Substantially complete application is an ANDA that on its face is sufficiently complete to permit a substantive review. Sufficiently complete means that the ANDA contains all the information required under section 505(j)(2)(A) of the Federal Food, Drug, and Cosmetic Act and does not contain a deficiency described in §314.101(d) and (e).
E. Failure to Provide Environmental Assessment (EA) or Claim of Categorical Exclusion
APPENDIX A: EXAMPLES OF MINOR DEFICIENCIES
1. An ANDA is required to contain either an environmental assessment (EA) or a claim of categorical exclusion…
未提供环境评价不再是主要缺陷（major deficiencies）
(3)
V. CHEMISTRY, MANUFACTURING, AND CONTROL DEFICIENCIES
A. Inactive Ingredients 3. Elemental Iron Levels
FDA will refuse-to-receive an ANDA if a daily elemental iron calculation is not included for products that contain iron…
APPENDIX A:
3. An ANDA must contain either a daily elemental iron calculation for products that contain iron…If FDA does not receive either the calculation or aforementioned statement within 7 calendar days of notification of the omission(s), FDA will RTR the ANDA.
如果申报资料未包括铁元素的计算，从“直接拒收”改为“通知7天内未收到回复将拒收”
(4)
V. CHEMISTRY, MANUFACTURING, AND CONTROL DEFICIENCIES
B. Inadequate Stability
1. Number of Batches and Length of Studies
covering a period of no less than 6 months…
2. Container Orientation
FDA will refuse-to-receive an ANDA if horizontal or inverted (i.e., worst-case scenario) accelerated stability…However, these drug products should also be evaluated for stability in the upright (or vertical) position. For routine stability studies, the applicant should pick the worst-case orientation for the study.
V. PRODUCT QUALITY DEFICIENCIES
B. Inadequate Stability
1. Number of Batches and Length of Studies
covering a period of no less than 6 months (180 days), with data from three time points (e.g., 0, 3, and 6 months).
2. Container Orientation
FDA will RTR an ANDA if both worst-case scenario and non-worst-case stability data adhering to the recommendations described in section V.B.1 and this section are not submitted for the described drug product batches: liquids, solutions, semi-solids, and suspensions
不充分的稳定性数据是2015年ANDA拒收常见问题之一。
修订版2关于稳定性3个时间点的表述更明确；关于溶液类放置方向表述更简练。
(5)
V. CHEMISTRY, MANUFACTURING, AND CONTROL DEFICIENCIES
D. Batch Records batch records, either commercial or executed, should contain an accurate and complete English translation of any portion of an application that is not printed or written in English.
APPENDIX A
2. An ANDA must contain an accurate and complete English translation of each part of the application that is not in English. This requirement includes the translation of all sections of the document (e.g., headers, titles). FDA will accept an ANDA with the English translation on a blank page next to the original text. FDA recommends that the translation be legible in size 12 font. The applicant should use its best judgment in determining how to fit the necessary information on a page without impacting the reviewer’s ability to read the information. If FDA does not receive English translation of each part of the application that is not in English within 7 calendar days of notification of the omission(s), FDA will RTR the ANDA.
other suggested types of supplemental dissolution studies include:
Half-tablet dissolution for drug products with functional score marks
Other suggested types of comparative (i.e. test product and RLD) supplemental dissolution studies include:
Half-tablet dissolution for modified-release drug products with functional score marks performed for each strength of test and RLD in the recommended media, or quality control (QC) media if there is no recommendation (alcohol dose-dumping studies are not recommended for half-tablet dissolution studies)
补充的溶出度数据要求更明确；强调参比制剂和试验样品的对比；对于刻痕缓释药品，强调每个规格的对比；
(7)
VI. BIOEQUIVALENCE AND CLINICAL DEFICIENCIES
E. Miscellaneous Factors
3. DBE, DCR, Office of Pharmaceutical Quality Receipt Reviews
(e.g., inappropriate or inadequate clinical endpoint, inappropriate indication for use, inadequate sampling, failure to measure appropriate active drug or active metabolites in PK sampling, use of an inappropriate patient population, or allowance of inappropriate concomitant medications).
生物等效性办公室、药品质量办公室推荐的拒收情况，删去了缺陷的举例
(8)
VI. BIOEQUIVALENCE AND CLINICAL DEFICIENCIES
E. Miscellaneous Factors 4. Sameness Criterion for Devices
On a case-by-case basis, FDA will refuse-to-receive an ANDA
4. Drug-Device Combination Products
On a case-by-case basis and in consideration of preliminary evaluations performed by consultant offices, FDA will RTR an ANDA
表述变化。修订稿 2 的表述为：基于具体问题具体分析，并且考虑咨询办公室进行的基本评估，...
(9)
APPENDIX A: EXAMPLES OF MINOR DEFICIENCIES
举例2
If, upon filing review of such an ANDA, OGD determines that the labeling submitted in the ANDA does refer to a use described in such use codes, OGD will not provide guidance or suggestions as to how the proposed labeling should be amended.
APPENDIX A: EXAMPLES OF MINOR DEFICIENCIES
举例6
Where a listed patent claims the drug substance and/or drug product and one or more methods of use, the applicant may provide a “split certification” to the patent (i.e., the applicant provides a statement that the applicant is not seeking approval for one or more methods of use claimed by the patent based on the use code(s) listed in the Orange Book (sometimes referred to as a “section viii” statement) and a patent certification to the remaining claims). If, upon filing review of such an ANDA, OGD determines that the labeling submitted in the ANDA does refer to a use described in such use codes, OGD will not provide guidance or suggestions as to how the proposed labeling should be amended.
原文：
FDA, in its discretion, provides applicants with the opportunity to correct minor deficiencies or amend the ANDA, within seven (7) calendar days. If within 7 calendar days the requested information is not received, FDA will RTR the ANDA. However, if FDA determines that an ANDA contains ten or more minor deficiencies or one or more major deficiencies, FDA will not consider the ANDA to be a substantially complete application under 21 CFR 314.101(b)(1). In such cases, FDA will notify the applicant that FDA considers the ANDA not to have been “received.” If the applicant decides to submit additional materials to correct the deficiencies, the resulting amended ANDA will be considered a new ANDA submission, received as of the date the amended ANDA is submitted (if deemed substantially complete), and the applicant will be required to pay a new ANDA fee. If an ANDA is not received and the applicant takes no action, FDA may consider the ANDA withdrawn after 1 year. An ANDA applicant’s failure to take action after a refuse-to-receive decision on an ANDA may be considered a request by the applicant to withdraw the ANDA, unless the applicant requests an extension of time in which to resubmit the ANDA.
翻译：
如果有少于10个一般缺陷，FDA将会给机会，让企业在7天内修订回复。如果7天内FDA未收到信息回复，FDA将会拒收（RTR）该ANDA。如果有10个以上一般缺陷，或者1个主要缺陷，FDA将会认为该ANDA不是实质性完整。在这些情况下，FDA将会通知ANDA已被拒收（not to have been “received”）。如果申请人决定递交更多的材料来纠正缺陷，这产生的纠正的ANDA（amended ANDA）将会被认为是新的ANDA，在纠正的ANDA递交的日期接收（如果是实质完整的），并且需要按照新的ANDA交费。如果ANDA被拒收，并且申请人未采取任何行动，FDA将会认为ANDA在一年后撤销（withdrawn）。ANDA申请人未能在拒收决定后对ANDA采取行动，将会被认为是“申请人请求撤销ANDA”，除非申请人请求延长时间以重新递交ANDA。
