State Food and Drug Administration: here comes the principle and procedure of drug sampling!

Drug administration of all provinces, autonomous regions and municipalities directly under the central government, drug administration of Xinjiang production and Construction Corps, and China food and Drug Control Research Institute: In order to standardize the random inspection and inspection of drug quality, according to the requirements of the notice of the State Food and Drug Administration on printing and distributing the measures for the administration of random inspection and inspection of drug quality (gjjg [2019] No 34), the State Food and drug administration has organized and formulated the principles and procedures for drug sampling, the application form for re inspection and the application receipt for re inspection, which are hereby printed and distributed to you for implementation, and the provincial drug regulatory department Specific work rules can be formulated according to the actual situation of each department Appendix: 1 Principles and procedures of drug sampling appendix: 2 Application form of retest appendix: 3 Application receipt of retest application Annex 1 principles and procedures of drug sampling 1 scope of application these principles and procedures are applicable to the sampling work implemented in accordance with the measures for the administration of drug quality spot check and inspection If there are other provisions in the relevant laws and regulations of the state, Pharmacopoeia of the people's Republic of China, regulatory inspection, inspection and law enforcement and other drug regulatory work, the corresponding provisions shall be implemented 2 terms and definitions the following definitions are used in this principle and procedure 2.1 batch number is used to identify a unique combination of numbers and / or letters for a specific batch 2.2 the same batch of drugs sampled in the sampling batch 2.3 the sampling unit is a drug packaging unit that is convenient for counting, handling and storage 2.4 unit sample the sample taken from a sampling unit is a unit sample 2.5 the smallest packaging unit that directly contacts the drug For ampoules, oral liquids, small bottles of solid injections, etc of less than 20ml (including 20ml), the packaging unit (such as box) in which such packaging is placed can be regarded as "the smallest packaging" 2.6 the same batch of drugs with uniform properties and quality The homogeneity inspection of the sampling process is mainly to check the homogeneity of the appearance of drugs 2.7 the same batch of drugs with different properties and quality of different parts of heterogeneous drugs 2.8 the normal physicochemical properties of drugs with normal heterogeneity can be shown as the same batch of drugs with heterogeneity but without changing their properties and quality (for example, suspension and liquid drugs that can separate out partial crystallization at low temperature and recover to the original state after rewarming) 2.9 the same batch of drugs with abnormal heterogeneity caused by factors such as failure to operate according to normal working procedures during the production or storage and transportation of drugs with abnormal heterogeneity 2.10 the final sample is a sample collected from different unit samples for inspection or investigation 3 Sampling principle 3.1 scientific, sampling operation, storage and transportation process should be scientific and reasonable to ensure sample quality 3.2 the sampling procedure shall be standardized and orderly and shall not be changed at will 3.3 the legality and sampling work shall meet the requirements of laws, regulations and normative documents such as the drug administration law of the people's Republic of China, the implementation regulations of the drug administration law of the people's Republic of China and the measures for the administration of random inspection and inspection of drug quality 3.4 fairness In the sampling process, the sampling personnel shall not be favoritism, objective and fair 3.5 representativeness: the samples taken shall be able to reflect the actual quality of the drugs represented in the sampling 4 Determination of sampling quantity 4.1 when preparing a sampling plan or sampling plan, the sampling quantity shall be determined according to the inspection requirements of standard inspection, supplementary inspection methods and / or exploratory research 4.2 generally, the sampling quantity shall be 2 times of the inspection demand, and 3 parts shall be repacked according to the proportion of 1:0.5:0.5 4.3 if there are different preparation specifications and packaging specifications for the same product, the preparation unit shall be calculated according to different specifications, and then the minimum packaging quantity of the sample shall be converted respectively (for example, the sterile powder for injection shall be calculated in grams and then converted into bottles, the liquid preparation shall be calculated in milliliters and then converted into bottles or bottles, etc.), and the special inspection items (such as microorganism) shall be met at the same time Limit, etc.) requirements for the minimum number of independent packages 4.4 the sampling amount shall be determined according to the principle of reasonable application, and shall not be simply accumulated according to a single inspection item (for example, the injection shall be inspected for other items after the inspection of visible foreign matters) 5 safety protection 5.1 when sampling radioactive, toxic, corrosive or flammable and explosive samples, the sampling personnel shall wear necessary protective equipment (such as protective clothing, protective gloves, protective glasses or protective masks, etc.) when carrying out on-site sampling, and handle with care At the same time, the samples shall be marked with dangerous goods to prevent accidents 5.2 inflammable and explosive samples shall be kept away from heat source 6 sampling procedure 6.1 preparation before sampling 6.1.1 personnel requirements Sampling personnel shall be familiar with laws, regulations and normative documents such as drug administration law of the people's Republic of China, regulations for the implementation of Drug Administration Law of the people's Republic of China, drug production quality management specifications, drug trade quality management specifications and measures for the administration of drug quality spot check and inspection, understand drug standard requirements such as Pharmacopoeia of the people's Republic of China, and be familiar with drugs The requirements of appearance, normal identification, storage conditions, etc., and the basic judgment of abnormal conditions can be made Sampling personnel shall correctly master all kinds of sampling methods and be proficient in using sampling instruments The sampling team shall be relatively stable and receive regular legal, regulatory and professional technical training 6.1.2 personnel organization sampling unit shall set up corresponding number of sampling working groups according to the objective requirements of the current sampling work, and the number of personnel in each sampling working group shall not be less than 2 In principle, the same person shall not undertake the sampling and inspection work at the same time The sampling unit shall carry