Embarrassing Two Different Worlds in Consistency Evaluation: Some about to Win, in the Wrong Track

With a half of 2017 past, it is only about one and a half year from the time limit for the consistency evaluation of the 289 generic drug varieties in 2018.

However, for the Chinese generic drug enterprises that have strength in conducting consistency evaluation, it is certain that they do not rush to carry out the consistency evaluation for varieties by following the list of those 289 varieties, but based on own core, advantageous or potential varieties, because the "early passing" means maximum benefits.

The most important point in the Opinions on Carrying out Quality and Efficacy Consistency Evaluation of Generic Drugs is: "The pharmaceutical product varieties passing consistency evaluation shall be provided with appropriate support in medical insurance payment, and medical institutions shall preferentially purchase and use them in clinical practice. If there are more than 3 manufacturers of the similar variety passing consistency evaluation, the drug variety failing to pass consistency evaluation shall not be selected in centralized procurement of pharmaceutical products."

There has been good news one after another: according to the drug administrations of Jiangsu and Zhejiang in succession, multiple varieties of many pharmaceutical enterprises have been completed preliminary examination in the provinces and reported to CFDA. Capable pharmaceutical enterprises want to be the first to break out in this "war" to seize the first chances.

However, another noteworthy news is that: 43 manufacturers of azithromycin were saddened after seeing the list of reference preparations of generic drugs issued by CFDA—because they failed to find the name of the reference preparation filed previously therein. What is the worst for them in "betting on the wrong horse" is that they may need to re-purchase the reference preparation and start again: the cost is not just starting all over again…

First to reach the "set point"

Zhejiang Food and Drug Administration announced on June 28 that they had completed the preliminary examination of the generic drug consistency evaluation of Rosuvastatin Calcium Tablets of Zhejiang Jingxin Pharmaceutical Co., Ltd.; they completed the onsite inspection, inspection report review, and data summary of the variety, issuance of preliminary examination opinions, and reporting to CFDA in 20 days.

Both the number and price of the stock of Jingxin Pharmaceutical increased by nearly 10% before and after the news was released, as its variety was the first reported to the CFDA in Zhejiang Province in consistency evaluation of generic drugs. This is apparently great news for Jingxin Pharmaceutical.

According to a research report of Haitong Securities, the rosuvastatin calcium has big import substitution space, and the consistency evaluation is an important track for enterprises to compete for the relevant market. There are at least 7 Chinese enterprises applying for the consistency evaluation of rosuvastatin calcium and close to each other in the progress, as shown by the drug clinical trial publicity system.

According to information, as rosuvastatin calcium is not among the said 289 varieties, the rosuvastatin calcium of Jingxin Pharmaceutical is just completed preliminary examination in theory and can be called reaching a "set point", but cannot be called a "variety passing consistency evaluation of generic drug".

There are also many lurkers having reached the "set point". The Food and Drug Administration of the Province Vigorously Promoting the Quality and Efficacy Consistency Evaluation of Generic Drugs published by Jiangsu Taizhou Food and Drug Administration lately said that there had been 6 varieties of 4 enterprises including Yangtze River Pharmaceutical Group, etc. completed consistency evaluation and applied to the provincial administration by the middle of June.

According to previous news, Jiangsu Food and Drug Administration had sent an inspection group constituted by professionals in pharmaceutical production site inspection and pharmaceutical product quality inspection to go to Yangtze River Pharmaceutical Group Co., Ltd. to conduct the onsite checking of the Enalapril Maleate Tablets, a variety in the consistency evaluation.

And as revealed by certain person of certain enterprise earlier, there have been several varieties of many Chinese enterprises completed technical evaluation, and already entering the application and approval stages in their workflow.

Collectively "betting on the wrong horse"?!

Some enterprises are at top speed in the hope of coming out on top, while some enterprises have collectively "bet on the wrong horse" and tumbled in the selection of reference preparation.

CFDA issued the lists of the third and fourth batches of reference preparations on Apr. 28, with 60 varieties in total, and plus the 84 varieties in the previous two batches, there have been 144 varieties officially published, accounting for more than a half of the first 289 varieties. CFDA requires comprehensive and accurate statement of the basic information of reference preparations, including enterprise name, batch No., specification, acquisition channel, and corresponding voucher, etc.

According to report of China Business News, 43 manufacturers of azithromycin failed to find the name of the reference preparation filed previously in the above list. In the reference preparation filing information published by the National Institutes for Food and Drug Control of China on Apr. 27, 2016, there were 43 filed reference preparations in total for 0.25g azithromycin tablets, and all the enterprises selected the Zithromax produced by Pfizer.

No one told that Zithromax could not serve as the reference preparation within the specified 60-day feedback time, thus, the 43 enterprises took such silence as tacit approval, and they worked against time to strive to be the first to get to the finish line, but, the list of the fourth batch of reference preparations published by CFDA determines that the reference preparation of such specification of azithromycin is not the Zithromax filed by those enterprises but the "Azitromycin 250 TEVA" of Teva Pharmaceuticals that is marketed in the EU and produced in Croatia. This news means to announce that all the 43 pharmaceutical enterprises have mistaken the reference preparation.

The importance of selecting the reference preparation has shown from the case of azithromycin. "The first thing enterprises do after the ‘starting gun is fired’ for the consistency evaluation is to determine and purchase the reference preparations; being wrong about the reference preparations is like contestants mistaking the finish and running farther and farther in the wrong direction," expressed by Li Tianquan, Co-founder of Yaozh.com.

Why were those enterprises wrong? A medical expert said, "There was only the capsule dosage form when Pfizer initially marketed azithromycin in the U.S., and its 0.25g tablets were not approved by the U.S. FDA until 1996; Pliva Company (based on Croatia), a manufacturer under Teva Pharmaceuticals, also has no 0.25g azithromycin tablets, but only the 0.125g and 0.5g specifications. By contrast, apparently, Pfizer’s product is more suitable. Varieties have been determined without public discussion, and all azithromycin manufacturers in China have been ‘hit’, so, in my opinion, the reasons for selecting reference preparations should be given. Or the problem should be addressed at the beginning so that no rework will be needed."