注射剂可见异物问题跟进
出自识林
注射剂可见异物问题跟进
笔记 2014-09-04 Lachman CONSULTANTS 我曾在2014年8月13日的文章中提出为什么有如此多的注射剂召回与可见异物相关，还在文章中征询建议和评论。虽然并没有从文章读者那里（大约400多位读者）获得许多反馈，但也了解到一少部分读者的想法。虽然没有人对这一问题有解决办法或具体改善建议，一些评论中指出的问题正是我们一直所预期的。有众多因素导致可见异物的形成，其中一些与配方有关，一些与储存条件有关，一些与工艺操作有关，一些与生产设备有关，还有一些我们在前面提到的文章中讨论过。 一位评论者指出，许多这些设施生产的产品销往美国和欧盟，在这两个监管区域之间的召回概况是否有不同。评论者不认为注射剂应该存在差异（大概是因为对于每个药监机构都应该高度关注可见颗粒），像对于口服剂型药监机构之间的理论差异更加“显著”。 另一位评论者表示，他们的合同生产商使用的标准与他们自己的标准不同，甚至通过与合同商讨论，合同商依旧同意这样的不一致！还有另一种推测，所有设施在几年前同时搞砸时，回忆他们QA的日子和旧的GWQAP（政府广泛质量保证项目）检查项目，也许FDA明确的“现行”颗粒检查标准应当因检测设备的进步或工艺的了解而收紧，他们推出了一系列检查以察看行业立场。 所有的想法和评论都很好，但是依然没有解决问题。在与Lachman的一些合规专家讨论中，有人向我指出，ISPE和FDA关于药品短缺主题做的一些工作，其中注射剂是一大部分内容。在一项调查中，ISPE询问受访者：贵公司最可能导致[无菌]药品短缺或未遂的一类[无菌]生产设备是什么？回复 – 无菌工艺设备是被个人和企业受访者对于这一问题报告的主要生产设备，冻干机紧随其后。虽然回答如此，但药品短缺以及这一具体注射剂问题（可见异物），具备十分明显的的多因素特征。 对于缓解企业所报告的药品短缺问题而言，ISPE认为较为有效的（当然也适用于注射剂）十大要素有
他们还确定了缓解短缺的策略，包括： 我们认为所有这些都是通过事后分析缓解策略方面相关关注领域的“秋后算账”。识别根源问题的难处是更加抽象和难以捉摸。在注射剂可见异物问题逐步明确的过程中，也许我们会在收集到更多数据的过程中增进了解，对问题的评估也将变得更加有针对性。 Lachman CONSULTANTS - Bob Pollock先生 2014-09-03 Follow-up on Visible Particulate Matter in Parenteral Products In a blog post on August 12, 2014 (here), I raised the question of why there have been so many recalls of parenteral products related to visible particulate matter. I also asked for suggestions and comments on the post. While we did not get a lot of feedback from the readers of the post (there were about 400+ readers), we did hear from a few of you. Although no one had a solution to the problem or specific suggestions to fix it, some of the comments pointed to what we had expected all along. There are a multitude of factors that lead to the formation of particulate matter, some of which have to do with formulation, some with storage, some with handling, some with manufacturing equipment and the like as was discussed in the blog referenced above. One commenter noted that many of these facilities manufacture product for both the US and EU and wondered if there was a difference in the recall profile between the two regulatory regions. It was noted that the commenter did not think there should be a difference for parenteral products (presumably because visible particulates should be a high concern for each Agency), like there might be for oral dosage forms where the philosophical differences between the regulatory bodies are more “stark”. Another commenter indicated that the standards that their contract manufacturer was using were different than what they used as their standards and, even through discussions with the contractor, they continue to agree to disagree! Still another speculated that, with all the facilities that got hit at the same time a few years back, and remembering back to their QA days and the old GWQAP (Government Wide Quality Assurance Program) inspection program, maybe FDA decided the "current" standard for particulate inspection should be tightened due to advancements in detection equipment or processes it became aware of and they launched a barrage of inspections to see where the industry stood. Well, all good ideas and observations but still no definitive answers. In discussions with some of our compliance experts at Lachman, I was pointed to the work International Society of Pharmaceutical Engineering (ISPE) has undertaken with the FDA on the specific topic of drug shortages, of which the parenteral products is a large subset. In one survey, ISPE asked respondents: What is one type of [sterile] production equipment that likely contributed most to the [sterile] drug shortage or near-miss at your company? The response - aseptic processing equipment was the major piece of production equipment reported as posing problems, reported by both individual and company respondents, with lyophilizers coming in a close second. But, with this said, the multi-factorial nature of drug shortages and this specific parenteral problem is ever-so obvious. ISPE has identified the top 10 factors that firms that are the most successful in mitigating drug shortage problems report (which also relate to parenteral products) which are as follows:
They also identified strategies for mitigating shortages which include:
All of these are the "usual suspects" we think of relative to areas of concern in terms of mitigation strategies through postmortem analysis. The problem of identifying root cause issues are a bit more abstract and elusive. As the problem of visible particulate matter in parenteral products continues to surface, perhaps we will learn more as more data is collected and evaluation of the problem becomes more targeted. 必读岗位及工作建议：
适用范围： 文件要点总结： 以上仅为部分要点，请阅读原文，深入理解监管要求。 必读岗位及工作建议：
适用范围： 文件要点总结：
以上仅为部分要点，请阅读原文，深入理解监管要求。 |
，校者注）：