Specification for quality control of non clinical studies of drugs
Chapter I General Provisions
First article In order to ensure the quality of clinical safety evaluation of the non drug, guaranteeing public safety, according to the "Peoples Republic of China" Drug Administration Law "Peoples Republic of China Drug Administration Law Implementing Regulations", the enactment of this specification.
Second article This specification applies to non clinical safety evaluation studies of drugs for registration of drugs. The relevant activities of non clinical safety evaluation of drugs should be observed in accordance with this regulation. Preclinical studies related to other drugs for registration purposes are carried out in accordance with this specification.
Third article The study of non clinical safety evaluation of drugs is the basic work of drug research and development, and should ensure the behavior specification, data is true, accurate and complete.
The second chapter, terminology and its definition
Fourth article What is the meaning of the following terms in this code:
(a) non clinical research quality management standards, requirements of the whole process of quality management refers to the operation and management of research institutions for non clinical safety evaluation and non clinical safety evaluation and research project test plan design, organization, implementation, inspection, record, archive and report etc..
(two) evaluation of clinical safety, for drug safety evaluation and test by experiment system under laboratory conditions, including the safety pharmacology experiment, single dose toxicity, repeated dose toxicity test, toxicity test, genetic toxicity test and carcinogenicity test, toxicity test, local immunity the original test, dependence test, toxicokinetic test and evaluation of drug safety tests.
(three) research institutions for non clinical safety evaluation (hereinafter referred to as research institutions), that has carried out non clinical safety evaluation and research personnel, facilities and equipment and quality management system and conditions, engaged in drug non clinical safety evaluation and research unit.
(four) multi site research refers to the research projects which are carried out jointly in different research institutions or in the same research institution. The research project has only one test plan, special person in charge, the formation of a summary report, is responsible for the special research institutions and the experimental system in which the "main places or places of study, other research institutions responsible for the implementation of work or place" research field".
(five) the person in charge of the organization refers to the personnel who are responsible for the organization and operation of a research institution in accordance with the requirements of this code.
(six) the "person in charge" refers to the person who is responsible for organizing the implementation of an experiment in nonclinical safety evaluation studies.
(seven) principal researchers refer to persons in a multi site study who represent subjects who perform trials at sub research sites.
(eight) the entrusting party refers to the unit or individual that commissioned the research institution to carry out the study of non clinical safety evaluation.
(nine) the quality assurance department, to fulfill the relevant non clinical safety evaluation and research work of quality assurance departments research institutions, responsible for the inspection of each study and related facilities, equipment, personnel, methods, and operation records, to ensure compliance with the requirements of this specification work.
(ten) standard operating procedures refer to the procedural documents that describe the operation, management and test operation of the research institution.
(eleven) master plan refers to information gathered within the research organization to help control workload and track the research process.
(twelve) a test plan is a document that describes in detail the purpose of the study and the design of the test, including its change documents.
(thirteen) the change of the test plan refers to the modifications made to the contents of the test program after the approval of the test program.
(fourteen) deviation from an unintended or unforeseen condition, which does not conform to the requirements of the test program or standard operating procedures.
(fifteen) the experimental system refers to the animals, plants, microorganisms, organs, tissues, cells, genes, etc. used in the study of nonclinical safety assessment.
(sixteen) subject matter / test substance is a substance that is evaluated for safety through nonclinical studies.
(seventeen) a reference substance; a substance to be compared with a subject.
(eighteen) a solvent used to mix, disperse, or dissolve a sample or reference substance in order to give it to a media substance in the experimental system.
(nineteen) batch number means a set of numbers, letters, or numbers used to identify a batch to ensure traceability of the subject or reference.
(twenty) to obtain original data, in the first time, the original records of the research work and relevant documents or materials, or certified copies, including work records, photographs, microfilm, computer print materials, magnetic carrier, equipment data etc..
(twenty-one) a specimen derived from an experimental system and used for analysis, determination, or preservation of materials.
(twenty-two) the date of commencement of the study, which refers to the date of signature and approval of the pilot scheme by the person in charge.
(twenty-three) the date of completion of the study, which refers to the date of signature and approval of the final report by the person in charge.
(twenty-four) a computerized system that refers to a set of hardware and software controlled by a computer to perform one or a set of specific functions.
(twenty-five) validation refers to activities that demonstrate that a process can consistently meet expected objectives and quality attributes.
