On July 22, 2015, the China Food and Drug Administration (formerly CFDA) issued the Announcement on Carrying out Self-examination and Verification of Drug Clinical Trial Data, comprehensively initiating the self-inspection and verification of drug clinical trial data to conduct serious investigation and punishment on fraudulent behaviors in registration application.
The state-driven construction of quality supervision system for generic drugs has been kicked off since then. Today, it has seen breakthroughs and the consistency evaluation is developing towards normalization.
In this issue, Dr. Lan Ke, an expert in pharmacokinetics research, is invited to interpret the significance, impact and future development trend of consistency evaluation, as well as the product layout of Hengkang.

Dr. Lan Ke
Founder of Chengdu Hengkang Pharmaceutical Technology Co., Ltd.
Associate Professor of the West China School of Pharmacy, Sichuan University

In 2007, Dr. Lan Ke graduated from the West China School of Pharmacy, Sichuan University. He is mainly engaged in drug metabolism and drug metabolomics research. He has accumulated many years of experience in bioequivalence research of generic drugs, early druggability research of innovative drugs, non-clinical pharmacokinetics research and clinical pharmacokinetics research.

He currently serves as the editorial board member of EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS, the member of young editorial board of The Chinese Journal of Clinical Pharmacology, the member of Younger Committee of the Drug Metabolism Committee of Chinese Pharmacological Society, the head of the clinical trial inspection team of the Center for Food and Drug Inspection of National Medical Products Administration, and the drug registration inspector of Sichuan Center for Food and Drug Evaluation, Inspection & Monitoring.

Thanks to pharmaceuticals industry’s rapid development since the reform and opening-up, China is now regarded as a big country in the production of generic drugs, but there’s still room for growth. Generic drugs, the underlying foundation of the drug pyramid, have not yet seen breakthroughs, and the exploration of independent innovation is still a long way off.

Three years ago, the state initiated the consistency evaluation of quality and efficacy of generic drugs through macro policies, thus transforming to a generic drug power from a generic drug country.

The first key factor is security. Drugs are special products for the treatment and prevention of diseases. Without rigorous assessment and supervision, serious social harm will occur in case of medication misadventure or non-therapeutic drug abuse.
The second is effectiveness. At present, many homemade generic drugs in the market are inferior to original drugs in quality and efficacy, and the domestic pharmaceutical market is even filled with many “safe” but ineffective adjuvant drugs. The lopsided development of ecological environment of generic drug R&D before the consistency evaluation is evident.
The third is economy. It is also known as accessibility, representing that everyone has access to safe and effective drugs at affordable prices through legal means.

Dr. Lan Ke said that due to the vicious competition in China’s pharmaceutical market before consistency evaluation and the poor level of industrial R&D, it is difficult to timely seize the opportunity in the domestic and foreign markets when patent medicines expire. Therefore, in order to ensure that the ecological environment of China’s pharmaceutical industry meets the objective laws of development in this field, the state has rolled out consistency evaluation policies.

Theoretically, a successful generic drug must progressively achieve pharmaceutical equivalence, bioequivalence and therapeutic equivalence with the original drug, which means that the ultimate success of the generic drug product lies in the therapeutic equivalence with the original drug.

How to determine the therapeutic equivalence?

Dr. Lan Ke said that therapeutic equivalence requires randomized controlled clinical trials with large patient populations, but randomized controlled clinical trials are costly and time-consuming, and do not meet the accessibility requirements that generic drugs should meet. Bioequivalence test is an internationally recognized clinical evaluation method for generic drugs based on pharmacokinetics - pharmacodynamics model of clinical pharmacology. For generic drugs and original drugs, if their exposure levels in the body are the same, the safety and effectiveness can be considered consistent.
The next level after bioequivalence is pharmaceutical equivalence. It requires the generic drug to have the same raw materials, prescriptions, processes and quality standards as the original drug. Since the prescription and process are trade secrets, generic drugs are hardly completely pharmaceutically equivalent to original drugs. Therefore, there are many cases of “pharmaceutically equivalent but not bioequivalent” and “bioequivalent but not pharmaceutically equivalent”, which need to be solved by designing professional R&D logic according to the key characteristics of original drug.

