注射剂可见异物问题为何如此之多？
出自识林
注射剂可见异物问题为何如此之多？
笔记 2014-08-13 Lachman CONSULTANTS 笔者在上周等待航班时，浏览了CDER网页所列出的召回信息。可以看到有相当数量来自不同企业的召回，但是最引起我关注的是25例召回之中，有12例源自可见异物（包括玻璃脱片）问题。 尽管从任何角度看，我都不是一位制造工艺专家，我仍试着思考这一问题的原因。由于未能遵循cGMP或者妥善管理陈旧设备，许多注射剂厂商（暂时或永久的）被迫关停并引发了药品短缺。有没有具体的例子呢？比如仍存有一些监管问题，限制企业新改不能及时获得进批准。从审评的角度看，新药的补充申请审评，必须按照付费法案在6个月内完成，或许问题不大。FDA的资源是否不足以支持相应的检查？这倒是有可能的，尤其为达成GDUFA绩效目标，不得不分散FDA很多精力。总之这算作我的一种假设吧。 除非我的估计完全错误，我想总能总结出一些诱发注射剂问题的不常见因素。是否有一些改进措施，比如容器、清洁问题、环境因素、处方的物理稳定性（这里使用QBD方法或有帮助）、物料来源与控制、加工、过滤技术、改善人工或自动放行检验的必要性、在更长的供应链范围内建立质量体系以应对温度变化等问题？我并不清楚，但我知道，FDA同样密切关注上述话题，虽然FDA尚未就此公开发布任何一般性的观点。此话题的复杂性确实值得FDA与业界仔细推敲。我不清楚是否可以有线索把所有这些召回串联起来，但是，或者，已经被人给出了。我会与我公司合规实践领域的同事探讨这一话题，也愿意听取来自诸位读者的观点与思考（可发邮件至 r.pollock@lachmanconsultants.com）我很乐于收集大家的看法并且另发一篇博客加以总结。当然，我会注意隐去评论者和公司的信息。 Particulate Matter in Parenteral Products - Why So Much? Last week while waiting for my flight home at an airport on the east coast, I decided to look at the recalls listed on the CDER web page. I realize that I have read about a number of recalls of parenteral products recently and those recalls were for a number of different firms, but what caught my attention was that 12 of 25 recalls listed were for visible particulate matter (including glass particles). While I am not a manufacturing expert by any stretch of the imagination, I started to wonder why this might be. There have been many a drug shortage caused by shutdowns (temporary and permanent) of parenteral facilities due to failure to follow cGMP or issues due to aging equipment that have contributed to some of their problems. Could this be the case here? Are firms still putting off upgrades at their facilities due to regulatory challenges of gaining approvals for the new upgrades? Well, one would think not for new drugs since they have a 6-month user fee clock for such supplements. Could it be lack of FDA resources to conduct the required inspections? That could be a problem especially now that FDA is gearing up to meet the GDUFA metrics which will drain a lot of the inspectional resources, but still there is a 6-month review clock on those NDA supplements, so I wonder if this is a real issue or one I am dreaming up. Whatever the reason may be, and, unless I am reading the tea leaves totally wrong, something rather unusual is going on out there in the parenteral world. Could it be the treatment of the vials, cleaning deficiencies, environmental factors, physical stability of formulations (QBD should help this), the source and control of materials and components, process, filtration technology, the need for improvements in manual/automated inspection, failure of quality systems or temperature stresses posed by longer supply chains?? I just don’t know! But what I do know is that FDA is looking closely at these issues, but there has been no single common issue that has been identified that has been made public by the Agency. The issue is indeed complex and FDA and the industry continue to work on this issue. I don’t even know if there is a thread that links all of these recalls together, but it seems to me that a more holistic look at the seemingly epidemic number of recalls for the same problem might be in order and perhaps this has already been done. I will discuss this issue with my colleagues in the Compliance Practice Area at Lachman Consultants further, but in the meantime, if anyone has any ideas or thoughts on this issue, please let me know at r.pollock@lachmanconsultants.com. I would be interested in hearing your views and would consider gathering your thoughts into another blog post – blinded of course to commenter and company! Let’s see what thoughts are out there! |