(twenty-six) electronic data, texts, charts and data, voice and image information of any electronic form, to complete its establishment, modification, maintenance, backup, archiving, retrieval or distributed by computer system.
(twenty-seven) electronic signature, a group of computer code used to replace handwritten signature, which has the same legal effect as handwritten signature.
(twenty-eight) inspection trajectory, refers to the system activities were recorded continuously according to the time order, the recording process, to rebuild the review system activities, activities and operating environment in order to grasp the changes may affect the final result.
(twenty-nine) peer review refers to a review procedure used to ensure data quality, reviewed by other experts and scholars in the same field, as well as on the investigators research plans or results.
The third chapter, organization and personnel
Fifth article The research institution shall establish a sound organization and management system with the head of the organization, the quality assurance department and the corresponding staff members.
Sixth article The staff of a research institution shall meet at least the following requirements:
(I) having received educational or professional training related to the job, and having the knowledge, experience and business ability required for the job;
(two) mastering the requirements related to the work in this specification and strictly implementing them;
(three) strictly enforce the standard operating procedures relating to the work undertaken, and shall keep a record of the deviations from the standard operating procedures in the study and report in writing to the principal or principal investigator;
(four) the strict implementation of test scheme, timely, accurately and clearly record the raw data, and the quality of the original data for deviation from the test plan research occurs in the situation should be promptly recorded and to the special person in charge or of a written report;
(five) to take the necessary protective measures according to the needs of jobs, minimizing the security risks of staff, while ensuring the test, the control and the experimental system is not affected by the chemical and biological or radioactive contamination;
(six) regular physical examination and health problems, in order to ensure the quality of the study, should avoid participation in the work that may affect research.
Seventh article The head of the organization is fully responsible for the operation and management of the research institution, and shall perform the following duties at least:
(1) ensuring that the operation and management of the research institutions meet the requirements of this specification;
(two) ensure that the research institutes have sufficient quantity, qualified personnel, and facilities, instruments, equipment and materials that meet the requirements of this specification, so as to ensure the timely and normal operation of the research projects;
(three) ensure the establishment of staff education background, work experience, training, job description and other information, and archive, save, update in a timely manner;
(four) to ensure that staff members clearly understand their responsibilities and responsibilities, and, if necessary, provide training related to these tasks;
(five) ensure the establishment of standard operating procedures in accordance with the requirements of the appropriate technology, and to ensure that the staff strictly comply with the standard operating procedures, all new and revised standard operating procedures required by the agency for approval shall be valid, the original file save as file;
(six) ensure that quality assurance plans are established within the research institutes, implemented by independent quality assurance personnel and ensure that they perform quality assurance duties as required by this specification;
(seven) ensure master schedule and timely update, ensure regular archiving of master schedule preservation, master schedule should include at least of name or code, the test name or code, experimental system, research types, research status, start time, topic, name of the person in charge of the entrusting party involved place to study, should also include research establishments and principal investigator of the information, so as to grasp the progress and the allocation of resources in all research institutions for non clinical safety evaluation and research work;
(eight) to ensure that each pilot is appointed a person with the appropriate qualifications, experience and training experience before the start of the study, and that the replacement of the person in charge shall be carried out in accordance with the prescribed procedures and recorded;
(nine) as the research site responsible person, in many places the case, a main research should have appropriate qualifications, experience and training of the designated person responsible for testing the replacement of the main researchers should be in accordance with the prescribed procedures and to record;
(ten) ensure that the quality assurance departments reports are dealt with promptly and take necessary corrective and preventive actions;
(eleven) ensure that the subject and reference products have the necessary quality characteristics information, and appoint a special person to be responsible for the management of the subject matter and reference material;
(twelve) assign a special person to be responsible for the management of archives;
(thirteen) ensure that computerized systems are applicable to their use and are validated, used and maintained in accordance with the requirements of this specification;
(fourteen) ensure that the research institutes are required to participate in necessary laboratory testing, proficiency testing and comparison activities according to the research requirements;
(fifteen) sign a written contract with the entrusting party to clarify the responsibilities of each party;
(sixteen) in a multi place study, the head of the organization in the study site shall fulfil all of the responsibilities mentioned above except as required under subsection (eight).
Eighth article The research institution shall set up an independent quality assurance department to check the implementation of this specification so as to ensure that the operation and management of the study meet the requirements of this specification.
