Veterinary medicine, natural medicine, technical guidelines for clinical trials


Ministry of Agriculture Bulletin No. 1596
To strengthen veterinary research guidance, regulate veterinary research activities, improve the level of veterinary research, according to the "Veterinary Regulations", "registered veterinary drugs" and "the new veterinary drug development of a management approach", my Ministry has developed "veterinary medicine, natural medicine, clinical trials, technical guidelines" and five guiding principles for veterinary research techniques, hereby release, please refer to the implementation.

Notice is hereby.

Attachment: veterinary medicine, natural medicine, clinical trials, technical guidelines, five technical guidelines

Veterinary medicine, natural medicine, clinical trials, technical guidelines, etc.
Five technical guidelines

Veterinary medicine, natural medicine, technical guidelines for clinical trials

First, an overview
Clinical trial is under controlled conditions in certain scientific investigation and evaluation of target animal veterinary treatment or prevention of specific diseases or syndromes of the efficacy and safety of the process. Adequate and reliable data to prove the clinical studies reporting the safety and efficacy of products based on.
Veterinary medicine, natural medicine, the development process, compared with Western veterinary medicine, both the same point, also has its particularity. First, the discovery of Chinese medicine or standing problems, and more directly from the clinical observation and experience that prompts; Second, the internal components of traditional Chinese medicine and complexity of the interactions leading to the pharmaceutical, pharmacodynamic and toxicological studies face more difficulties; Furthermore, research findings influence the objectivity and accuracy factors were also relatively high. Therefore, the clinical trial efficacy and safety of traditional Chinese medicine assessment with more
Plus special significance.
In order to ensure that veterinary medicine, natural medicine really reliable conclusions of clinical trials, standardized clinical research conduct, according to the "registered veterinary drugs" and "the development of new veterinary drug management approach" to develop the guidelines. The guidelines are intended to explain veterinary medicine, natural medicine, clinical trial design and implementation process should take the general principles and key issues for veterinary medicine, natural medicine, new product development to provide technical guidance.
Second, veterinary medicine, natural medicine, the basic content of clinical trials
According to the different test purposes, veterinary medicine, natural medicine, clinical trials generally include target animal safety trials, experimental clinical trials and expanded clinical trials. Application for registration of new veterinary drugs should be classified according to registration requirements and specific needs of the situation, for one or more clinical trials.
(A) the target animal safety test
Target animal safety test is to observe the effect of different doses on the target animal veterinary subjects after the effective role to the toxic effects from even the lethal effect of the dynamic process of change. The test subjects to examine the use of veterinary drugs in target animal safety and safe dose range, dosage regimen for further clinical trials provide the basis for the formulation.
(B) experimental clinical trials
Experimental clinical trials is consistent with the target indication of the onset of natural or artificial test cases for the study animals, veterinary subjects confirmed the target of target animal efficacy and safety of indications, and clinical trials to expand the reasonable dose and provide a basis to determine the dosage regimen. Experimental clinical trials of new animal drugs intended to confirm the clinical efficacy, to ensure the objectivity and accuracy of research findings.
(C) the expansion of clinical trials
Expand the subjects of clinical trials is the clinical efficacy and safety of veterinary drugs further validation of the general incidence of the animal should be a natural object of study.
Third, veterinary medicine, natural medicine, clinical trials of common requirements
(A) the theory as a guide in the veterinary
Medicine for the prevention of animal diseases and improve production performance has a long history and has formed a complete theoretical system. Based on the laws of life activities and the overall concept of genetic disease, the veterinary treatment of the disease is usually based on by adjusting the organs, meridians, blood and other body functions to establish the steady-state environment, maintain the air out of the body movements, functional activities orderly, increase the body's ability to adapt to the external environment. Therefore, the characteristics and advantages of Chinese medicine "overall adjustment", which chemicals "allopathy" are essentially different.
Veterinary medicine, natural medicine, clinical trials assessing treatment outcome indicators established, not only proceed from a simple biomedical model, focusing only on external pathogenic factors, or biological changes in the pathogenesis of micro-and local signs, but from the overall level of on the selection and functional status, syndromes associated multidimensional outcome measures. In traditional Chinese medicine clinical trial design, it will be positioned on the treatment efficacy of a disease or part of the cause of direct confrontation, or shortly after treatment only to the few indicators of mortality, the study, significantly
However, it is unreasonable.
Indication of the efficacy of positioning, in addition to the treatment or prevention, but also fully positioned level with the use of such adjuvant therapy, remission of disease or certain types of drugs and other synergies.
(B) The trial design principles
Veterinary medicine, natural medicine, clinical trials should be designed to follow the randomized, controlled, and the principle of repetition.
1. Randomly
Random means each of the animals tested the principle of equality of opportunity randomly assigned to experimental and control groups, the purpose is to make the group of non-equilibrium conditions of the same experimental factors, in order to eliminate non-experimental factors on the test results.
2. Control principle
Control is the basis of comparison subjects to evaluate the safety and efficacy of veterinary drugs, we must have comparable control. Reasonable to set the control to eliminate or reduce the experimental error, visually judge the changes before and after treatment of animal subjects (such as signs, symptoms, detection of indicators of change and death, recurrence, adverse reactions, etc.) is a veterinary subjects, and not by other factors (such as the development of the disease or the body's natural changes in the environment) caused.
Test group and control group animals, groups should be from the same subjects, the two basic conditions should be similar. Experimental group and control group the only difference is that the test group subjects received veterinary treatment, while the control group received no drug treatment or control veterinary medicine.
3. The principle of repetition
Experimental group and control group should be appropriate sample size is too small or too large has its drawbacks. Sample size is too small, test performance is low, resulting in general have been unable to test out the differences, but not sample the bigger the better. If the sample size increases indefinitely, will undoubtedly increase the experimental scale, to extend the test of time, waste of manpower and material resources, but also may introduce additional confounding factors.
Determine sample size (number of cases) no more than a few aspects of the factors. First, the sample included with the degree of individual differences. Greater differences between individuals, the observed number of cases required more; the other hand, if the small differences between individuals, the required number of cases observed on less. Secondly, with the effect of differences between the groups related to the degree. The greater the effect of differences between the groups, the less the required number of cases observed; the contrary, the observed number of cases needed more. Furthermore, with the nature of statistics. To count data or ranked data for comparison between groups effect, the required sample size, larger than the measurement data. In addition, the stringency of statistical inference (that is the basis of significance tests carried out by statistical inference, the conclusions consistent with the degree of authenticity) also affects the size of the sample content.
In general, the clinical trial sample size should be at least meet the minimum requirements of clinical trials the number of cases (see Table 1 and Table 2), while the actual case, the request should be based on scientific and statistical flexibility to determine the sample size.

