How To Avoid Stepping On The "Red Line" In The Development Of Biomedical Enterprises?

Recently, the criminal law amendment (11) of the people's Republic of China (hereinafter referred to as the "criminal law amendment") has been passed recently. Many of the amendments involve the biomedical industry, including the production and sale of counterfeit drugs, the registration and falsification of drugs, the amendment of China's human genetic resources (hereinafter referred to as "human heritage") and the implantation of cloned human embryos into human or animal bodies 。

"China's criminal law is also constantly improving, which attaches great importance to the safety of biomedical products that cause serious harm to human health or have risks. This is also the main reason for bringing drug registration fraud and human heritage crimes into criminal law supervision. The whole life cycle of drugs is included in the criminal law supervision to prevent biomedical safety risks." Wang Chenguang, Professor of Law School of Tsinghua University and director of Health Law Center, said in an interview with 21st century economic reporter recently.

Wang Chenguang pointed out that in the past, many people believed that the falsification of clinical data was not a major event and did not cause social harm. Therefore, it was not included in the criminal law supervision. However, if we did not pay attention to the drug from the source to the final product, it would cause great social risks and threats. Once the risk is caused, such as the crime of human genetic resources, it will cause great disaster The amendment of criminal law is more to prevent risks.

Wang Rong, a lawyer from Zhejiang Xinmu law firm, also told reporters of the 21st century economic report that the above amendments reflect the concern of the criminal law on people's livelihood, and are also connected with the drug administration law and the biosafety law, indicating that the state has strengthened its attention to public health safety, food and drug safety, biological safety and life safety. The relevant industries should also do a good job in the compliance of enterprises and formulate the corresponding work system according to the legal provisions, which will also affect the development of the whole industry.

Control the source

For drug registration, regulatory authorities have always attached great importance to the issue. In 2015, it has become the focus of attention, and set off a storm of clinical data self-examination in the industry.

On July 22, 2015, the former State Food and Drug Administration (CFDA) requested the announcement on carrying out self inspection and verification of drug clinical trial data, which was known as "the most stringent data verification requirement in history".

The above announcement requires the applicant to conduct self-examination on the authenticity, integrity and standardization of the clinical trial data of 1622 registration applications applied for listing and import. After deducting 193 exemption clinical trials, a total of 1429 varieties need to be self inspected. The applicant can withdraw the registration application with problems in clinical trials on his / her own initiative and apply again after supplement and improvement.

Since October 2015, the original CFDA organization will carry out verification on the registration applications to be approved. By the end of June 2016, 1193 enterprises had voluntarily withdrawn their applications, accounting for 83% of the total number of self inspections. As of the end of September 2016, a total of 117 registration applications have been verified, and 30 of them with authenticity problems have been decided not to be approved, accounting for about 2% of the varieties that should be verified by self-examination; and 11 clinical trial institutions and contract research organizations (CRO) of 27 varieties suspected of data fraud were put on file for investigation.

There are many reasons for the voluntary withdrawal of enterprise self-examination. The person in charge of the pharmaceutical chemical registration department stressed that some of them did not conform to the quality management standards of clinical trials, which affected the scientificity and accuracy of the test results; some of the data were incomplete and could not be traced back to the source, which was not enough to prove the safety and effectiveness of the declared drugs; some data were not true, which did not exclude intentional fraud.

However, since then, the counterfeiting of drug registration has sounded a heavy alarm to enterprises. In 2017, under the powerful promotion of the original CFDA new policy, the supreme law and the highest detection platform passed the judicial interpretation of drug clinical trial data fraud as punishment.

Wang Chenguang pointed out that drug registration mainly reviews the safety, effectiveness and quality controllability of drugs, and the data recorded in clinical trial reports mainly reflect these inspection indicators of experimental drugs. Therefore, the clinical trial data report must truly and objectively reflect the situation of the trial. This not only determines whether the drug can be approved, but also determines the safety and effectiveness of the drug after clinical use.

"The two high-tech companies actively intervene in the governance of clinical trial data fraud by means of judicial interpretation, which means that criminal justice formally intervenes in the regulation of drug registration application data fraud, which is undoubtedly of great significance for purifying the environment of new drug R & D application, maintaining the order of drug registration application, and improving the efficiency of drug listing approval." Wang Chenguang pointed out that although there are not many related cases at present, it also shows the deterrent effect of law from the side.

