中文字幕一级黄色A级片|免费特级毛片。性欧美日本|偷拍亚洲欧美1级片|成人黄色中文小说网|A级片视频在线观看|老司机网址在线观看|免费一级无码激情黄所|欧美三级片区精品网站999|日韩av超碰日本青青草成人|一区二区亚洲AV婷婷

在ANDA申報(bào)中，3.2.S.4和3.2.P.4分別是對(duì)API和輔料的質(zhì)量控制，二者有著相似的模式，如依照質(zhì)量標(biāo)準(zhǔn)、分析方法、方法驗(yàn)證和justification 的思路編輯申報(bào)資料，也有著不同點(diǎn)，以下將進(jìn)行解讀。

3.2.S.4 Contains all information about the control of the drug substance.包括所有drug substance的控制信息

3.2.S.4.1 Contains the drug substance specifications. These specifications include the tests, acceptance criteria, and references to methods in tabular form.

解讀：包括制劑商對(duì)API的放行質(zhì)量標(biāo)準(zhǔn)，和API廠商的質(zhì)量標(biāo)準(zhǔn)。這些質(zhì)量標(biāo)準(zhǔn)需以表格的形式呈現(xiàn)：包括檢測(cè)項(xiàng)、接受標(biāo)準(zhǔn)和參考。

3.2.S.4.2 Contains the description of analytical procedures (compendial and/or in-house).包含分析方法的描述(藥典或內(nèi)控方法)

3.2.S.4.3 Contains the validation of analytical procedures including: 包含分析方法的方法驗(yàn)證

(1) full validation reports for in-house methods and their equivalence to United States Pharmacopeia (USP) procedures if available for the drug substance; 內(nèi)控方法的全驗(yàn)證

(2) verification of USP <1226> or DMF procedures, when referenced;若引用的話，按USP <1226>或DMF方法確認(rèn)

(3) legible spectra and chromatograms for reference standards and test samples; 對(duì)照品和測(cè)試樣品清晰的光譜和色譜圖 

(4) Sample Statement(s) of Availability and identification of the drug substance, along with associated lot numbers原料藥樣品可得和鑒別的申明，并寫(xiě)明批號(hào)。

解讀：

? 若有USP方法，但企業(yè)使用自己開(kāi)發(fā)的內(nèi)控方法，除了要做全驗(yàn)證，還需證明和USP方法等同。

? 譜圖需清晰，不可讀的圖譜可能會(huì)發(fā)缺陷信

? ANDA申報(bào)時(shí)，是用兩批的API生產(chǎn)三批的drug product 進(jìn)行，需在這一章節(jié)申明這兩批API可得，一旦FDA需要，可供其鑒別檢測(cè)等。

3.2.S.4.4 Contains the batch analysis including the Certificates of Analysis (COAs) from both the drug substance manufacturer (s) and drug product manufacturer for the batches used to produce the exhibit batch(es) of the drug product.包含原料藥廠家和制劑商批次的批分析COA(這些批次用來(lái)生產(chǎn)執(zhí)行批的制劑) 

3.2.S.4.5 Contains the justification of the specifications including, but not limited to, references to compendia (e.g., USP, European Pharmacopeia (EP), and the Japanese Pharmacopeia (JP)), ICH, and/or RLD analysis. FDA recommends that applicants complete the Summary Tables for the Listing and Characterization of Impurities and Justification of Limits in Drug Substance

包含質(zhì)量標(biāo)準(zhǔn)的justification，包括但不限于，參照藥典(如USP，EP，JP, ICH或RLD)。

解讀：

? FDA建議申請(qǐng)者以列表的形式表示雜質(zhì)的justification。

? 對(duì)于雜質(zhì)限度，不能簡(jiǎn)單的依據(jù)USP或照搬DMF，需查詢product的MDD，根據(jù)ICHQ3A 推導(dǎo)其IT、QT等

3.2.P.4 Contains information on the controls of excipients including the identity of the source of inactive ingredients and the grades (e.g., compendial or noncompendial). 

3.2.P.4.1 Contains the testing specifications including retest schedule and the excipient manufacturer’s or supplier’s COA.包含復(fù)測(cè)期的質(zhì)量標(biāo)準(zhǔn)和供應(yīng)商的COA

3.2.P.4.2 Contains the analytical procedures for the testing.包含分析方法

3.2.P.4.3 Contains the validation data of the analytical procedures.分析方法驗(yàn)證

3.2.P.4.4 Contains the justification of the specifications and includes: (1) the applicant’s or drug product manufacturer’s COA(s); (2) residual solvents statement(s) from manufacturer(s); and (3) bovine spongiform encephalopathy (BSE), transmissible  spongiform encephalopathy (TSE), and melamine certifications, as applicable.質(zhì)量標(biāo)準(zhǔn)的justification：制劑商放行輔料的COA；供應(yīng)商出具的殘溶申明，BSE/TSE申明，三聚氰胺申明。

解讀：

? 3.2.S.4.1包含制劑商和原料藥廠商對(duì)API的質(zhì)量標(biāo)準(zhǔn)，3.2.S.P.4.1只包含制劑商對(duì)輔料的放行標(biāo)準(zhǔn)和供應(yīng)商COA。即輔料無(wú)需供應(yīng)商質(zhì)量標(biāo)準(zhǔn)，且供應(yīng)商COA在3.2.S.P.4.1章節(jié)，而API的供應(yīng)商COA在3.2.S.4.4.

? 對(duì)于3.2.S.4.4對(duì)API的批分析數(shù)據(jù)，但在3.2.P.4, 輔料供應(yīng)商的COA和制劑商對(duì)輔料的放行COA分別在3.2.P.4.1和3.2.P.4.4章節(jié)。

? 對(duì)于justification，3.2.S.4.5比3.2.P.4.4復(fù)雜，對(duì)于輔料，justification需供應(yīng)商出具的殘溶申明，BSE/TSE申明，三聚氰胺申明。

? 對(duì)于殘溶，比如某溶劑，可能在API和輔料中都有用到，請(qǐng)注意，兩者的加和要小于ICH殘溶標(biāo)準(zhǔn)。