20150730 ECA新闻：FDA公布质量量度指南

20150730 ECA新闻：FDA公布质量量度指南

2015-07-30 21:06:41

GMP News
30/07/2015

FDA publishes Quality Metrics Guidance

FDA公布质量量度指南

In the last months, the U.S. Food and Drug Administration (FDA) has set up an initiative to use Quality Metrics for planning their risk based inspections. This development was triggered by the Food and Drug Administration Safety and Innovation Act (FDASIA; Title VII, section 706). The goal of the Guidance is to give FDA the authority to collect Quality Metrics from production sites supplying APIs, medicinal products, Biotech, OTC etc. to the US. They should provide data about the "quality level" in each manufacturing site. By this, FDA wants be able to see how well quality systems are maintained. In the future companies will need to conduct continual monitoring, assessment and reporting on the state of quality across their drug products and facilities regulated by FDA. This should then enable FDA to schedule inspections based on risk assessment, improve the efficiency and effectiveness of these inspections and also reduce product-related shortages and recalls. FDA also wants to "encourage the pharmaceutical industry to implement state-of-the-art, innovative quality management systems for pharmaceutical manufacturing".

在上个月，美国FDA已开始使用质量量度来制订其基于风险的检查。这次的研究是由FDA安全和创新法规激发的。指南的目的是给予FDA权限来从向美国供应原料药、制剂、生物制品、OTC等的生产场所收集质量量度数据。这些场所应该提供各生产场所的“质量水平”的数据。通过这个方法，FDA想要看到该场所的质量体系维护的有多好。在将来，公司需要实施持续的监测，评估和报告则FDA监管的药品和场所的质量状态。这些数据使得FDA可以基于风险评估来制订检查计划，提高这些检查的效率和效果，同时降低与产品相关的短缺和召回。FDA还想要“鼓励制药行业在药品生产中实施理想状态、创新质量管理体系”。

What needs to be reported? 哪些需要报告？

FDA asks for data to be compiled and reported on:

FDA要求汇总和报告的数据包括：

• The number of lots attempted of the product.
• 产品生产批数
• The number of specification-related rejected lots of the product (during or after manufacturing).
• 与质量标准有关的拒收产品数量（在生产前或生产后）
• The number of attempted lots pending disposition for more than 30 days.
• 待处理时间超过30天的批数
• The number of OOS results for the product, including stability testing.
• 产品OOS结果数量，包括稳定性试验结果
• The number of lot release and stability tests conducted for the product.
• 对产品进行的放行和稳定性测试批数
• The number of OOS results for lot release and stability tests for the product which are invalidated due to lab error.
• 产品批放行和稳定性测试中由于实验室错误而宣布检验结果无效的OOS结果数量
• The number of product quality complaints received for the product.
• 产品质量投诉数量
• The number of lots attempted which are released for distribution or for the next stage of manufacturing the product.
• 放行销售或放行用于产品下一步生产批数
• If the associated APRs or PQRs were completed within 30 days of annual due date for the product.
• 产品的APR或PQR是否在期限30天内完成
• The number of APRs or PQRs required for the product.
• 产品要求的APR或PQR数量
  

FDA intends to calculate the following Quality Metrics for each product and establishment (where applicable):

FDA想要对每个产品和工厂计算以下质量度量（适用时）

• Lot Acceptance Rate = 1 - x (x = the number of specification-related rejected lots in a timeframe divided by the number of lots attempted by the same establishment in the same timeframe).
• 批接受率 = 1 – x（x=同一工厂同一时间内与质量标准相关的拒收批数除以总生产批数）
• Product Quality Complaint Rate = the number of product quality complaints received for the product divided by the total number of lots of the product released in the same timeframe.
• 产品质量投诉率 = 收到的质量投诉产品数量除以同一时间内放行的总批数
• Invalidated Out-of-Specification (OOS) Rate = the number of OOS test results for the finished product invalidated by the establishment divided by the total number of OOS test results divided by the total number of tests performed by the establishment in the same timeframe.
• 宣布无效的OOS结果率 = 无效OOS结果数除以该工厂同一时间内OOS总数再除以总测试数
• Annual Product Review (APR) or Product Quality Review (PQR) on Time Rate = the number of APRs or PQRs completed within 30 days of annual due date at the establishment divided by the number of products produced at the establishment.
• 年度产品回顾（APR）或产品质量回顾（PQR）及时率 = 在每年到期30天内完成的QPR或PQR数量除以该工厂生产产品数
  

Who needs to report?  谁要报告？

FDA intends to request the submission of data from establishments that are required to register under section 510 of the Food, Drug and Cosmetic (FD&C) Act and that are subject to inspection under section 704 of the FD&C Act (704 allows inspections of regulated entities). Establishments that receive requests under section 704(a)(4) would be encouraged to submit quality metrics data also for certain foreign establishments that are not required to register.

FDA想要要求根据食品药品和化妆品法案的510部分需要注册，以及根据该法案704部分（该条款要求法规检查）需要检查的工厂提交数据。鼓励根据704(a)(4)收到要求的企业同时也提交不需要注册的指定的国外工厂的质量量度数据。

So basically the Guidance applies to every legal entity engaged in the manufacture, preparation, propagation, compounding, or processing of a drug product for the US market or an API used in the manufacture of such a drug product. FDA sees the Quality Control Unit (QCU) generally to be the one to compile the reports.

因此基本上来说，该指南适用于每一个从事美国市场销售的药品，或用于这样药品的原料药生产、配制、宣传、配制、或处理的法人主体。FDA认为质量控制部门（QCU）通常是汇编报告的部门。

How many reports should be submitted? 要提交多少报告？

FDA intends to get one report for each finished dosage form and one report for each API of a covered drug product.

FDA希望针对每个制剂提交一份报告，每个原料药提交一份报告。

When do the reports should be submitted? 要何时提交这些报告？

Reports should be submitted after request. Quality metrics data reports should be submitted for a one-year period that begins after FDA issues its requests. They should then be submitted within 60 days of the end date of the reporting period.

应在收到要求后提交报告。质量度量数据报告应在FDA签发要求后开始每年提交。提交时间为报告周期的结束日期前60天内。

What will happen in the case of non-reporting? 如果没有报告会怎么样？

This will change FDA's risk assessment and may lead to an earlier inspection. In addition, the respective products may be deemed adulterated and subject to enforcement action.

这会改变FDA的风险评估，可能会导致更早的现场检查。另外，相关产品可能会被怀疑做假，可能会被采取强制措施。

What are the challenges? 挑战是什么？

Certainly a challenge for both industry and FDA will be how to span the scope of all segments like branded, generic, biotech and OTC products, APIs, various finished dosage forms (solid oral, modified release, liquid, sterile, etc.) and domestic and foreign products with possible language barriers. This will create a lot of data. And Quality Metrics are just one part of the picture, intended to be enhancing FDA's analysis but not replacing existing measures. The program will likely need to learn and evolve through continuous improvement.

可以肯定的是，FDA和企业都会面临一个挑战，即如何划分这些范围，如专利药、仿制药、生物技术和OTC药品、原料药、不同剂型（固体口服、改释、液体、无菌等）和国内及可能会有语言障碍的国外药品。这会生成大量的数据，而质量量度只是这其中一部分，用来提高FDA的分析，但并不会取代现有措施。该项目可能会需要通过持续改进而提高。

Comments and suggestions regarding the Draft Guidance for Industry "Request for Quality Metrics"should be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance.

关于此草案的建议请在联邦注册公布本草案的60天内提交。