Table 1 target animal safety trials the minimum number of animals in each group

Number of animal species animal subjects

Horses, cattle and other large animals, 5
Sheep, pigs and other animals in the 8
Rabbit, mink, fox and other small animals 10
Dogs, cats and other pets 8
Poultry 15

Table 2 Clinical trials of experimental minimum number of animals in each group

Number of animal species animal subjects

Natural cases of the disease model

Horses, cattle and other large animals, 105
Sheep, pigs and other animals in 2010
Rabbit, mink, fox and other small animals 20 15
Dogs, cats and other pets 15 10
Poultry 30 15


Table 3 clinical trials to expand the minimum number of animals in each group

Number of animal species animal subjects

Mass model of sporadic cases

Horses, cattle and other large animals 20 30
Sheep, pigs and other animals in 3050
Rabbit, mink, fox and other small animals 30 50
Dogs, cats and other pets 20 30
Poultry 50 300


(C) the program
1. Test program development and approval
Clinical trials should develop practical testing program. Test program undertake clinical trials by the applicant and was jointly developed in consultation and stamped signature, the applicant reported that the provincial veterinary administrative department for approval before implementation. Need to use a class of pathogenic microorganisms, it should be in accordance with "pathogenic microbiology laboratory bio-safety regulations" and "highly pathogenic animal pathogens laboratory bio-safety approval," and so the relevant provisions, the Ministry of Agriculture to carry out examination and approval procedures. Clinical trial approval, the approval shall be effective within the time. Clinical trials should be in accordance with the approved clinical trial program.
In general, clinical trials program should include the following: (1) title and purpose of clinical trials; (2) clinical trials unit and the main person in charge to bear; (3) test sites; (4) test the progress and expected completion time; (5) clinical trials with use of veterinary drugs and veterinary control; (6) case selection or manual basis and methods of disease; (7) experimental design; (8) Main Outcome Measures choice; (9) Data processing and statistics; (10) evaluation standard; (11) case record form.
2. Veterinary subjects
Under normal circumstances, veterinary subjects, including clinical trials with the use of veterinary drugs and veterinary control.
Clinical trials with veterinary drugs should be tested or listed in the product, its content, specifications, trial batch, trial date, expiry date, pilot or production company name and other information should be clear and should be marked "for clinical trials," the words .
With veterinary drugs should be used against legitimate products, options, should follow the same comparable, recognized effective principles. In the test program and the report should clarify the basis for selection against veterinary drugs, both in function and indication of the comparability analysis, and clearly their common name, content, size, lot number, manufacturer, validity and quality standards Recommended Dosage and so on. Way to control the use of drugs, usage, dosage requirements and quality standards should be consistent.
Controlled clinical trials with the use of veterinary drugs and veterinary inspection required by the provincial veterinary laboratories, inspection before qualifying for clinical trials.
3. Bacteria (viruses, worms) species
Incidence of the use of artificial bacteria (viruses, worms) species should be clear, generally requires the use of standard strains have been recognized. Using other sources of bacteria (viruses, worms) species, should provide detailed background information, including sources of authoritative reports and identify key biological characteristics.
4. Effect of the choice of indicators
Observed effect is the right choice of indicators and make judgments based on the protection of conclusions of the study objective and accurate is crucial. The main effect indicators generally should have relevance, objectivity, accuracy, sensitivity and specificity.
Relevance of the selected indicators and research purposes are essentially linked, should be closely related to efficacy and safety, and accurately reflect the test the effects caused by veterinary drugs.
Objectivity of clinical trials should be selected with a strong objective indicators, or create on the qualitative indicators or quantitative observation system of soft targets to reduce or overcome by the researchers observed the process of bias caused by subjective factors. Ke Guanxing includes two meanings, first, the indicators themselves should have the objective characteristics, through appropriate means and methods to measure and test to be objective, and to a certain value express his observations; second refers to the measurement, observation of objectivity, that measure, the results of observations should be able to really properly
Reflect the status and extent of the field.
Accuracy, including accuracy and reliability, the former reflects the true value is close to the observed value and the extent to which observed the same phenomenon that, to achieve the same or similar results many times the same level.
Sensitivity high sensitivity observations can improve the positive rate, but should pay attention to the sensitivity caused by high false-positive results.
Specific choice of indicators should reflect the effect of specificity, other factors not susceptible to interference.
In addition, you should see a number of diseases is often manifested in the body function, metabolism, structure and other aspects of comprehensive change, the reaction of the use of veterinary drugs may also be multi-faceted, and therefore the evaluation of drug effects is essential indicators comprehensive. Generally speaking, if necessary and possible, from clinical symptoms and signs of indicators, function or metabolism, and other aspects of etiology and serological observations set to make a comprehensive can effect the determination.
5. Therapeutic efficacy.
To determine the efficacy must be objective, clear, workable standard. Efficacy levels are usually divided into cured, markedly effective, effective and ineffective. It should be noted that different diseases have different clinical course, response to drug treatment are not the same, and thus the efficacy of the classification is not to generalize.
(D) Test record
A unit responsible for all clinical trial data and the entire testing process to do a detailed record, preserve and manage in accordance with regulations, for review personnel.
(E) statistical methods
Analysis and processing of test data, generally using appropriate statistical methods. Correct use of statistical methods, statistical inference is directly related to the rational and scientific conclusions.
Clinical research statistics can be divided into measurement data and count data. Different types of data to be analyzed using different statistical methods, not to be confused.
(F) conclusions derived
Conclusion is an extrapolation based on the data, data analysis, statistical significance test, based on information from the sample and push the overall process. Conclusions to be extrapolated to study the homogeneity of the sample is based.
Conclusions derived should take into account significant differences in clinical and practical significance. If a new control measures, both clinical significance, but also statistically significant, this will be what we expect. If the comparison of efficacy, the difference of clinical significance, but not reach statistically significant level, you should consider whether the test sample is large enough.
(G) Clinical trials report
Veterinary clinical trial reports to reflect the clinical trial design, implementation, and the test results and make analysis and evaluation of the summary document, is whether the correct evaluation of veterinary important basis for clinical application.
