Recently, discussions about generic drugs and original research drugs have been heated, and the appearance of identical data in consistency evaluation has become the first "oolong" in the pharmaceutical industry in 2025. However, in the public opinion field, the voices of pharmaceutical companies and CRO (pharmaceutical research and development outsourcing) companies are almost inaudible. Even a CRO company told the reporter of "Daily Economic News" that "there has been no generic drug (consistency) test in the past five or six years."

This was hard to imagine eight years ago. In March 2016, the "Opinions of the General Office of the State Council on Conducting Consistency Evaluation of Generic Drug Quality and Efficacy" kicked off the domestic consistency evaluation of generic drugs. Pharmaceutical companies are willing to spend millions of yuan on consistency evaluation, and CRO companies are also very busy.

The business of consistency evaluation of generic drugs by CRO companies has cooled down because generic drugs are marginalized in the minds of pharmaceutical companies. On January 26, an insider of a domestic CRO company told the reporter of "Daily Economic News" that the regulatory authorities' requirements for consistency evaluation are as strict as ever, but the market is being eliminated. In the future, only by letting generic drug companies "survive" first can they make drugs from "qualified" to "better".

The head of a generic drug company believes that the centralized procurement wants to buy qualified drugs at the lowest price, pharmaceutical companies want to ensure reasonable profits while ensuring quality, and patients want to have a variety of inexpensive and high-quality drug options. These original intentions are all correct, "but the problem is how to keep this "triangle" in a stable and reasonable balance."

The "sweet cake" that fell from the sky: consistency evaluation business orders reached their peak in 2019

The full name of consistency evaluation is the consistency evaluation of generic drug quality and efficacy. It is a review system promoted by the National Medical Products Administration (NMPA) to improve the quality of generic drugs and ensure that they have the same efficacy as original drugs. The system was officially launched in 2016, mainly targeting oral solid dosage generic drugs approved for marketing before 2007, requiring them to be consistent with the original drugs in quality and efficacy, and to be clinically interchangeable.

As a researcher in drug analysis and quality research, Zhang Ming (pseudonym) said that when the consistency evaluation was just launched, almost 95% of generic drugs had to be "re-processed" and re-made. In addition to the time pressure of "closing if not evaluated within three years, and centralized procurement if three companies pass the evaluation", many pharmaceutical companies turned to CRO companies for professional services.

If CRO companies want to get this "sweet cake" that fell from the sky, they have to rely on their skills. According to a research report by Soochow Securities in 2016, the workflow of generic drug consistency evaluation can be mainly divided into five links: "finding reference preparations - obtaining reference preparations - in vitro comparative studies - bioequivalence tests - application and approval". There are difficulties such as "complex processes, short time limits, high costs, and few resources". Ideally, it takes 19 months and costs 4 million to 6 million yuan to complete the evaluation of a variety, but it may encounter obstacles such as tight time, inability to find reference preparations, and insufficient resources for bioequivalence tests (BE).

Zhao Qiang (pseudonym) is the founder of a domestic CRO company. He experienced the era from 2017 to 2019 when the consistency evaluation business orders exploded and peaked. He told reporters that among these links, the two most core ones are in vitro comparative studies and bioequivalence tests. In in vitro comparative studies, whether the dissolution curves of generic drugs and original preparations (at different pH concentrations) are consistent is an important indicator for judging whether the quality of the two is consistent. On this basis, bioequivalence tests are also needed to prove that the efficacy of generic drugs is consistent with that of original drugs.

According to Zhao Qiang, BE tests are conducted in healthy people, and the number of subjects is usually between 24 and 48. However, the difficulty of the tests varies for different varieties, and some varieties may require more than 100 subjects, so the charging standards are also different. Generally speaking, when the consistency evaluation work was just started in China, the CRO company's in vitro comparative study quotation was 3 million to 5 million yuan, and the cost of the BE test depended on the number of subjects and the length of blood drawing time, and the test cost ranged from 2 million to 8 million yuan. Overall, the cost of entrusting a CRO company to conduct a consistency evaluation of a variety is generally several million yuan. For more difficult varieties, it is possible to spend more than 10 million yuan or even 20 to 30 million yuan. The implementation of the consistency evaluation of generic drugs has accelerated the development of the CRO industry. Public data shows that domestic CROs developed in the early 21st century. Around 2000, CRO companies such as Zhaoyan Pharmaceutical, WuXi AppTec, and Tiger Pharmaceuticals were established one after another. However, except for Tiger Pharmaceuticals, which landed on the A-share market in 2012, WuXi AppTec, Corning Life Sciences, Zhaoyan Pharmaceuticals, etc. all landed on the capital market intensively from 2017 to 2019. The market size of China's CROs has also increased from 3 billion yuan in 2006 to 22 billion yuan in 2013, and has now exceeded the 100 billion yuan mark.

