There was no need for testing at all, judging from the appearance and smell of the sample, it was far from the expected result, so Fang Hanmin decided to temporarily stop the test and find out the cause first.

Since the patent protection of generic drugs is about to expire and the details of the patent have already been made public, Fang Hanmin took out the original text of the patent and carefully studied it, and checked it with the formulated test plan one by one, and found no problems.

"Director Fang, is it possible that the expression of the original patent is inaccurate and misleading?" Guo Peng analyzed.

Fang Hanmin didn't answer, but just shook his head thoughtfully.

In his previous life, the traverser was very familiar with the various synthesis processes of this calcium antagonist antihypertensive drug, and the process route selected for the imitation test is the classic preparation method of this drug, which has been fully verified in actual production and is widely used.

"This preparation method has been patented by the inventor in many countries, and I have compared several main versions, and the content is completely consistent, so there should be no problem with the patent expression." Fang Hanmin said with great certainty.

Guo Peng frowned and was helpless, "It seems that imitation is not simple, so what is the problem?" ”

After pondering for a long time, Fang Hanmin turned to ask: "Do all the raw materials used in the test have test data?" ”

Guo Peng picked up two test reports and handed them to Fang Hanmin, "This is the quality inspection data of the two raw materials we developed ourselves," and opened the drawer and flipped through it, "There are also test results for several other purchased raw materials, this is the quality inspection report." ”

Fang Hanmin repeatedly checked the quality inspection data of each raw material, but he did not see any problems in the black and white letters on the report sheet, which made him deeply confused.

Pacing back and forth in the laboratory, Fang Hanmin suddenly thought of a problem, in the original patent specification, only the number of various raw materials was indicated, and the specification content and impurity control indicators of the raw materials were not indicated, but the quality indicators of various raw materials used in the imitation test were 96%, 97% and 98%.

Stopping, Fang Hanmin suddenly asked: "The content of the two raw materials developed by myself is only 96% from the test results, can we still improve the quality a little?" ”

"Director Fang, do you suspect that the quality of raw materials is unqualified?"

"To find out the reason, all kinds of possibilities have to be considered, and the quality of raw materials is of course one of the factors that is questionable."

"But ......," Guo Peng stopped talking, looking very embarrassed.

"If you have anything to say, why do you want to spit it out?" Fang Hanmin looked at the other party puzzled.

"Director Fang, our research group is only responsible for the synthesis of the original drug, regardless of the quality of the raw materials!"

Fang Hanmin nodded in agreement, "You are right, whether the quality of raw materials can be further improved is a matter for the raw material development research group, and I have to discuss with them." ”

When Fang Hanmin asked them to continue to improve the quality of raw materials, the two shook their heads in unison, "Director Fang, these two raw materials can achieve 96% content, it is not easy, and it is too difficult to improve the quality of these two raw materials!" ”

"I know that if it weren't for the difficulty, wouldn't it have been more than 99% a long time ago? But I would like to remind you that our current job is in the technical center of the Red Star Pharmaceutical Factory! The task of the technology center is to develop new products, new technologies and new processes, and many technical problems will inevitably be encountered in the process, and our task is to solve technical problems! Fang Hanmin did not give his subordinates any reason to retreat.

"But Director Fang, we have done our best to reach the current level, you let us further improve the content, we really have no choice, I don't know what to work from."

Fang Hanmin knew the personalities of Gong Jianchang and Xu Hui, but as long as they could come up with a little way, they would not back down, "Okay, I'll figure out a way with everyone, Jianchang, let me see the test records during this time." ”

From the end of last year to the present, in less than three months, the technicians and test workers of the raw material research group have worked day and night to finally make samples of the two raw materials in advance, so that the generic drug test can be carried out as planned.

However, from several large test records, Fang Hanmin found that many aspects of the test process were not precise and rigorous enough, "If the process conditions are further optimized, the sample content may be increased." ”

Gong Jianchang was the leader of the project for the first time, his technical level and work ability were limited, and he lacked confidence in himself, he thought that Fang Hanmin was blaming him for not doing a good job in the test, and hurriedly defended: "Director Fang, we are all in strict accordance with the test plan you formulated to carry out the test, I don't know what aspects to optimize?" ”

The plan given by Fang Hanmin is only a directional guide to the test process, and does not involve too many details, ignoring the reality of the lack of experience of Gong Jianchang, the leader of the research group, which is caused by his poor consideration, and he certainly did not blame Gong Jianchang.

"It's not that you didn't strictly implement the test plan, but it was precisely because of the test according to the formulated plan that the samples of the two raw materials were successfully developed in such a short period of time. However, to further improve the quality of the sample, the only way to do this is to optimize the preparation process and work on the details. Fang Hanmin didn't want Gong Jianchang to have any ideological burden.

"What do we need to do next to optimize the process conditions?"

Fang Hanmin thought for a while, "For example, can we analyze what process conditions can be improved to reduce the generation of by-products?" In addition, you can do some calculations to see if the current fractionation column is high enough in the sample refining stage. Is it possible to increase the height of the column to increase the sample content? ”

Because of the two important positions of factory director and technical center, Fang Hanmin could not be exhaustive in the process of technology development, he could only point out the general direction and let the technical personnel of the research group implement it.

