(Temporary Regulation)
(SDA Order No. 14)
Effective September 1, 1999
Chapter One: General Provisions
Article 1: This Good Practices of Non-clinical Drug Research ("Practice") is promulgated in accordance with the "Drug Administrative Law of the People's Republic of China", to improve the quality of non-clinical drug research and to ensure the authenticity, integrity and reliability of experiment data.
Article 2: This Practice is applicable to non-clinical research conducted for the purpose of drug registration application. Organizations undertaking non-clinical research shall abide by this Practice.
Article 3: Definitions:
(1) Non-clinical research: means toxicity experiments conducted under laboratory conditions on experiment subjects to evaluate the safety of a drug, including toxicity experiments in which a drug is administered once or more than once, genetic toxicity experiments, experiments causing mutations, carcinogenicity experiments, various stimulation experiments, dependency experiments and other toxicity experiments related to the safety evaluation of a drug.
(2) Non-clinical Research Organization: means a unit or a department undertaking non-clinical research of a drug, including a safety research center, safety research institute, safety research office or research group, etc.
(3) Experiment Subjects: mean animals, plants, microbes, and cells etc., which are used in toxicity research.
(4) Quality Control Department: means the department within the non-clinical research organization which ensures that all work of the organization conforms with this Practice.
(5) Project Director: means the person responsible for organizing the implementation of a certain research project.
(6) Experiment substances: means a drug, or a substance intended to be developed into a drug, which is to be tested in non-clinical research.
(7) Comparative substances: means a drug and other products which are used to establish a basis which can be compared to the experiment substances in non-clinical research.
(8) Original Data: means original observation records and relevant documents which record research work, including working records, note books, various photographs, microfilms, micro-copies, computer printings, magnetic carriers, and records made by automatic instruments, etc.
(9) Specimen: means any material collected from experiment subjects for purposes of analysis, observation, and testing.
(10) Authorizing Party: means a party that contracts with a non-clinical research organization for non-clinical research of a drug which it has researched and developed. (11) Batch Number: means a group of digits or, letters and digits, which is used to identify the "batch" to enable any experiment substances and comparative substances to be traced and their history checked.
Chapter Two: Organization and Staff
Article 4: A non-clinical research organization shall establish a complete management system based on this Practice, appoint the director of the organization, a director of the quality control department and other relevant staff who shall undertake management responsibilities according to their positions.
Article 5: Each staff member of a non-clinical research organization shall meet the following qualifications:
(1) possess a rigorous scientific spirit, high occupational ethics and an appropriate diploma; received professional training in his field and have the knowledge, experience, and professional ability required to undertake the assigned research work;
(2) understand the basic provisions of this Practice, strictly perform his respective duties, master and strictly implement relevant standard operating procedures;
(3) a researcher shall duly record experiment observations in a precise and clear manner and report to the project director in writing any conditions existing during the research that may affect test results;
(4) a researcher shall dress according to his position, observe regulations on personal hygiene and health, and prevent experiment substancess, comparative substancess and experiment subjects from being contaminated;
(5) a researcher shall undergo a periodic health examination, those who suffer from a disease that may affect the reliability of research results may not participate in the research work.
Article 6: The director of a non-clinical research organization shall, at a minimum, have a bachelor's degree in medicine, pharmacy or other relevant fields and have corresponding professional qualifications and abilities. In fulfilling his duties, the director shall:
(1) fully assume responsibility for the establishment and administration of the non-clinical research organization;
(2) establish and maintain files of the educational degrees, professional training and relevant work experience of staff;
(3) ensure the various facilities, equipment and experiment conditions meet the requirements in this Practice;
(4) ensure sufficient qualified staff with clearly assigned responsibilities who can conduct research work according to the requirements of this Practice;
(5) employ a director for the quality control department and ensure that he complies with the requirements of this Practice;
(6) make a master schedule to ensure the development of each research project;
(7) organize the drafting and revision of standard operating procedures and promotion of the mastery of relevant standard operating procedures for each staff member;
(8) employ a project director before commencing each research project; record the reason and date of any replacement;
(9) examine and approve the experiment protocol and summary reports;
(10) duly process reports of the quality control department; record in detail the adopted measures;
(11) ensure the quality and stability of experiment substances and that comparative substances conform with requirements;
(12) execute contracts with cooperation units or authorizing parties.
