FDA发布当前在市ARB中亚硝胺临时限度 20181219

翻江鼠

FDA presents interim limits of nitrosamines in currently marketed ARBs

FDA发布当前在市ARB中亚硝胺临时限度

Update [12/19/2018] FDA is publishing interim acceptable intake levels of nitrosamine impurities in angiotensin II receptor blockers (ARBs) for manufacturers to useto ensure their finished drug products are safe for patients.

更新日期【20181219】FDA现发布ARB中亚硝胺杂质的临时可接受摄入水平供生产商用以确保其制剂产品对患者是安全的。

The agency evaluated safety data for N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA) to determine an interim acceptable intake level for these impurities in the ARB class. NDMA and NDEA are probable human carcinogens and should not be present in drug products. We are currently aware of NDMA and NDEA in certain valsartan, irbesartan and losartan-containing products, and those products and some active pharmaceutical ingredients (API) used to manufacture them have been recalled from the U.S. market. See the list of valsartan products under recall and the list of irbesartan products under recall.

FDA已评估了NDMA和NDEA的安全数据，确定了ARB类药品中这些杂质的临时可接受摄入水平。NDMA和NDEA为潜在人体致癌物质，不应出现在药品中。我们了解目前在一些含缬沙坦、厄贝沙坦和氯沙坦的药品中出现了NDMA和NDEA，这些药品和其生产所用的API已从美国市场召回。参见召回清单。

Drug products that contain NDMA or NDEA above the limits in the table below pose an unacceptable risk to patients. The agency will use the interim limits to recommend manufacturers conduct a voluntary recall if laboratory testing confirms the presence of nitrosamine impurities infinished drug product. FDA is working with industry and international regulators to ensure products entering the market do not contain these impurities, but we are tolerating the impurities below the level established inthe table for a short period of time to avoid a possible shortage of ARBs.

含有超出下表中所列NDMA或NDEA水平的药品对患者的风险是不可接受的。FDA将以临时限度为标准，建议经实验室检测确认存在亚硝胺杂质的生产商主动召回其产品。FDA正与企业和国际药监机构合作，确保进入市场的药品不含有这些杂质，但我们在短期内容许杂质水平低于下表中限度的药品销售，以避免可能的ARB药品短缺。

The agency reminds manufacturers they are responsible for developing and using suitable methods to detect impurities, including when they make changes to their manufacturing processes. If a manufacturer detects a new impurity or higher level of impurities, they should fully evaluate the impurities and take action to ensure the product is safe for patients. To aid industry and regulatory agencies, FDA has developed and published methods to detect NDMA and NDEA impurities – the gas chromatography/mass spectrometry (GC/MS) headspace method, the combined GC/MS headspace method, and the combined GC/MS direct injection method. These methods can be used for drug substances and products, and users should validate them as part of good manufacturing practices and where data are used to support a regulatory submission or required quality assessment of the API or drug product.

FDA提醒生产商，其负有责任开发和使用适当的方法检出杂质，包括他们在对其生产工艺进行变更时。如果一个生产商检出了新的杂质或更高水平的杂质，他们应全面评估这些杂质，并采取措施确保药品对患者是安全的。为协助企业和药监机构，FDA已开发和发布了检测NDMA和NDEA杂质的方法—气相色谱/质谱（GC/MS）顶空方法、GC/MS联用顶空方法和GC/MS联用直接进样法。这些方法可用于原料药和制剂检测，如果数据用于支持注册申报或所需API或制剂的质量评估，作为GMP的一部分，用户应对其进行验证。

Not all ARB products contain NDMA or NDEA impurities, so pharmacists may be able to provide an alternative medication not affected by the recalls, or health care professionals may prescribe a different medication that treats the same condition.

并不是所有的ARB药品都含有NDMA或NDEA杂质，因此药师或可提供未受召回影响的替代药品，医生或可开具处方对相同症状采用不同治疗方式。

Interim Limits for NDMA and NDEA in Angiotensin II Receptor Blockers (ARBs)

ARB中NDMA和NDEA的临时限度

Drug	Maximum  Daily Dose (mg/day)	Acceptable  Intake NDMA (ng/day)*	Acceptable  Intake NDMA (ppm)**	Acceptable  Intake NDEA (ng/day)*	Acceptable  Intake NDEA (ppm)**
药品	最大日剂量（mg/天）	可接受摄入NDMA（ng/天）	可接受摄入NDMA（ppm）	可接受摄入NDEA（ng/天）	可接受摄入NDEA（ppm）
Valsartan 缬沙坦	320	96	0.3	26.5	0.083
Losartan 氯沙坦	100	96	0.96	26.5	0.27
Irbesartan 厄贝沙坦	300	96	0.32	26.5	0.088
Azilsartan 阿齐沙坦	80	96	1.2	26.5	0.33
Olmesartan 奥美沙坦	40	96	2.4	26.5	0.66
Eprosartan 依普罗沙坦	800	96	0.12	26.5	0.033
Candesartan 坎地沙坦	32	96	3.0	26.5	0.83
Telmisartan 替米沙坦	80	96	1.2	26.5	0.33

* The acceptable intake is a daily exposure to a compound such as NDMA or NDEA that results in a 1:100,000 cancer risk after 70 years exposure 可接受摄入量是70年每天暴露于一种物质如NDMA或NDEA之后产生10万分之一患癌风险的暴露量。

** These values are based on a drug's maximum daily dose as reflected in the drug label 这些值是依据药品标签上反映的各药品的每日最大剂量

For comparison with the levels of NDMA found in some common foods, please see our Aug. 20, 2018,update.

NDMA在一些常见食品中的出现水平比较参见20180820发布的数据。

摘自 Julia法规翻译

zysx01234

华海是沙坦大户啊，杜桥园区听说朗华也是沙坦类占比较大

胜利者

美国人要投降？