WHO Drug Information Vol. 16, No. 2, 2002
(2002; 91 pages) Voir le document au format PDF
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Ouvrir ce répertoire et afficher son contenuHerbal Medicines
Ouvrir ce répertoire et afficher son contenuCurrent Topics
Fermer ce répertoireGood Clinical Practices
Afficher le documentDevelopment of Chinese good clinical practices (GCP)
Ouvrir ce répertoire et afficher son contenuSafety Information
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Ouvrir ce répertoire et afficher son contenuEssential Medicines
Ouvrir ce répertoire et afficher son contenuRecent Publications and Sources of Information
Afficher le documentProposed International Nonproprietary Names: List 87
 

Development of Chinese good clinical practices (GCP)

Sang Guo-wei
State Drug Administration
Beijing, China

The State Drug Administration (SDA) was established in August 1998 to enhance government administration of drug regulation and took over responsibility for regulating pharmaceutical products and medical devices from the Ministry of Public Health. Through new regulations, the SDA is making efforts to upgrade pharmaceutical regulations and strengthen their implementation to meet international standards and thereby ensure the safety and efficacy of medicines. In line with China's adhesion to the World Trade Organization (WTO), the SDA will continue to improve pharmaceutical product legislation and will implement the “rule of law” in the pharmaceutical sector, including regulations covering clinical trial performance and protection of trial subjects, through good clinical practices (GCP).

On 28 February 2001, the newly revised Drug Administration Law of the People’s Republic of China was approved by the National People’s Congress and entered into force on 1 December, 2001. Detailed Rules of Drug Administration Law are about to be promulgated. The main objectives of the new regulations and law are:

1. To ensure protection of rights, safety and welfare of human subjects.

2. To conform with international, generally recognized principles on clinical trials, ethical standards and scientific principles.

3. To ensure that clinical trials of all drugs, including biotechnology products and traditional medicines (in whatever phase, including human bioavailability or bioequivalence studies) are performed according to Chinese GCP.

4. To ensure that the clinical trial process is standardized and the results scientific and credible.

5. To emphasize the importance of ethics committees and informed consent to ensuring the protection of trial subjects.


Drug Administration Law

The new law addresses implementation of clinical trials in China. This law has been enacted to:

• strengthen drug administration;

• ensure drug quality and safety; and

• protect people's health and their legitimate rights and interests in the use of drugs.


All institutions and individuals engaged in research, production, distribution, use, or administration of drugs in the People’s Republic of China shall abide by this law. The drug regulatory authority, the SDA, is responsible for drug administration nationwide. Practical, effective and new drug administrative procedures covering research and development of new drugs are included in the new law.

Before approval for conducting a clinical trial can be obtained, a dossier for new drug research and development should be submitted to the SDA specifying:

• the manufacturing process;
• quality specifications;
• results of pharmacological and toxicological studies;
• related data and samples.


Finally, this new law clearly indicates that the clinical research institution shall implement GCP. Therefore, Chinese GCP has become an important part of law which can be legally enforced.

Major regulations on new drug clinical evaluation

China has made significant progress in recent years to improve its medicinal product regulatory and evaluation procedures. Within the structure of the SDA, two major departments deal with drug registration and drug safety and inspection. They are jointly responsible for the evaluation and inspection of conducting clinical trials and inspecting new drugs. Since April 1999, certain provisions have been introduced by SDA to replace and update regulations established in 1985. Table 1 above gives details of major regulations on new drug clinical evaluation and their interaction.

Table 1. Regulations concernig new drug evaluation and management in China

Key elements related to GCP and protection of trial subjects in the New Drug Approval provisions

1. The sponsor and clinical research institution shall comply with the requirements of “good clinical practice” (GCP) stipulated by the State Drug Administration when a clinical study for a new drug is carried out.

2. When submitting the application for a clinical trial, the sponsor should select the principal clinical research institution and the research sites from the clinical research bases designated by the SDA (except for Phase IV clinical trials). The selection should be approved by the SDA. If an additional research site is needed or the clinical study will be performed in hospitals other than clinical research bases for a particular reason, additional applications should be submitted for approval.

