GMP News
08/10/2014
New FDA Interim Guidance for Human Drug Compounding Outsourcing Facilities
FDA发布新的人用药调制生产外包场所暂行指南
In the USA, the compounding of medicinal products was not regulated very well. The compounding of medicinal products can be outsourced to specific compounders (Compounding Pharmacies) bypassing the authority and GMP regulations. Also quantitative limitations don't play any role so that those compounders could produce at industrial scale and thus also win a substantial share of the medicinal products market.
在美国，药品的调制没有很好地管理。药品的调制可以外包给指定的生产商（调制药房），而绕过药监当局和GMP法规。这时，定量的限制起不到任何作用，这些调制商可以采用工业规模生产，从而获得实质性的药品市场份额。
So far, they have been in a sort of no man's land in the USA. Manufacturers of medicinal products are regulated at federal level by the FDA, whereas pharmacies - including also Compounding Pharmacies - face a respective heterogeneous regulation at the level of the 50 federal states. In 2002, the Supreme Court refused FDA's attempts to intervene with regulations.
到目前为止，美国对此并没有管理。药品生产商是由FDA从联邦层次进行管理，而药房—也包括调制药房—面临的是50个州不同的规定要求。在2002年，高等法院拒绝了FDA企图介入该法规的要求。
The inglorious culmination of this situation was the case New England Compounding Center (NECC) in 2012. A steroid solution for epidural injection had a fungal contamination and had been administered to approx. 14,000 patients. About 50 patients died of meningitis and over 700 had to be treated against fungal infection.
上述混乱的情形在2012年新英格兰调制中心（NECC）的一个案件中达到了顶峰。硬脑膜外注射用的甾类溶液被真菌污染，并被注射给约1万4千患者，约有50名病人死于脑膜炎，超过700人不得不接受抗真菌治疗。
In 2013, the regulations in the USA were adjusted - DQSA Pub. L 113-54 - to transfer to the FDA the monitoring of outsourced compounding facilities. The subsequent inspections with a lot of Warning Letters issued to the compounders (partly with outrageous quality deficiencies) clearly showed the consequences of inexistent inspections over many years.
在2013年，美国的法规进行了调整，将对外包调制工厂的监控转移给FDA管理。随后的检查中，FDA签发了许多警告信给这些调制工厂（一部分是因为令人震惊的质量缺陷），事实清楚地表明了过去许多年缺乏监管的后果。
The FDA has recently announced that it will regulate this area in the future in accordance with the cGMP. Until appropriate regulations have been developed, the FDA has - in the meantime - expressed its expectations for this transitional period in a Guidance for Industry - Current Good Manufacturing Practice - Interim Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act. This Guidance is based on the 21 CFR parts 210 and 211 with regard to cGMP. The FDA has tried to take into consideration the differences between industrial medicinal products manufacturing and compounding, and to adjust the specific aspects of the compounders. The FDA has announced that it will focus its inspections efforts to the points which present the highest danger for patient safety. One should thus not be surprised - also in view of the past incidents - that these efforts will particularly address the securing of sterility. Decidedly, the following topics are addressed:
FDA最近宣布在将来会要求这些区域按CGMP要求操作。在制订出适当的法规前，FDA同时也在一份行业指南中“GCMP---根据FD&C法案503B项下人用工调制外包工厂暂行指南”表达了其对过渡期间的期望。该指南是基于21CFR第210和211部分关于CGMP的内容制订的。FDA试图考虑到工业化药品生产和调制之间的差异，对调制的某些方面进行了调整。FDA已经宣布，其将集中检查对患者安全性造成最高危害的方面。回看过去的事故，我们会很惊讶，因为这些努力特别强调了无菌的安全问题。不管怎样，以下问题在其中进行了要求：
- Facility Design
- 设施设计
- Control Systems and Procedures for Maintaining Suitable Facilities
- 控制系统和维护适当设施的程序
- Environmental and Personnel Monitoring
- 环境和人员监控
- Equipment, Containers, and Closures
- 设备、容器和密闭情况
- Components
- 组分
- Production and Process Control (General Production and Process Control / Aseptic Drug Processing)
- 生产和工艺控制（一般生产和工艺控制/无菌药工艺）
- Release Testing
- 放行测试
- Laboratory Controls
- 化验室控制
- Packaging and Labels
- 包装和标签
- Quality Assurance Activities / Complaint Handling
- 质量保证活动/客诉处理
One interesting thing is that the FDA itself isn't quite sure about certain aspects, whether its requirements will be suitable for compounders. In the chapters "Components" and "Laboratory Controls", an "Alternative Approach for Comment" is respectively presented in the Guidance to both topics "Reducing the Need for Laboratory Testing of Incoming Components" and "Minimize Need for Facilities to Have an In-House Laboratory".
一件有意思的事情是，FDA自己并不是很确定其规定是否适用于化合物生产商的某些方面。在“组分”章节中和“化验室控制”章节中，指南分别对“减少化验室对进厂组成检测”和“减少设施具备自有化验室需求”给出了“替代方法建议”。
All in all, this is an interesting development, and most of all has been a necessary evolution in the regulation of compounders which comes a few years too late.
不管怎么，这是一个有趣的发展，最重要的是在几年后，化合物生产商法规规定有一些了进展。
Sources:
Guidance for Industry - Current Good Manufacturing Practice - Interim Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act
Guidance - Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act
Warning Letters to companies producing sterile drugs
http://zhuyujiao1972.blog.163.com/blog/static/9869472720149173154581/
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