Article 7: A non-clinical research organization shall establish an independent quality control department with the number of staff of such department being determined by the scale of the non-clinical research organization so as to ensure its management of equipment, facilities and experiment processes conform to the requirements of this Practice. A quality control department shall:
(1) keep copies of the master schedule, experiment protocol and summary reports of the non-clinical research organization;
(2) examine and verify an experiment protocol, experiment records and summary reports according to the requirements of this Practice;
(3) inspect and supervise each research project, and make an inspection schedule corresponding to the type and length of the research project, the details of the examination including existing problems, the corrective measures which are adopted etc., shall be recorded in detail, and sign and maintain such records;
(4) periodically inspect animal raising facilities, experiment instruments and record keeping;
(5) duly report to the organization director and project director problems detected in the inspections, propose solutions and write an inspection report; and,
(6) participate in the drafting of standard operating procedures and maintain the copies.
Article 8: A project director shall be employed for each research project and shall:
(1) be responsible for the overall operation and management of the research project;
(2) formulate an experiment protocol and recommend revisions or additions to the standard operating procedures; analyze research results and prepare summary reports;
(3) strictly implement the experiment protocol, any amendment of which shall be approved by the organization director;
(4) ensure clearly assigned responsibilities of research staff and their mastery of relevant standard operating procedures;
(5) control the progress of research work, check various experiment records to ensure they are direct, accurate and clearly written;
(6) record in detail any accidents and supplemental corrective measures;
(7) upon completion of the experiment, transfer to record keeping office for filing the experiment protocol, the original data, the specimen that should be kept, all the relevant records, documents and the summary reports; and
(8) ensure all phases of a research project conform to the requirements of this Practice.
Chapter Three: Experiment Facilities
Article 9: A non-clinical research organization shall construct proper experiment facilities according to the requirements of this Practice and the needs of respective research projects.
All experiment facilities shall be kept clean and be appropriately laid out to prevent cross contamination and environmental conditions shall be adjusted and controlled according to the requirements of various equipment.
Article 10: A non-clinical research organization shall be equipped with appropriately designed and properly disposed animal raising facilities. The environmental conditions such as temperature, humidity, air cleanness, ventilation, illumination, etc. shall be adjustable according to needs. Animal raising facilities mainly include:
(1) facilities for raising and administering animals of different species and genus or of different experiment subjects;
(2) animal quarantine facilities, and isolation and medical treatment facilities for sick animals;
(3) facilities to collect and dispose of experiment wastes;
(4) cleansing and sterilization facilities; and,
(5) facilities for the management of experiment substances and comparative substances containing volatile, radioactive and biologically harmful components.
Article 11: A non-clinical research organization shall be equipped with proper storage facilities for feed, bedding, cage and other items for animal use so as to prevent cross contamination with experiment subjects. Items which may spoil or deteriorate shall be maintained in appropriate ways.
Article 12: A non-clinical research organization shall be equipped with facilities to administer experiment substances and comparative substances, including:
(1) facilities to receive and store experiment substances and comparative substances, and
(2) facilities to prepare and maintain experiment substances and comparative substances.
Article 13: A non-clinical research organization shall establish laboratories according to the needs of research work. Special laboratories shall be established for the use of biologically harmful materials, microbe, etc.
Article 14: A non-clinical research organization shall have record keeping facilities to maintain experiment protocol, various kinds of specimen, original records, summary reports and relevant documents.
Article 15: A non-clinical research organization shall install environmental control and administration facilities as needed.
Chapter Four: Instrument, Equipment and Experiment Materials
Article 16: A non-clinical research organization shall be equipped with relevant instruments and equipment according to the needs of research work. They shall be appropriately located, a special person shall be responsible to manage them. They shall be regularly checked, cleaned, maintained, tested and calibrated to ensure stable and reliable functions.
There should be standard operating procedures regarding the maintenance, calibration and usage of instruments and equipment in the laboratory where they are located. The date and the name of the operator shall be recorded in detail for each usage, inspection, test, calibration, and repair situation.
