在ANDA申報中，3.2.S.4和3.2.P.4分別是對API和輔料的質量控制，二者有著相似的模式，如依照質量標準、分析方法、方法驗證和justification 的思路編輯申報資料，也有著不同點，以下將進行解讀。

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API的放行質量標準，和API廠商的質量標準。這些質量標準需以表格的形式呈現：包括檢測項、接受標準和參考。

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; 內控方法的全驗證

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

(3) legible spectra and chromatograms for reference standards and test samples; 對照品和測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，并寫明批號。

解讀：

? 若有USP方法，但企業使用自己開發的內控方法，除了要做全驗證，還需證明和USP方法等同。

? 譜圖需清晰，不可讀的圖譜可能會發缺陷信

? ANDA申報時，是用兩批的API生產三批的drug product 進行，需在這一章節申明這兩批API可得，一旦FDA需要，可供其鑒別檢測等。

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(這些批次用來生產執行批的制劑) 

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

包含質量標準的justification，包括但不限于，參照藥典(如USP，EP，JP, ICH或RLD)。

解讀：

? FDA建議申請者以列表的形式表示雜質的justification。

? 對于雜質限度，不能簡單的依據USP或照搬DMF，需查詢product的MDD，根據ICHQ3A 推導其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.包含復測期的質量標準和供應商的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.質量標準的justification：制劑商放行輔料的COA；供應商出具的殘溶申明，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API的質量標準，3.2.S.P.4.1只包含制劑商對輔料的放行標準和供應商COA。即輔料無需供應商質量標準，且供應商COA在3.2.S.P.4.1章節，而API的供應商COA在3.2.S.4.4.

? 對于3.2.S.4.4對API的批分析數據，但在3.2.P.4, 輔料供應商的COA和制劑商對輔料的放行COA分別在3.2.P.4.1和3.2.P.4.4章節。

? 對于justification，3.2.S.4.5比3.2.P.4.4復雜，對于輔料，justification需供應商出具的殘溶申明，BSE/TSE申明，三聚氰胺申明。

? 對于殘溶，比如某溶劑，可能在API和輔料中都有用到，請注意，兩者的加和要小于ICH殘溶標準。