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| Technical standards for quality and efficacy of generic drugs (interim) |
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| Author：中國銘鉉 企劃部 Release Time：2017-9-27 11:24:20 Number Browse：1901 |
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Medical network - September 26 September 22, generic quality consistency evaluation of the effect of office issued "the quality of generic drugs and curative effect evaluation declaration data consistency archives review technical standards (provisional)". The document provides references for the applicant, facilitates the filing of the information, strengthens the self-examination, and improves the quality of the declared information.
Consistency according to the administration about the quality of generic drugs and curative effect evaluation of relevant matters announcement no. 100 (2017), generic quality and curative effect evaluation should declare data consistency "establish a review". To evaluate the integrity and evaluability of the r&d work and the reporting data through the "volume review" to improve the quality and efficiency of the reporting.
Technical standards for quality and efficacy of generic drugs (interim)
According to the requirements of the general administration's notice concerning the quality of generic drugs and the work related to the evaluation of the quality and efficacy of the work, the filing of the declaration should be reviewed. Through review "archives" evaluation declaration data and the integrity of the research and development work and scalability, can greatly improve the quality of reporting data, ensure the follow-up review, examination and approval work carried out effectively and orderly.
Declaration data should comply with the "total bureau releases about chemicals generics oral solid preparation quality and curative effect evaluation declaration data consistency requirements (trial) circular no. 120 (2016) and the relevant provisions of the requirements, shall provide a complete overview, pharmaceutical research data, evaluation of in vitro, in vivo evaluation of the relevant materials and accessories, and provide information summary table and its electronic version.
In order to facilitate the filing of the information of the applicant and improve the quality of the filing, the technical standard (provisional) for the preparation of this filing will be prepared for the reference of the applicant.
1. Format requirements
The requirements of the format should be in accordance with the provisions of the medical registration information system (fda) (no. 98, 2011).
The documents shall be independently covered with the name of the drug, the information item number, the name of the information project, the research unit and the relevant items of the personnel (if applicable), the name of the application agencies, etc. The information item number is indicated in the upper right corner and the official seal shall be stamped by the applicant. Clinical study report shall set up separate title page, name, name of drug, and contains the test number, the starting and ending time test, the main researchers, head of the applicant's name, research institutions/name of the applicant, the applicant contact and contact way, the raw data of the report date, save the address and other necessary information. A summary of the research report should be provided, a catalogue of the research reports, and a number of pages.
The summary section
According to the bureau of quality and release chemicals generics oral solid preparation of curative effect evaluation declaration data consistency requirements (trial) circular no. 120 (2016) and the relevant provisions of the required, including history, approved and listed, self assessment, clinical information, and adverse reactions, and ultimately determine the composition of prescription and production process, biopharmaceutics classification, etc.
3. Pharmacy
(1) summary of information summary of pharmaceutical research
Released in accordance with the administration of chemicals generics oral solid preparation quality and curative effect evaluation declaration data consistency requirements (trial) circular no. 120 (2016) prescribed format and writing requirements, provide the main information in pharmaceutical research data, and provide the electronic version.
(2) declaration materials for pharmaceutical preparations
Released in accordance with the administration of chemicals generics oral solid preparation quality and curative effect evaluation declaration data consistency requirements (trial) circular no. 120 (2016) and so on to the relevant provisions of the request, with reference to relevant technical guidelines, provide product research information. It mainly includes: dosage form and product composition, product reevaluation research, production information, control of raw auxiliary materials, quality control of preparation, control products, packaging materials, stability, etc.
1. Prescription composition
Documentation, quality standards, inspection reports and BSE/TSE risk statements for raw materials, auxiliary materials and materials are required.
2. Product reevaluation research
Should be provided, including an API key physical and chemical properties, the role of complementary makings in prescription analysis, provide prescription change development process and determine the basis, to provide a detailed technical research materials, collect research and development in the process of representative batches of samples, and process validation studies.
3. Production information
Should provide a detailed description of the production process and process control, and provide information about the actual production line of the main production equipment, and explains the batch of mass production and formulation basis, change after the production process and key factors and the existing differences and advantages of the original process, detailed research data to determine the critical process steps and parameters. For the variety of process change, provide process verification plan and blank batch production record sample and related undertaking, or process verification report. Explain the production of batch sample of clinical test.
4. Control of raw materials
Sources of raw materials, supporting documents and implementation standards shall be provided. Determine the key quality control of raw materials and key accessories. Provide related inspection reports and whether there is a BSE/TSE risk statement.
5. Quality research and control of preparations
Sufficient experimental data and documentation should be provided to demonstrate the consistency of the quality of generic preparations and quality of reference preparations. Provide the basis for inspection methods and selection, optimization process and standard setting of quality standards. Provide information on impurity spectrum analysis and determine whether controls and limits are controlled. Any impurities beyond the identification limit shall be further studied in accordance with the requirements of relevant guidelines at home and abroad.
6. Control products
Information on all controls used during the study should be provided.
7. Packaging materials
Provide packing material type, source and supporting documents. If there is a change in the prescription process, we should provide information on the compatibility of this product and the internal packaging material.
8. Stability
According to the relevant guiding principles, data of influencing factors, acceleration and long-term stability test data and atlas are provided.
