Appendices! Product quality documents. Technical guidelines. (Translation from Original Chinese Version)

Transcription

1 Appendices! (Translation from Original Chinese Version) Product quality documents Technical guidelines

2 Appendix I General tests for various dose forms of pcms The general tests for various dose forms of pcms are listed below, the applicant should decide other tests which are required according to the product quality (e.g. heavy metals and toxic element test, pesticide residues test, etc.). For dose forms not listed below, it is the applicant to decide on the test items and provide the basis for his/her choice for approval by the Chinese Medicines Board. Dose form General tests 1. Pill Determination of water, weight variation, packing variation, disintegration test, 2. Powder Uniformity, determination of water, packing variation, degree of fineness of powder, 3. Granule Size of granules, determination of water, determination of dispersibility, hardness, packing variation, weight variation, 4. Tablet Weight variation, disintegration test, hardness (friability), dissolution rate, 5. Troch Weight variation, disintegration test, ph value, 6. Concentrated Relative density, insoluble materials, filling, ph value, Decoction 7. Glue Filling, determination of water, total ash, 8. Syrup Filling, relative density, ph value, 9. Cataplasm (babu Adhesion test, test for excipient property, assay plaster) 10. Mixture Filling, relative density, ph value, clarity of solution, 11. Dripping pill Weight variation, disintegration test, determination of water, microbial limit test 12. Capsule Determination of water, packing variation, disintegration test, microbial limit test 13. Medicinal wine Total solids, determination of methanol, filling, 14. Tincture Determination of methanol, filling, 15. Liquid extract ph value, total solids, determination of ethanol,, filling 16. Extract Microbial limit test, filling 17. Plaster Weight variation, softening test, skin irritation test 18.Adhesive plaster Assay, heatproof test, cold-proof test, tension 19. Ointment Filling, skin irritation test, 20. Medicinal ph value, distillate 21. Medicinal tea Determination of water, weight variation, determination of dispersibility, hardness, 22. Injection Packing variation, clarity of injection, sterility, particulate matter, ph value, pyrogen, hemolysis, irritation test 23. Suppository Weight variation, disintegration test, ph value, 24. Nasal drops Filling, 25. Eye drops Clarity of solution, particle size of suspension, filling,, ph value, osmotic pressure, viscosity 26.Aerosol and spray Delivery rate, total amount of sprays, total number of deliveries per container, emitted quantity in each delivery, content of active ingredient in each delivery, particle size, spray test, filling, 27. Liniment Filling, ii

3 Stability tests Appendix II Technical guidelines Stability test is to establish the stability and shelf life of a product by retaining the product at a specific temperature and humidity for a period of time and to carry out tests in according to the dose form. (A) Test methods (1) Accelerated stability test - For accelerated stability tests, 3 or more batches of the product in their clinical trial or sales packaging are being kept in a controlled environment with temperature at 37 ~40 and relative humidity at 75%± 5%. The test batches are inspected and tested once every month for 3 consecutive months. If the qualities of the batches remain stable, the shelf life of the product is equivalent to 2 years. When conducting the inspections, attention should be paid to observe any changes in the quality of the medications that have direct contact with the packaging material. - Please refer to the attached table at item (B) for the suggested tests for various dose forms. (2) Real-time stability test - For real-time stability test, 3 or more batches of the product in their sales packaging are being kept in ambient conditions (in general, temperature at 25 ±2 and relative humidity at 60% ± 5%). The test batches are inspected once every month for 3 consecutive months. After the initial period of 3 months, the inspections will be conducted every 6 months. Different test intervals should be drawn up for different dose forms. When conducting inspections, attention should be paid to observe any change in the quality of the medications that have direct contact with the packaging material. - Please refer to the attached table at item (B) for the suggested tests for various dose forms. (3) General stability test - Depending on the history of local manufacture and sales of the pcm, and also its claimed shelf life, the applicant shall conduct tests according to the following schedule on the retained samples. The test reports submitted will form the basis to support its claimed shelf life. In any case, the proposed shelf life should not exceed 4 years. iii

