因玻璃掉屑导致颗粒异物

From time to time we receive GMP Questions from our Members. Today we cover the subject glass delamination.

时不时我们会收到来自我们成员的GMP问题，今天我们来谈谈玻璃瓶掉屑问题。

The formation or flakes of glass particles on the inside of glass containers is referred to as delamination. These glass fragments, created by the interaction of the solution with the container walls, can pose a risk - especially when it comes to parenterals. Glass is considered to be an inert packaging material; however that is not wholly correct depending on the composition of the contained solution and the composition of the glass in question.

玻璃掉屑是指玻璃颗粒异物在玻璃瓶容器内表面形成和脱落。这些玻璃碎与溶液相互作用后会导致风险——特别是对注射剂。玻璃瓶是一种内包装材料，然而也不是完全正确，这取决于所装溶液的成分和玻璃材料的成分。

Delamination and the resulting particle release have been a recurring reason for recalls in the past couple of years. There aren't any known cases of patients being harmed; authorities like the FDA still see a risk for the particles to cause embolism or thrombosis, though. According to applicable US law, the formation of glass particles in a sterile container is intolerable. 21 CFR 211.94 states that product containers may not be reactive or additive or influence the quality of a product. The pharmaceutical manufacturer is responsible for preventing glass delamination.

掉屑及其所导致的颗粒异物已经成为过去几年所发生的召回中常见的原因了。也没有看到有病人受此危害的案例，然而，监管当局如FDA一直认为颗粒异物会导致血栓。根据当前美国法律，无菌容器不得有玻璃颗粒异物。21CFR 211.94规定产品容器不得化学性质活泼、易释出、或影响产品质量。药品生产者有责任防止玻璃瓶掉屑。

Delamination is facilitated by:

掉屑由以下原因导致：

• Production of vials made of tubular glass; Vials made from molded glass are less susceptible to delamination.

• 使用管制玻璃瓶的生产；模制玻璃瓶则不容易掉屑。

• Solutions with an alkaline pH value may facilitate delamination; so may several buffers (e.g. citrate and tartrate).

• 碱性溶液可能会更容易导致掉屑；如很多缓冲液（柠檬酸盐和酒石酸盐）

• Long contact times between a product and the inner glass surface can also promote glass delamination. This has a direct effect on the storage life of the product.

• 产品和玻璃内表面长时间接触也可能导致掉屑，这直接影响了产品的储存效期。

• Elevated storage temperatures; lower temperatures make delamination less likely.

• 较高的储存温度，低温则不容易导致掉屑。

• The heat treatment during terminal sterilisation also has a negative effect on glass stability and may foster delamination.

• 最终灭菌过程的热处理也对玻璃瓶稳定性有不良影响并可能引起掉屑。

The FDA recommends the use of resistant glass like borosilicate glass for products with elevated risk. Pharmaceutical manufacturers should take special care when it comes to choosing a supplier for glass vials and re-examine established suppliers or rather their quality management systems to minimize the phenomenon of delamination.

FDA建议对高风险的产品使用稳定的玻璃，如硼硅玻璃。药物生产者在选择一个玻璃瓶供应商和对已有供应商，准确的说是对他们的质量管理体系进行再检查时应该特别小心以减少掉屑的现象。