Surface engineering of particulates used in the quality control processes of the pharmaceuticals industry (with Mallinckrodt Pharmaceuticals)

制药行业质量控制过程中使用的颗粒表面工程（与 Mallinckrodt Pharmaceuticals 合作）

• 批准号: 462080-2013
• 负责人: Tavares, JasonRobert
• 金额: $ 1.38万
• 依托单位: École Polytechnique de Montréal
• 依托单位国家: 加拿大
• 项目类别: Collaborative Research and Development Grants
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=576799
• 关键词: Surface; engineering; particulates; used; quality

The Canadian pharmaceuticals industry, particularly its sub-sector on the preparation of parenteral (injected) drugs, is highly dependent on both automated and operator-driven visual inspection methods to detect the presence of foreign particulates or other defects. These inspection methods must be regularly validated to ensure appropriate quality control of the final products. As a result of recent significant improvements to the prefilled syringe process at the Mallinckrodt Pharmaceuticals plant in Pointe-Claire (Québec), the 500-um polymer beads used to challenge the visual inspection methods have been found to be too easy to detect. The company would like to challenge its validation processes using either smaller standardized polymer beads (150 um for immediate use, smaller particles to future-proof the process), or actual potential contaminants sampled from the process line. However, such smaller particulates suffer from dispersion issues: when they are placed within challenge syringes, they stick to the syringe walls, thus preventing detection from the motion-based automated sensors. The company has attempted (both in-house and with an outside contractor) to use surfactants to stabilize these challenge particle suspensions, but their efforts have been unsuccessful - the surfactants either have poor shelf life or lead to the stabilization of air bubbles (once again making the challenge syringes too easy to detect). Rather than use surfactants to stabilize the finer challenge particles, we propose a photochemical surface functionalization method (PICVD) developed at École Polytechnique de Montréal. This low-cost, scalable surface engineering method shows great promise to promote stable dispersion of fine particulates, thus providing significant cost savings to the company. The development of stable challenges syringes will be transferrable to a wide range of Canadian pharmaceutical companies, and the synthesis of "native contaminant" challenge syringes should prove to be a highly novel contribution to the state of the art.

加拿大制药业，特别是其非肠道（注射）药物制备分部门，高度依赖自动化和操作员驱动的目视检查方法，以检测是否存在外来颗粒或其他缺陷。必须定期验证这些检验方法，以确保对最终产品进行适当的质量控制。由于最近对位于Pointe-Claire（Québec）的Mallinckrodt Pharmaceuticals工厂的预充式注射器工艺进行了重大改进，发现用于挑战目视检查方法的500 μ m聚合物微珠太容易检测。该公司希望使用较小的标准化聚合物珠粒（150 μ m可立即使用，较小的颗粒可保证该过程的未来性）或从生产线上取样的实际潜在污染物来挑战其验证过程。然而，这种较小的颗粒存在分散问题：当它们被放置在挑战注射器内时，它们粘附在注射器壁上，从而阻止基于运动的自动化传感器的检测。该公司尝试（内部和外部承包商）使用表面活性剂稳定这些挑战颗粒混悬液，但他们的努力没有成功-表面活性剂的有效期不佳或导致气泡稳定（再次使挑战注射器太容易检测）。而不是使用表面活性剂来稳定更精细的挑战颗粒，我们提出了一种光化学表面功能化方法（PICVD）在蒙特利尔理工学院开发。这种低成本、可扩展的表面工程方法在促进细颗粒的稳定分散方面显示出巨大的潜力，从而为公司节省了大量成本。稳定挑战注射器的开发将可转移到广泛的加拿大制药公司，并且“天然污染物”挑战注射器的合成应被证明是对最新技术水平的高度新颖的贡献。