The pharmaceutical vial capping process: Container closure systems, capping equipment, regulatory framework, and seal quality tests

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• 作者：Roman Mathaes^a ; ^{roman.mathaes@lonza.com" class="auth_mail" title="E-mail the corresponding author} ; Hanns-Christian Mahler^a ; Jean-Pierre Buettiker^a ; Holger Roehl^a ; Philippe Lam^b ; Helen Brown^a ; Joerg Luemkemann^a ; Michael Adler^a ; Joerg Huwyler^c ; Alexander Streubel^a ; Silke Mohl^a
• 关键词：CCI ; container closure integrity ; CCS ; container closure system ; CT ; computer tomography ; mCCI ; microbial container closure integrity ; pCCI ; physical container closure integrity ; PDA ; parenteral drug association ; RSF ; residual seal force ; TR ; technical report ; USP ; United States Pharmacopeia
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：99
• 期：Complete
• 页码：54-64
• 全文大小：2528 K

文摘

Parenteral drug products are protected by appropriate primary packaging to protect against environmental factors, including potential microbial contamination during shelf life duration. The most commonly used CCS configuration for parenteral drug products is the glass vial, sealed with a rubber stopper and an aluminum crimp cap. In combination with an adequately designed and controlled aseptic fill/finish processes, a well-designed and characterized capping process is indispensable to ensure product quality and integrity and to minimize rejections during the manufacturing process.

In this review, the health authority requirements and expectations related to container closure system quality and container closure integrity are summarized. The pharmaceutical vial, the rubber stopper, and the crimp cap are described. Different capping techniques are critically compared: The most common capping equipment with a rotating capping plate produces the lowest amount of particle. The strength and challenges of methods to control the capping process are discussed. The residual seal force method can characterize the capping process independent of the used capping equipment or CCS. We analyze the root causes of several cosmetic defects associated with the vial capping process.