"This amendment to the criminal law is more strict than the judicial interpretation in the constitution of crimes. According to the judicial interpretation, a crime is an act crime. According to the judicial interpretation, the crime is constituted as long as the false registration materials are provided. According to the amendment, it belongs to the plot crime. It is not only necessary to implement the act of providing false registration materials, but also must be "enough to seriously endanger human health". The constitution of the crime is more strict than the judicial interpretation Feng Yongqiang, executive director and partner of Jiangsu Yicheng law firm, explained.

However, a person in the industry who did not want to be named pointed out to the reporter of the 21st century economic report that under the condition of tight medical resources, the previous clinical trials of some new drugs were just "on the stage", and the extremely important data in the clinical trials were often ignored in China.

According to a survey conducted by Chinese Journal of clinical pharmacology in 2013, the rate of non-standard test records was 85.7% (including original data preservation, case report form filling, original medical record writing, error modification, rectification of supervision and audit, etc.), which was the most problematic link in clinical trials, and only 1 / 7 institutions in China did not Find problems.

The drug registration fraud into the punishment is conducive to the industry norms, also beneficial to patients.

Wang Chenguang pointed out that in the main body, the applicant of drug registration is generally also the applicant of clinical trials, and the clinical trials of drugs need to be entrusted to clinical institutions. Therefore, the clinical trial institutions and their operators also constitute the relevant subjects in the legal relationship of drug registration. In addition, in the field of pharmaceutical manufacturing, a kind of intermediary organization cro has been formed to provide pharmaceutical R & D outsourcing clinical trial scheme for pharmaceutical enterprises, including the selection of hospitals, doctors, clinical trial supervision, data collection and management, statistical analysis and writing of statistical analysis reports.

Feng Yongqiang pointed out to the 21st century economic reporter that Article 142 of the criminal law is a double penalty clause, that is, individuals and units can become the subject of crimes, that is, individuals or units engaged in the acts specified in this article. If a unit constitutes the subject of a crime, a fine shall be imposed on the unit according to Article 150 of the criminal law, and the person in charge and other persons directly responsible shall be punished in accordance with the provisions of each article.

"As for the subject of punishment, we can't generalize, but we should determine it according to individual cases. For example, if the registration fraud is discussed by the board of directors of a pharmaceutical company or known by the major shareholders of the company, the company may constitute a unit crime. If the cro does not know about the fraud, or even explicitly opposes the fraud, the unit will constitute a crime, and he will not be the responsible person; on the contrary, if the cro knows and cooperates with the fraud, or even is the main participant, he will become responsible People. Whether the hospital should bear the responsibility of unit crime is similar. If only individual employees of the pharmaceutical company or individual doctors of the hospital cheat, then the company and the hospital do not constitute unit crime. " Feng Yongqiang pointed out.

A person in charge of a listed pharmaceutical enterprise told the 21st century economic report that pharmaceutical companies are now focusing on the negotiation and centralized purchase of national medical insurance. However, after the "722" regulatory storm, the whole industry is cautious about drug registration. However, due to the limitation of medical resources and other factors, some irregularities may inevitably exist.

Is nonstandard test record considered false? Feng Yongqiang pointed out that this article is an intentional crime. Subjectively, the subject must be intentional to constitute a crime. Nonstandard is generally caused by management negligence, which is not intentional and does not constitute a crime. Moreover, this article is aimed at the act of "deception", that is, subjectively, it is specially emphasized that it is direct intention.

"This is undoubtedly a wake-up call to the pharmaceutical manufacturing, marketing industry and pharmaceutical enterprises, and it is also a sharp blade on the head of pharmaceutical enterprises, reminding the industry and enterprises not to tolerate any falsehood when applying for drug registration, and greatly reduce the fraud in drug registration application. We have strengthened the responsibilities of pharmaceutical service outsourcing, medical institutions and other units related to drug registration application. " Feng Yongqiang pointed out that it may further promote the development of pharmaceutical service outsourcing industry. In general, this clause will increase the cost and risk in drug registration application. In order to balance the cost, efficiency and risk in drug registration application, pharmaceutical enterprises will use more pharmaceutical service outsourcing enterprises to carry out the relevant work in the registration application.

