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Process Validation is defined as; -
The collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality products
In simple terms, it's proving, through documented evidence, that your manufacturing process reliably and consistently produces a drug product that meets all its predefined quality attributes (e.g., purity, potency, identity, safety).
It's not just testing the final product; it's about ensuring the process itself is the source of quality.
The Core Principle: Quality by Design (QbD).
The modern approach to process validation is built on the "Quality by Design" (QbD) principle. Instead of just testing quality into the final product, QbD means you build quality into the process from the very beginning by understanding and controlling the variables that affect it.
The Three Stages of Process Validation (The Lifecycle Approach)
The current regulatory expectation is a lifecycle approach, which is divided into three distinct stages:
Stage 1: Process Design
This is the research and development phase. The goal is to design a process suitable for commercial manufacturing that can consistently produce a product meeting its quality targets.
Activities:
Define Target Product Profile (TPP): What are the critical quality attributes (CQAs) of the drug? (e.g., dissolution rate, assay, impurities).
Identify Critical Process Parameters (CPPs): Which process variables (e.g., temperature, mixing speed, reaction time) have a direct impact on the CQAs?
Establish a Control Strategy: Determine the ranges for your CPPs that will ensure your CQAs are met. This often involves Design of Experiments (DoE) to understand the relationship between variables.
Output: A well-understood process design and a initial control strategy.
Stage 2: Process Qualification (PQ)
Now that the process is designed, you must confirm that the manufacturing equipment and facility are capable of consistently executing the process.
This stage has two parts:
Facility/Equipment Qualification:
Design Qualification (DQ): Verifying the design of the equipment/facility meets GMP requirements.
Installation Qualification (IQ): Documenting that the equipment is installed correctly according to the manufacturer's specifications.
Operational Qualification (OQ): Demonstrating that the equipment functions as intended over all anticipated operating ranges.

Performance Qualification (PQ):

This is the critical step of running the process using the actual drug substances, components, and trained personnel in the commercial facility.

Activity: Typically, three consecutive commercial-scale batches are manufactured under normal conditions and fully monitored.

Goal: To demonstrate with a high degree of confidence that the process is effective and reproducible. All data must show that the product consistently meets all quality specifications.

Stage 3: Continued Process Verification (CPV)
Validation is not a one-time event. After successful Process Qualification, you must continuously monitor the process to ensure it remains in a state of control throughout its commercial life.

Activities:

Establishing ongoing monitoring and control of CPPs and CQAs.

Using statistical process control (SPC) tools to track trends.

Investigating any deviations or trends that signal the process may be drifting out of control.

Implementing changes (through a formal change control system) and re-validating if necessary.

Goal: To provide ongoing assurance that the process remains validated during routine production.