Clinical Trials Unit issued its clinical trials should report stamped and certified, and is responsible for the authenticity of the test report. Responsible for clinical trials and major participants in the clinical trial report to be signed and bear the moral and professional liability.
A unit should be consistent with clinical trials, the Ministry of Agriculture under the relevant qualification requirements. Responsible for the new veterinary clinical trial, researchers should have veterinary qualifications and related tests for more than the required expertise and working background.
Fourth, the target animal safety trials
Should be used to test the health of target animals, the general and clinical application of the same route of administration, time interval and treatment.
The recommended clinical dose setting based on at least three dosage groups, usually 3, 5 times the dose, if necessary, set up 10-fold dose group.
Observed indicators generally include clinical signs, hematological, blood biochemical parameters, two will be so conditionally or if necessary for an autopsy and histopathological examination.
Fifth, experimental clinical trials
(A) - general principles
In the experimental design and the specific implementation process, should be strictly controlled test conditions, test results may affect the accuracy of the factors that reduce to a minimum. Ensure that each group in the same experimental test environment, and reliable isolation. Experimental groups of disposal methods should be clear, including dosage, route of administration and methods, administration time and interval, delivery period, observation time, and disposal of animals. Dose selection, setting a single dose, administered to determine the cycle should be based on pharmacodynamic and other tests and safety trials based on data. To achieve an accurate dose of science, the individual should be administered in different trials, and indeed equal.
(B) the artificial model of Syndrome disease or copy
1. Animals tested
General adoption of healthy animals. For animal feeding and management should reach a level above or management requirements of laboratory animals. Source of animal subjects, species, age, gender, weight, health, immunization, diet composition and feeding management background should be clear, the same test should be relatively consistent as possible with background animals.
2. Disease or modeling methods
Modeling human disease or in general should adopt the widely accepted methodology. New methods, new methods should explain the advantages and establish the basis, including bacteria (viruses, worms) species, drugs, artificial environment, the choice of risk factors, exposure, or the choice of route of administration, dose selection process, After the biological effects of exposure should be accompanied by research data and necessary documentation.
Should be clear, detailed description of the incidence of the methods and processes, and the incidence of success assessed.
3. Test group
Test set of each group depends on the characteristics of veterinary inspection, also if the need for effective screening dose related. General should be set no less than three doses of the experimental group (ie high, medium and low-dose group, the dose to be recommended dose) and three control groups (ie, veterinary control, positive control and negative control group).
(C) the clinical trials of natural
Natural disease when the animals as subjects, the accuracy of patient selection is essential. To this end, researchers should develop diagnostic criteria for patient selection, inclusion criteria, exclusion criteria and the case removed and off to determine the eligibility conditions for j in animal subjects, the diagnostic criteria, inclusion criteria and exclusion criteria are complementary, indivisible, with avoid selection bias.
1. Diagnostic criteria Diagnostic criteria refers to the ability to accurately diagnose a disease or syndrome criteria. Select or develop diagnostic criteria should be consistent with specific, scientific, objective and operational principles, and can be considered: (1) national standard: the government departments, national academic organizations to develop diagnostic criteria. (2) recorded in the agricultural colleges and textbooks on diagnostic criteria. (3) local academic organizations to develop diagnostic criteria. Explain the adoption of the standard diagnostic criteria should be the source or provenance. Not
With current standards or existing standards are defective, shall adopt or improve relevant diagnostic criteria. Diagnostic criteria of content, including not only the clinical diagnosis or syndrome, but also necessary pathological autopsy, physiological and biochemical detection, serology, etiological diagnosis and other data as evidence, to ensure the accuracy of patients included.
Positioned in the main medical treatment card veterinary syndromes, in addition to the theory of dialectical veterinarian, diagnosed cases of the syndrome to develop standards, in general, but also in the substance of syndromes based on the analysis, as far as possible the appropriate modern animal medical diagnostic indicators (physiological and pathological changes, serology, etiology, etc.). Some of the different sub-clinical disease type or stage, and different type, stage has its obvious clinical features, should be clearly type or in installments.
2. Case inclusion criteria
Inclusion criteria is eligible animals tested should have the condition. In a specific study, to be included in the study of objects, in addition to meet the diagnostic criteria, the researchers must also be based on specific research purposes and the feasibility of implementation, the study of other conditions are regulated. Generally include disease type, stage of disease, duration, variety, age, gender, body mass, parity and other conditions. Selected cases can come from different units of farm or veterinary clinic, but each individual animal can not have too much difference.
3. Case exclusion criteria
Exclusion criteria should not be included in the study refers to the conditions, such as certificates or other diseases while suffering from complications who have received treatment may affect the indicators of effects were observed, accompanied by observations and results of impact indicators to determine the effect of other physiological or pathological conditions (such as the reproductive cycle), and other incidental factors.
4. Case Record Form
Case record form to collect and record first-hand clinical data form. The success of clinical trials may depend on the design of case record form, fill in bad form can cause the contents of unreliable, incomplete data collection. In the case record form design, the design should be carefully controlled trials of observation, and strive to careful and detailed, clear and concise.
Researchers should ensure that any observations and found that accurate and complete record of the case record form to record on the table should be signed and dated.
5. Test group
General setting of high, medium and low-dose group and positive control group, prevention trials should be set the negative control group.
Fifth, to expand clinical trials
(A) General principles
General adoption of healthy animals or natural disease cases, the choice of cases should be precise diagnostic criteria and appropriate inclusion criteria to reduce the variety, physical, gender and other factors on test results.
(B) The trial design
1. Test group
Treatment trials generally set the recommended dose and drug control, prevention trials set the recommended dose, veterinary medicine does not deal with the control group and the control group. The recommended dose should test basis.
2. Dosage regimen
Recommended dose, administration method and such should be the standard treatment, the recommended usage of the draft specification is consistent.

