scientific needs.

Once the URS is established, the next step is conducting a risk assessment. This can be aligned with ICH Q9, which focuses on quality risk management. Here, potential failure modes are identified, and their impact on product quality is evaluated. Various techniques, such as Failure Modes and Effects Analysis (FMEA), can be adopted to prioritize risks and ascertain the necessary controls to manage these risks effectively.

Step 2: Protocol Design

After establishing a clear URS and conducting a risk assessment, it’s time to design the validation protocol. The validation protocol, a formal document outlining the methodology and expectations for validation activities, should align with both regulatory guidelines and the specific operations of the facility. According to the FDA’s Guidance Document, the protocol must articulate the objectives, materials and methods, acceptance criteria, and an analysis plan.

The protocol should consist of several key sections, which include:

• Objective: Clear articulation of the goals.
• Scope: Define the process or system that will be validated.
• Methodology: Describe how validation will be conducted, including sample sizes and statistical methodologies.
• Acceptance Criteria: Set clear, measurable criteria for success.

Additionally, ensure that electronic data management practices are included when dealing with computer systems. This aligns with 21 CFR Part 11 and confirms that systems utilized for validation follow stringent data integrity standards.

Step 3: Qualification Phases – IQ, OQ, and PQ

The next stage in the validation workflow is executing qualification activities denoted as Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ). Each phase has distinct objectives and requirements:

Installation Qualification (IQ): This phase verifies that the equipment or system has been installed correctly and operates according to the manufacturer’s specifications. Documentation must include detailed records of equipment specifications, manufacturer qualifications, and verification of utilities and environmental conditions.

Operational Qualification (OQ): Once installation is confirmed, the next phase tests whether the system operates as intended under all specified operating conditions. This involves executing predefined test cases against the acceptance criteria defined in the protocol. The evidence generated during this phase must be meticulously documented to support compliance.

Performance Qualification (PQ): This stage involves testing the system’s performance to confirm that it consistently produces results meeting predetermined acceptance criteria. PQ typically involves simulating actual production conditions using representative product formulations. During this phase, the data collected should support the validation of the process under typical operating circumstances.

Step 4: Process Performance Qualification (PPQ)

After the initial qualification activities are complete, the next step involves Process Performance Qualification (PPQ). PPQ is essential for demonstrating that a process can consistently produce an acceptable product under commercial manufacturing conditions. This phase should be well-documented and adhere to regulatory standards outlined in ICH Q8 to Q10.

During PPQ, multiple batches of the product should be manufactured using the validated processes. Key activities during PPQ include:

• Batch Records: Review of manufacturing records ensures compliance with all established protocols.
• Statistical Analysis: Analytical methods, including control charts and capability studies, must demonstrate that process performance is stable and operating within specified limits.
• Sampling Plans: Define the method for sampling in such a way that it accurately reflects the properties of the production batch.

Acceptable outcomes from the PPQ stage provide a strong foundation for the ongoing validation lifecycle, confirming that the process is fit for its intended use.

Step 5: Continued Process Verification (CPV)

Following successful completion of the PPQ, Continued Process Verification (CPV) is the ongoing monitoring procedure needed to ensure that the process continues to operate in a validated state throughout its lifecycle. CPV aligns with ICH Q10 and emphasizes the necessity of maintaining process controls and monitoring performance throughout the product lifecycle.

Implementing a CPV program requires a robust combination of statistical and analytical approaches:

• Data Collection: Regularly collect process data to assess consistency and stability over time.
• Trend Analysis: Utilize statistical methods to analyze collected data and discern patterns that may indicate process drift or deviations.
• Response Plans: Establish clear strategies for addressing non-conformance outcomes, including investigation protocols and corrective actions.

Documentation of CPV activities is critical for maintaining compliance with regulatory expectations, thereby providing evidence of continuous assurance that the process remains under control.

Step 6: Revalidation

Revalidation is an essential aspect that ensures the validation remains suitable over time. Regulatory guidance suggests conducting revalidation under circumstances such as product changes, equipment modifications, or significant changes in production methods. The timing for revalidation activities will depend on risk assessments, including potentially high-risk changes that could impact product quality and safety.

When performing revalidation, the same rigorous documentation, and analysis practices applied during initial validation should be adopted. This includes:

• Documentation Review: Comprehensive review and potential update of documentation reflecting changes to the system or process.
• Performing Validations: Depending on the nature of the change, re-execute critical components of IQ, OQ, PQ as necessary.
• Final Review and Approval: The final combination of documentation and results must be presented to the relevant stakeholders for approval.

In conclusion, the structured workflow of process validation—encompassing URS creation, protocol design, qualification, PPQ, CPV, and revalidation—provides pharmaceutical and biologics professionals with foundational knowledge for compliant operations. Each step must be carefully documented and executed in alignment with guidelines set forth by international regulatory bodies like the FDA and EMA. Such diligence ensures not only regulatory adherence but also the continuous delivery of safe and effective products to market.