20171004 ECA新闻：投诉和召回处理缺陷导致警告信

beiwei5du

20171004 ECA新闻：投诉和召回处理缺陷导致警告信

原创 2017-10-05 JULIA Julia法规翻译

04.10.2017

Deficiencies in Complaint and RecallHandling cause Warning Letter投诉和召回处理缺陷导致警告信

Dueto deficiencies in the investigation of the scope and root causes ofreported complaints, the U.S. Food and Drug Administration (FDA) has issued awarning letter to an Indian drug manufacturer. The FDA inspection already tookplace in December of 2016. Because of the non-satisfactory reply in regards tothe inspection findings by the manufacturer, the FDA issued the warning letterin August 2017.

由于对所报告的投诉调查范围和根本原因存在缺陷，FDA签发了警告信给一个印度药品生产商。FDA检查是在2016年12月。由于不满意生产商对检查中发现缺陷的回复，FDA于2017年8月签发了警告信。

TheFDA inspectors noticed that investigations into process deviations andout-of-specification (OOS) laboratory results were insufficient, and didnot include scientifically-supported conclusions. According to FDA themanufacturer′s response to this observation was inadequate because,amongst others, it failed to fully investigate the scope and root causesof a reported complaint. The FDA now expects the manufacturer toretrospectively review all complaint, manufacturing, and laboratoryinvestigations associated with each product that is produced for the U.S.market. Furthermore, a plan to ensure that all future investigations arethorough, scientifically sound, and result in appropriate and effective CAPA(corrective actions and preventive actions) should be provided.

FDA检查人员注意到受检公司对OOS结果和工艺偏差的调查是有充分的，未包括有科学性支持的结论。依据FDA的说法，生产商对此缺陷的回复是不充分的，因为未能充分调查所报告的投诉的范围和根本原因。FDA现在期望生产商能回顾性地审核所有与销售至美国市场所的产品有关的投诉、生产和化验室调查。另外，要有一份计划来确保未来所有的调查都会是彻底、科学合理的，并应提供适当有效的CAPA。

Anothermajor deficiency was that the firm failed to follow thecompany′s own written procedures regarding the recall of failing products(for example: after receiving a complaint sample the defect has beenconfirmed, but a product recall as directed by company′s own proceduresregarding recalls of defective products has not been initiated in time).Therefore, the FDA demands to provide a list and summary explanation for allother instances in which product(s) distributed within the last five yearsfailed to meet established specifications, but for which actions prescribed inthe firm′s Quality System Manual and recall procedure have not been taken.Additionally, the planned CAPA for each such instance should be providedincluding an explanation of CAPAs for ensuring to follow own proceduresregarding product quality and recalls.

另一个主要缺陷是公司未遵守公司自己的书面不合格产品召回程序（例如，在收到投诉样品并且确定产品缺陷之后，但公司并未依照其自己的程序及时启动对缺陷产品的召回）。因此，FDA要求其提交一份清单，总结所有在过去5年内不符合既定质量标准但已销售，并且未按公司的质量体系手册和召回程序进行采取措施的所有情形说明。另外，还要提交每种此类情形下所计划的CAPA，包括CAPA解释，以确保会遵守自己关于产品质量和召回的程序。

Inaddition the FDA observed deficiencies in cleaning operations. The authoritydemands sampling procedures and analytical methods used to test residues foundduring the inspection, including validation protocols and validation reports.Furthermore, a plan is required to ensure that personnel responsible forcleaning, verifying equipment cleanliness, and maintaining equipment areappropriately trained and capable of performing their assigned duties. Anoverall assessment of the adequacy of your cleaning program for all equipment,with special emphasis on difficult-to-clean parts should be provided.

此外，FDA还发现清洁操作方面的缺陷。当局要求其提交检查中所发现的用于检测残留的取样程序和分析方法，包括验证方案和验证报告。还要提交一份计划以确保负责清洁、核对设备清洁度和维护设备的人员经过适当的培训，有能力履行其指定的任务。要提交对所有设备的清洁程序的充分性进行的整体评估，特别是难以清洁部分。

Anotherdeficiency was found regarding Process Controls. The FDA observed that thefirm "does not have an adequate ongoing program for monitoring processcontrol to ensure stable manufacturing operations and consistent drugquality". FDA’s guidance document, Process Validation: General Principles and Practices, forgeneral principles and approaches that FDA considers appropriate elements ofprocess validation, should be followed.

发现的另一个缺陷是关于工艺控制。FDA发现公司“没有充分的持续监测工艺控制的程序，不能确保稳定的生产操作和持续的药品质量”。应遵守FDA的指南文件“工艺验证：通则和规范”，其中的通则的方法FDA认为适当的工艺验证要素。

Findthe details in the original FDA Warning Letter to Hetero Labs Limited.

详细内容参见FDA警告信。

beiwei5du

现在很多企业清洁都存在这个问题（特别是针对于原料药），标示清洁状态为“已清洁”,而实际却能经常发现白色粉末或印记。

2. Your firm failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.67(a)).

Our investigators observed multiple (b)(4), which you identified as clean, containing colored residue and/or in poor condition.

For example, (b)(4) PDE-2095 had white (b)(4) residue on and around a white interior gasket. Our investigator documented a gap in the gasket that could allow processed materials to accumulate. The ends of the gasket were also in poor condition.（这个大法兰垫片确实是一个清洗难点，不知道大家实际是怎么操作的呢？？）

Your response states that you sampled and analyzed residues to identify and quantify chemical and microbiological contaminants, and the results met microbial attributes. You attributed the white residue to “… part of [the] overall finish of (b)(4) surface” and the “…drying of water drops after cleaning.”

In response to this letter, provide:

• The sampling procedures and analytical methods you used to test the white residues. Include validation protocols and validation reports.
• Your procedures to install and maintain the “(b)(4) type” gasket in (b)(4) PDE-2095. Assess all (b)(4) that use similar gaskets in product contact areas. Justify the suitability and continued use of these gaskets in your (b)(4).
• Your plan to ensure that personnel responsible for cleaning, verifying equipment cleanliness, and maintaining equipment are appropriately trained and capable of performing their assigned duties. Include cleaning validation studies for your (b)(4).（经培训合格的清洁专人确认以及设备维护是一个关注点啊）
• An overall assessment of the adequacy of your cleaning program for all equipment, with special emphasis on difficult-to-clean parts.

beiwei5du

工艺验证的strage 3持续工艺确认现在成了FDA的关注重点了。

小金库

楼主辛苦