Veterinary medicine, natural medicine, the principles of clinical trial report writing
First, an overview
Veterinary medicine veterinary clinical trial reports to reflect the clinical trial design, implementation, and test results of analysis, evaluation of the summary file is the correct evaluation of veterinary drugs are clinically important basis for practical value, is required for registration veterinary important technical information. Professional moral responsibility report writers, report issued by the unit liable.
Clinical trial reports not only to analyze the test results, need to pay attention to the clinical trial design, test management, test process and complete expression, the clinical effect can be made for reasonable veterinary evaluation. To clarify the scientific basis of test findings, so as a design science, management, standardized testing is only through science, clear expression, it was easy to accept the conclusion. Veterinary clinical trial report writing expression, veterinary subjects directly affecting the safety, effectiveness evaluation, therefore, test report writing methods and approaches is very important.
True and complete description of the facts, scientific and accurate analysis of data, objective and comprehensive assessment of outcome is the basic norms of the test report writing. Only reliable conclusions can withstand a real test repeated testing, and repeat the test stand is the basic feature of scientific character.
This guideline applies to veterinary medicine and natural medicine, clinical trials report writing. Chinese medicine analysis of clinical trial reports should describe the subjects and the importance of veterinary drugs in the indications, the target animal, use and other aspects of Chinese medicine characteristics.
The guiding principles of clinical trial reports only the general framework of the structure and content of elements described. As the complexity of clinical trials, reporting structure and content to be the basis of the specific conditions of appropriate adjustment, and clinical trials with increasing levels of research, clinical trials, the methods of report writing will continue to improve and perfect.
Second, clinical trials report the structure and content
(A) the report cover or title page
1. Title.
2. Clinical Trials Unit and date stamped.
Have read the report stated, and is responsible for the authenticity of the report.
3. Principal investigator signature and date.
4. Seal of the implementation of clinical trials and the date.
5. Principal investigator on the study of the test report the statement.
Declare to have read the report, confirmed that the report accurately describes the testing process and results.
6. Author signature and date.
(II) Contents
Each chapter, annex, schedule page.
(C) Abbreviations
Abbreviations the first time the body should be standardized spelling, and Chinese name in brackets. Should be in the form of a list of abbreviations used in the report, special or common definitions of terms or units of measure.
(D) Summary
Summary of the report should be concise, clear description of the following points, usually not more than 600 words.
1. Test questions.
2. Purpose of testing and design methods.
3. Findings.
4. Efficacy and safety conclusions.
(E) body of the report
1. Test Title
2. Foreword
Generally include: veterinary subjects research background; research units and researchers; target indications and experimental animals or patients, treatment; animals tested sample size; trial start and end dates; clinical trials for approval; to develop pilot programs, followed by principles, design basis; between the applicant and the clinical trials unit agreement for specific tests or meetings, etc. should be described or description. After a brief description and results of clinical trials.
3. Test purpose
Should provide a statement of the specific purpose of testing (including primary, secondary purpose). Specify the subjects of the trials factor, subjects, study effect, a clear test to answer the main question.
4. Test Method
4.1 Experimental Design
General description of the overall research design and program. If during the test program are correct, should explain the reasons to change the content and basis.
The basis of the overall design of the trial, a reasonable discussion of appropriate, specific design characteristics of the content should be targeted as exposition.
Provide the specific sample size calculation method, calculation, and calculation of the statistics used in the estimate of its source basis.
4.2 randomized design
Detailed description of randomization methods and operations, including how the program randomly assigned randomly to hide, and explain the grouping methods, such as central distribution method, the test unit internal distribution method.
4.3 study
Animal subjects should describe the selection criteria. Including the diagnostic criteria and their basis, using the inclusion criteria and exclusion criteria, exclusion criteria. Note that under the program described in disease-specific conditions; description of specific inspections, classification or physical examination results; describe the clinical history of specific features, such as previous treatment failure or success, etc.; choose the object of study should also consider other potential prognostic factors and age, gender or species factors. Animal subjects should be discussed whether the purpose for testing.
The disease and ways to study disease and syndrome, the disease is necessary to clear diagnostic criteria, but also in the veterinary certificate listing the diagnostic criteria.
Artificial model of the disease or clinical trials of artificial reproduction, should describe the source of experimental animals, species, varieties or strains, age, weight, sex distribution, health and immunization status. The same should also be suitable for the purpose of testing whether animal subjects to be discussed.
4.4 based on control methods and their
Should describe the type of control and control methods, and describe reasonable.
Should indicate the use of veterinary drugs and controlled clinical trials and indications in veterinary medicine in the functional comparability.
4.5 Test Process
The name should describe the veterinary subjects, sources, size, lot number, packaging and labeling. Instructions were provided with veterinary drugs. If it involves bacteria, virus, worm species, should be the source, the size of virulence, exposure pathway, exposure dose and exposure after the onset of and so on.
Specify the treatment method (ie, via administration, dose, administration frequency and treatment duration, interval), should explain the basis for determining dosage.
4.6 Evaluation of indicators and methods
Main outcome measures should be clearly and secondary outcome measures.
For the main indicators, should be noted that the basis for their choice. Should describe the project to be carried out laboratory tests, schedule (test day, measurement time, time window and its relationship with the drug), and determination.
Indication of the veterinary syndromes, attention should be related syndromes describe the evaluation methods and standards.
4.7 Safety evaluation and methods
Should be clear for the evaluation of safety indicators, including symptoms, signs, laboratory project and its schedule, determination, evaluation criteria.
Clearly the expected adverse reactions; describe the clinical trials adverse reactions observed, recorded, processed, reporting requirements. Description of the test drug and the adverse event causality, severity of adverse events to determine methods and standards.
4.8 Quality Control and Assurance
Clinical trial must have the whole process of quality control, quality control should be a brief description of circumstances. In different trials, prone to bias, error links and factors may vary, state should focus on these aspects and factors for the quality control measures taken.
4.9 Data Management
Clinical trials report must clearly taken to ensure data quality measures, including collection, verification, entry, blinded review, data locking and other measures.
4.10 Statistical analysis
Describes the statistical analysis plan and statistical methods to obtain the final result.
Focuses on how to analyze, compare, and statistical tests as well as outliers and missing values ​​handling, including descriptive analysis, parameter estimation (point estimates, interval estimates), hypothesis testing and analysis of covariates (including multi-center research center between the effects of treatment). Should explain the assumptions and to test the treatment effect to be estimated, statistical analysis methods and statistical models involved. The estimated treatment effect
Should also give confidence intervals, and explain the method of calculation. Hypothesis testing should be used is clearly one-sided test or two-sided test, if the use of one-sided test, should be justified.
5. The results
Recommended as far as possible all data sets and data sets were consistent with the program for the efficacy analysis. Subjects of veterinary drugs used but not included in analysis of the effectiveness of animal subjects of the data set should be described in detail.
All important indicators of the efficacy of response (primary and secondary efficacy sub-index, card index, etc.) before and after treatment comparison group, and the test group and control group comparisons. Multi-center study of the center is to provide multi-center clinical trial centers summary table. Summary table of the center by the center's principal investigator is responsible, must have completed the unit's seal and signature of the person. The center should include the selection of test animals, the test process management, the serious and important cases and deal with adverse events, the principal investigator of the centers participating in clinical trials for the authenticity of the commitments.
Center clinical trial reports need to effect analysis.
Should describe the serious adverse events and other important adverse events. Should be noted that due to adverse events described (whether or not to be negative and drug-related) subjects prematurely withdrew from the study of animal or death of animals. Principal investigator of serious adverse events and that's important to report adverse events should open a separate summary and analysis. Should be provided for each occurrence of major adverse events and serious adverse events reported cases of animal subjects, including case number, the occurrence of adverse events (time of occurrence,
Duration, severity, treatment measures, the outcome) and causal judgments.
6. Discuss
In the test method, test quality control, statistical analysis methods to evaluate, based on the comprehensive results of the statistical significance and clinical significance. On the subjects of drug efficacy and safety results and the relationship between risk and benefit to make the discussion and evaluation. Its contents should neither be a simple repetition of the results should not introduce new results.
Around the subjects veterinary treatment characteristics, made possible conclusion, the development of value to discuss the problems during the test and the test results. Encouraged to explore the theory in veterinary clinical efficacy and safety of the medication guide, to promote therapeutic effects through the analysis of disease and syndrome.
7. Conclusion
Shows the final conclusion of this clinical trial, focusing on safety, effectiveness, the final comprehensive evaluation, a clear recommendation to declare whether registered or continue to study.
8. References
Out the relevant reference lists.
(F) attachments
1. Where the provincial veterinary administrative documents of approval issued by the department of clinical research.
2. The final case record form (sample).
3. Ministry of Agriculture of the pathogenic microorganisms involved in clinical trials of a class of documents of approval.
4. Control with veterinary instructions, quality standards, clinical trials with veterinary drugs (such as listed drugs) instructions.
5. And principal investigator of serious adverse events that require reporting of important adverse events were reported.
6. Multi-center clinical trial centers summary table.