out special training for the sampling personnel according to the requirements of the sampling task The sampling personnel shall carefully study the background information, make basic judgment on the sampling requirements, determine the specific matters of on-site inspection and sampling, and negotiate with the inspection institution on the specific matters such as inspection items, sampling links and sampling quantity when necessary 6.1.3 for the sampling tools that directly contact the drugs, they shall be cleaned and dried in time before and after use, without chemical reaction with the drugs, pollution of the samples and the remaining drugs When sampling powder solid samples and semi-solid samples, the stainless steel sampling rod with one side slotted and sharp front end is generally used for sampling, and the porcelain or stainless steel spoon can also be used for sampling When taking low viscosity liquid samples, pipette, beaker, spoon, funnel, etc shall be used according to different situations; when taking corrosive or toxic liquid samples, pipette assistant shall be used; when taking high viscosity liquid samples, glass rod can be used for dipping When taking aseptic samples or samples of items such as microbial test and bacterial endotoxin test, the sampling tools must be sterilized or pyrogen removed 6.1.4 the material of the packaging container that directly contacts the drug shall not react with the contents, have good barrier performance, and meet the storage conditions of the drug, and the potential migration materials shall not affect the test results Before sampling, check the integrity of the outer packaging of the packaging container The shape and specification of the packaging containers that directly contact with the drugs shall be suitable for the shape and quantity of the samples taken The storage of the liquid samples can be in the form of bottle sealed containers, and the storage of the solid samples can be in the form of bag containers Containers that directly contact sterile samples or need to do microbiological examination, bacterial endotoxin examination and other project samples must be sterilized or pyrogen removed, and have sealing performance 6.1.5 before sampling documents and certificates, the sampling personnel shall check the work plan or implementation plan, power of attorney or administrative law enforcement certificate, sample seal (attachment 1), drug sampling record and certificate (attachment 2), drug sampling notice and feedback sheet (attachment 3), sample (material evidence) sealed bag and other necessary certificates 6.2 spot inspection 6.2.1 the sampling personnel shall check the production and operation qualification and relevant materials of the sampled unit, check the environmental control measures, operation status, monitoring records, storage marks, etc of the storage place, check the name, approval number, batch number, validity period, drug listing license holder, etc of the package label on the site, and check the appearance package of the drug (such as damage, dampness , contaminated or counterfeit signs, etc.) 6.2.2 when suspected drug quality problems are found in the on-site inspection, targeted sampling can be carried out; if potential problems affecting drug quality are found or illegal production, operation and use behaviors are found, relevant evidence shall be fixed and transferred to the drug supervision and administration department with jurisdiction over the sampled unit for disposal 6.3 sampling 6.3.1 field sampling method, number of sampling units (n) and determination of sampling units field sampling method, number of sampling units (n) and determination of sampling units can refer to Appendix 4 6.3.2 the sampling method and the preparation of the final sample of Chinese herbal medicine and Chinese herbal pieces shall refer to the method specified in the Pharmacopoeia of the people's Republic of China "sampling method of Chinese herbal medicine and Chinese Herbal Pieces" Except for special cases, samples from the unsealed complete package shall be taken, and relevant evidence shall be retained for the packaging The sampling method of preparation and API and the preparation of final sample can refer to Appendix 5 For special samples, the sampling personnel can randomly designate the samples to be sampled, and accompany or supervise the quality personnel of the sampled unit to conduct on-site sampling 6.4 packaging, seal, record and information submission 6.4.1 each sample of packaging shall be separately packed and sealed and kept in accordance with the conditions specified in the instructions 6.4.2 the sealing sampling personnel shall use the special seal (see attachment 1) to seal the sample, complete and accurately fill in the sealing contents, which shall be signed by the sampling personnel and relevant personnel of the sampled unit, and stamped with seal or model; the sealing shall ensure that the sample cannot be exchanged 6.4.3 the record sampling personnel shall complete, accurately and normatively fill in the special drug sampling record and certificate (Appendix 2) and drug sampling notice and feedback form (Appendix 3), which shall be signed by the sampling personnel and relevant personnel of the sampled unit, and stamped with seal or model During the sampling process, the sampling process, sample information, sampling environment and other information can be recorded by means of taking photos, video recording and keeping relevant bills 6.4.4 after the information is submitted to the sampling personnel to complete the on-site sampling, the sampling information shall be timely submitted through the corresponding information platform in accordance with the relevant work requirements 6.5 storage and transportation 6.5.1 during the storage and transportation of samples, corresponding measures shall be taken and recorded according to the requirements of storage and transportation conditions to ensure that the whole process meets the requirements of drug storage conditions and that the samples are not deteriorated, damaged or polluted 6.5.2 the sample shall be sent (sent) to the inspection institution by the sampling personnel When it is necessary to entrust others for transportation, the unit with corresponding storage and transportation qualification and conditions shall be selected If necessary, the transportation and Storage Condition Guarantee Agreement shall be signed to avoid the loss, wrong delivery, pollution and deterioration of the sample during transportation 6.5.3 the storage and transportation of special drugs shall be carried out in accordance with the relevant provisions of the state 6.5.4 according to the requirements of sampling inspection plan or implementation plan, the sampling documents and relevant data shall be sent (sent) to the inspection agency with the samples 7 when formulating the sampling inspection plan or implementation plan, the sample Purchasing Drug Supervision and administration department shall specify the settlement method, settlement time limit and payment unit (such as sampling Organization Department, sampling unit, inspection unit, etc.) After the sampling personnel complete the sampling and fill in the sample purchasing information, the payee (which may be the user, sales unit, production unit or the holder of the drug listing license, etc.) shall present the relevant bills and