Article 17: The administration of experiment substances and comparative substances in a non-clinical research organization shall comply with the following:
(1) A specific person shall be designated to be responsible for experiment substances and comparative substances, for which, complete procedures for receipt, registration and distribution shall be established. The batch number, stability, content or concentration, purity and other chemical characters shall be correctly recorded. If a comparative substance is a commercial commodity, its label or other labeling information may be used to replace relevant experiment determinations;
(2) Experiment substances and comparative substances should be stored under appropriate conditions. A container shall be labeled with the name, abbreviated name, code, batch number, validity period and storage conditions;
(3) Contamination and deterioration must be avoided during the distribution of experiment substances and comparative substances, which, once distributed, shall be duly and accurately labeled with corresponding batch numbers with respective weights and the dates of distribution and return;
(4) If it is necessary to mix an experiment substance or comparative substance with a medium, the mixture should be tested for homogeneity [uniformity] before administering it. The respective concentrations and stability of experiment substances and comparative substances in the mixture shall also be regularly tested, if necessary. The expiration date of any component in the mixture shall be clearly marked on the label. If two or more components have expiration dates, the earliest date shall be marked on the label.
Article 18: All reagents and solvents in a laboratory shall be labeled clearly with the name, concentration, storage conditions, date of preparation, and validity period, etc. The use of a deteriorated or expired reagent and solvent is prohibited in experiments.
Article 19: A non-clinical research organization shall select qualified experiment animals and feed according to the relevant regulations, and raise and manage these animals.
The use of any detergent, sterilizer and insecticide in animal raising houses must not affect experiment results. The names, concentration, usage, time of use, etc. should be precisely recorded.
Periodical inspection of feed and water for animals shall be conducted so that nutrition standards are met and contamination factors which may influence experiment result are lower than stipulated standards. The inspection results shall be filed as original data.
Chapter Five: Standard operating procedures
Article 20: A non-clinical research organization must establish standard operating procedures suitable for experiment work and the standard concerning its editing and administration. Standard operating procedures are required for the following work:
(1) the reception, identification, labeling, storage, processing, preparation, distribution and sample analysis of experiment substances and comparative substances;
(2) the preparation of animal houses and laboratories; the adjustment and control of environmental conditions;
(3) the maintenance, calibration, usage and administration of experiment facilities, instruments, and equipment;
(4) the operation and administration of computer systems;
(5)the management of the transportation, quarantine, numbering and raising of experiment animals;
(6) the observation records of and experiments conducted on experiment animals;
(7) the techniques for the collection of various kinds of experiment samples, their examination and the determination of each index, etc.;
(8) the examination and disposal of dying or dead animals;
(9) the postmortem, histological, and pathological examinations of animal corpses;
(10) the collection, numbering and test of experiment specimen;
(11) the processing of various experiment data;
(12) the health examination system for research staff;
(13) the standards concerning the editing and administration of standard operating procedures; and,
(14) other work for which a non-clinical research organization regards it necessary to establish standard operating procedures.
Article 21: Standard operating procedures should be signed and confirmed by the quality control department and approved by the organization director before becoming effective. All copies of invalid standard operating procedures shall be duly destroyed, with only one copy filed.
Written records should be made and properly filed concerning preparation, amendment, effective periods, distribution and destruction of standard operating procedures.
The standard operating procedures should be filed so as to be convenient for use. During the research process, any deviation from standard operating procedures should be approved by the project director and also recorded in the original data. Any important change to the standard operating procedures should be confirmed by quality control department and approved in writing by the organization director.
Chapter Six: Implementation of a Research Project
Article 22: A non-clinical research organization shall determine a topic name or a code for each research project which shall be used consistently throughout all relevant documents and experiment records.
Each specimen collected in experiments shall be labeled with the topic name or code of the research project, the animal number, and the date of collection.
Article 23: A project director shall prepare an experiment protocol in writing, and duly sign and seal the protocol. The protocol may not be implemented until it passes the examination of the quality control department and receives approval from the organization director. The date of approval is regarded as the commencement date of the experiment. For a research project authorized by others, the relevant experiment protocol should be examined and approved by the authorizing unit.
Article 24: An experiment protocol shall include:
(1) the topic name or code and the purpose of the research project;
(2) the names and the addresses of the non-clinical research organization and the authorizing unit;
(3) the names of the project director and the staff participating in the experiment;
(4) the names, abbreviated names, codes, batch numbers, relevant physical and chemical features and biological characters of experiment substances and comparative substances;
(5) the experiment subjects and the reason of selection;
(6) the species, genus, quantity, age, sex, range of weight, origin and grade of the experiment animals;
(7) the identification methods of experiment animals;
(8) the environmental conditions of experiment animal raising and management;
(9) the name or code of feed;
(10) the solvent, emulsion and other medium used in the experiment;
(11) the route and method of drug administration, dosage, frequency, time and the reason of selection;
(12) the name of the document containing the main principles for toxicity research;
(13) the testing frequency and methods of the data in each index;
(14) the statistical processing method of data; and
(15) the storage place of experiment data.