Veterinary medicine, natural medicine, safety pharmacology research technical guidelines

First, an overview
Safety Pharmacology is the study of the test substance in the therapeutic range or above the range of treatment doses, the physiological function of the potential adverse effects are not expected to appear.
Safety pharmacology study aimed to determine the test substances may be related to non-target animal safety in hopes of a drug effect; evaluation of test substances in toxicology and / or clinical research in the observed adverse drug reactions and / or pathological physiological role; Institute of observed and / or presumed mechanism of adverse drug reactions.
Through the safety pharmacology studies for clinical research and drug safety information, but also for long-term toxicity test design and development of new indications for reference.
The guiding principle applies to Chinese medicine, natural medicine, safety pharmacology studies.
Second, the basic principles
Important function of the system of life safety pharmacology studies should generally perform veterinary quality control of non-clinical studies, additional and / or supplement the safety pharmacology studies should be possible to maximize adherence to non-clinical study veterinary medicine quality control.
Chinese medicine, natural medicine, the situation is complex, impossible to cover the guiding principles of Chinese medicine, natural medicine, safety pharmacology study of all reality, when the traditional Chinese medicine, natural medicine, safety pharmacology studies, analysis of specific issues should follow the principle.
Experimental design should be consistent with randomized, controlled, repeat the basic principles.
Third, the basic content
(A) the test substance
Test substance should be able to fully represent the clinical trial samples and veterinary medicine to be listed, so the preparation process should be stable, in line with quality standards for clinical trial samples. General use in the above test or pilot-scale samples, and indicate its name, origin, batch number, the content (or specifications), storage conditions and preparation methods. If the due administration of limited capacity or delivery method, can be used to extract (such as extract, effective parts, etc.) to experiment. Solvent used in the experiment and / or accessories should be marked such as batch number, specifications, production widely at home.
(B) the biological material
In order to obtain scientific information and effective safety pharmacology, should choose the most suitable animal or other biological material. Choose the factors to be considered of biological materials including biological materials, sensitivity, repeatability,
Whole animal species, strain, sex and age, the subject matter of background information. Should choose a special animal shows / models, and other biological materials reasons.
Whole animals commonly used in mice, rats, guinea pigs, rabbits, or target animals. Animals should be chosen to match with the test method, should also pay attention to strain, sex and age and other factors. Used awake animals for testing. If you are using anesthetized animals, should be noted that the choice of anesthetic drugs and turn control the depth of anesthesia.
Biological materials can be used to support in vitro studies (such as research activity of the test substance characteristics, test observed in vivo pharmacological effects of the mechanism, etc.). Common in vitro biological materials include: isolated organs and tissues, cells, organelles, receptors, ion channels and enzymes.
(C) the number of samples and controls
In order to test data for scientific and meaningful interpretation of safety pharmacology studies of animals and in vitro test sample should be sufficient to meet the needs. Each group of mice or rats for generally less than 10. In principle, animals should be male and female, to be used when clinically when single-sex, sex animal can be used accordingly.
Trial design should be considered a reasonable gap, negative control, positive control should be located if necessary.
(D) route of administration
In principle, the proposed route of administration should be consistent with the clinical. Such as using different routes of administration, should be justified.
(E) dose or concentration
In vivo studies: should try to determine the dose-effect relationship between adverse reactions and time relationships (such as adverse reactions and duration), should be set at least three dose groups. Low-dose should be equivalent to an effective dose Pharmacodynamic high doses does not produce serious toxicity is limited.
In vitro studies: should try to determine the dose of test substances. Response relationship. The upper limit of the test substance concentration should be as much as possible without affecting the physical and chemical properties of biological materials and other special factors impact assessment.
(F) delivery times and the detection time
Should generally be single dose. If the efficacy of the role of test substance administered some time after the emergence, or repeated administration of non-clinical studies or drug use resulting in a target animal safety issues, these effects should be based on rational design of delivery times or problems. The test substance should be based on pharmacodynamic and pharmacokinetic properties, select the parameters of safety pharmacology testing time.
Function of organ systems and life according to the importance of the choice of the relevant organ system for safety pharmacology studies. Cardiovascular system, respiratory system and central nervous system is an important life-sustaining systems, pre-clinical safety pharmacology tests must complete the general observation of these systems. When other non-clinical trials and clinical trials observed or speculated on the target animal may have some adverse reactions, should be further added to the front-critical systems in-depth study or additional studies of other organ systems.
1. Important life functions of the system's safety pharmacology studies
Based on the importance of the functions of life, observe the test substances on the central nervous system, cardiovascular system and respiratory system.
Direct observation of the central nervous system of animals after administration of general behavior, posture, gait, with or without salivation, muscle trembling, and pupillary changes; qualitative and quantitative evaluation of spontaneous activity of animals after administration and body coordination and so on. Such as the apparent excitability, inhibit or other central nervous system reactions, should be appropriate in vivo or in vitro test of further research.
Cardiovascular system measured and recorded before and after administration such as heart rate and rhythm changes. Significant dose heart rate, rhythm abnormalities, should be appropriate for further in vivo or in vitro studies.
Respiratory measured and recorded before and after administration of respiratory rate, rhythm and depth of breathing. Dose apparent respiratory excitability or inhibition, should be appropriate in vivo or in vitro test of further research.
2. Additional or supplemental safety pharmacology studies
According to the central nervous system, cardiovascular system and respiratory system in general clinical observation and research, in vivo and in vitro experiments or literature, etc. to predict the test substance may have some adverse reactions, should be properly selected and Qi added additional safety pharmacology studies content, to further clarify the generation of these adverse reactions may cause.
All of the following items need to study in a comprehensive analysis of non-clinical and clinical data based on the actual situation to select the appropriate research projects.
Additional safety pharmacology studies in the central nervous system, drugs can be observed on the behavior, learning and memory and so on; the cardiovascular system, drugs can be observed on blood pressure, electrocardiogram, cardiac output, myocardial contraction, vascular resistance and so on; respiratory system, drugs can be observed on airway resistance, pulmonary arterial pressure, blood gas analysis of the impact.
Additional safety pharmacology studies in the urinary system, can be observed the impact of drugs on renal function, such as urine, specific gravity, osmotic pressure, pH, electrolyte balance, proteins, cells and blood biochemistry (such as urea nitrogen, creatinine, protein), etc. target detection; gastrointestinal system, the observed effects of drugs on the gastrointestinal system, such as the secretion of gastric juice volume and pH, gastrointestinal damage, bile secretion, transit time in vivo, in vitro ileum contraction testing; other organ systems, such as Other relevant studies have not been studies on the impact of the following organ systems (such as the immune, endocrine and skeletal muscle effects, etc.), but out of security concerns, they should consider the impact of these drugs.
(H) the results and analysis
Should be based on detailed test records, the appropriate choice of statistical methods, the results of qualitative and quantitative statistical analysis, and should pay attention to the evaluation of individual test results. According to statistics, analysis of the safety of pharmacological effects of test substances, in combination with other safety testing, efficacy testing and quality control test results, a comprehensive evaluation.
Fourth, Glossary
Pharmacodynamic study: test substance and the desired therapeutic purposes related activity and / or role modeling.
Safety pharmacology studies: the test substance in the therapeutic range or above the range of treatment doses, do not expect the potential emergence of adverse effects on the physiological function of the study.
Additional safety pharmacology studies: According to the pharmacological effects of drugs and chemical type, estimated the possible adverse reactions. If the animal and clinical trials have cast doubt on the results, may affect target animal safety should be additional safety pharmacology study, on the central nervous system, cardiovascular system and respiratory system for in-depth study.
Additional safety pharmacology studies: to evaluate the tested drugs on the central nervous system, cardiovascular system and respiratory function of other organs, including the urinary system, autonomic nervous system, gastrointestinal system and other organ systems research. When critical systems safety pharmacology studies and long-term toxicity studies are not conducted on these organ system functions related to research, but out of security concerns, should be supplemented by safety pharmacology studies.