The duties of a quality assurance personnel shall include at least the following aspects:
(1) to keep copies of the test program and test program under implementation, a copy of the current standard operating procedures, and a copy of the master plan in good time;
(two) to review whether the test scheme meets the requirements of this regulation, the examination work shall be recorded and filed;
(three) according to the research content and duration of making inspection plans, conduct inspections of each study, to confirm that all studies are conducted in accordance with the requirements of this specification, and record the inspection content, found problems and suggestions;
(four) regularly check the operation and management of the research institutions, in order to confirm the work of the research institutions according to the requirements of this specification;
(five) any problems found in the inspection and the suggestions made shall be checked, checked and verified;
(six) in writing in a timely manner to the responsible person or special reports to the person in charge of inspection results, for the multi site study, the person in charge of personnel to ensure the main research findings report to its research institutions and institutions of quality research sites, as well as the main research sites, special agencies responsible person in charge and quality ensure staff;
(seven) review summary report, signed quality assurance statement, define the content and time of examination and inspection inspection statements, report to the responsible person, the person in charge, the main research topics (multi site case study) to confirm the exact date, a complete description of the research methods and procedures, the original. The data reflect the true research;
(eight) review all current standard operating procedures within the research organization and participate in the formulation and revision of standard operating procedures.
Ninth article The person in charge of the study shall be responsible for the implementation and summary of the study, and shall at least include the following aspects:
(1) to approve the change of the test plan and the test plan by signing the name and date, and ensure that the quality assurance personnel and the test personnel obtain the copy of the test plan and the change of the test plan in time;
(two) timely put forward relevant suggestions for revising and adding standard operating procedures;
(three) ensure the test personnel to understand the test plan and test plan changes, grasp the corresponding standard procedures, and comply with its requirements, ensure the timely recording of any deviation from the test plan or standard operating procedures for the research in place, and to evaluate the effects of these conditions on the research data of the quality and integrity of the cause, when necessary we should take corrective measures;
(four) mastering the progress of research and ensuring the timely, accurate and complete record of the original data;
(five) timely handle the problems raised by the quality assurance department to ensure that the research meets the requirements of this specification;
(six) ensure that the instruments, equipment, and computerized systems used in the study are validated or validated and in a state of application;
(seven) ensure that the subjects and reference preparations in the study were adequately tested to ensure that their stability, concentration, or uniformity were consistent with the requirements of the study;
(eight) ensure that the final report reflects the raw data in a true and complete manner and approves the name and date of approval in the summary report;
(nine) ensure that all materials related to the study are archived and documented, such as test plans, summary reports, raw data, specimens, retention materials, samples, etc.;
(ten) in the multi site research, ensure that the pilot program and summary report clearly explain the main researchers involved, the main research sites and sub research sites, respectively, to undertake tasks;
(eleven) to ensure that part of the experimental work undertaken by the principal investigator meets the requirements of this specification in multiple site studies.
The fourth chapter facilities
Tenth article The research institution shall establish corresponding facilities in accordance with the needs of the study on nonclinical safety evaluation, and ensure that the environmental conditions of the facilities meet the needs of the work. Various facilities shall be reasonably arranged, functioning normally, and shall have necessary functional divisions and partitions, so as to effectively avoid possible interference with the study.
Eleventh article Equipped with animal facilities to meet the needs of the study, and can adjust the temperature, humidity, air cleanliness, ventilation and lighting according to the requirements. The conditions of the animal facilities shall be in conformity with the experimental animal classes used, and the layout shall be reasonable so as to avoid mutual pollution between the experimental system, the subject matter, and the waste.
Animal facilities shall meet the following requirements:
(1) different species of experimental animals can be effectively isolated;
(two) experimental animals of the same species and different studies should be able to be effectively isolated to prevent possible cross interference between different subjects and reference products;
(three) quarantine and disease testing of experimental animals, isolation and treatment facilities for animals;
(four) when the subjects or control samples containing volatile, radioactive or biological hazards such as material, this study provides effective isolation, the animal facilities should be research institutions, to avoid adverse impacts on other research;
(five) equipped with cleaning and disinfection facilities;
(six) the storage facilities for feed, bedding, cage and other experimental articles, and perishable articles shall be properly kept.