Article 25: Any change to an experiment protocol during the experiment shall be examined by the quality control department and approved by the organization director. The changes, reason and date of change(s) shall be recorded and filed together with the original protocol.
Article 26: A project director is fully responsible for the operation and management of a research project. Research staff shall implement the experiment protocol strictly according to the standard operating procedures and if abnormal phenomenon are discovered, duly report to the project director.
Article 27: All data shall be duly recorded in a direct, accurate and clear manner and shall not be easily canceled. The recording date shall be indicated together with the signature of the recorder. The original record should be kept clear and identifiable when it is amended. The reason and date of amendment shall be indicated together with the signature of the person making the amendment.
Article 28: When an experiment animal become sick, such sickness not caused by experiment substances, or show abnormal conditions possibly affecting research purposes, it shall be isolated immediately. When a drug is required to treat an animal, the project director's approval shall be acquired. The reason of treatment, approval procedures, examination record, prescription, date and result of the treatment, etc. shall be recorded in detail. Treatment measures must not affect the research.
Article 29: When a research project is completed, the project director shall duly prepare a summary report, and sign and seal the report. The report shall be submitted to the director of the quality control department for examination and comments and to the organization director for approval. The date of approval shall be regarded as the completion date of the research project.
Article 30: A summary report shall mainly include:
(1) the topic name or code and the purpose of the research project;
(2) the names and addresses of non-clinical research organization and authorizing parties;
(3) the commencement and completion date of the research project;
(4) the names, abbreviated names, codes, batch numbers, stability, contents, concentration, purity, components and other characteristics of experiment substances and comparative substances;
(5) the species, genus, quantity, age, sex and range of weight, origin, certificate number of qualified animal, distribution unit, date of reception and raising conditions of experiment animals;
(6) the route, dosage, method, frequency, and time of administration of the experiment substances and comparative substances;
(7) the basis of dosage design of experiment substances and comparative substances;
(8) the abnormal situations that affect reliability of the research and cause deviation from the experiment protocol;
(9) the test frequency and methods of the data in each index;
(10) the names and responsibilities of the project director and all research staff;
(11) the statistical method used in data analysis;
(12) the results and conclusions of the experiment; and,
(13) the storage places of original data and specimen.
Article 31: If a summary report which has been signed by the organization director is to be amended or supplemented, the person concerned shall elaborate the changes, the reason, and the date of the amendment or supplement. The changes shall be approved by the project director, examined by the director of the quality control department and approved by the organization director.
Chapter Seven: Data Files
Article 32: At the close of a research project, the project director shall, according to the requirements of the standard operating procedures, organize the documents of experiment protocol, specimen, original data, literature records, original summary report, all written documents related to the experiment, investigation report from quality control department, etc., and then transfer them to the record keeping office. These documents shall be numbered and filed in accordance with the requirements of standard operating procedures.
When a research project is cancelled or suspended, the project director shall provide a written explanation concerning the reason of cancellation or suspension, and organize and file the documents as described above.
Article 33: A specific person shall be appointed to be responsible for the administration of a record keeping office according to the requirements of the standard operating procedures. The experiment protocol, specimen, original data, literature records, summary reports and other documents shall be kept for at least 5 years after the drug is marketed.
Wet specimens, the quality of which is liable to change, such as tissues and organs, electronic mirror specimens, blood smear, reproductive toxicity experiment specimen, etc., shall be stored as long as the quality can be evaluated.
Chapter Eight: Administration, Inspection and Certification of Qualification
Article 34: The State Drug Administration is responsible for the administration, inspection and qualification certification of a non-clinical research organization.
Article 35: Any unit dealing with non-clinical research for the purpose of drug registration in the People's Republic of China shall be the subject of administration, inspection, and qualification certification.
Chapter Nine: Miscellaneous
Article 36: The State Drug Administration is responsible for the interpretation of this Practice.
Article 37: This Practice becomes effective on November 1, 1999.
