如果一个产品中有几个未知的杂质，绝对量相对较小，在M7的要求下，按周期给药，每天剂量分别为不超过120μg/d、20μg/d、10μg/d和1.5μg/d，但不满足Q3的要求，即未知杂质小于或等于1.0%的限制。那么，我们能否说这对患者的安全没有影响？
根据提供的信息，该产品的杂质不满足Q3的限制，这可能会对患者的安全造成潜在影响。因此，不能简单地认为该产品对患者的安全没有影响。需要对杂质进行更详细的评估，并按照相关法规制定合适的限值。[1][3][4]
[1] "二者取较低者。 例如， 如果终生给药时根据化合物特异性风险评估方法所推导的可接受摄入量为15μg/d， 用药周期短于终生给药时的限值（按表1比例）， 则可以增加至100μg/d（＞l～10年治疗时长）， 200μg/d（＞l～12个月）或1200μg/d（＜1个月）。 但是， 对于一个具有最大日服用剂量的药物， 例如， 100mg， 则小于1个月时长的可接受摄入量应限制在0.5%（500μg）， 而不是1200μg。 本指导原则中描述的杂质潜在致突变性的评估方法可用于所有给药途径。 除非存在特定给药方式的问题， 否则无需调整可接受摄入量。"
[2] "dietary exposure to...
[2] "dietary exposure to the substance resulting from the proposed use is at or below 1 percent of the acceptable daily intake as determined by safety data in the Food and Drug Administration's files or from other appropriate sources; (3) The substance has no technical effect in or on the food to which it migrates; and (4) The substance use has no significant adverse impact on the environment. (b) Notwithstanding paragraph (a) of this section, the Food and Drug Administration reserves the right to decline to grant an exemption in those cases in which available information establishes that the proposed use may pose a public health risk. The reasons for the agency's decision to decline to grant an exemption will be explained in the Food and Drug Administration's response to the requestor. (c) A request for the Food and Drug Administration to exempt a use of a substance from regulation as a food additive shall include three copies of the following information (If part of the submitted material is in a foreign language, it must be accompanied by an English translation verified to be complete and accurate in accordance with § 10.20(c)(2) of this chapter): (1) The chemical composition of the substance for which the request is made, including, whenever possible, the name of the chemical in accordance with current Chemical Abstract Service (CAS) nomenclature guidelines and a CAS registry number, if available; (2) Detailed information on the conditions of use of the substance (e.g., temperature, type of food with which the substance will come into contact, the duration of the contact, and whether the food-contact article will be for repeated or single use applications); (3) A clear statement as to whether the request for exemption from regulation as a food additive is based on the fact that the use of the substance in the food-contact article results in a dietary concentration at or below 0.5 parts per billion, or on the fact that it involves the use of a regulated direct food additive for which the dietary exposure is at or below 1 percent of the acceptable dietary intake (ADI); (4) Data that will enable the Food and Drug Administration to estimate the daily dietary concentration resulting from the proposed use of the substance. These data should be in the form of: (i) Validated migration data obtained under worst-case (time/temperature) intended use conditions utilizing appropriate food simulating"
[3] "则杂质的可接受摄入量参考表1进行调整，...
[3] "则杂质的可接受摄入量参考表1进行调整， 再结合其他因素制定合适的限值。 例3根据TTC可接受摄入量计算限值 某C药中含2类杂质c， C药临床用量为1.5mg/d， 每3天增加0.5～1mg， 成人最大给药量为20mg/d， 终身治疗时间不超过3～6个月。 参考表1， C药治疗期在大于1～12个月的范围内， 杂质c最大可接受摄入量调整为20μg/d。 C药的每日最大临床剂量为20mg/d， 则杂质c的限值为： 20μg/d÷20mg/d=0.1% 3类杂质经（Q）SAR方法测试确定为3类的杂质， 可进行细菌回复突变试验， 若试验结果显示有致突变性， 则杂质归为2类， 按2类杂质制定限值。"
[4] "as a food additive ...
