【工藝驗證】為什么生產工藝和包裝工藝必須經過驗證?

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.

對于大多數生產和包裝工藝，檢查每一個產品(100%檢測)在技術上不可行或太昂貴。相反，隨機抽樣依賴于在持續進行的工藝中特定時間的抽樣(中間控制)，或者隨機抽樣用于在上市放行之前對最終產品進行質量控制。

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，使用這些隨機樣本幾乎不可能在大海撈針中找到顯著的針。因此，除了最終產品檢查和IPC之外，法律還要求驗證生產和包裝工藝。公司必須證明所有的工藝都是可靠的，在日常的常規生產條件下，它們能生產出高質量和可重復的藥品。

Process validation

工藝驗證

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).

工藝驗證是耗時的，必須在批準上市許可之前對每個產品進行驗證。它必須在生產和包裝工藝的開發完成后進行，并且該工藝已適應生產環境(經過優化的)。

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.

工藝驗證的計劃和實施可能因公司和產品的不同而有很大差異。因此，每個制藥商必須在驗證主計劃(VMP)中描述驗證在實踐中是如何組織的，例如，誰屬于驗證團隊、誰創建、檢查和批準驗證文件，以及誰負責做出哪些決定。

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.

必須為每個單獨的產品創建驗證計劃，詳細描述各個產品的驗證程序。所需的努力在很大程度上取決于產品的類型。

Is the manufacturing or packaging process straightforward or complex?

生產或包裝過程是簡單的還是復雜的?

Does it require special equipment and specially trained personnel?

是否需要特殊的設備和受過特殊訓練的人員?

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

產品風險是否特別高，例如，因為產品非常敏感或必須無菌?

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

公司在類似工藝和產品方面有多少經驗?

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

是否有可靠的控制機制在產品出廠前檢測出質量問題?

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

驗證團隊使用質量風險分析來評估這類問題。

Depending on the results of the risk evaluation, the team decides on the extend of validation studies needed. For example:根據風險評估的結果，團隊決定所需驗證研究的范圍。例如:

How many batches have to be produced as validation batches?

需要生產多少批次作為驗證批次?

What other tests have to be carried out?

還需要進行哪些測試?

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

需要達到什么結果來確保工藝是絕對可靠的(可接受標準)?

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

每件事都必須在驗證計劃和測試計劃中詳細描述，并在驗證批次開始生產之前得到批準。

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