The craze is gradually fading: the number of BE test hospitals has increased from dozens to hundreds, and the stock market has bottomed out

According to Zhao Qiang's recollection, since 2019, the company's consistency evaluation orders have gradually decreased, and the number of consistency evaluation projects carried out each year has been reduced to single digits. On January 25, a reporter from the "Daily Economic News" consulted 3-4 domestic CRO companies, some of which have completely stopped doing generic drug business, and some bluntly said that "there have been no generic drug trials in the past five or six years."

Why are consistency evaluations being conducted in such large numbers, first hot and then cold? "If they fail to pass the evaluation within three years, they will be closed down" is an important reason. According to the "Opinions of the General Office of the State Council on Conducting Consistency Evaluation of Quality and Efficacy of Generic Drugs", the oral solid preparations of chemical generic drugs approved for marketing before October 1, 2007 in the National Essential Medicines List (2012 Edition) should complete consistency evaluation by the end of 2018. Among them, varieties that require clinical effectiveness trials and have special circumstances should complete consistency evaluation by the end of 2021; those that fail to complete the evaluation within the deadline will not be registered again.

In addition, the price determined by the supply and demand relationship has also changed. Zhao Qiang said that in 2017, when the consistency evaluation business orders began to increase, there were only a dozen hospitals in China that could conduct BE tests (qualified to conduct phase I clinical trials), and CRO companies were not proficient in conducting consistency evaluation business and did not master the methods well enough, so the overall quotation was high. However, as the number of hospitals with BE test qualifications increased to several hundred, the costs of pharmaceutical research and BE have decreased, and the overall cost of consistency evaluation has also decreased significantly.

"On the one hand, the hospital fees and testing fees have been reduced, and the cost has become lower; on the other hand, there are fewer people doing it, and the overall demand has become smaller. In addition, there are too many CRO companies, and everyone is scrambling to do it, so the price is lower." Zhao Qiang believes that the reduction in consistency evaluation business is normal, because the market stock of generic drug consistency evaluation is limited, and most of the work will be completed before 2020, and the market will naturally be saturated.

Zhang Yue (pseudonym), a scholar who has long been concerned with the research of medical policies and regulations, drug registration review and approval, and market access system, also added that on the one hand, the number of institutions that can provide BE services has increased, and the client has found that the market size of generic drugs that have completed consistency evaluation is not as expected, and their enthusiasm has been affected. Between the increase and the decrease, market shrinkage has become an inevitable result.

As the profits of generic drugs shrink, pharmaceutical companies and CRO companies are forced to transform to innovation.

Lin Xueyi (pseudonym), the boss of a generic drug company, had long predicted the reduction in profits from centralized procurement of drugs, but the degree and speed of the reduction were beyond his expectations. He told the reporter of Daily Economic News, "The first sign was that provinces began to implement centralized procurement, and there was a trend of winning bids at low prices. But at that time, our prices in this province were not good, and we could sell in another province. But we predicted that it would be sooner or later to carry out unified national procurement, and predicted that the profits of generic drugs would become thinner than a razor blade in ten years. The actual situation shows that it will not take ten years at all."

So, does the reduction in business orders and price reductions for consistency evaluation mean that the standards of CRO companies have also been lowered? Zhao Qiang does not think so. According to his observation, the regulatory authorities have always been strict with the consistency evaluation of generic drugs. For example, although the changes such as the change of production excipients after the generic drugs are launched are minor, the regulatory authorities will not specifically require the manufacturers to conduct BE tests again, but will require the manufacturers to conduct comparative studies on preparations using original excipients and new excipients. When making changes, the manufacturers need to submit relevant materials to the Drug Administration, otherwise the Drug Administration will not approve them at will.