Nowadays, China’s economic growth is shifting from extensive mode to intensive mode. Dr. Lan Ke believes that the consistency evaluation system is the outcome of medical system reform, which helps reshape the ecology of pharmaceutical industry and refocuses on the basic attributes of drug.

In August 2017, the Interpretation of Several Issues Concerning the Application of Laws in Handling Criminal Cases of Falsifying Registration Materials for Drugs and Medical Devices was issued, clarifying the punishment on the falsification of drug R&D materials. This helps regulate the industry order and medical market, and also provides a solid legal guarantee for advancing the development of a true and reliable consistency evaluation system.

Dr. Lan Ke said frankly that in the process of reshaping the industrial ecology, a large number of small pharmaceutical enterprises will be eliminated from the market due to the lack of timely access to the three basic attributes of drugs and their inability to keep up with the pace of national reform policies. The large-scale influential pharmaceutical enterprises will be the main players in competition.

With the development of consistency evaluation, under the premise of ensuring the quality of drugs, the drug prices will inevitably decrease. However, even if so, the company can still make considerable profits through the increase of sales volume, and can further invest in generic drugs and innovation pipelines, thus forming a good business ecological cycle.

In addition, a temporary shortage of some drugs may occur during the remodeling of industrial ecology. However, he firmly believes that policy and capital will attach importance to these scarce drugs due to market demand and clinical demand. The drug supervision system will also issue a list of scarce drugs on a regular basis, and open a series of green channels to encourage enterprises’ R&D and production. He believes that all obstacles to reform will be gradually erased.

The specific actions of human body in absorbing, distributing, metabolizing and excreting different drug molecules vary greatly. Scientifically completing efficient R&D through accumulation of experience or mature theories is one of the crucial ways to save pharmaceutical costs. The effective implementation of this method must be based on real and reliable R&D data. Therefore, how to scientifically control the integrity and accuracy of the data link, that is, to grasp the scale of compliance, is equally important.
 

Hengkang carefully controls the compliance, and develops reasonable design plans for customers, including key risk control and dynamic adjustment of key points of the test plan for the data obtained, to help customers complete the consistency evaluation efficiently at a reasonable cost.
 

Dr. Lan Ke with team members

Furthermore, Hengkang also features innovative layout in the R&D of small molecule targeted tumor drugs and the clinical transformation of drug metabolomics technology. Based on the profound academic background in these two aspects, Hengkang has enriched its expertise for many years.
Up to now, the consistency evaluation project undertaken by Hengkang has not failed once due to its solid foundation.
 

In 2016, Dr. Lan Ke founded Hengkang in Tianfu Life Science Park. Although he has experienced many difficulties that he has never encountered in his work in colleges, he said that he should meet the needs of the country and adapt to the development of times, and make a contribution to improving the ecological environment of medicine to gain a sense of accomplishment.

Speaking of the overall medical development environment in Chengdu, Dr. Lan Ke said that compared with the Yangtze River Delta region, Chengdu, an inland city located in southwest China, should focus on how to accurately identify valuable “seed” projects for cultivation. For this purpose, it is necessary to raise the professional level of government and commercial capital and further the collaboration between them.

Moreover, Chengdu has pooled a myriad of universities and research institutes, such as the Sichuan University, University of Electronic Science and Technology of China, Chengdu University of TCM, Chengdu Institute of Organic Chemistry of Chinese Academy of Sciences, and Chengdu Institute of Biology of Chinese Academy of Sciences. It can be seen that Chengdu takes the leading position in western China in talent accumulation.
 

“Thanks to the opportunities brought by the development of the country and the society, my partners and I have already taken the initiative and actively engaged in innovation and entrepreneurship. I hope that more scholars will partake in the trend of the times, so that theoretical research results can come to fruition in real life to generate more medicine products benefiting the public.” Dr. Lan Ke said heartily.