Twelfth article The facilities associated with the subject matter and the reference shall meet the following requirements:
(a) have received, tested and controlled product storage, preparation and preparation preparations keeping independent room or area, and take the necessary measures, in order to avoid the test and control of cross contamination or confusion, related facilities should meet the needs of different subjects and control for the environment storage temperature, humidity, illumination and other requirements, to ensure that the test and control products remained stable in the period of validity;
(two) the storage areas of the subject and reference substances and their preparations should be effectively isolated from the areas in which the experimental system is located to prevent adverse effects on the study;
(three) the storage areas of the subject and reference substances and their preparations shall have the necessary safety measures to ensure the safety of the subject matter and the reference substance and its preparations during storage and storage.
Thirteenth article The facilities for archival storage shall meet the following requirements:
(1) to prevent personnel from unauthorized access to records;
(two) computerized filing facilities have security measures to prevent unauthorized access and virus protection;
(three) equipped with necessary equipment according to the storage conditions of the archives, effectively control fire, water, insects, rats, power outages and other hazards;
(four) adequate monitoring of archives storage facilities with regulatory requirements for specific environmental conditions.
Fourteenth article A research institution shall have facilities for collecting and disposing of experimental wastes, and shall have conditions for temporary storage or transshipment for wastes not disposed of within the research institution.
The fifth chapter: instrument and experiment material
Fifteenth article Research institutions should be based on the need of research work with the appropriate equipment, its performance should meet the purpose, location and reasonable, regular cleaning, maintenance, testing, calibration, validation or verification, to ensure that its performance meets the requirements.
Sixteenth article A computerized system (or equipment containing a computer system) used for data acquisition, transmission, storage, processing, archiving, etc., should be validated. The electronic data generated by the computerized system should have a complete audit trail and electronic signature to ensure the integrity and validity of the data.
Seventeenth article The equipment should have standard operating procedures detailed requirements of the use and management of the equipment, on the use of equipment, cleaning, maintenance, testing, calibration, validation or verification and maintenance should be recorded and archived.
Eighteenth article The use and management of test objects and reference materials shall meet the following requirements:
(a) test and control should be taken care of, have perfect reception, registration and distribution procedures, each batch of test and control product batch number, stability, content or concentration, purity and other physicochemical properties should be recorded, the control product is commercially available, can be used the label or manual content;
(two) the storage conditions should be consistent with the specific requirements of storage test and control products, storage containers with labels in storage, distribution and use shall indicate the name, abbreviation, name, code or Chemical Abstracts (CAS) registration number, batch number, concentration or content, validity period and storage conditions and other information;
(three) the subject and reference shall be protected from contamination or deterioration during distribution and shall record the date and quantity of distribution and return;
(four) when the test and control products and solvent, should ensure the stability analysis, the test and reference preparation is stable and regular determination of concentration, homogeneity in mixture preparation test and control products;
(five) around the study of more than the duration of the test, the use of each batch test and control articles shall be collected enough samples to prepare for the needs of re analysis, and after the completion of the study as to the archive file.
Nineteenth article Laboratory reagents and solutions shall be labeled with the name, concentration, storage conditions, date of preparation and validity. Spoilage or expired reagents and solutions shall not be used in the study.
The sixth chapter is experimental system
Twentieth article The management of laboratory animals shall meet the following requirements:
(1) the use of laboratory animals shall be concerned with animal welfare, following the principles of "reduction, substitution and optimization", and the approval of the animal ethics committee before the implementation of the pilot scheme.
(two) source, a detailed record of the experimental animal to date, quantity, health information; laboratory animal facilities should be carried out into the new isolation and quarantine, to ensure its health conditions meet the requirements of research; research process of experimental animal such as sickness, should be timely isolation and treatment measures of treatment, diagnosis and the corresponding treatment should be recorded.
(three) the experimental animals should have enough time to adapt to the test environment before the first test or control substance is given.
(four) the experimental animals should have suitable individual identification marks to avoid confusion among different individuals of the experimental animals when they are removed or moved.
(five) the environment and related equipment used by laboratory animals should be regularly cleaned and disinfected to keep hygienic. The cleaning agents, disinfectants and pesticides used in animal rearing shall not affect the result of the test, and the name, concentration, method of use and time of use shall be recorded in detail.
(six) feed, bedding and drinking water for laboratory animals shall be inspected periodically to ensure that they are in line with nutritional or pollution control standards, and that the test results shall be archived as raw data.
