Cleaning validation is a critical component of quality assurance in the pharmaceutical industry. It helps ensure that manufacturing equipment is cleaned appropriately to avoid cross-contamination between products, which could have serious implications on patient and product safety and as well as efficacy. For cleaning validation experts, staying ahead of actions initiated by process verification activities is vital. This insight article dives into the concept of ongoing process verification, the advantages it presents for cleaning validation, and a real-world example of its implementation, guided by regulatory frameworks such as Europe's Annex 15.

What is Ongoing Process Verification?

Traditionally, cleaning validation has been a point-in-time exercise, helping ensure that cleaning protocols meet predetermined acceptance criteria. However, this static approach may not be enough in the dynamically evolving production environments. Ongoing Process Verification (OPV) offers a more continuous, data-driven approach to validate the cleaning process. It doesn't just confirm that the process works; it helps ensure that it continues to be effective over time.

As defined in Annex 15 , OPV focuses on the production process, but its principles can—and should—be extrapolated to apply to cleaning and its validation. Instead of a one-time validation, OPV involves continuous data collection and analysis throughout the lifecycle of the cleaning process. This ensures sustained compliance and process optimization will be possible.

The Role of Process Analytical Technologies (PAT)

Key to the successful implementation of OPV in cleaning validation is the use of Process Analytical Technologies (PAT). PAT involves using advanced analytical devices that provide real-time measurements of critical process parameters (CPPs) during cleaning. These may include:

• Temperature: How the cleaning effect is affected by varying temperatures?
• Contact Time: Is the duration of exposure to the cleaning solution reflective of cleaning efficacy?
• Mechanical Action: Are the flow rates and pressures within the systems sufficient for removing residues?
• Cleaning Agent Concentration: Is the concentration (e.g. conductivity as a lead parameter) of the cleaning solution sufficient for removing residues most effectively?

Collecting this data brings unprecedented insights into the cleaning process, shifting from uncertainty and extensive revalidation to a more knowledge-rich, controlled, and flexible approach.

Monitoring and Digital Integration: Beyond the Basics

Many sites already monitor parameters such as flow rate or pressure control at spray devices, but the future of cleaning validation lies in integrating these measurements into a digital system that identifies trends and anomalies over time. By continuously monitoring CPPs like pressure and flow, validation experts can develop a comprehensive picture of the cleaning efficacy, catch potential issues early, and adapt protocols with minimal disruption.

A Tactical Example

Let’s take a look at a Pharma company that has successfully implemented an OPV program. They track critical cleaning parameters and have developed a routine for monitoring high-risk scenarios:

1. Establishment of Cleaning Process Capability Scores: These scores are calculated based on trends from critical cleaning process data collected over time, offering a quantitative measure of the cleaning process reliability.
2. Risk-Based Analysis: Aligning with EMA guidelines, this company evaluates the toxicity of subsequent products being manufactured and correlates this with process capability data. The result is a log-based risk score that dictates frequency and depth of their verification process .
3. Sampling Frequency Tailored to Product Risk: By categorizing products into high, medium, and low risk, the company has significantly reduced sampling frequency for lower-risk categories without compromising quality.
4. Efficiency Gains: The reduction in sampling and the optimized use of equipment facilitated by this risk-based approach has yielded higher productivity. More batches can now be produced within the same timeframe, positively impacting capacity and profitability.

Conclusion: The Future Is Continuous

Moving towards ongoing verification and control within cleaning validation is not just a regulatory expectation; it is a strategic business decision aimed at better resource utilization, increased productivity, and enhanced product safety. By implementing digital tools, correlating process data with risk assessments, and monitoring trends over time, companies can turn the cleaning 'black box' into a transparent, manageable element of their manufacturing process.

For cleaning validation experts, the future is clear: embracing continuous verification paves the way for a more efficient, reliable, and compliant production environment. As the industry progresses, those who adopt these practices early on will lead the way in operational excellence and regulatory compliance.