目的 探索建立通過仿制藥一致性評(píng)價(jià)品種上市后藥品質(zhì)量一致性快速評(píng)判方法，用于市場(chǎng)仿制藥質(zhì)量快速評(píng)價(jià)。方法 基于拉曼光譜法，根據(jù)質(zhì)量控制需求，分別采用一致性評(píng)價(jià)參比制劑、申報(bào)批、同批次制劑作為參比標(biāo)準(zhǔn)，以相似度值、置信區(qū)間、不確定度作為評(píng)判指標(biāo)。檢驗(yàn)流程分為建庫和快檢 2 部分，建庫：參比制劑和申報(bào)批的拉曼光譜作為標(biāo)準(zhǔn)譜圖存于云端數(shù)據(jù)庫，或取市售仿制藥某批樣品自身某片藥品建庫；快檢：采集 10 片藥物制劑樣品拉曼光譜分別上傳，與拉曼光譜庫“四同”（同生產(chǎn)企業(yè)、同品種、同規(guī)格、同批號(hào)）樣品標(biāo)準(zhǔn)譜圖比對(duì)，在標(biāo)準(zhǔn)拉曼光譜庫中未能獲取標(biāo)準(zhǔn)譜圖時(shí)，進(jìn)行市售批自身片與片之間比對(duì)?；谥袊?guó)拉曼光譜云計(jì)算中心“藥品追溯”模塊，優(yōu)化升級(jí)成“仿制藥評(píng)價(jià)”模塊，與仿制藥評(píng)價(jià)專用手持式拉曼光譜儀聯(lián)合，形成“仿制藥質(zhì)量拉曼光譜快速評(píng)價(jià)系統(tǒng)（CEVAR 系統(tǒng)）”。該項(xiàng)目在2020 年度山東省藥品質(zhì)量風(fēng)險(xiǎn)監(jiān)測(cè)項(xiàng)目中進(jìn)行了應(yīng)用，共征集到省內(nèi) 18 家企業(yè)、45 個(gè)品種（73 個(gè)品規(guī)）、225 批次的市售批樣品；征集到 3 家企業(yè)、3 個(gè)品種、5 個(gè)批次的參比制劑；3 家企業(yè)、4 個(gè)品種、12 個(gè)批次的申報(bào)批樣品。取瑞舒伐他汀鈣片參比試劑和市售批用拉曼光譜成像系統(tǒng)進(jìn)行驗(yàn)證。結(jié)果 將相似度 99% 作為通用判定閾值；征集到的絕大多數(shù)品種的自身相似度都大于 99%，但是有 5 個(gè)品種樣品雖然平均相似度值大于 99%，但是每批次有 3～5 片與標(biāo)準(zhǔn)比對(duì)相似度小于 99%；充分證實(shí)CEVAR 系統(tǒng)檢測(cè)的準(zhǔn)確性。瑞舒伐他汀鈣片拉曼光譜成像系統(tǒng)的驗(yàn)證結(jié)果與 CEVAR 系統(tǒng)結(jié)果一致。結(jié)論 通過大批量樣品測(cè)試數(shù)據(jù)，相似度 99% 可以作為質(zhì)量?jī)?yōu)劣判定的閾值，CEVAR 系統(tǒng)適合于對(duì)藥物制劑工藝質(zhì)量的普遍篩查。

Objective To establish a rapid evaluation method of drug that passed the consistency evaluation of generic drugs, which can be used to quickly evaluate the quality of the generic drugs in the market. Method Based on Raman spectroscopy, according to the quality control needs, the reference preparations, the submitted batch, and the batches of the same batch of the drug were used as reference standards respectively, and the similarity index, the confidence interval, and the uncertainty were used as evaluation indicators. The inspection process is divided into two parts: building a database and fast inspection. The building of the database: The Raman spectra of the reference preparations and the submitted batch are stored as standard spectra in the cloud database or built by taking a certain batch of a commercial imitation drug. The fast inspection: The Raman spectra of 10 drug preparations are collected and uploaded separately, and compared with the standard Raman spectra of the "four same" (same manufacturer, same variety, same specifications, and same batch number) samples in the Raman spectral database. When the standard Raman spectra of the database cannot be obtained, the comparison is made between the same batch of the commercial imitation drug and the same batch of the drug. Based on the China Raman Spectrum Cloud Computing Center's "Drug Traceability" module, the "Imitation Drug Evaluation" module is optimized and upgraded, combined with the imitation drug evaluation dedicated handheld Raman spectrometer, forming the "Imitation Drug Quality Raman Spectrum Rapid Evaluation System (CEVAR system)". This project was applied in the 2020 annual drug quality risk monitoring project in Shandong Province, a total of 18 enterprises from the province, 45 varieties (73 specifications), and 225 batches of commercial batch samples were collected; 3 enterprises, 3 varieties, and 5 batches of reference preparations were collected. Three enterprises, four varieties, and twelve batches of application batch samples were collected. The reference reagent and the in-market batch-use Raman spectrometry imaging system were used for validation. Result A general threshold of similarity of 99% was used as the criterion; the majority of the varieties collected had a self-similarity of greater than 99%, but five varieties had an average similarity value greater than 99%, but 3-5 pieces per batch had a similarity value with the standard less than 99%. This strongly confirms the accuracy of the CEVAR system. The validation results of the Raman spectrometry imaging system for Rosuvastatin calcium tablets were consistent with those of the CEVAR system. Conclusion According to data of mass sample testing, the similarity of 99% can be used as the threshold value for the determination of quality, and this method is suitable for the general screening of process quality of pharmaceutical preparations

山東省食品藥品安全檢測(cè)工程技術(shù)研究中心自擬課題（SDIFDC-KY-2-2021036）