制药企业清洁验证中对包装组件和包装设备的特殊考虑

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制药企业清洁验证中对包装组件和包装设备的特殊考虑
来源：OurGMP


　　10.10 Packaging Components andPackaging Equipment


　　包装组件和包装设备


　　10.10.1 Primary Packaging Components


　　内包装组件


　　Productcontact surface of primary packaging closures and containers should be free ofmaterials that could adulterate the drug product to the extent that fitness foruse would be compromised. An evaluation of suitability may include considerationsof manufacturing process residues, cleaning agents/solvents, particles,bioburden and/or endotoxin.


　　内包材密封件和容器与产品接触的表面应不得掺杂异物，导致药品不再适合预定用途。适用性评估可能包括考虑制造过程残留、清洁剂/溶剂、粒子、微生物和/或内毒素。


　　10.10.1.1 Oral Dosage FormsPrimary Packaging Components


　　口服剂型内包装组件


　　Cleaning of containers and stoppers used for oral dosage forms is based on arisk analysis. The risk should be assessed and appropriate cleaning levelsdefined that will control the risks to acceptable levels. Cleaning ofcontainers for solid oral dosage forms, related to risk analysis, could belimited to removing of solid material by blowing a stream of compressedfiltered air into the bottles while inverted. From a microbial perspective,most solid oral drug products will not allow microorganisms to proliferate, dueto the extremely low water activities of these types of products.


　　用于口服制剂的容器和塞子的清洁应基于风险分析。应对风险进行评估，并确定适当的清洁水平，将风险控制在可接受的水平。固体口服制剂容器的清洁，涉及到风险分析的，可仅限于用经过滤压缩空气吹扫倒置的瓶子，将固体异物去除。从微生物的角度来看, 由于这些类型的产品具有极低的水活性，大多数固体口服制剂不利于微生物繁殖。


　　Someconsideration could be provided for the cleaning of containers for liquid oraldosage forms even if the liquid does inhibit growth of microorganisms, due topresence of components, like preservatives or sugar at high concentrations, ora final terminal heat treatment.


　　应关注液体口服制剂容器的清洁，即使液体制剂本身确实能够阻止微生物的生长，因为存在组分如防腐剂或高浓度的糖，或有最终的终端热处理步骤。


　　10.10.1.2 Parenteral Dosage FormsPrimary Packaging Components


　　注射用药物内包装组件


　　Cleaningof containers and stoppers used for parenteral dosage forms is based on a riskanalysis. The risk should be assessed and the cleaning levels validated at theacceptance criteria. Since the parenteral container/closure components are incontact with the drug product, similar cleaning qualification considerations asfor direct product contact surfaces for manufacturing equipment should beaddressed.


　　用于注射剂的容器和胶塞的清洁应基于风险分析。应进行风险评估，清洁程序应经过验证并符合可接受标准。因为注射剂容器/密封组件与药品直接接触，其清洁确认应与直接接触产品的生产设备的清洁确认类似。


　　Forcleaning processes used as a depyrogenation step for container/closurecomponents, the qualification should demonstrate successful endotoxin removal(36). The efficiency of the cleaning process to depyrogenate can be assessed byspiking containers or closures with known quantities of endotoxin, followed bymeasuring endotoxin content after cleaning. The studies are typically performedby applying a reconstituted endotoxin solution onto the test surfaces andallowing the solution to air dry.


　　对用于容器/密封件除热原的清洁工艺，应确认其可以成功去除内毒素(36)。可通过在容器或密封件上涂布已知量的内毒素，在清洁后测定内毒素含量，以评估清洁工艺去除热原的效率。该试验中，通常将复溶的内毒素溶液涂布在待测试表面，并自然晾干。。


　　Positivecontrols (test surfaces with applied endotoxin but without the endotoxinreduction process) should be used to measure the percentage recovery in thetest method. Data should demonstrate that the cleaning process reduces theendotoxin content by at least a 3-log reduction in a spiking study.


　　应采用阳性对照(在待测试表面上涂布内毒素，但不进行可能降低内毒素的工艺)来测量检验方法的百分回收率。内毒素涂布试验中，研究数据应能证明清洁工艺可以降低内毒素含量至少3个对数单位。


　　Containerwasher qualification should start by using a spray coverage test to verify allthe surfaces are efficiently rinsed. The cleaning performance qualificationshould consider removal of residues coming from the surface treatment (ifapplicable) and/or particles (which, as an example, could come from burnedglass molding lubricant as well as glass particles if breakage occurs beforewash).


　　容器的清洁确认从采用喷淋覆盖测试来确认可有效冲洗所有表面开始。清洁效果确认应考虑去除来自表面处理(如适用)的残留和/或颗粒(例如，来自玻璃成型中润滑剂燃烧产物，以及清洗前容器破裂产生的玻璃颗粒)。


　　Forclosures (such as stoppers), the cleaning performance qualification shouldconsider removal of residues coming from the closure manufacturing process,like the lubricant and cleaning agent used, as well as particles.


　　密封件(例如塞子)的清洁效果确认应该考虑去除来自密封生产过程的残留物，如使用的润滑剂和清洁剂，以及颗粒。

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