Risk prevention

In addition to preventing risks at the source of drug registration, the amendment of the criminal law has also made risk prevention in the field of biosafety, such as human genetic resources.

Wang Rong, a lawyer from Zhejiang Xinmu law firm, pointed out that the amendment to the criminal law is connected with and consistent with the biosafety law. The problem of human genetic resources is not only a question of biotechnology, but also a matter of human health, ethics and public interest.

Feng Yongqiang, for example, said that human genetic resources are closely related to certain regions, races and nationalities. Once the unreasonable or malicious use and utilization of these resources and information will bring about great consequences and influence, which will directly affect a group or even a nation and pose a great threat to national security and national survival.

As far as this year's epidemic situation is concerned, biosafety has already been raised to the issue of national security system. It can be said that biosafety is related to the survival of human beings.

Feng Yongqiang pointed out that China already had legislation on human genetic resources as early as 1999, but at that time, it was only a departmental regulation, the Interim Measures for the management of human genetic resources, and it was not until 2019 that the legislation on human resources was upgraded into administrative regulations, that is, the regulations on the management of human genetic resources. This time, it was upgraded to criminal law legislation, which was also a process of gradual upgrading.

In October 2018, the Ministry of science and technology released the news that six companies or institutions, including BGI, AstraZeneca, Yaoming Kant and Shanghai Huashan Hospital, were punished for violating the regulations on the management of human genetic resources. It is understood that some punishment decisions were made in 2015 and 2016. This is also the first time that the Ministry of science and technology announced the administrative punishment of human genetic resources.

In this regard, Wang yuedan, Professor of immunology, School of basic medicine of Peking University, pointed out that this actually reflects the importance of the relevant national departments on the safety of Chinese genetic and genetic information, and ensures China's strategic security and people's health while promoting international scientific research cooperation.

Especially after the outbreak of Xinguan epidemic, biosafety has attracted great attention at the national level. On October 17, this year, the biosafety law of the people's Republic of China was promulgated. Then, on November 23, Jin srui, a listed biomedical enterprise in China, announced that on November 21, Zhang Fangliang received an arrest notice issued by the anti smuggling Bureau of Zhenjiang customs. The reason for the arrest was that Zhang Fangliang was suspected of smuggling goods prohibited by the import and export provisions of Chinese laws. According to the industry, it may be closely related to human genetic resources.

It is understood that relevant enterprises are also actively seeking more legal and compliance solutions.

Recently, a person in charge of an enterprise told the reporter of the 21st century economic report that "after the promulgation of the bill, we have been studying it all the time. We look forward to the introduction of more implementing laws and regulations to give more specific and detailed guidance to the industry. In the process of formulating these specific measures, we also hope that the industry can have the opportunity to explain our technical connotation to the government departments Potential risks and risk prevention and control measures. In this way, enterprises can continue to maintain China's leading edge in biotechnology in the world while practicing the legal provisions. "

Just half a year ago, in order to guard against the relevant risks, mingma biotechnology, a subsidiary of Wuxi Kant group, announced its reorganization, integrating its overseas business into a new company, genesis science. The board of directors is composed of expatriates. Its business focus is on the United States, Iceland and Ireland, no longer involving Chinese business. Since then, genius science and mingma biotechnology entities in China have been independent of each other, becoming two independent operating entities without equity connection at home and abroad, and they have developed respectively.

In fact, the biosafety law and the amendment to the criminal law have raised the safety of human genetic material to an unprecedented height. Human genetic resource materials refer to the organs, tissues, cells and other genetic materials containing human genome, gene and other genetic materials. As an important part of human genetic resources, how to ensure the safety of genes has been concerned by the public. According to public information, gene synthesis also has the potential to be developed into biological weapons. This also leads to the discussion on the safety of gene synthesis, which is also an important issue in the development of gene synthesis industry, such as whether gene synthesis belongs to human genetic resources, whether it belongs to dual-use items, and whether there are relevant restrictions on import and export.

An expert from the Chinese society of medical biotechnology pointed out to the reporter of the 21st century economic report that the rapid development of gene synthesis and other technologies also brings certain challenges to the regulation: "in terms of regulation of gene synthesis, the biggest problem now is what can be synthesized and what cannot be synthesized. If genetic compounds are well known, then there is no problem. If biochemical drugs or biological weapons are synthesized, rules need to be made on what can and cannot be done. "

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