Twenty-first article The number of sources, other than the experimental animal experiment system (volume), quality attributes, receiving date should be recorded in detail, and the preservation and operation under suitable environmental conditions; before use shall carry out the applicability evaluation, such as quality problems should be given appropriate treatment and re evaluate their applicability.
The seventh chapter standard operating procedures
Twenty-second article A research institution shall formulate standard operating procedures suitable for its operations to ensure data reliability. Publicly published textbooks, documents, user manuals and other technical data produced by manufacturers can be used as a supplement to standard operating procedures. Standard operating procedures that need to be formulated include, but are not limited to, the following aspects:
(1) establishment, revision and management of standard operating procedures;
(two) quality assurance procedure;
(three) acceptance, identification, preservation, treatment, preparation, sampling and analysis of test objects and reference products;
(four) preparation of animal room and laboratory and regulation of environmental factors;
(five) the maintenance, maintenance, calibration, use and management of laboratory facilities and instruments;
(six) computer system security, verification, use, management, change control, and backup;
(seven) receiving, quarantine, numbering and feeding management of laboratory animals;
(eight) the observation record and experimental operation of the experimental animals;
(nine) collection of various test samples, inspection and measurement of various indicators and other operating techniques;
(ten) the inspection and treatment of dying or dead experimental animals;
(eleven) the anatomy and histopathology of the experimental animals;
(twelve) collection, numbering and testing of specimens;
(thirteen) management and processing of all kinds of test data;
(fourteen) health management system for staff;
(fifteen) treatment of carcasses and other wastes of laboratory animals.
Twenty-third article Standard operating procedures and their revised versions shall be effective only after examination by the quality assurance personnel and approval by the person in charge of the institution. The standard operating procedures for failure shall be destroyed in time in addition to the original filing and preservation of the original documents.
Twenty-fourth article The standards for the establishment, revision, approval, effective date and distribution and destruction of standard operating procedures shall be recorded and archived.
Twenty-fifth article The distribution and storage of standard operating procedures shall ensure the ease of use of staff.
The eighth chapter is the implementation of the research work
Twenty-sixth article Each test shall have a name or code name and shall be used in conjunction with the relevant documents, data and test records. All the samples collected in the test shall be marked with the name or code number, sample number and date of collection.
Twenty-seventh article Before the start of each study, shall draw up a test plan, by the quality assurance department to conforms to the requirements of this specification of the examination and approval of the person in charge of the project shall be valid after the approval of the person in charge of the project, as of the date of the start date of the. Acceptance of the commissioned study, the pilot program should be approved by the commission.
Twenty-eighth article When the test plan needs to be modified, the alteration of the test plan shall be carried out and approved by the quality assurance department and approved by the person in charge of the project. The change of the test plan shall include the content, reason and date of the change, and be saved together with the original test plan. When the study is cancelled or terminated, the cause of the cancellation or termination shall be explained and the method of termination shall be explained.
Twenty-ninth article The main contents of the test plan should include:
(1) the name or code number of the study; the purpose of the study;
(two) the name, address and contact information of all the research institutions and clients involved in the study;
(three) special manager and main staff to participate in the name of the test, many places should work on site, clearly responsible for each part of the experimental work of the name and bear;
(four) the experimental standards, technical guidelines or literature, and the non clinical research quality management standards for the study;
(five) the name, abbreviation, code number, batch number, stability, concentration, content, purity and classification of the tested substance and reference substance, and their physical and chemical properties and biological characteristics;
(six) the name, batch number, physical and chemical properties, or biological characteristics of solvents, emulsifiers, and other mediums used in the study;
(seven) experimental system and selection reasons;
(eight) the species, system, quantity, age, sex, weight, range, origin, grade and other relevant information of the experimental system;
(nine) the identification method of experimental system;
(ten) the environmental conditions of the test;
(eleven) name, code number, source number, batch number and main control index of feed, bedding, drinking water, etc.;
(twelve) the routes, methods, dosage, frequency, duration of drug use and reasons for selection of subjects and controls;
(thirteen) detection methods and frequency of various indexes;
(fourteen) data statistic processing method;
(fifteen) the place of preservation of the archives.