3. The designated clinical research institutions should be aware of the properties, action, efficacy and safety of the test drug. The institution should subscribe to the clinical trial protocol with the sponsor in accordance with the requirements of GCP and conduct the trial strictly in line with the protocol.

4. The sponsor should appoint a qualified person to monitor the clinical trial so as to ensure implementation of the protocol in compliance with the requirements of GCP. Drug administration bodies at provincial level are responsible for the supervision and inspection of the clinical study as requested by the SDA.

5. In case of the occurrence of serious adverse events during the clinical study, the research sites must immediately take all necessary measures to protect the subject from risk, and report the events to the local drug administration at provincial level and the SDA within 24 hours.

Development of Chinese GCP

In order to guarantee the safe and proper use of new drugs, and to participate in international competition and cooperate in the field of medical and pharmaceutical science, technology and trade, the drug regulatory department and scientists in China are fully aware that Chinese regulations and laws regarding the development of a new drug must be in line with international standards. SDA concluded that the existing regulations were inappropriate for the change from a planned to a market economy, in particular after China’s entry into the WTO. Since 1992, China recognizes GCP as the international ethical and scientific standard for designing, conducting, recording, and reporting clinical trials that involve the participation of human subjects.

The International Guidelines for Biomedical Research Involving Human Subjects, prepared by the Council of International Organization for Medical Sciences (CIOMS) indicates how ethical principles set forth in the Declaration of Helsinki can be effectively applied, particularly in developing countries, with consideration of their socioeconomic circumstances, laws, regulations, executive and administrative arrangements.

Table 2 on page 127 summarizes activities undertaken in the preparation and development of Chinese GCP guidelines. These were adopted by the SDA on 23 July 1999 and entered into force from 1 September 1999

Ethical principles and trial subject protection

Table 2. Development of GCP in China

1986-1992

Information/data collection

1993

Translation into Chinese of Code of Federal Regulations and FDA guidelines; WHO GCP; GCP from EC, Australia, Canada, France, Japan, Nordic coun tries, and Republic of Korea

1994

Preparation meeting and workshop on GCP

1995

Establishing a 5 member draft group for Chinese GCP

1996

Training course on GCP; A computer-based clinical research training and reference system was introduced into China

1998

Chinese GCP was promulgated by Ministry of Public Health

1999

Chinese GCP was revised and promulgated by SDA, and entered into effect

2000

GCP training and teaching material published by SDA

2001

Translation into Chinese of ICH GCP and revised Declaration of Helsinki

2002

SDA commences re-revision of Chinese GCP

1999-2001

Training and implementation on GCP by SDA’s Training Centre

Table 3. Designation and Development of Drug Clinical Research Bases in China

Year

Number of bases

Disciplines

Designator

1990

46

30

MOPH

1998

113

70

MOPH

2000

132

66

SDA

Chinese GCP contains 13 chapters and includes 66 articles. The Declaration of Helsinki is included as an appendix. Fundamental articles relating to ethics and protection of trial subjects are as follows:

1. All research involving human subjects shall be conducted in accordance with the ethical principles contained in the Declaration of Helsinki, namely justice, respect for persons, beneficence (maximize benefits and minimize harms and wrongs) and non-maleficence (do no harm) (Article 4).

2. Prior to planning a clinical trial in humans, specific aims, problems to be solved, anticipated efficacy and possible risks must be considered thoroughly. Anticipated benefits should prevail over possible risks. The chosen clinical trial solutions must conform to scientific and ethical standards (Article 5).

3. An ethics Committee should be established within the medical institution where the clinical trial is to be conducted to ensure the protection of the rights and welfare of human subjects taking part in the trial and to provide public reassurance (Article 9).

4. Prior to a clinical trial, the protocol must be approved by the Ethics Committee before implementation. During the trial, any subsequent protocol amendment must be approved by the Ethics Committee before its implementation. All serious adverse events occurring during the trial must be reported to the Ethics Committee (Article 10).

5. In order to protect the rights and welfare of trial subjects, the Ethics Committee should review the protocol strictly (Article 12).

6. Investigators, or their appointed representatives, should provide trial subjects with detailed information relating to the clinical trial (Article 14).

