三批中的两批应达到目标批量的至少10%，或至少100,000最小制剂单位，取
其中较大者（即中试批次）。第三批可以比目标批量的10%小，但不能低于中试批量的25%。我们建议稳定性数据由目标市售包装三批ANDA申报批产生。建议所有包装形式至少包括100,000个最小制剂单位。三批申报批中具有代表性的样品应有足够数量进行市售包装，满足21CFR211.166(a)（1-5）和211.166（b）的要求。
(b) Powders/Solutions/Suspensions: 粉剂/溶液/混悬剂
Two of the three batches should be at least 10 percent of the proposed maximum
size commercial batch. The third batch can be smaller than 10 percent of the proposed commercial batch, but not less than 25 percent of the pilot scale batch. To capture variability introduced by packaging, the product from all the batches should be used in the packaging process. We recommend packaging representative samples from all three batches of a sufficient number of proposed marketing presentations to comply with 21 CFR 211.166(a)(1-5) and 211.166(b) .
3批中的2批要求是商业最小批量10%的批量。第3批可以小于提出的商业批量
的10%，但不小于中试批准的25%批量。为了发现包装引起的差异，所有批次产品均应采用申报的包装工艺进行包装。 我们建议根据21 CFR
211.166(a)(1-5) 和 211.166(b)中的要求，对所有3批中均按申请的上市包装
对足够数据样品进行包装获得代表性样品。
Parenterals Solutions/Powders for Solutions (lyophilized
cakes)/Suspensions/Sterile Topicals (Ophthalmic and Otic drug products):
注射液/溶液用粉剂（冻干粉）/混悬剂/无菌局部（眼用和耳用剂）
Two of the three batches should be at least 10 percent of the proposed maximum
size commercial batch (i.e., pilot scale size) or 50 L (per batch), whichever is larger. The third batch can be smaller than 10 percent of the proposed commercial batch, but not less than 25 percent of the pilot scale batch. To
capture variability introduced by packaging, the product from all the batches should be used in the packaging process. Representative samples from all the three batches should be packaged in a sufficient number of proposed marketing presentations to comply with 21 CFR 211.166(a)(1-5) and 211.166(b). We recommend manufacturing all the batches to meet sterility requirements.
3批中的2批应是申报的商业批量至少10%批量（即中试批量）或50L（每批），
取大者。第3批可以小于申请的商业批次的10%，但不小于中试批量的25%。应根据21 CFR 211.166(a)(1-5) 和211.166(b)中的要求，对所有3批中均按申请的上市包装对足够数据样品进行包装获得代表性样品。我们建议所有批准生产均满足无菌要求。
Transdermal Patches 经皮给药贴剂
Two of the three batch sizes for each strength should be at least 10 percent of the
proposed commercial production batch or 25,000 units (for each strength), whichever is greater. The third batch can be smaller than 10 percent of the proposed commercial batch, but not less than 60 percent of the pilot scale batch. For transdermal matrix products, where different strengths are identified by the transdermal patch size (surface area), to comply with the three batch size recommendation, we recommend providing data on patches manufactured using three distinct matrix laminates at the time of submission. (Each laminate can be cut to support multiple strengths in the application, where applicable.) We recommend you contact the appropriate review division if you are manufacturing transdermal patches using other technologies (e.g., reservoir).[2]
各不同剂量的3批中的2批批量应至少为申报商业批量的10%，或23000个最
小单位（每个剂量），取其大者。第3批可以小于申报的商业批量的10%，但不能小于中试批量的60%。对于经皮给药支架产品，如果剂量差异与贴剂尺寸（表面积）差异相同，符合3个批量的推荐，我们建议在申报时提供采用3个明显区别的支架压板（适用时，每个压板可以剪切以支持申报中的不
同剂量）。如果你采用了其它技术（例如膏药）来生产经皮给药贴剂，我们推荐你联系适当的审核部门，
You should include a representative sample from all three batches using different
components of backing, adhesives, release liner, and other critical excipients used in packaging a sufficient number of proposed marketing presentations to comply with 21 CFR 211.166(a)(1-5) and 211.166(b).
你应该包括所有3个批号采用不同基底成份、粘性材料、防粘衬里和其它用于包
装的关键辅料的代表性样品，采用上市包装获得足够数量的样品，以满足
21 CFR 211.166(a)(1-5) 和 211.166(b)的要求。
Topicals 局部用药
(a) Creams/Lotions/Gels: 膏剂/洗液/胶
For nonsterile semi-solid dosage forms[3], the two pilot scale batches should be at
least 100 Kg or 10 percent of the production batch, whichever is larger. The third batch can be smaller than 10 percent of the proposed commercial batch, but not less than 40 percent of the pilot scale batch. We recommend packaging representative samples from all the three batches in a sufficient number of proposed marketing presentations to comply with 21 CFR 211.166(a)(1-5) and 211.166(b) .
对于非无菌半固体剂型，应有2批中试批次，批量至少100kg或商业批量的10%，
取其大者。第3批可以小于商业批量的10%，但不得小于中试批量的40%。我们推荐所有3个批次均有足够数据上市包装的代表性样品，以符合21 CFR
211.166(a)(1-5) 和 211.166(b)的要求。
(b) Inhalation Solutions/Nasal Sprays (nasal nonmetered dose atomizer): 吸
入溶液/鼻腔喷剂（鼻腔非定量喷雾器）
Please refer to the following guidances for industry for information: Nasal Spray
and Inhalation Solution, Suspension, and Spray Drug Products – Chemistry,
Manufacturing, and Controls Documentation, and Bioavailability and Bioequivalence Studies for Nasal Aerosols and Nasal Sprays for Local Action.
请参见以下行业指南：鼻腔喷雾剂和吸入溶液，混悬液，和喷雾药品------化学，
生产，和控制文件，和鼻腔气雾剂和鼻腔喷剂的生物有效性和生物等效性研究
Please contact OGD to discuss other dosage forms and/or routes of
administration not covered in this document.
如需讨论其它剂量形式和/或在本文件中未涵盖的给药方法，请联系OGD。
Q14: Is it acceptable to use a technical grade of the drug substance for the
small scale batches or one of the two pilot scale batches of finished product?
是否可以采用技术级的原料药用于小批量或两个中试批中的一批的药品生产？
A14: No. CGMP requirements for ANDA submission are expected for the drug
substance and drug product. Because the drug substance quality can affect the drug product stability, the drug substance used for the ANDA batches (supporting the application) should be of the same quality intended for the market product. We would consider data from the use of a different grade drug substance for a product as supporting data. This does not satisfy the submission batch recommendations.
不可以。ANDA申报要求原料药和制剂均在CGMP状态下生产。由于原料药质
量可能会影响药品稳定性，用于ANDA批次的原料药（支持申报）应具有上市药品相同的品质。我们会考虑采用不同级别原料药生产所得的数据作为支持性数据，但这并不符合申报批次的要求。
[1] For nasal aerosols (meter-dose inhalers) and nasal sprays (meter-dose spray pumps), you
should submit three different lots of drug substance.
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