In the pharmaceutical industry, ensuring product quality, safety, and efficacy is top most requirement / expectation. The concept of process validation underpins the entire lifecycle of a pharmaceutical product, from development through commercial production, and is critical for maintaining patient safety and product efficacy.
Taking this as a note, concept of process validation is a regulatory requirement from the different pharmaceutical regulatory agencies like the FDA and EMA. Expectation is that to ensures manufacturing processes consistently produce products meeting predetermined quality criteria and intended use.
Fig.: Difference between Process validation and Process Performance Qualification
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Here we will go through with the details on;
１. Define
terms of Process validation and PPQ
ï¼’. Comparison
between “Process validation” and “PPQ
３. Key
Regulatory Guidance references
ï¼”. Key
Regulatory Guidance highlights
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Define the term “Process validation” and “PPQ”.
Process validation is a critical element in pharmaceutical manufacturing, mandated by regulatory agencies to ensure that processes are well-controlled and capable of consistently yielding high-quality products. Regulatory guidelines, such as FDA’s “Guidance for Industry: Process Validation: General Principles and Practices” and EMA’s “Guideline on Process Validation for Finished Products,” outline a lifecycle approach to process validation. This approach is divided into three stages:
Stage 1: Process Design
Stage 2: Process Qualification
Stage 3: Continued Process Verification
Process Performance Qualification (PPQ) is a key component of Stage 2 of the process validation lifecycle. Regulatory agencies require PPQ to be conducted before commercial production begins, serving as the final assessment to ensure the manufacturing process is ready for routine operation.
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Comparison between “Process validation” and “PPQ” two important terms of pharmaceutical industry;
|
Aspect |
Process Validation |
|
|
|
Definition |
A comprehensive, documented approach to
ensure that a manufacturing process consistently produces a product that
meets predetermined quality attributes. |
A specific component of process validation,
focused on verifying that the manufacturing process performs as expected
under commercial-scale conditions. |
|
|
Purpose |
To provide assurance that the entire manufacturing process is capable,
reliable, and consistently produces quality products throughout the product
lifecycle. |
To confirm that the process can consistently produce products meeting
quality specifications when run at full commercial scale. |
|
|
Scope |
Encompasses the entire lifecycle of the process,
from design and qualification to ongoing verification during routine
production. |
Focused on the qualification phase (Stage 2) of
process validation, specifically testing the process in actual production
conditions. |
|
|
Lifecycle Stage |
Involves three
stages: 1) Process Design, |
Occurs within
Stage 2 (Process Qualification) of the process validation lifecycle. |
|
|
Key Activities |
- Design of the process based on scientific
principles. |
- Execution of multiple production batches under
actual commercial conditions. |
|
|
Documentation |
Includes protocols, reports, and data from all stages of validation to
demonstrate process understanding, control, and capability. |
Requires a specific PPQ protocol and report detailing the testing,
sampling, and results obtained during the qualification runs. |
|
|
Regulatory Expectation |
Regulatory agencies require comprehensive process
validation to ensure the manufacturing process is under control and
consistently produces quality products throughout the lifecycle of product. |
Regulatory agencies require successful PPQ
results as evidence that the process is ready for routine production with
consistency. |
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Key Regulatory Guidance references
The regulatory guidance forms the basis for regulatory expectations regarding process validation and PPQ in pharmaceutical manufacturing.
They provide the necessary framework and best practices for ensuring that manufacturing processes are well-controlled, reproducible, and capable of consistently producing quality products.
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Key Regulatory guidance highlights with respect to Process validation and PPQ
U.S. Food and Drug Administration (FDA) guidance;
Published in January 2011, with the title “Guidance for Industry: Process Validation: General Principles and Practices”
🔎 Describes the FDA’s expectations for process validation across the product lifecycle
🔎 Outlines the three stages of process validation: Process Design, Process Qualification (which includes PPQ), and Continued Process Verification.
🔎 Emphasizes a lifecycle approach to validation, focusing on the integration of process design, qualification, and ongoing verification.
European Medicines Agency (EMA) guidance;
Published in November 2016, with the title “Guideline on Process Validation for Finished Products - Information and Data to be provided in Regulatory Submissions”.
🔎 Provides guidance on the data and information required for process validation in marketing authorization applications.
🔎 Focuses on the lifecycle approach to process validation, including process design, process performance qualification (PPQ), and ongoing process verification.
🔎 Discusses expectations for PPQ, including the number of batches, testing strategies, and the need for protocols and reports.
International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidance;
Discuss the concept of Process validation under the guidance ICH Q8 (R2): "Pharmaceutical Development" published in August 2009 & ICH Q9: "Quality Risk Management" published in January 2023.
🔎 ICH Q8 (R2) discusses principles of pharmaceutical development, including process design, which is integral to Stage 1 of process validation.
🔎 ICH Q9 provides a framework for quality risk management, which is essential for identifying and mitigating risks in process validation and PPQ.
World Health Organization (WHO) guidance;
Published in October 2014, with the title “WHO Guidelines on the Validation of Manufacturing Processes”
🔎 Discussed the detailed guidance on process validation, including the need for PPQ.
🔎 Emphasizes the importance of validation during the entire lifecycle of the product, including process design, qualification, and continuous monitoring.
🔎 Provides specific recommendations for PPQ, including the need for well-documented protocols and reports.
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In summary, Process Validation and Process Performance Qualification (PPQ) are essential steps in ensuring that pharmaceutical products are consistently made to the highest standards of quality and safety. Regulatory bodies like the FDA, EMA, ICH, and WHO have set out clear guidelines to help companies navigate these processes. They emphasize a lifecycle approach, starting with designing a robust process, verifying its performance through PPQ, and continuously monitoring it during production. The goal is to ensure that every batch of medicine meets the necessary quality criteria, keeping patients safe and maintaining trust in the product.
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Learn More….
What is Validation? Basic overview
What is Product Lifecycle Management...? An Overview
What is Process Validation? What are the Types of validation?
Validation study: Why Three batch for validation study?
10 Key Steps for Successful Process Validation in Pharma
5 Common Challenges in Pharma Drug substance Process Validation
5 Common Issues Encountered During Process Validation and solutions
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