4 (i) Schedule for inspection of retained samples Table 1: pcms which are eligible for transitional registration: Proposed Accelerated Schedule for inspection of retained samples 0 year 1 st year 1 st 2 nd 2 nd year 2 nd -3 rd 3 rd year 3 rd 4 th shelf-life stability test year year year 4 th year 1 2 years years years years years years Table 2: pcms which are not eligible for transitional registration but with history of local manufacture or sale of 2 years or more: Proposed Accelerated Schedule for inspection of retained samples 0 year 1 st year 1 st 2 nd 2 nd year 2 nd -3 rd 3 rd year 3 rd 4 th shelf-life stability test year year year 4 th year 1 2 years years years years years years Table 3: pcms which are not eligible for transitional registration and with history of local manufacture or sale of less than 2 years: Proposed Accelerated Schedule for inspection of retained samples 0 year 1 st year 1 st 2 nd 2 nd year 2 nd -3 rd 3 rd year 3 rd 4 th shelf-life stability test year year year 4 th year 1 2 years years years years years years Remarks: 9 - tests are required 8 - tests are not required 0 year - tests are required when the batches released from the manufacturer (ii) Inspection requirements for retained samples - 3 or more batches of the product in their sales packaging are being kept under room temperature or the same storage conditions as recommended for the product at the manufacturer. The applicant shall conduct tests on the retained samples in according to the dose form of the product, and the results of the tests should meet the product specification of the pcm. When conducting the inspections, attention should be paid to observe any changes in the quality of the medications that have direct contact with the packaging material. iv

5 - Please refer to the attached table at item (B) for the suggested tests items of various dose forms. - The applicant shall, within the specific time period, submit test reports to the Chinese Medicines Board for approval. Should the quality of any product falls below the required standard before the expiry of the products, the Chinese Medicines Board may require the applicant to revise the claimed shelf life and the test schedule accordingly. (iii) Submitting general stability test reports - For pcms which are eligible for transitional registration, the applicant shall, within 5 years from the deadline of application for transitional registration (i.e. before 30 June 2009), submit to the Chinese Medicines Board the test report of at least one batch of product and a documentary proof showing that test on the remaining batch(es) has been commenced. Test report of the remaining batch(es) should be submitted upon the renewal of such registration. Should the quality of any pcm falls below the required standard during the inspection period, the applicant should conduct accelerated stability tests, revise the shelf life and adjust the test schedule accordingly. - For pcms which are not eligible for transitional registration but with a history of local manufacture or sale before the commencement of pcm registration system (i.e. before 19 December 2003), the applicant should submit to the Chinese Medicines Board the test report of at least one batch of product and a documentary proof showing that test on the remaining batch(es) has been commenced upon the renewal of such registration. Test report of the remaining batch(es) should be submitted upon the 2 nd renewal of such registration. - For pcms with a history of local manufacture or sale after the commencement of pcm registration system (i.e. on/after 19 December 2003) and before the deadline of application for transitional registration (i.e. before 30 June 2004), the applicant should submit to the Chinese Medicines Board the accelerated stability test report, inspection plan of retained samples, results of initial tests conducted on at least one batch of product when release from the manufacturer (0 year) and a documentary proof showing that test on the remaining batch(es) has been commenced upon application. Thereafter, the applicant should conduct tests according to the plan, and submit test report of at least one batch of product after completion of test. Test report of the remaining batch(es) should be submitted upon the renewal of such registration. v

6 (B) Stability tests-suggested tests for various common dose forms Dose form Tests Description, identification, clarity of injection, ph value, sterility, 1. Injection pyrogen, hemolysis, irritation test, assay 2. Mixture Description, identification, clarity of solution, relative density, ph value, assay, 3. Syrup Description, identification, relative density, ph value, assay, 4. Medicinal wine Description, identification, determination of ethanol, total solids, assay, 5. Pill Description, identification, disintegration test, determination of water, assay, 6. Powder Description, identification, uniformity, determination of water, fineness of the powder, assay, 7. Concentrated decoction Description (crystallization, forming layers), identification, relative density, dissolution test, ph value, assay, 8. Capsule, dripping pill Description, identification, determination of water, disintegration test, assay, 9.Tablet Description, identification, hardness, disintegration test, assay, 10. Liquid extract Description, identification, ph value, determination of ethanol, total solids, assay, 11. Extract Description, identification, assay, 12. Emulsion Description, identification, assay, 13. Granule Description, identification, determination of water, size of granules, assay, 14. Suspension Description, identification, assay, 15. Ointment Description, identification, assay,, skin irritation test 16. Plaster Description, identification, softening point, assay, skin irritation test 17. Adhesive plaster Description, identification, tension, assay, skin irritation test, coldproof test, heatproof test 18. Glue Description, determination of water, identification, assay, microbial limit test 19. Troch, suppository Description, identification, disintegration test, ph value, assay, 20. Aerosol Description, identification, spraying efficacy, odour, irritation test, assay, 21. Membrane Description, dissolution test, irritation test, ph value, assay, 22.Other dose forms Determination items should be selected depending on the features of the specific dose form of the medicine vi