Review: Progress of Acceptance Work of Generic Drug Consistency Evaluation in 2017

Since the start of the essential drug consistency evaluation in China on August 17, 2016 when CFDA released information of varieties to be completed the generic drug consistency evaluation be the end of 2018, the consistency evaluation policy has become clear by now. By December 20, 2017, there were 70 supplementary applications for consistency evaluation of generic drugs with approval numbers that were directly accepted by the CFDA or transferred from provincial administrations to CFDA for acceptance, involving 41 varieties, including 18 listed in 289 Catalog, and 23 not listed therein, separately accounting for 44% and 56% of the total quantity accepted.

Zhejiang Huahai has become the biggest winner in the acceptance of applications for generic drug consistency evaluation through the method of "domestic sales of commodities originally produced for export"

There are only two ways for the marketing of generic drugs with approval numbers: firstly, conduct pharmaceutical research in a down-to-earth manner and conduct BE test in good faith to guarantee fast and good completion of the evaluation work; secondly, "sell commodities in China originally produced for export", namely, to utilize the ANDA approval of existing products in the EU or U.S., and achieve "corner overtaking" as encouraged by the policy that treats priority review and conversion of overseas marketing into application in China as passing the consistency evaluation.

Among the accepted supplementary applications for consistency evaluation of generic drugs with approval numbers, Zhejiang Huahai is the leader upon the great advantage in "domestic sales of commodities originally produced for export". All Huahai’s 8 varieties of 10 specifications accepted this time have received ANDA approval of FDA, however, the products accepted this time could be called the tip of the iceberg for Huahai which possesses 35 ANDA approvals.

In addition, Zhejiang Hisun has also received the fast review of applications for consistency evaluation of two specifications of Tacrolimus Capsules and three specifications of Irbesartan Tablets upon the same strategy: those two varieties were separately approved in the EU and U.S. in 2010 and 2016.

Verities of Huahai Pharmaceutical Accepted for Generic Drug Consistency Evaluation

On-site inspection of the first batch has been launched, and the marketing of generic drugs with approval numbers is approaching

The Center for Food and Drug Inspection of CFDA (CFDI) released the notice of CFDI Started the On-site Inspection of First Batch of Varieties for Generic Drug Consistency Evaluation on November 29, 2017 to describe the for-cause on-site inspection of the first batch of varieties for generic drug consistency evaluation that was started on November 23: 6 inspection teams were dispatched in this inspection, to conduct on-site inspection of products in Beijing, Chongqing, Zhejiang, Jiangsu, Hunan, and Jiangxi. The situation of the applications for consistency evaluation involved in those 6 provinces and municipalities was: 1 variety of 1 enterprise in Beijing; 1 variety of 1 enterprise in Chongqing; 4 varieties of 2 enterprises in Zhejiang; 10 varieties of 6 enterprises in Jiangsu; 2 varieties of 1 enterprise in Hunan; and 2 varieties of 1 enterprise in Jiangxi, however, CFDI did not release the list of varieties involved in the inspection of the first batch. It is hoped that the first batch of varieties could be officially approved at the end of this year or beginning of next year after the last step of the approval for the generic drug consistency evaluation.

The progress of consistency evaluation is unbalanced, with varieties to be evaluated showing the inversion phenomenon

A troubling fact is that there has been no enterprise applying for the consistency evaluation of the top 10 varieties by quantity of approval numbers in the 289 Catalog so far, and the proportion of varieties that have been completed evaluation and accepted in the 289 Catalog is only 6%: the evaluation progress seems unsatisfactory and the progress clearly lags; also, in terms of enterprises’ reference preparation filing situation earlier published by the National Institutes for Food and Drug Control of China by June 20, 2017, enterprises were not enthusiastic about the reference preparation filing of the top 10 varieties by quantity of approval numbers in the 289 Catalog, with some varieties even untouched. Calculated according to the time required for pharmaceutical research and BE evaluation, if those varieties were still not evaluated or their evaluation process was not smooth, their approval numbers would be canceled by the deadline in 2018 according to the current policy requirements; however, if those varieties disappeared, there would be the risks of drug shortage clinically and failure to meet the drug demands of the people, which is not the original intention of the consistency evaluation.

On the contrary, under the "racing" mechanism, enterprises have showed a positive attitude towards varieties outside the 289 Catalog, no matter from the perspective of quantity of reference preparation filing or quantity of applications. As mentioned above, among the supplementary applications for consistency evaluation of generic drugs with approval numbers, the quantity of accepted applications of varieties outside the 289 Catalog is more than that in the 289 Catalog. Many enterprises would rather choose those varieties without time limit to seize the first chances of the market than choose the varieties of little value in the 289 Catalog, therefore, there is the inversion phenomenon in the evaluation of the varieties in the 289 Catalog and varieties not listed therein.

It’s worth noting that Amoxicillin Capsules and Amlodipine Besylate are the varieties most enterprises do not want to give up, seen from the earlier filing situation. There have been separately 3 enterprises’ applications for those two varieties accepted. If all goes on well with the subsequent review, CSPC, United Laboratories, and Zhejiang Conba will become the first 3 enterprises passing the consistency evaluation of amoxicillin, and Jiangsu Yellow River Pharmaceutical, Yangtze River Pharmaceutical, and Novartis will become enterprises passing the consistency evaluation of amlodipine besylate. According to CFDA’s provision that if there are more than 3 manufacturers of the same variety passing consistency evaluation, the drug variety failing the consistency evaluation will not be selected in centralized procurement of pharmaceutical products, etc., the above situation will leave a cloud over enterprises that are conducting evaluation of Amoxicillin Capsules and Amlodipine Besylate.

About the author:

Erxiao, Master of Pharmacy from Shanghai Jiaotong University, pharmaceutical industry practitioner, engaged in imported drug and new drug registration, and focused on registration regulations and new drug dynamics.