放射药品生产不符合性报告

20151223 ECA新闻：放射药品生产不符合性报告  

GMP News
23/12/2015

Non Compliance Report inRadiopharmaceutical Manufacturing

放射药品生产不符合性报告

The manufacturing of radiopharmaceuticalproducts confronts the producing establishment with a collection of challenges.On the one hand there is the challenge by the contradictory requirements ofquality and safety guidelines of pharmaceutical products and the standards ofstaff safety and radiation protection. On the other hand there are issues ofsmall batch sizes and short shelf life. The short shelf life necessitates fasttransportation and application to the patient. These circumstances mean thatclassical requirements like sterility testing before release and applicationcannot be fulfilled.

放射药品生产场所正面临许多挑战。一方面是药品质量安全要求指南与员工安全和防辐射标准之间的冲突，另一方面是批量很小与货架期很短的问题。货架期短需要快速运输，并被患者使用。这些情况意味着传统的要求如放行和使用前的无菌测试要求无法满足。

But with international guidelines likein PIC/S Guideline P010, Annex 3, the establishment can find necessaryrequirements and state of the art recommendations for manufacturingradiopharmaceuticals in a good practice.

但是在一些国际指南如PIC/S指南P010附录3中，工厂可以找到必要的要求，以及按优良规范生产放射药品的理想实施建议。

On 15 December, the Italian MedicinesAgency published a "Statement of Non-Compliance with GMP" for anItalian manufacturer of Radiopharmaceuticals, IASON Italia SRL. The Agencywrote about the nature of Non-Compliance in their report:

在12月15日，意大利药监局公布了意大利公司IASON，一个放射药品生产商的“GMP不符合声明”。药监局在其报告中写下了不符合情况：

"During the inspection 19deficiencies were identified, 3 of them were rated as critical deficiencies and11 as major deficiencies. The main deficiencies were related to the QualityManagement and the Quality Assurance Systems also in terms of sterilityassurance and risk of contamination/defects of the final product.

“在检查中，发现了19个缺陷，其中3个被定级为关键，11个为主要。主要缺陷是质量管理和质量保证体系，还有无菌保证以及成品污染/缺陷风险。

One critical deficiency was related tofailure to fully investigate and document out-of-specification results formicrobiological environmental monitoring in class A isolator and class B/Csurrounding areas, in manufacture of radiopharmaceuticals aseptically prepared.The company didn't carry out an appropriate and full-scale investigation todetermine what caused the OOSs. An appropriate level of corrective actionanalysis was not applied during the investigation and the true root cause(s)were not determined. Failure to address the root cause due to ineffective CAPArevealed a lack of the quality assurance framework system.

一个关键缺陷是放射药品无菌生产中，对A级隔离器和B/C级环境中微生物环境监测OOS结果调查和记录不全面。公司没有采取适当的全面调查，以确定OOS的原因。在调查过程中未实施适当水平的纠正措施分析，真正的根本原因并未确定。由于CAPA无效，导致未能改正根本原因，说明缺乏质量保证框架体系。

Another critical deficiency was reportedwith regards to production processes which were considered not satisfactorycontrolled: it was found that for the manufacture of some batches of theradiopharmaceutical Pcolina (Iasocholine) a non suitable reagent was used(expired dibromomethane).

另一个关键缺陷是生产工艺控制被认为未能令人满意：期间发现有些放射药品PCOLINA批次生产中使用了不适当的试剂（过效期）。

Moreover, for some batches of releasedRPs master batch documents were incomplete. No adequate review by QA or QP.Furthermore, preparation of the starting material set for radiopharmaceuticalswas performed in condition not appropriate to guarantee an adequate level ofchemical and microbiological containment.

另外，有些已放行批次的生产记录不完整，QA或QP没有进行充分审核。还有，放射药品起始物料制备条件不适于保证化学和微生物污染控制达到足够水平。

The inspection's team has rated also ascritical the observation related to the number of personnel in force to themanufacturing site, which were considered not appropriate to conduct all theactivities in accordance with the GMP and to maintain the quality managementsystem and its effectiveness. The remaining major deficiencies were related tospecific aspects of the Quality Assurance System with regards to PQRassessment, revalidation and recalibration of critical equipment, dataintegrity in the context of HPLC management, storage of materials anddocumentation system."

检查组还将生产厂里人员数量的缺陷列为关键，人员数量不足以根据GMP完成所有活动，以及维护质量管理体系和其有效性。余下的主要缺陷是关于质量保证体系与PQR评估、关键设备再验证和再校验、HPLC管理方面数据完整性、物料和文件体系缺乏。”

Following the inspection and documenteddeficiencies, the company suspended the manufacturing of some 18F-products andthe manufacturing authorisation was suspendend by the responsible authority.All details about this report can be found in the Statement of Non-Compliance at the EudraGMDP website.

在检查及缺陷记录之后，公司停止了一些18F药品的生产，生产许可证被相关药监局搁置。此报告的详细信息可以在EUGDMP数据库里找到。

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