【工艺验证】为什么生产工艺和包装工艺必须经过验证?

For most manufacturing and packaging processes it is technically not feasible or much too expensive to check every single unit of resulting product (100% control). Instead, random samples are relied on which are taken on an ongoing basis at specific times during the process (in-process controls), or random samples are taken for quality control of the final product prior to market release.

对于大多数生产和包装工艺，检查每一个产品(100%检测)在技术上不可行或太昂贵。相反，随机抽样依赖于在持续进行的工艺中特定时间的抽样(中间控制)，或者随机抽样用于在上市放行之前对最终产品进行质量控制。

However, it would hardly be possible to find the famous needle in the haystack using these random samples. For this reason,validatedmanufacturing and packaging processes are required by law in addition to the final product checks and IPCs. The company must prove that the processes are all so reliable that, under everyday routine manufacturing conditions, they result in medicinal products of a high and reproducible quality.

然而，使用这些随机样本几乎不可能在大海捞针中找到显著的针。因此，除了最终产品检查和IPC之外，法律还要求验证生产和包装工艺。公司必须证明所有的工艺都是可靠的，在日常的常规生产条件下，它们能生产出高质量和可重复的药品。

Process validation

工艺验证

Process validationis time-consuming and has to be carried out on every single product before the marketing authorisation is granted. It must be carried out after the development of the manufacturing and packaging process has been completed and the process has been adapted to the manufacturing environment (optimised).

工艺验证是耗时的，必须在批准上市许可之前对每个产品进行验证。它必须在生产和包装工艺的开发完成后进行，并且该工艺已适应生产环境(经过优化的)。

The planning and implementation of process validation can vary greatly depending on the company and products. For this reason, every pharmaceutical manufacturer must describe in avalidation master plan(VMP) how validations are organised in practise, e.g. who belongs to the validation team, who creates, checks and approves the validation documents, and who is responsible for making what decisions.

工艺验证的计划和实施可能因公司和产品的不同而有很大差异。因此，每个制药商必须在验证主计划(VMP)中描述验证在实践中是如何组织的，例如，谁属于验证团队、谁创建、检查和批准验证文件，以及谁负责做出哪些决定。

Avalidation planmust be created for each individual product, describing the validation program for the respective product in detail. The effort required depends largely on the type of product.

必须为每个单独的产品创建验证计划，详细描述各个产品的验证程序。所需的努力在很大程度上取决于产品的类型。

Is the manufacturing or packaging process straightforward or complex?

生产或包装过程是简单的还是复杂的?

Does it require special equipment and specially trained personnel?

是否需要特殊的设备和受过特殊训练的人员?

Is the product risk particularly high, e.g. because the product is very sensitive or because it must be sterile?

产品风险是否特别高，例如，因为产品非常敏感或必须无菌?

How much experience does the company have with similar processes and products?

公司在类似工艺和产品方面有多少经验?

Are reliable control mechanisms in place that detect quality issues before the product leaves the company?

是否有可靠的控制机制在产品出厂前检测出质量问题?

The validation team evaluates these sorts of questions usingquality risk analyses.

验证团队使用质量风险分析来评估这类问题。

Depending on the results of the risk evaluation, the team decides on the extend of validation studies needed. For example:根据风险评估的结果，团队决定所需验证研究的范围。例如:

How many batches have to be produced as validation batches?

需要生产多少批次作为验证批次?

What other tests have to be carried out?

还需要进行哪些测试?

What results need to be achieved to ensure that the process is absolutely reliable (acceptance criteria)?

需要达到什么结果来确保工艺是绝对可靠的(可接受标准)?

Everything must be described in detail in thevalidation planand test plans and approved before manufacture of the validation batches begins.

每件事都必须在验证计划和测试计划中详细描述，并在验证批次开始生产之前得到批准。

The tests that are specified in the plans, and any observations or difficulties are documented invalidation recordsduring manufacture.