7. Informed consent is obtained after a sufficient and comprehensive explanation of the trial (Article 15).

8. The contents of a trial protocol should include the following (Article 17):

• Purpose and objectives of the trial, including the known potential risks and benefits to human subjects.

• Criteria for inclusion and exclusion of trial subjects and process of recruitment, methods of allocation of subjects, withdrawal criteria.


9. The investigator is required to conduct the clinical trial in an institution with sound medical facilities, laboratory equipment and staff. The institution should have all necessary emergency facilities to ensure safety of trial subjects (Article 21).

10. The investigator is responsible for medical decision-making in relation to the trial, and to ensure adequate medical treatment to be provided to the subject whenever any adverse event occurs (Article 24).

11. The investigator is obliged to take necessary measures to ensure the safety of subjects, and such measures should be documented. In case of serious adverse events, the investigator must take appropriate measures to protect subjects, and report to the drug regulatory authorities, the sponsor and the Ethics Committee immediately (Article 25).

12. As soon as a serious adverse event occurs, the sponsor must discuss this with the investigator(s), take necessary measures to safeguard trial subjects, report in a timely manner to drug regulatory authorities, and notify the other investigators involved in the same trial (Article 39).

13. The sponsor should provide insurance and treatment compensation to trial subjects to cover trial-related injuries or death, and provide indemnity (legal and financial coverage) for the investigator, except for claims resulting from medical malpractice (Article 42).


Requirements for foreign agencies conducting clinical studies in China (Interim)

1. A foreign agency can conduct a clinical study in China only after the SDA approves the application filed by the Chinese agent.

2. Foreign products intended to be studied within a clinical study in China must be registered abroad or have entered into Phase II clinical trials for drugs and Phase III for vaccines.

3. The application form for a Clinical Trial of a Foreign Drug in China should be completed and submitted with the relevant dossiers for approval.

4. The protocol of the clinical study must be formulated and implemented according to Chinese GCP.

5. If, at any time, the drug demonstrates serious or unexpected adverse reactions in any other countries, it must be reported in a timely way to the SDA according to regulations.


Globalization tends to ignore individual needs, especially those of developing countries. When clinical trials are planned in China, it is the ethical duty of investigators and pharmaceutical companies to consider the specific needs and benefits of the Chinese people. The newly Revised Declaration of Helsinki (5th Amendment at the 52 General Assembly, Edinburgh, October 2000) should be followed.

Shortcomings in GCP management

The following problems have been encountered during the application of GCP within China.

1. There is a wide range in the practice and implementation of clinical trials, of considerable variety, (although most leading investigators follow GCP and ICH).

2. In some cases, clinical trials have started without approval by SDA and an ethics committee. This practice also involved foreign vaccine trials.

3. Not all institutions have an ethics committee. In others, the ethics committee may not have the required membership, or correctly follow meeting schedules and record-keeping.

4. Use of a written informed consent containing inadequate information. The explanation given is that doctors worry that if all potential adverse effects are listed in the informed consent form, the subject will not wish to enrol.

6. Conduct of the clinical trial may not follow strictly the protocol.

7. The protocol may be changed or modified without informing the ethics committee and drug regulatory authority.

8. Domestic sponsors are less aware of the Declaration of Helsinki and GCP principles.


Conclusion

1. Basic requirements for conducting a clinical trial of medical products in China should meet internationally-recognized principles on ethics issues and protection of subject’s rights, welfare and safety.

2. All clinical trials conducted in China should be performed according to the Drug Administration Law, Chinese GCP and related regulations.

3. Familiarity with and implementation of the principles of the Declaration of Helsinki, WHO or ICH GCP will enable data from clinical trials conducted in China to be accepted internationally.

4. It is important for investigators, sponsors and regulatory authorities to join in efforts to improve the current status of implementation of GCP in China thereby protecting subject’s rights, welfare and safety.

5. Special guidelines for biotechnology products and vaccine clinical trials should be formulated on the basis of their specific characteristics. More attention should be paid to the safety of vaccines and recombinant products in relation to ethical considerations.

6. A general training programme for medical doctors, manufacturers and the public on the ethical principles and protection of subjects in drug clinical trial is strongly recommended in China in order to comply with international standards.

 

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