在ANDA申报中，3.2.S.4和3.2.P.4分别是对API和辅料的质量控制，二者有着相似的模式，如依照质量标准、分析方法、方法验证和justification 的思路编辑申报资料，也有着不同点，以下将进行解读。

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.

解读：包括制剂商对API的放行质量标准，和API厂商的质量标准。这些质量标准需以表格的形式呈现：包括检测项、接受标准和参考。

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(药典或内控方法)

3.2.S.4.3 Contains the validation of analytical procedures including: 包含分析方法的方法验证

(1) full validation reports for in-house methods and their equivalence to United States Pharmacopeia (USP) procedures if available for the drug substance; 内控方法的全验证

(2) verification of USP <1226> or DMF procedures, when referenced;若引用的话，按USP <1226>或DMF方法确认

(3) legible spectra and chromatograms for reference standards and test samples; 对照品和测试样品清晰的光谱和色谱图 

(4) Sample Statement(s) of Availability and identification of the drug substance, along with associated lot numbers原料药样品可得和鉴别的申明，并写明批号。

解读：

 若有USP方法，但企业使用自己开发的内控方法，除了要做全验证，还需证明和USP方法等同。

 谱图需清晰，不可读的图谱可能会发缺陷信

 ANDA申报时，是用两批的API生产三批的drug product 进行，需在这一章节申明这两批API可得，一旦FDA需要，可供其鉴别检测等。

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.包含原料药厂家和制剂商批次的批分析COA(这些批次用来生产执行批的制剂) 

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

包含质量标准的justification，包括但不限于，参照药典(如USP，EP，JP, ICH或RLD)。

解读：

 FDA建议申请者以列表的形式表示杂质的justification。

 对于杂质限度，不能简单的依据USP或照搬DMF，需查询product的MDD，根据ICHQ3A 推导其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.包含复测期的质量标准和供应商的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.分析方法验证

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.质量标准的justification：制剂商放行辅料的COA；供应商出具的残溶申明，BSE/TSE申明，三聚氰胺申明。

解读：

 3.2.S.4.1包含制剂商和原料药厂商对API的质量标准，3.2.S.P.4.1只包含制剂商对辅料的放行标准和供应商COA。即辅料无需供应商质量标准，且供应商COA在3.2.S.P.4.1章节，而API的供应商COA在3.2.S.4.4.

 对于3.2.S.4.4对API的批分析数据，但在3.2.P.4, 辅料供应商的COA和制剂商对辅料的放行COA分别在3.2.P.4.1和3.2.P.4.4章节。

 对于justification，3.2.S.4.5比3.2.P.4.4复杂，对于辅料，justification需供应商出具的残溶申明，BSE/TSE申明，三聚氰胺申明。

 对于残溶，比如某溶剂，可能在API和辅料中都有用到，请注意，两者的加和要小于ICH残溶标准。