Iv. In vitro evaluation
Reference preparation in accordance with the common oral solid preparation to select and determine the guiding principles, the general oral solid preparation dissolution test technique guiding principles, the general oral solid preparation dissolution curve determination and comparison of guiding principles, the drug dissolution tester machine validation guiding principles and related guidelines, provide reference preparation quality inspecting and dissolution curve etc. The quality consistency evaluation shall indicate whether the quality of the generic preparation is consistent with the quality of the original products or reference preparations, and provides detailed quality comparison research data and results. In the research data of the similarity evaluation of dissolution curve, it is necessary to establish the dissolution test method which can objectively reflect the characteristics of the preparation, and to investigate and compare the dissolution curve of the generic preparation and the reference preparation.
The biological equivalent
(I) bioequivalence research report
Bioequivalence study should be according to ICH E3 and CFDA promulgated the pharmacokinetic parameters for the finish evaluation index of chemical drugs generic human bioequivalence study technical guidelines "requirements, mainly is suitable for the pharmacokinetic parameters for the finish evaluation of bioequivalence test data of the declaration, pharmacodynamics index as the equivalence test data can be appropriately at the end of the reference. Study should provide the detailed information of the bioequivalence test include a clear description of key experimental design, study plan, test method, test process, using statistical analysis method, the results of the study, the research conclusion, any plan deviation test relevant information, such as always failed bioequivalence test should be briefly described in the research background, and the appropriate analysis.
The body of the study of bioequivalence should include but not limited to the following information:
• table of abbreviations
• research background
• research organization information
• ethical requirements
• research objectives
• experimental design
• subject selection criteria
• subjects administered the drug
• test meal
• biological sample collection and management
• combined use of medication
• safety evaluation indicators
• test termination criteria
• special case handling
• test implementation
• drug concentration detection in the subject's biological samples
• data management and statistical analysis
• safety evaluation results
• research conclusions
• test quality assurance
• references
(2) biological sample analysis report
The biological sample analysis report is an important basis for bioequivalence research data. Its structure and content should be well organized, detailed information, complete data and easy to review. Subject biological sample analysis and methodology verification report can be independently written and can be used as two parts in the same report. Should provide the source of the compounds used in biological samples analysis, key steps in the detailed information and analysis of process quality control, the results of the analysis, any deviation and the corresponding processing and other related information.
Biological samples analysis report should be based on the 2015 edition of the China pharmacopoeia appendix IV "9012 biological samples quantitative analysis methods validation guidelines" requirements, mainly is suitable for the chemical concentration in biological samples detection, biological macromolecular drug concentration in biological samples test data writing can also be reference, and according to the concrete research content appropriate optimization.
1. Methodology verification
The methodology verification report should provide sufficient detailed information to explain the analysis process, otherwise the standard operating procedure (SOP) will be required after the report. All source data should be saved in its original format and provided as required. Any deviation from the methodology verification plan should be recorded.
The methodology verification report should include at least the following information:
• a summary of the results of the methodology
• analytical methods
The details of the analytical methods used should be described, and the source of the analytical method is given if the existing methods are referenced. The analysis steps (analyte, internal standard, sample preprocessing, extraction and analysis) are described. Control standard products (source, batch number, analysis certificate, stability and storage conditions); Calibration of sample and quality control samples (matrix, anticoagulant, pretreatment, preparation date and storage conditions, etc.
• analysis of acceptance criteria
• analyze batch data
All analytical batch lists should be included, including calibration ranges, response functions, return concentration, and accuracy; A list of quality control samples for all analytical batches; The stability data of the reserve liquid, working solution and quality control under the storage conditions; Selectivity, quantitative lower limit, residual, matrix effects and dilution investigation data.
• method deviation
The unexpected results obtained in method verification should fully explain the reasons for taking the measures; Describes and describes deviations from the method validation plan or standard operating procedures.
All measurement results and each calculated concentration must appear in the validation report.
2. Subject's biological sample analysis
The method of sample analysis of the unknown sample should be consistent with the methodology verification report. In the sample analysis report, we should briefly describe the methods used in the sample analysis, and the specific details can be used to validate the report. In the report, the sample analysis process should be described in detail, otherwise the sample analysis standard operating procedure (SOP) should be attached after the analysis report. All source data should be kept in its original format and provided as required. Any deviation from the test plan, analytical procedure or standard operating procedures should be discussed in the analysis report.
The biological sample analysis report shall include at least the following information:
• basic information
Should include control standards (source, batch number, analysis certificate, stability and storage conditions); Calibration sample and quality control sample (storage condition) information.
• analytical method acceptance criteria
A brief description of the acceptance criteria of the analysis batch, and references to corresponding test plans or standard operating procedures;
• sample tracks (receiving date and content, sample status, storage location and condition);
• subject biological sample analysis
A list of all analytical batches and test samples should be included, including the date and results of the analysis; List of standard curves for all accepted analytical batches; The list of quality control results of all analytical batches should be clearly marked out of the acceptance criteria; Failed analysis batch number and date of complete information.
• analytical method deviation
Deviations from the method or standard operating procedures should be described and corresponding measures taken.
• repetitive analysis
Description of repeated analysis should be described, not including failure approval (list description, including repeated analysis of sample identification, the cause of repeated analysis, initial analysis results and repeated analysis results).
• biological sample reanalysis (ISR)
Should contain quantity analysis of biological samples and sampling principle, biological samples and the analysis of the results in the methodology validation report, the subjects of biological sample analysis report or in a separate report.
3. Chromatogram
After the biological sample analysis report, the total chromatographic map of the methodology verification and the subject analysis batch should be attached according to the regulations, including the corresponding quality control samples and calibration samples of the chromatogram. The chromatogram should be legible and contain key information of biosample analysis.
The content recommended by this document is based on current understanding and can be optimized according to specific research content.
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