Veterinary medicine, natural medicine named general guidelines

Veterinary medicine veterinary medicine generic name is the legal name, but also in veterinary medicine quality standards set out the name of the collection.
For veterinary medicine, natural medicine, the generic name more scientific, clear, brief, so that each has different characteristics of veterinary products has a unique common name, formulated guidelines.
First, the basic principles
Veterinary medicine, natural medicine, the generic name should be scientific, clear and brief.
Veterinary medicine, natural medicine should be avoided naming may suggest to the user to the relevant pharmacology, anatomy, physiology, pathology or therapeutics name, not starting a code or easily misunderstood and confused with the name of the name.
For the long-established name of the medicine, generally do not easily change, such as the need to change, its former name may be listed as a transition.
Veterinary medicine, natural medicine brand name generic name not be used (including the foreign name and Chinese name), nor a brand name or trade name which is part of, nor used for trademark registration.
Second, the naming rules
(A) medicine named
Chinese Herbal Medicine for veterinary medicinal means, extract, prescription preparation of raw materials of plant, animal and mineral medicine. Chinese herbs should include the name of the name (with Pinyin) and the Latin name.
1. Herbs Chinese name
General practice should be used in most parts of the country named; such as learning to use the name all over the inconsistent or difficult to set more appropriate name, the choice of plants named.
The main chemical components of herbs with same name should be name the herbs, the chemical name called vice, such as "Glauber's salt (sodium water)."
Chinese medicinal herbs to increase part of the name should be clearly medicinal parts. Such as: self-Chine.
Artificial methods of medicinal products, the system extract, its name should be the name of the natural products differ. Such as: artificial bezoar.
2. Pinyin name medicine
Reform Commission in accordance with the provisions of Chinese characters spelling the first letter to be capitalized, and pay attention to the pronunciation of drugs habit. Such as: Astragalus Huangqi.
Pinyin phonetic symbols do not. Some of the letters in the alphabet as the previous letters merged with other sounds can read, use the noise symbols. Such as: grass Di'ercao Achyranthes to ear in the "i" and "e" between the use of sound symbols.
Name of the drug long (generally more than words), divided into two groups according to syllables as pinyin. Such as pearl Speranskia Zhenzhu Tougucao.
3. Latin name herbs
Latin name commonly used medicinal species name or generic name name.
Apart from a few medicinal herbs may indicate the location, the need to identify medicinal parts, and its Latin name of the first to write name of the drug, with the first frame, written after the medicinal parts, with the second grid, if the adjective, is set out in the end, All words are in capital letters. Such as: Polygalaceae POLYGALAE RADIX.
The named species: There are several varieties belong to the source, respectively, as the use of different Chinese herbal medicines, here named as France: Angelica ANGELICAE SINENSIS RADIX, independent living ANGELICAE PUBESCENTIS RADIX, Angelica ANGELICAE DAHURIOAE RADIX.
The name is a name: only one in the same species for medicinal purposes, or in this case there are several varieties of sources, but as a Chinese herbal medicine use. Such as: Ginkgo GINKGO SEMEN (one is only one species for medicinal purposes), and ephedra EPHEDRAE HERBA (a genus of several species for the same medicinal use). Some Chinese herbal plant (moving) objects belong to the same source although there are several different plant species for medicines use, but the habit has been adopted is a masterpiece Latin name, and generally do not change. In the case of the presence of other varieties of different herbs for use, put the same species of herbs with other kinds of names, according to the species name, so that distinction. Such as: Asarum ASARI RADIX ET RHIZOMA (have been accustomed to using the Latin name is a masterpiece), Du Heng ASARI FORBESII HERBA (and Asarum species with the same species of the masterpieces of Latin name).
A medicine consists of two different medicinal parts, if harvested at the same time, put the main or most parts of the habitual use of the medicinal parts of Latin ranked in front of the other medicinal parts of the Latin name is listed in the back, the two connection between the use of''ET''. Such as: rhubarb RHEI RADIX ET RHIZOMA.
If you do not harvest the same time, the naming of the medicinal parts separate, the two Latin names side by side, the main at the top. Such as gold buckwheat FAGOPYRI CYMOSI HERBA FAGOPYRI CYMOSIRHIZOMA.
The source of a medicine for different family and genus of two cultivation (moving) objects or the same plant (moving) objects in different medicinal parts to be listed as tied for the two Latin names. Such as: Daji CIRSII JAPONICI HERBA CIRSII JAPONICI RADIX.
The source of a medicine for the same family are two different plants, then the naming of the genus name alone, two Latin names side by side, the main at the top. Such as Geranium ERODII HERBA GERANII HERBA.
The species named: for usage, should be less. Such as: Pomegranate GRANATI PERICARPRJM.
To a representative of the species named: several varieties belong to the same sources for a medicinal use, but not for herbs is a masterpiece of Latin names, places representative of a species named. Such as: Polygonum, Polygonum Polygonum hydropiperl water and dry Polygonum P. fiaccidum Meisn two; and herbs of Polygonum multiflorum there, water carbon mother and other herbs, is a masterpiece not to Polygonum Latin name herbs, and to a wider use of surface water in the scientific name Polygonum representatives, as POLYGONI HYDROPIPERIS HEBRA.
The international community has a common name for the Latin of the herbs, and the same varieties and foreign sources, can be directly used. Such as: Scorpio SCORPIO not BUTHUS.
(B) the name Pieces
Pieces refers to medicine through the net system, cutting system, or processed after processing, the name should correspond with the name of medicine.
Net system, cutting system with slices of raw, original medicine named; special management of toxic ingredients, the name should be added before "life" characters, such as: sward, so hygiene Arisaema; fresh products should be added before the name Pieces "fresh" the word. Such as: fresh Houttuynia.
The fried, steamed, calcined and other methods Pieces cooked in herbs were preceded by the processing methods or suffix to the form name after cooked. Pieces of cooked add accessories, accessories should be labeled name. Such as: fried Hawthorn (processing methods), Burnet carbon (after processing the form name), wine from Shao (known as the auxiliary name).
(C) to extract named puzzle
Chinese medicinal herbs or extracts of the net means processed products by the appropriate method of extraction, purification of Chinese medicine made for the production of raw materials.
To extract the name of the general medicine name plus extract composition. Label use when necessary, process, and effective ingredients. Such as: Forsythia extract.
Has been purified to a certain type of ingredient names should be added to medicinal ingredient categories named vice name can be added if necessary. Such as: andrographolide.
(D) prescription drug formulations named
Prescription drug formulations means the herbs, slices, or herbal extract and other drugs, the appropriate method for producing the various formulations. Prescription preparations, including the name of Chinese names, Chinese pinyin name, Latin name should be a single herb preparation.
1. Chinese name prescription preparations
Chinese name prescription preparations should be made clear dose category, the general name on the back.
Should not use names, company names.
Inherent in the use of celebrity names, etc. should not be a specific meaning the term homonym.
Should not be used exaggerated claim, unrealistic terms. Such as "treasure", "Spirit", "music", "Bristol", "quick", "special effects" and so on.
Should not be used feudal superstition and unhealthy content language.
Generally not a "compound" word name.
General words are not more than 8 characters.
2. The naming of a single herb preparation
Single herb preparation should generally be used herbs, or herbal extract plus Pieces formulations name. Such as: Bupleurum injection.
Extract single herb preparation containing the name, if necessary, and the Latin name or its abbreviation name medicine.
3. Compound naming
Prescription can be composed of different situations named the following methods:
The main medicines used abbreviation for the name prescription and dosage forms with name, abbreviated name of medicine can not be combined into a violation of other requirements of the meaning of the name. Such as the herb, woody, medicinal composition of the agents berberine shamisen can be named as "fragrant herb with scattered."
Names and functions using the main ingredients and add dosage form with name. Such as "Longdanxiegan casual''and so on.
Smell the use of prescription number, name of medicine, herbs, and add features such formulations name. Such as "Liu Wei Di Huang San''.
From the side of the ancient species, such as the name does not violate the principle can be the name of the ancient side. Such as "Sini Tang."
A certain type of component or single component of the compound of the name, dosage form should be named added ingredients.
Main function name plus the use of formulations. Such as "Zhili scattered."
Smell the herbs used name or number and Smell the main number and function combined formulations name. Such as the "seven clean sepsis particles."
Compared with formulations using pictographic name. Such as "golden solid fine powder" attending kidney Hua Jing, described as golden as the role of solid fine.
Necessary, to add the objects used in clinical drug. Such as "healthy pigs loose."
If necessary, add in the name of the drug usage. Such as "rub scabies scattered."
4. Medicine and other drugs Combivir naming, naming should be consistent with the basic principles of traditional Chinese medicine, taking into account other drug name.
5. Prescription preparation of the pinyin name
Reform Commission in accordance with the provisions of Chinese characters spelling the first letter to be capitalized; name of the drug by a long syllable is divided into two or three groups as Pinyin, a phonetic alphabet for each group to be capitalized. Such as: Taishan rock powder (Taishan Panshi San).
6. Named veterinary medicine injections. Powder known as "liquid injection injection ×××'', called" × × × injection. "
7. Extract preparations name. Generally, "formulations of medicinal name +" or "component + formulations''are named.


