2000年4月4日警告信(也可以参考吧)

朱丹

2000年4月4日警告信

  

WARNING LETTER警告信

文件编号: 00-NWJ-27

The significant observations are as follows: 重要的缺陷如下：  

1. Failure to have a quality control unit. 1．没有质量控制部门。  

2. Failure to validate the manufacturing process for the drug product Caffeine USP. Additionally, the firm has no validation plan in place that identifies and evaluates the processing steps,

operating ranges, critical processing parameters, required equipment, sampling and testing data to be collected.

2．没有验证咖啡因制造工艺。另外，公司没有验证计划来确认和评估工艺步骤，操作范围，关键工艺参数，所需的设备，取样方法和测试数据。  

3. Failure to validate the reprocessing operation for the drug product Caffeine USP. There is no testing conducted and no evaluation made to assure that all batches of Caffeine manufactured using reprocessed material are of the purity and quality equivalent to normally produced batches. 3．没有验证咖啡因再加工的操作过程。没有测试和评估来确保所有使用再加工制造的咖啡因具有和正常批号产品一样的纯度和质量。  

4. The firm blends failed batches of Caffeine (failed in–process specifications) with passing

Caffeine batches to achieve acceptable product. Additionally, the firm does not document failing in–process blend results.

4．公司将不合格的咖啡因批次（不符合工艺规格标准）和合格的咖啡因批次混合来达到可以接受的产品。另外公司没有记录。  

5. Failure to perform the required USP testing on each production „batch” of the product Anhydrous Caffeine USP. For example:

5．生产每批无水咖啡因没有进行要求的USP测试。例如：  

a) The firm tests for Assay, Residue on Ignition (Ash), Identification, and other Alkaloids on a “lot” of Caffeine product, which could consist of as many as 16 production batches. The testing is only conducted on one composite sample taken from multiple batches.

a) 公司测试了含量，灰分，鉴定和“大量”咖啡因中的其他生物碱，包括了16个批次。仅仅对多个批次的样品混合样品进行了测试。  

b) The firm does not conduct assay testing using HPLC analysis, as required by USP

Supplement #9, effective November 15 1998. The method currently used to assay Caffeine, USP has not been shown to be equivalent to, or better than the current USP method. b) 公司没有按照1998年11月15日生效的USP附录9的要求进行液相分析。公司现行的分析咖啡因含量的方法没有被证明和USP方法有等效性或是更好。  

c) The firm does not perform the USP Organic Volatile Impurities (OVI) Test, Method #l. c)公司没有进行USP 有机挥发性杂质测试（方法1）。  

6. Inadequate laboratory controls for testing the crude, in-process, and finished Caffeine USP. For example:

6．粗品，中控和成品咖啡因的测试没有足够的实验室控制。例如：  

a) The primary Caffeine USP reference standard is not used. The secondary reference standard in use has not been qualified.

a) 没有使用一级咖啡因USP对照品。使用的是没有确认过的二级对照品。

b) The reference standards used to perform the Caffeine USP tests (Caffeine, Potassium Biphthalate, Potassium Iodide, Mercuric Chloride) are not stored under adequate conditions.

b) 进行咖啡因测试（咖啡因，苯二甲酸氢钾，碘化钾，氯化汞）标准品没有贮存在合适的环境中。  

c) Laboratory notebooks do not document critical information including test methods, reagents used, weights of samples, and drying times and temperatures achieved during testing.

c) 实验室记录本中没有记录包括测试方法，所使用的试剂，样品重量，干燥时间和测试中达到的温度等等关键信息。  

d) The equipment used to analyze Caffeine product were not calibrated prior to use. d) 分析咖啡因产品的设备使用前没有校验。  

e) The laboratory hood is not certified. e) 实验室使用的防护罩不合格。  

f) Laboratory equipment maintenance logbooks are not maintained. f) 实验室设备维护记录本没有维护。  

g) The laboratory bench, sample jars, and equipment were dirty. They were covered with a white powdery material.

g) 实验台，样品瓶和设备都很脏，被白色粉状物覆盖污染。

7. Production controls for Caffeine USP are inadequate. For example: 咖啡因生产控制不够。例如：  

a) Filter changes for the 30 inch, 24 inch, and 18 inch filter presses are not documented. a) 压滤中30英寸，24英寸和18英寸过滤器的变更没有记录。  

b) There is no calibration program for the critical production monitoring devices. b) 关键生产监控设备没有校验规程。  

c) All equipment maintenance and repairs are not documented. c) 所有设备的维护和修理没有记录。  

8. The production records for Caffeine USP are inadequate. For example: 咖啡因生产批记录有不足。例如：  

a) Mixing times are not documented for crude and semi–refined Caffeine mixing steps. Also, tank temperatures are not documented during semi-refined Caffeine heating operations.

a) 粗的和半精制的咖啡因混合操作的时间没有记录。在半精制咖啡因加热操作中的罐温也没有记录。  

b) Production flow rates for filtration of crude and semi–refined Caffeine are not documented.

除品过滤和半精制咖啡因的生产流程图没有记录。  

c) Centrifuge speeds and times for crude and semi-refined Caffeine are not documented. c) 粗品和半精制咖啡因的离心速度和时间没有记录。  

9. The firm has no written procedures for complaint handling, recall operations, change control, equipment maintenance and calibration, product failure investigations, and reprocessing of batches.

9．公司没有书面的规程来处理客户投诉，召回，变更，设备维护和校验，产品失败调查和再加工操作。  

10. Failure to perform an investigation regarding two complaints for foreign particles in Caffeine USP, lot #2-452 and #2–455. The complaints reported that lot #2–452 contained “wood–like” particles and lot #2-455 contained “burnt” particles in the Caffeine product.

10．没有对两项客户投诉进行调查，投诉说两批咖啡因，批号2-452 和2–455，分别被“木头样”物质和“灼烧物”污染。  

11. There is no established GMP training program for the firm‟s employees. 11．没有建立公司员工GMP培训程序。

弈剑听雨

以前国内是没有质量保证部门，这老外是没有质量控制部门，这谁来检验

愚公想改行

谢谢，值得注意和借鉴！

一沙一叶

这个是有点旧了   

tian200100

值得学习参考

七-月

很低级的错误？？？

怀谷

学习了，谢谢！