According to "China Business News" reported on July 2nd, 43 azithromycin manufacturers were collectively heartbroken after seeing the catalogue of reference preparations for generic drugs published by the State Food and Drug Administration-they did not find the names of reference preparations backed up before.

The selection of reference preparation is the most critical step in the consistency evaluation of generic drugs. "After the starting gun of consistency evaluation started, the first thing everyone did was to determine and purchase the reference preparation. Once the reference preparation is wrong, it is as if the contestants made a mistake at the end and ran further and further in the wrong direction. " Li Tianquan, co-founder of Yaozhi.com, told CBN.

Since the State Food and Drug Administration announced the catalogue of this batch on April 28th, 43 enterprises have been in a panic. For them, the worst result of betting on the wrong treasure is that they may need to re-purchase the reference preparation and go on the road again, and the price paid is not just a reinvention.

With the mission of paying off debts for history and letting Chinese use drugs with quality and efficacy reaching the original research level, the conformity evaluation of generic drugs has been started in China for almost a year and a half. This time, so many pharmaceutical companies all chose the wrong reference preparation, which made this scene encounter embarrassment.

Collective bet on the wrong treasure.

In March, 2016, the General Office of the State Council issued the Opinions on Evaluating the Consistency of Quality and Efficacy of Generic Drugs (hereinafter referred to as the Opinions). The consistency evaluation of generic drugs started from this document, and the government and enterprises have invested great enthusiasm.

Consistency evaluation determines the life and death of many enterprises’ drugs and the fate of zombie batch numbers. At the same time, the document also gives many temptations: "Drug varieties that have passed the consistency evaluation should be given appropriate support in medical insurance payment, and medical institutions should give priority to procurement and give priority to clinical use. If there are more than three manufacturers of the same variety of drugs that have passed the consistency evaluation, the varieties that have not passed the consistency evaluation will no longer be selected in the centralized procurement of drugs. "

Without consistency evaluation, there is only a dead end, and with consistency evaluation, there is still a living way out. The speed determines the size of the benefits. In the first round of consistency evaluation, 289 varieties in the National Essential Drugs Catalogue (2012 Edition) were included, and azithromycin, as an anti-infection "big drug", was included, which was 0.25 g specification of azithromycin tablets.

“At the beginning of consistency evaluation, the state requires enterprises to record their selected reference preparations. If no comments are given within 60 days, everyone can start work according to the registered varieties.. After filing, we spent 10 months doing drug research, prescription process verification test, etc. Now we have entered the drug verification batch to do bioequivalence (BE) test. "Zhang Chenguang, director of the preparation room of Yiling Pharmaceutical Research Institute, told CBN.

In the filing information of reference preparations released by the Central Inspection Institute on April 27, 2016 (as of April 20), there were 43 reference preparations for 0.25 g azithromycin tablets, and everyone chose them without exception.Hisumi(Zithromax，Produced in Pfizer, USA.)。

Within the prescribed 60-day feedback period, no one told me that Histamine could not be used as a reference preparation. 43 companies took this silence as the default, and in order to be the first to reach the finish line, everyone worked against time.

Just before entering the critical moment, the Food and Drug Administration announced the fourth batch of reference preparations, in which it was determined that the reference preparation of azithromycin of this specification was not Histamine previously filed by pharmaceutical companies, butTevaPharm B.V, Israel"Azitromycin 250 TEVA", listed in the European Union, originated in Croatia. This news is equivalent to announcing that all 43 pharmaceutical companies have got the reference preparation wrong.

"All manufacturers have chosen the wrong reference preparation for azithromycin tablets? This problem is a bit big, but why is there such a big deviation? " Zhang Chenguang is not the only one who is puzzled.

Is it reasonable to use TevaPharm B.V’ s products as reference preparations? Zhang Chenguang combed the development history of azithromycin. In the 1970s, a new macrolide antibiotic named azithromycin was discovered in Pliva, the former Yugoslavia. In 1981, Pliva Company applied for the patent of azithromycin in Yugoslavia, and then applied for the patent all over the world (including the United States).

At that time, Pfizer, USA, realized the potential of azithromycin and took the initiative to contact Pliva Company to obtain the authorization of azithromycin. In 1986, the two companies reached an agreement, and the agreement period expired in 2006. According to the agreement,Pfizer has obtained the global distribution rights of azithromycin, while Pliva Company has retained the distribution rights in Central and Eastern Europe..

Subsequently, Pliva Company listed in Central and Eastern European countries with Sumamed as the trade name of azithromycin; Pfizer is listed in other countries outside Central and Eastern Europe under the trade name of Histamine.

"When Pfizer first listed azithromycin in the United States, it only had capsule dosage form, and the tablet of 0.25 g specification was approved by FDA (US Food and Drug Administration) in 1996; Pliva company has not listed azithromycin tablets with the specification of 0.25g, only with the specifications of 0.125g and 0.5g..In contrast, Pfizer’s products are more suitable. However, the varieties were determined without public discussion, which made azithromycin manufacturers all over the country’ win the trick’. Should the reasons for choosing reference preparations be announced? Or solve the problem at the beginning, it won’t lead to rework."A medical expert said.

Anyway, this time, azithromycin manufacturers made a collective bet wrong.