Veterinary medicine, natural medicine, quality control of technical guidelines

First, an overview
Veterinary medicine veterinary medicine quality control throughout the development, production, storage and transportation of the whole process systems engineering, from raw materials, process, quality standards, stability, packaging and many other research.
In order to ensure that veterinary medicine, natural medicine, quality stable, controllable, effective control of raw materials, intermediates and final product quality, especially the development of veterinary medicine, natural medicine, quality control of technical guidelines.
Veterinary medicine, natural medicine, quality control of basic research include: prescription and raw materials, preparation, quality research and quality standards, stability studies.
Given the complexity of the composition of their own medicine, advocates make a specific analysis of specific issues, to encourage their own products based on the characteristics of targeted research.
Second, prescription and raw materials
(A) prescription medicines in the medicine should meet the statutory requirements of the standard. If there is no legal standard of medicine, herbs should be studied to establish the appropriate standard, along with appraisal reports. New medicinal plants, their plant-based source identification research units to be issued by the national evaluation report.
(B) the prescription of the extract should be consistent with the statutory standards. If you can not set the standard extract, the extract should be to establish the appropriate standard.
(C) Western prescription compound preparation of chemicals should be consistent with the statutory standards, and legal sources of raw materials should be used.
(D) toxic prescription medicines should be made based on the total prescription volume and the conversion, the conversion amount and toxicity of medicinal herbs after the statutory standard prescribed daily dose in comparison, if the over dose, should provide relevant research and literature on its safety.
(E) change the dosage of existing national standards, and its prescription Smell, the proportion of the prescribed dose should be consistent with national standards.
(F) the use of herbs should be as clear as possible variety, origin and so on.
Third, the preparation process
(A) shall ((veterinary medicine, natural medicine, preparation of technical guidelines "," veterinary medicine, natural medicine extraction and purification process of technical guidelines "," veterinary medicine, natural medicine in the pilot study technical guidelines " principles of research.
(B) should be at least 3 batches, 1000 preparation unit 10 times more in a pilot to examine the scale-scale, the process of stability and maneuverability, and provide pilot test and inspection data to reflect process amplified the basic situation.
(C) the materials used should meet the standard requirements of pharmaceutical excipients. The use of such materials to its safety or effectiveness may have a greater impact, and should provide research data to confirm its safety or effectiveness.
(D) process is no qualitative change in the product, its production process should be consistent with national standards, and shall not change the process route and process parameters such as the amount of manufactured goods.
Fourth, quality research and quality standards
(A) the quality of research literature
Smell should provide prescriptions contained in the main chemical ingredient, particularly effective composition of the relevant literature, including the main ingredient or category of ingredients of the physical and chemical properties, identification, detection and determination and so on.
(B) the quality of experimental data
Quality of experimental data including the quality of raw materials and preparation of quality research in two parts.
1. Quality of raw materials test data
Quality of raw material research and identification of sources, including the basis for effective site selection, producing process, characteristics, organizational characteristics, physical and chemical properties, identification, inspection, determination and other research data (methods, data, pictures, and conclusions), and literature. . Extract screening process should also include research. Statutory standards contained in the closed species, should meet the relevant standards; can not set standards, and should study the establishment of appropriate standards, the standards should be consistent with the "China Veterinary Pharmacopoeia" The current version of the format. The amount and toxicity of medicinal herbs involving the use of endangered species should be consistent with relevant national regulations.
Materials research, including physical and chemical properties, dosage, quality and compatibility studies.
2. Quality of preparation of test data
Quality of preparation of the test including preparation of the traits, identification, inspection, extract or other determination, the data in the study results should be stated.
(C) the quality of drafting instructions and draft standards
A science, complete veterinary quality standards should be fully reflected in all aspects of the evaluation of veterinary drugs, in addition to findings of the evaluation of pharmacy, pharmacology, toxicology, pharmacokinetics, and clinical trial data are to develop quality standards for veterinary drugs Draft an important basis for a comprehensive multi-disciplinary research. Including quality specifications, test methods and clinical application.
1. The premise of quality standards
"Safe and effective''is a prerequisite for the establishment of veterinary drugs must be prescribed in the study of mature, raw materials and preparation conditions, the preparation of the test products, conduct research and development of quality standards, the following three pre-set standards conditions:
(1) prescription fixed
Before the development of quality standards, must require a fixed prescription, the number and amount of raw materials, true and correct, without reservation, it can be quality standards of research and experimental design.
(2) raw materials (herbs, slices, extract) and accessories in addition to medicinal herbs and stable position, producing, harvesting and processing quality of the pros and cons involved, the important thing is the authenticity of medicinal drugs and regions used to identify species and application.
(3) Preparation and stability
2. Quality standard content and drafting instructions
(1) API quality standards and drafting instructions
API quality standards should include the name, Pinyin, herbs Latin name, source, characteristics, identification, inspection, extract, determination, processing, properties and go through, functions, indications, usage and dosage, attention and storage, etc. items. Written format and terminology with reference to the current edition of "China Veterinary Pharmacopoeia." Such as national standards or provinces, municipalities and autonomous regions have received the standard set, should indicate the source of its base, medicinal parts, the main sources of origin and the reference standard. Sources should include the original medicinal plant (moving, ore) material family name, Chinese name, Latin name, medicinal parts, harvesting season and the origin and processing, mineral drugs should include the mineral class, family, rock mineral name or names, composition and origin of the main processing. Medicine should be fixed its origin. Original plant (moving, ore) material to be identified by the relevant units. Traits, including herbs shape, color, surface characteristics, texture, smell and describe the cross-section, generally full of dry herbs based, easily broken broken part j must check the description includes impurities, moisture, ash, acid insoluble ash, heavy metals , arsenic salt, pesticide residues, the toxic components of other projects. Should establish a reasonable processing processing processing technology, specifically the amount of materials and processed products of quality requirements. Identification, determination of identification with the preparation, determination of entry.
Drafting instructions should indicate the development of quality standards in the grounds of each project, provided the basis for the project indicators, technical conditions and precautions, which requires both theoretical explanations, but also a summary of the work practice and test data.
(2) preparation of quality standards and drafting instructions
To the quality standards should reflect the true and final product quality control. The contents typically include Chinese names, Chinese pinyin, prescription, system, method, properties, identification, inspection, extract, determination, functions, indications, usage and dosage, attention, specifications, storage, valid for other projects. Written format and terminology with reference to the current edition of "China Veterinary Pharmacopoeia."
Drafting instructions should set the project in the draft standard research methods and method validation, etc. are explained. Reasons including the development of various projects to provide the basis for the project indicators, technical conditions and precautions. Specific content related to the experimental principle of interpretation of test data acquisition and experimental results, and reviews. Specific requirements are as follows:
① Name: should be "veterinary medicine, natural medicine named general guiding principles" for.
② prescription: should list all the Smell and amount of all prescriptions should be made of 1000 units of finished preparations quantity. Smell the order should be based on the principles set side by Jun, Chen, Zuo, so the importance of the order or the order. Processed products must be marked. Veterinary Pharmacopoeia contained in processed products is not received, processing methods should indicate clearly the amount of materials and processed products of quality requirements.
③ Method: Preparation should be stated in the whole process of setting out the key process of technical conditions, parameters and technical requirements. Mainly describes the total number of prescriptions taste, the Smell of the key technology and process and quality control-related parameters, such as extract of the relative density, supplies the name, dosage, and standards, such as the total amount of manufactured goods. Drafting instructions should be described in detail the operation; of key processes and key indicators of the semi-technical quality standards, and to determine the final preparation process and the technical conditions of the reasons.