"There is no problem with the consistency evaluation itself, and China's standards are not low. There is no need to worry too much about the quality of generic drugs that have passed the consistency evaluation. However, we cannot completely hope that generic drugs that have passed the consistency evaluation are completely consistent with the original drugs. This is not objective." Zhao Qiang told reporters that the basic principle of bioequivalence of preparations was determined in the early 1990s, that is, the 90% confidence interval of the geometric mean ratio of the main pharmacokinetic parameters (AUC and Cmax) of the test preparation and the reference preparation should fall between 80% and 125%. Since BE trials are usually based on dozens of healthy people, even if the results of generic drugs and original drugs in these people are basically the same, it cannot be guaranteed that in actual applications, generic drugs and original drugs have the same efficacy for everyone. In addition, original drug companies may have some unpublished internal control standards that generic drug companies may not know. For example, a raw material manufacturer once told Zhao Qiang that in addition to requiring raw materials to meet the US Pharmacopoeia standards, a certain original drug factory also has additional requirements for particle size distribution. These requirements are not reflected in the pharmacopoeia and will not become requirements for the consistency evaluation of generic drugs. If you want to prove that the efficacy of generic drugs and original drugs is 100% consistent, it is best to conduct real-world research, but the cost of head-to-head trials is too high, even exceeding the sales scale of generic drug products, and companies are usually unwilling to bear it.

Zhao Qiang believes that the country has a complete system for the management of generic drugs after they are listed. One is the adverse reaction reporting system; the other is that the drug regulatory authorities, including the drug regulatory authorities of various provinces, will spot-check the drugs circulating in the market, and if they are unqualified, they will be fined and notified. He believes that the current supervision is sufficient.

Let generic drug companies "survive" so that products can go from "passing" to "doing better"

Zhao Qiang believes that a question worth discussing is how much profit margin should be left for generic drug companies in order to let them "survive". "The profit is too thin, (companies) may have no motivation to make the quality (of generic drugs) better, and have no energy to engage in research and development."

In recent years, generic drugs have been quoted at unexpectedly low prices in centralized procurement. In particular, in the tenth batch of drug procurement in December 2024, the commonly used drug aspirin enteric-coated tablets reported a low price of 3.4 points, which not only made peer companies exclaim "cannot do it", but also made clinicians and patients worry that such low-priced generic drugs are difficult to guarantee qualified quality.

In this regard, the relevant person in charge of the National Medical Insurance Administration told the media in January this year that if a company has a low price, it may be a competitive strategy or malicious low price of individual companies, but the "first group" including the head pharmaceutical companies have reported similar prices. All parties should respect the results of market competition, rather than just "feeling" high or low prices based on subjective conjectures.

Zhang Yue observed that in the drug procurement conducted in previous years, there was a phenomenon of low-price winning bids. "Because my country's pharmaceutical market is still a highly homogeneous market, some generic drugs are unable to develop the out-of-hospital market. Once they fail in the centralized procurement, they will lose business opportunities. Therefore, they can only report prices that are "shocking" to both the industry and the outside world. Although such prices are low, they do not conform to the business rules for a product or enterprise to operate normally."

In order to dispel the outside world's doubts about the "substandard" quality of generic drugs, Zhang Yue believes that the Medical Insurance Bureau can start with improving the centralized procurement rules, such as removing the highest and lowest bids in each variety. "Then the companies that report unreasonably low prices will consider whether their low prices are for others, thereby reducing the probability of malicious low-price competition and the risk that companies cannot continue to guarantee supply or cannot supply according to quality and quantity after winning the bid at a low price. In addition, companies should be allowed to report prices that vary when participating in different rounds of centralized procurement, rather than only lower and lower prices. This is because companies may have different inventory and costs of varieties at different stages, and companies cannot only be allowed to quote lower prices but not higher prices."

Zhang Yue finally said that the contribution of centralized procurement is unquestionable, but centralized procurement should also match the current status of the industry, and use a long-term and systematic perspective to judge the impact of centralized procurement on the industry. Lin Xueyi believes that centralized procurement wants to buy qualified drugs at the lowest price, pharmaceutical companies want to ensure reasonable profits while ensuring quality, and patients want to have diversified and inexpensive drug options. These original intentions are all correct, "but the problem is how to keep this 'triangle' in a stable and reasonable balance."

Source: https://finance.eastmoney.com/