According to Fang Hanmin's prompt, Gong Jianchang first increased the height of the fractionation column in the next test, and the obtained sample passed the test, and its content reached 97.5%.

Gong Jianchang happily told Fang Hanmin the news, but he seemed very calm, "One result doesn't explain anything, continue the experiment and see how reproducible the results are?" ”

In the following tests, Gong Jianchang's research group obtained almost consistent test results, and the content of multiple batches of samples of the two raw materials developed reached 97.5%.

Although this is exciting news, but Fang Hanmin is not satisfied with this, he knows very well that as a pharmaceutical raw material, it is related to the efficacy and toxicity and side effects of drugs, and it is not too high to put forward high requirements for its quality.

"Director Fang, we have improved the fractionation column and increased the sample content, what do we need to do next?" Gong Jianchang looked sad.

"You should know that there are many factors that affect the content, and the height of the fractionation column is only one of them, for example, as I said before, optimizing the synthesis process can also reduce the generation of by-products, and this factor is worthy of your serious study."

Although he was very reluctant in his heart, Gong Jianchang couldn't refuse Fang Hanmin's request, so he had to agree to it.

Back to the research group, Gong Jianchang conveyed Fang Hanmin's instructions to the employees, as soon as his voice fell, the people below were discussing, not only the technical staff thought that the next work was a bit redundant, but even the test workers felt that Fang Hanmin's requirements for quality were too strict.

Xu Hui has only recently joined the raw material research group, although he has the title of deputy director of the technology center, his task is to assist the research group to apply the laboratory test results to industrial production, and at this stage he is still familiar with the work of the research group, so he generally does not express opinions on the affairs of the group.

A few years ago, Xu Hui had two or three years of working with Fang Hanmin, from whom he not only learned advanced pharmaceutical technology knowledge and experimental skills, but also Fang Hanmin's rigorous and pragmatic scientific research spirit had a profound impact on him.

After listening to the discussion of the employees, Xu Hui felt that it was necessary for him to stand up and say a fair word, "Everyone may have misinterpreted the meaning of Director Fang, he just wants to further improve the sample content by optimizing the process conditions, and he does not deliberately embarrass everyone." I was also present for the next step of the work, and the director of the factory has pointed out the general direction of the work, and in the next test, we only need to try to change the test conditions on the basis of the existing conditions, until the best process conditions are obtained. ”

After all, Xu Hui is the deputy director of the technology center, and he very much supports Fang Hanmin's decision, and all the employees of the raw material development research group, including Gong Jianchang, are not good to say anything on the surface.

After more than ten days of repeated tests, it was finally found that the synthesis reaction was carried out in an inert solvent, which could inhibit the occurrence of side reactions to the greatest extent, not only maintained a high conversion rate of raw materials, but also had the least impurities in the product, and the purity of the sample obtained was as high as 99% through distillation separation!

When reporting the results to Fang Hanmin, Gong Jianchang seemed to have some regrets, "Although the purity of the sample has been improved, the solvent must be recovered first, and the separation and refining process has been doubled, is it worth it?" ”

"Of course it's worth it!" Fang Hanmin said without hesitation, "Why are many imported drugs better than domestic drugs with lower efficacy and lower side effects?" One of the main reasons is that imported drugs have a higher content of raw materials and fewer impurities, and the control of impurities should start from the source, that is, the raw materials of synthetic drugs! Therefore, as long as the formation of impurities can be reduced, even if the refining separation process is extended, it is worth it! ”

......

To improve the purity of self-made raw materials, the research team led by Guo Peng started the generic drug test again, and Fang Hanmin told them that they must strictly control the process conditions and pay attention to the abnormal phenomena that occur during the test.

At ten o'clock in the morning, Fang Hanmin had just returned to his office from the laboratory of the technology center, and Deputy Director Liang, who was in charge of logistics, pushed the door in and handed Fang Hanmin a stack of manuscript paper in his hand, "Look at this, if there is something inappropriate, I will revise it." ”

Fang Hanmin looked at the other party inexplicably, "What is this?" ”

"You can look at the housing allocation plan I have drawn up preliminarily."

"You've just started digging the foundation, right? The house will not be handed over until the end of the year at the earliest, so is it too early to discuss the housing allocation plan now? ”

"It's not early at all. Don't look at the more than half a year, this housing allocation plan is not so easy to determine, I have asked for your opinion, I also have to solicit the opinions of other members of the team, after comprehensive consideration, before it can be submitted to the team meeting for discussion and approval. Soliciting opinions back and forth, it is inevitable that the draft will be changed several times, and it would be good to be able to settle it in half a year! ”

Fang Hanmin thought about it and felt that what Lao Liang said made sense, "Let's put it here first, I'll take the time to take a look." ”

"Director Fang, you'd better take a look at it as soon as possible, and put forward your opinions, after I revise it, I will let you see it."

Lao Liang asked for advice on the surface, but in fact, he was pointing fingers at the other party's work, which sounded very awkward.