Thirtieth article In the study, the staff shall strictly execute the test plan and the corresponding standard operation procedures, record all the data from experiment, and timely, direct and accurate, clear and not easy to eliminate, at the same time must indicate the recording date, record signature. When the recorded data needs to be modified, the original record shall be kept legible, and the reasons for the revision and the date of revision and the signature of the modifier shall be indicated. The generation and modification of electronic data shall meet the above requirements.
Any deviation from the test plan and standard operating procedures of the process, should be timely record and report to the person in charge of the main research topics, in many places the case should also be reported to be responsible for the test. The principal or principal investigator should assess the impact of the reliability of the research data and take corrective action when necessary.
Thirty-first article For peer-reviewed reviews, the peer-reviewed plan, management, documentation and reporting should meet the following requirements:
(a) the peer-reviewed work of pathology should be described in detail in the pilot program or in the change of the experimental program;
(two) the process of Pathology, peer review, and review of specimens and documents should be documented and traceable;
(three) to formulate procedures for the treatment of disagreements between peer-reviewed pathologists and special pathologists;
(four) when the results of the peer review and the results of the special pathologists diagnosis have changed significantly, they should be discussed in the summary report;
(five) after the peer review is completed, a peer-reviewed statement will be issued by the peer-reviewed pathologist and signed to indicate the date;
(six) in the summary report, the names, qualifications and units of the peer-reviewed pathologists should be noted.
Thirty-second article All studies should have a summary report. The final report shall be examined by the quality assurance department, which shall be signed and approved by the person in charge of the subject matter, and the approval date shall be the date of completion of the study. When the study is cancelled or terminated, the person in charge shall write a brief test report.
Thirty-third article The main contents of the summary report should include:
(1) the name, code number and research purpose of the study;
(two) the name, address and contact information of all the research institutions and clients involved in the study;
(three) the experimental standards, technical guidelines or literature, and the non clinical research quality management standards for the study;
(four) study the date of start and stop;
(five) the person in charge of the project, the principal investigator and the names of the principal participants and the work to be undertaken;
(six) the name, subject matter and control the abbreviated name, code, batch number, stability, content, concentration, purity, composition and other characteristics, quality test and control results of preparation, for the study of solvent, emulsifier and other medium name, batch number, related physical and chemical the nature or biological characteristics;
(seven) the species, Department, quantity, age, sex, weight range, origin, certificate number of experimental animals, date of acceptance and feeding condition of the experimental system;
(eight) the route, dose, method, frequency and duration of administration of the subjects and the reference substance;
(nine) dose design basis of subject matter and reference substance;
(ten) detection methods and frequency of various indexes;
(eleven) statistical methods used in the analysis of data;
(twelve) results and conclusions;
(thirteen) the place of preservation of the archives;
(fourteen) all the conditions that affect the conformity of this specification and the reliability of the data studied;
(fifteen) quality assurance statements signed by the quality assurance department;
(sixteen) statements signed by the principal responsible for the study of statements in conformity with this code;
(seventeen) in the case of multi site research, it should also include reports of the relevant test sections signed by the principal investigator on the name and date.
Thirty-fourth article The summary report is approved, you need to modify or supplement, it shall be amended or supplemented by the revised file form, a detailed description of the revision or supplement the content, reason, and by the quality assurance department, the project signed by the person responsible for the name and date of approval. In order to meet the requirements of the registration declaration, the revision of the form of the summary report does not belong to the revision of the summary report.
The ninth chapter is quality assurance
Thirty-fifth article The research institutes should ensure the independence of quality assurance work. Quality assurance personnel may not participate in the implementation of specific research, or undertake other tasks that may affect the quality assurance independence of their work.
Thirty-sixth article The quality assurance department shall establish a written quality assurance plan and specify the executive personnel to ensure that the research work of the research institutes meets the requirements of this specification.
Thirty-seventh article The quality assurance department shall formulate standards of quality assurance activities and corresponding procedures including quality assurance, quality assurance department operation, formulate plans and inspection of the implementation of the plan, record and report, and related data archiving and preservation etc..
Thirty-eighth article Quality assurance inspection can be divided into three types of inspection:
(a) based on research inspections, such inspections are generally based on the schedule and critical phases of a particular research project;
(two) based on facility inspections, such inspections are generally conducted on a general facility and activity (installation, support services, computer systems, training, environmental monitoring, maintenance, and calibration) within the research facility;
(three) process based inspection, which is generally not based on specific research projects, but is based on a repetitive process or process.
