a per capita disposable income level of 300 yuan per year. The per capita disposable income level in some poor areas is not even 150 yuan per year!"

"What does 150 yuan per year mean for the average income per person?"

"The per capita level of 150 yuan per year means that an ordinary family of four, at today's price level, after deducting the most basic necessities of oil, salt, sauce, vinegar, clothes, shoes, quilts and hats, and buying seeds, fertilizers, pesticides and other agricultural supplies, may not even be able to save yuan... This does not include weddings and funerals and sending children to school. If all these are taken into account, it is already very good to live without borrowing money."

“Even basic living is a problem. You expect them to buy expensive imported medicines when they get sick? This is unrealistic!”

At this point, Tugou's tone became a little sharper: "Leaders should know that I come from the countryside. With the reform of the rural primary medical system, in today's rural areas, the situation of "minor illnesses rely on endurance, and major illnesses rely on waiting" is everywhere!"

"This is not in line with our country's core values!"

"But the objective conditions of the country are there, and you have to face them!"

After a brief moment of confusion, Lu Yingying's tone gradually became firm: "So, a very cruel reality is..."

"If generic drugs are required to undergo clinical trials like original drugs, then most people won't even be able to afford generic drugs! If you get sick, you can only wait to die... Which clinical trial abroad doesn't start at tens of millions or even hundreds of millions of yuan? And the R&D costs will all be reflected in the price of the drug. Even if the country balances the price in the form of subsidies, how much can it subsidize on average for tens of thousands of different types of drugs!?"

"In fact, the consensus in the industry is that, precisely because the original drug has accumulated clinical experience, the effectiveness and safety of the active ingredient have been confirmed, and there is no need to repeat the safety and effectiveness research... This will only result in a huge waste of resources."

"Generic drugs only need to focus on two things: doing good pharmaceutical research and doing good equivalence research with the original research."

"And if there is a third thing that we need to focus on with generic drugs... then in our country, we must bring the prices down, and keep bringing them down, until the people in poor areas can walk into the pharmacy without any psychological burden when they get sick!"

At this point, Lu Yingying's face became terribly serious: "Leaders, it is better to live a miserable life than to die a good death."

"If given a choice, no one would be willing to endure the pain of old wounds and work hard under the scorching sun!"

"No one is willing to quietly curl up in a ragged quilt and gamble their life with three bowls of cold boiled water!"

"In today's China, it doesn't matter whether the efficacy of generic drugs is 80% or 60%. What matters is that the people at the bottom of society can afford medicine when they need it, even if they don't have to sell their only cow!"

When it came to the emotional part, Lu Yingying, who had to suppress the urge to slam the table, took a deep breath and then stared at the fat old man: "Leaders, I know that the city also wants to benefit the local people and always cares about the health of our Dezhou people... So I can understand the mentality of striving for perfection."

"That's right, absolutely right!"

"Not to mention Director Liu and other leaders, even for a small employee like me, when I heard that I was the first one to lead the rural grassroots drugstore chain project, the first thing I thought about was how to let those grassroots people get the cheapest and most effective medicine!"

"So, regarding the question Director Liu just raised, I can only answer you with great shame... Given China's current national conditions, the rural grassroots pharmacy project that Dahua Company has put all its efforts into launching can only meet the problems of [having] and [not having] Western medicine in the first phase, and can only solve the problem of whether the generic drugs listed on the market can achieve a score of 60."

"As for whether these generic drugs can achieve 80 points or even 100 points through continuous improvement and optimization, it is a long and arduous process... I can only hope that in my lifetime, I can witness with my own eyes that our country's medical level can fully surpass that of foreign countries!"

The fat old man knew that the income in rural areas of the country is relatively low nowadays, but when he heard Lu Yingying say the eight words "Be patient for minor illnesses and wait for major illnesses", he couldn't help but feel his forehead twitching.

Of course he knew what the word "wait" meant.

A fire mixed with shame, anger and powerlessness rose from his chest, and at one point he even wanted to shrink back and let the project hearing go through without any trouble.

He had no doubt that the package plan launched by Dahua Company was really intended to allow the working people to have access to cheap generic drugs.

Mr. Yang, who was born in Southwest Drilling Company No. 1 or to be more precise, was born in Drilling Company No. 1 and now holds the power in Dahua Company, has always been known for his willfulness. With the support of two lucrative state-owned enterprises, it is not surprising that Mr. Yang unscrupulously does things that seem to be no different from crazy to outsiders... This man is originally a country boy, and he and the group of people under him have a very strong complex for the countryside. In addition, since the influence of the chicken sending incident last year, the young man surnamed Yang has been using practical actions to "repay" those villages.

So, he really didn't doubt Dahua Company's motives.

From a standpoint, this rural grassroots chain of pharmacies, and the package of original research localization plans behind it, are typical examples of "losing on small details but not losing out on big ones"; no matter where it is placed in any economically underdeveloped inland city, it will receive recognition and support from local authorities.

but……

The collateral impact of this package plan is too great. Texas has not yet completely emerged from its predicament. Once so many small and medium-sized pharmaceutical companies are divested and reorganized, what will happen to the employees who are eliminated? What will happen to the upstream and downstream companies that rely on their original business to make a living?
Thinking of this, the fat old man gritted his teeth and took a deep breath. It was as if he had not looked at Ye Tao beside him from beginning to end. His whole temperament suddenly changed, and he looked at Lu Yingying calmly: "Manager Lu said it very well... Indeed, at different stages and under different national conditions, different things need to be given priority. Distinguishing between major contradictions and minor contradictions at different stages is also a working method that the country has always advocated."

"So... since Manager Lu mentioned the national conditions, let's talk about the national conditions."

After a slight pause, the fat old man looked around at the other people in the conference room expressionlessly, and finally stopped his gaze on Ye Tao's face: "What is the current social situation? What is the current international situation? I believe everyone is very familiar with it... The more times like this, the more careful and cautious we need to be in our work."

"I won't talk about the big picture, but from my perspective, as a drug that is directly related to the health of the public, its sensitivity is beyond words. At this moment, the possible sensitivity cannot be overemphasized!"

He sighed meaningfully: "Comrades, at this critical juncture, we cannot let the masses be disappointed in us or even dissatisfied with us!"

Everyone's expressions changed.

Although everyone knows that Director Liu actually has other considerations, it is not unreasonable to link the therapeutic effects and safety of generic drugs with some life-threatening things after assuming some negative reactions... Anyone who has some understanding of the actual domestic and international environment in 1990 knows that this is not groundless worry.

Seeing that everyone's expressions were thoughtful, the fat old man nodded gently, then turned his head and looked at Lu Yingying seriously: "Manager Lu, I actually approve of your company's rural grassroots chain drugstore project, but the premise of all this is that this package of cheap generic drugs can indeed play the desired therapeutic effect."

After a slight hesitation, the fat old man finally sighed imperceptibly: "So, Manager Lu, please answer a question for me directly... Do you have the confidence that after we promote the reorganization, you can provide relevant technical guidance to those reorganized pharmaceutical factories, and then overcome the differences between generic drugs and original research in terms of dissolution curves and bioequivalence?"

Dissolution...curve!!?
Following the fat old man's fatal blow, Tugou's expression finally changed...

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PS: Please call me "the stubborn one-gen beast"!
(End of this chapter)