[4] "as a food additive because it becomes a component of food at levels that are below the threshold of regulation if: (1) The substance has not been shown to be a carcinogen in humans or animals, and there is no reason, based on the chemical structure of the substance, to suspect that the substance is a carcinogen. The substance must also not contain a carcinogenic impurity or, if it does, must not contain a carcinogenic impurity with a TD50 value based on chronic feeding studies reported in the scientific literature or otherwise available to the Food and Drug Administration of less than 6.25 milligrams per kilogram bodyweight per day (The TD50, for the purposes of this section, is the feeding dose that causes cancer in 50 percent of the test animals when corrected for tumors found in control animals. If more than one TD50 value has been reported in the scientific literature for a substance, the Food and Drug Administration will use the lowest appropriate TD50 value in its review.); (2) The substance presents no other health or safety concerns because: (i) The use in question has been shown to result in or may be expected to result in dietary concentrations at or below 0.5 parts per billion, corresponding to dietary exposure levels at or below 1.5 micrograms/person/day (based on a diet of 1,500 grams of solid food and 1,500 grams of liquid food per person per day); or (ii) The substance is currently regulated for direct addition into food, and the dietary exposure to the substance resulting from the proposed use is at or below 1 percent of the acceptable daily intake as determined by safety data in the Food and Drug Administration's files or from other appropriate sources; (3) The substance has no technical effect in or on the food to which it migrates; and (4) The substance use has no significant adverse impact on the environment. (b) Notwithstanding paragraph (a) of this section, the Food and Drug Administration reserves the right to decline to grant an exemption in those cases in which available information establishes that the proposed use may pose a public health risk. The reasons for the agency's decision to decline to grant an exemption will be explained in the Food and Drug Administration's response to the requestor. (c) A request"
[5] "age or physiologica...
[5] "age or physiological state; and when age or the conditions of pregnancy or lactation are specified, in excess of 45 micrograms for infants, 105 micrograms for children under 4 years of age, 225 micrograms for adults and children 4 or more years of age, and 300 micrograms for pregnant or lactating women. (b) To assure safe use of the additive, in addition to the other information required by the Act, the label of the additive shall bear: (1) The name of the additive. (2) A statement of the concentration of the additive in any mixture. § 172.379 Vitamin D2. Vitamin D2 may be used safely in foods as a nutrient supplement defined under § 170.3(o)(20) of this chapter in accordance with the following prescribed conditions: (a) Vitamin D2, also known as ergocalciferol, is the chemical 9,10-seco(5Z,7E,22E)-5,7,10(19),22-ergostatetraen-3-ol. Vitamin D2 is produced by ultraviolet irradiation of ergosterol isolated from yeast and is purified by crystallization. (b) Vitamin D2 meets the specifications of the 2015 Food Chemical Codex, 9th edition (through Third Supplement), effective December 1, 2015, pp. 1260-1261, which is incorporated by reference. The Director of the Office of the Federal Register approves this incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the United States Pharmacopeial Convention, 12601 Twinbrook Pkwy., Rockville, MD 20852 (Internet address http://www.usp.org). Copies may be examined at the Food and Drug Administration's Main Library, 10903 New Hampshire Ave., Bldg. 2, Third Floor, Silver Spring, MD 20993, 301-796-2039, or at the National Archives and Records Administration (NARA). For information on the availability of this material at NARA, call 202-741-6030 or go to: http://www.archives.gov/federal-register/cfr/ibr-locations.html. (c) The additive may be used as follows: | Category of Food "
不能直接说对患者安全没有影响。虽然根据M7指南，未知杂质的限量可以满足该产品的给药量限制，但是如果超出了Q3中的要求，说明该产品的纯度没有达到要求，存在一定的不确定性和潜在风险。
因此，需要对该产品的未知杂质进行深入的风险评估和安全性评估，以确定是否对患者安全产生影响。这些评估需要综合考虑多种因素，例如：
- 该未知杂质的性质和来源，以及可能产生的不良影响；
- 产品的剂量和给药途径，以及该未知杂质在患者体内的代谢和排泄情况；
- 目标人群的特点，例如年龄、性别、基础疾病、用药史等因素。
根据评估结果，可以确定是否需要采取进一步的措施，例如优化生产工艺、加强质量控制、调整用药方案等，以确保患者的安全性。因此，在任何情况下，都应该对未知杂质进行充分的评估，并采取适当的措施，以确保产品的质量和患者的安全。
无法直接断言该产品对患者的安全性是否有影响，需要综合考虑多种因素。
虽然几个未知杂质的绝对量比较小且符合ICH M7中的要求，但其超过了ICH Q3中规定的未知杂质限制，可能会引起一定的担忧。首先需要评估这些未知杂质在体内的药理学活性、毒性和代谢途径等，并结合给药剂量和周期，进行安全性风险评估。
此外，还需要考虑其他因素，例如该产品的治疗效果和临床必要性、患者特殊情况（如年龄、性别、病史等）以及可用的治疗替代方案等。综合考虑这些因素后，才能得出针对该产品对患者的安全性是否有影响的结论。
建议在进行上述评估和判断时，应该遵循相关的法规和标准，确保该产品在严格的质量控制下使用，并尽可能减少任何与患者安全性相关的风险。
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