The quality assurance inspection shall be documented and reported, and shall be submitted to the regulatory authorities for inspection when necessary.
Thirty-ninth article The quality assurance department shall review all research projects in compliance with this specification and issue a quality assurance statement. The quality assurance statement shall contain complete research identification information, relevant quality assurance inspection activities, and the date and stage of the report. Any modification or supplement to the completed summary report shall be reviewed and signed.
Fortieth article Quality assurance personnel in quality assurance signed statement before, shall confirm the test meets the requirements of this specification, compliance test plan and standard operating procedures, to confirm the report accurately and reliably reflect the original data.
The tenth chapter is the data file
Forty-first article The person in charge of project should ensure that all of the data, including the test plan of the original, original data and samples, the relevant test report, sample from various original documents and related research samples and control samples, the summary report, in the process of study completion or timely filing, no longer than two weeks. According to the standard procedures after finishing requirements, as the research archives to be saved.
Forty-second article When the study is cancelled or terminated, the person in charge of the subject shall file the above-mentioned research materials as archives for archival preservation.
Forty-third article Other information does not belong to the research category of archives, including the quality assurance department all the inspection record and report, schedule, staff education background, work experience, training and qualifications, job description to materials, equipment and computer system related information, research institutions and personnel structure, all files Standard Practice for the history documents, monitoring data and other environmental conditions, shall be regularly filing. The specific filing time limit and the responsible personnel should be clearly defined in the standard operating procedures.
Forty-fourth article Records shall be managed by the person designated by the person in charge of the organization in accordance with the requirements of the standard operating procedures, and shall be responsible for their integrity. At the same time, the archives index shall be established to facilitate retrieval. Access to archive facilities requires authorization. The materials placed or taken out in the archives shall be accurately recorded.
Forty-fifth article The storage period of the archives shall meet the following requirements:
(1) for the study of registration materials, the filing period shall be at least five years after the listing of the drugs;
(two) is not used to study the application materials (such as termination of registration), at least five years after the filing for approval on the summary report;
(three) other information that does not belong to the category of research archives shall be stored for at least ten years after its creation.
Forty-sixth article At the expiration of the archival custody, the necessary treatment, including destruction, may be adopted for the files, and the measures and procedures adopted shall be carried out in accordance with standard operating procedures and have accurate records. Where possible, the processing of the research archives should be approved by the entrusting party.
Forty-seventh article For quality change files, such as tissues, organs, electron microscopy specimens, blood smears, test objects and reference samples, should be effectively evaluated for retention period. For electronic data, the standard operating procedures for data backup and recovery shall be established to ensure its safety, integrity and readability, and the storage period shall comply with the requirements of the forty-fifth article of this specification.
Forty-eighth article Research institutions for business reasons no longer carry out the requirements of this specification, and there is no legitimate successor, the custody of the archives shall be transferred to the client or archival facilities designated by the entrusting party archives facilities for safekeeping, until the final file retention period. The archives facilities for receiving and transferring archives shall strictly comply with the requirements of this regulation, and shall effectively manage the archives they receive and be subject to the supervision of the regulatory authorities.
The eleventh chapter is the entrusting party
Forty-ninth article As the initiator of the study and the declaration of the result of the study, the entrusting party shall be responsible for the research materials used for the declaration of registration, and shall bear the following responsibilities:
(1) to understand the requirements of this regulation, in particular the responsibilities of the head of the organization, the person in charge of the project, and the principal investigator;
(two) commissioned the evaluation of non clinical safety research, through investigation and other methods to assess the research institutions, to confirm that it can comply with the requirements of this specification for research;
(three) before the start of the study, the test plan should be approved by the entrusting party;
(four) inform the research institutes of the relevant safety information of the subjects and the reference products to ensure that the research institutes take necessary protective measures to avoid the potential risks of personal health and environmental safety;
(five) the characteristics of the test and control samples were detected of the work can be done by the entrusting party and the entrusted institution or laboratory, the entrusting party shall ensure the supply of the subject matter, characteristic information is true and accurate control;
(six) ensure that the study is carried out in accordance with the requirements of this code.
The twelfth chapter is the supplementary provisions
Fiftieth article This Regulation shall come into force on September 1, 2017, and the regulation on the quality control of non clinical research on Drugs issued in August 6, 2003 (No. second of the State Food and Drug Administration) shall be abolished at the same time.