④ traits: general formulation and description should be removed after the packing or coating color, shape, smell and so on. Injection should describe the color, condition and other physical traits. Injection because of its raw materials, the impact of allowing a certain color, but color of the same batch of finished products must be consistent; between different batches of finished products, should be controlled within a certain range of color, the color of injection should not be too deep, so for clarity check.
⑤ identification: identification methods include microscopic identification (biopsy, powder), physical and chemical identification, Spectroscopy, Chromatography, etc. Requires specific, sensitive, reproducible. Microscopic identification should focus on the characteristics described in easy to see the police. Physics and chemistry, spectroscopy, chromatography identification, description should be accurate, terminology, units of measurement should be standardized. Chromatography should choose the appropriate reference standard or reference drug. According to the prescribing information to determine the composition and establishment of appropriate research projects to identify, in principle, deal with all prescription Smell
To identify research, studies to establish the identification of items with special properties, in particular, the preferred herbs, expensive drugs, toxic drugs and adulterants more taste, a small amount of the prescription or interference, and can not be detected by application of experimental results shows . Good reproducibility can really reflect the taste characteristics of the feature set of prescriptions or chromatographic fingerprint identification also. Optional.
Drafting instructions should explain the basis and method of identifying the selected experimental conditions (such as thin layer chromatography adsorbent, the agent, color agent selected, etc.), physical and chemical identification and chromatographic identification of the negative control test results should be listed to prove its specificity, and provide samples of three batches of the above test results to prove their repetitive. Identification-one correspondence with the identification of the object, and a detailed description. Veterinary Pharmacopoeia of the test solution containing not received, should indicate the preparation method and basis. Powder characteristics microscopic identification should be attached map, color photographs should be attached to thin-layer chromatography, spectroscopy, chromatography spectrum should be photos, maps, color photographs should be clear and true. Characteristic pattern or fingerprint must have the basis of experimental data and to confirm its reproducibility. Chromatography and the control reference substance used in medicine, materials research should be the standard technical requirements.
⑥ inspection: the inspection program should indicate the reasons for their test data to determine the inspection items to clarify the meaning and limits of indicators based on, and to develop appropriate limited range. For the preparation of heavy metals, arsenic and salt should also be checked. Process using the first and second class of organic solvents, organic solvents should have the corresponding residue checks. Injection in addition to the "China Veterinary Pharmacopoeia" The current version of Appendix injection under the provisions of the inspection items are checked, the route of administration should be based on different requirements for color, pH
Value, protein, tannin, resin, oxalate, potassium ions, pyrogens, heavy metals, arsenic salts, residue on ignition, moisture, abnormal toxicity, hemolysis test, irritation test, allergy testing, determination of total solids and other items related research study.
⑦ extract: According to the chemical composition and indicators of the extract composition determination and to establish limits. Should explain the reasons for the project requirements, using solvents and methods based on measured data are listed, a variety of leaching conditions on the extract amount of influence, formulate the basis for the limits of extract, and submit test data.
⑧ Determination: Smell should be established to counter the main ingredients in the determination of project priority, monarch Satsukai prescription ingredients known method for the determination of active ingredients, and the study methodology, based on experimental results to develop a reasonable level limits. General response to the main prescription drugs, expensive drugs and other appropriate determination of the development project. Toxic drugs (such as brucine, etc.) agents, should be established method for the determination and concentration limits. For both the toxic components containing the active ingredient is measured indicators, should provide content range (minimum formulation). Chinese and Western medicines chemical compound in the assay method should be established. Effective parts of the preparations, should generally be an effective representative of the location and composition containing the main measurement methods, and to provide effective parts of the content range. Active ingredient preparations, should be clearly labeled amount of active ingredients to provide the scope of its content. The content limits should be based on at least 10 batches of 20 samples of test results, status of medicinal content, stability, transfer rate under process conditions, stability study results with measurement data to determine. Necessary quality standards can be measured with the establishment of multiple indicators to improve the controllability of product quality. Assay linearity, precision, reproducibility and recovery tests, etc. should follow the "veterinary medicine, natural medicine, quality standards for analytical method validation guidelines."
Can be measured to establish the appropriate pattern or other biometric methods for quality control.
Drafting instructions should describe the object and the determination of selected elements determined basis. Prescription process and formulations according to the characteristics, select the appropriate measurement method, and method for the determination of the principles set out to determine the methodology of the determination of reference and related maps. Determination of the material should be consistent with the standard requirements.
⑨ functions, indications, usage and dosage, attention, storage, and expiration date: According to the preparation of research data, narrative description of their needs, including taboos, Yun Xu, young animals, and other disorders of the taboos.
⑩ Spec: preparation unit weight, volume or label content and other equipment.
3. Material content standards and requirements
Quality standards required in the standard material, such as closing the current national drug standards set by the China Institute of Veterinary Drug Control, or Chinese medicines and biological products provider, can be directly used by category, but it should be noted that the standard material batch number, category and so on. Variety of other sources according to the following requirements are to provide material and reference material calibration, and report to China Institute of Veterinary Drug Control examination and verification.
(1) reference substance
① Source: from plants, animals, raw materials extraction to note the family name, Latin name and location and the specific medicinal extraction, separation processes, methods; chemical compounds indicate the sources of supply and process methods.
② validation: validation of known structure of the compounds required to provide the necessary parameters and patterns, and should be consistent with literature values ​​or patterns, such as literature is no record, according to requests for unknown parameters is sufficient to confirm its structure. Such as elemental analysis, melting point, IR, UV, NMR and MS.
③ purity: the purity of chemical reference substances should be checked. Purity test to follow the type used in chromatography, such as thin layer chromatography, the amount of point-like inspection method should be applied 10 times the amount of point-like volume, select three or more solvent system launched and offer color photos. Chromatographic spots should be no significant impurities.
④ content: content was determined with reference substance, content (purity) should be more than 98% for identification of content with the chemical reference substance (purity) should be more than 90%, and to provide assay methods and test data and relevant maps.
⑤ stability: according to regular inspections, report production, use phase and provide the basis to determine.
⑥ Packing and storage: According to the stability of the test results to determine the storage conditions.
(2), medicine
① species identification: After accurate identification of herbs and indicate the source and variety of sources, medicine, must have the identification of common characteristics.
② Quality: selected in line with national standards of veterinary standards or requirements of high-quality pharmaceutical ingredients.
③ uniformity: must be crushing screening, take the uniform powder packing applications.
④ stability: the stability should be investigated, and determined to provide lifetime basis.
⑤ Packing and Storage: sealed container home, dark, cold, dry storage.
(3) reference materials for use
Reference substance should be indicated in the English name, molecular formula, lot number, use the period and for which detection methods, determination of the chemical reference substance should be specified content. Chinese herbs should specify the control name, Latin name, lot number, use the period and storage conditions.
Fifth, the stability test requirements preparation
Veterinary stability is an important quality veterinary evaluation is to determine the veterinary medicine, natural medicine, based primarily on the period of preparation. Study the stability of the preparation of indicators for the preparation of quality standards established by the characteristics, identification, inspection, extract, determination, health studies and other projects, if necessary, according to the need to increase the sensitivity of the indexes, in order to fully reflect the product stability. Stability samples should be used in pre-production samples, to be listed on the packaging. Stability of the experimental design to study the side
Act shall, "veterinary medicine, natural medicine stability test technical guidelines" for. Active ingredient or active ingredient formulations of light, heat,. Moisture-sensitive formulations, the stability factor test should be conducted to fully examine the product to light, moisture, heat stability, etc., for packaging materials, storage conditions provide the basis for selection. The validity of the product, storage conditions, in order to determine the stability of the findings.

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