If you’re a manufacturer in the pharmaceutical or biotech industry, you know how necessary and efficient it is to process your product in multi-batches. You should also know that the major challenge that comes with this process is cross-contamination.
According to the most recent data we could find, recalls in 2023 in the pharmaceutical sector increased by 7.7% in 2023, with safety concerns, including contamination, being a leading cause.
Understandably, all regulators, manufacturers, and engineers treat this issue seriously. The slightest trace of residual material from a previous batch can compromise the safety and quality of the current batch, which a GMP-compliant facility can’t simply allow.
The prevention of cross-contamination influences audit outcomes, batch release times, product recalls, and, ultimately, the safety of the end user. In this guide, we’ll explore some practical ways to prevent cross contamination in multi-batch GMP vessels, so you can keep your facility compliant with global GMP standards.
Why Cross Contamination in Cleaning is a Critical Risk in GMP Vessel Operations
For a non-technical person, preventing cross-contamination might seem easy. But any expert will tell you that the cleaning process varies between different products, which can be problematic if you need to use the same equipment across multiple lines. Additionally, there are different kinds of residue, and for each, you need different ways to prevent cross contamination.
This is the reason why regulatory bodies pay such strict attention to this aspect of manufacturing. The EU’s Annex 15 and FDA’s cGMP standards require validated cleaning protocols and a system that takes adequate measures to prevent cross contamination between batches.
In spite of these regulations and scrutiny, ISPE data reveals that cross contamination remains one of the top five causes of FDA warning letters. This tells us that a lot of facilities are still struggling to meet expectations.
The consequence of cross-contamination is far worse than a rejected batch – it could trigger full product recalls and cause damage to relationships with your clients.
Common Causes of Cross-Contamination in Multi-Batch Production
Contrary to popular belief, cross-contamination in multi-batch production doesn’t occur because of major lapses in your cleaning systems. Many times, they happen in ways that are easy to overlook, like:
- The cleaning process didn’t reach every area, resulting in residual matter remaining in vessel corners or contact surfaces.
- The vessel was inadequately rinsed, or validated cleaning parameters weren’t achieved.
- An issue was caused by human error, such as inconsistent SOP adherence or incorrect cleaning agent concentrations.
It’s a well-known fact that manual cleaning methods have a higher risk of contamination compared to validated automated systems.
Core Principles of a GMP Cleaning Procedure
An effective GMP cleaning in place system is built on repeatability, traceability, and validation. It’s not just about what gets cleaned; it also includes the how, the when, and the documentation that will support the thoroughness of the system. Let’s explore a couple of core principles of the cleaning procedure.
1. Cleaning Frequency and Changeover Protocols
A changeover between product batches must follow a validated sequence of steps. This will typically include an initial rinse, detergent cycle, intermediate rinse, and final rinse with high-purity water.
Following this, you’ll need a documented visual or an analytical inspection. The frequency of cleaning is determined by product risk profiles and exposure to the equipment.
2. Visual Inspection vs. Analytical Testing
A visual inspection isn’t enough on its own to ensure a thorough cleaning. For effective validation, Total Organic Carbon (TOC) testing, ATP swabs, or microbial sampling are standard.
The guidelines also suggest that TOC levels should remain under 10 µg/cm² on product-contact surfaces. All this data must be traceable and reviewable during audits.
Designing Vessels to Reduce Contamination Risk from the Start
A major factor that determines the effectiveness of cleaning is the design of the equipment. In GMP manufacturing, vessels need to be engineered keeping in mind their function and ease of cleaning.
A thoughtful vessel design reduces the reliance on aggressive cleaning agents and minimises the risk of cross contamination between batches. We’re talking about things like sloped bases, fully drainable ports, and seamless transitions in welds and joints. All these things help to eliminate areas where residue can collect.
Additionally, properly integrating cleaning devices such as spray balls or rotating nozzles ensures that cleaning-in-place systems can access every surface uniformly. According to EHEDG, vessels that follow these design principles can reduce cleaning time by up to 40%, improving operational efficiency while also making the validation process more predictable and repeatable.
How Cleaning in Place Systems Support Batch Integrity
A cleaning in place system is essential for cleaning in GMP environments because it brings consistency and traceability to the cleaning process. Here’s how:
1. Automated Cycle Repeatability and Audit Trails
CIP systems help remove the variability that comes with manual intervention using programmable parameters. Each CIP system cycle can be replicated, logged, and reviewed. This helps support internal quality systems and simplifies external audits.
2. Water Temperature and Flow Control Parameters
When you’re following GMP cleaning procedure, it’s important to ensure that the water and cleaning solutions are reaching the right places. They also need to have the right pressure and temperature to clean the surface properly. According to a 2024 report, an automated CIP system is able to reduce water use by about 30%, which makes these systems cost-effective as well.
Validation and Monitoring: Measures to Prevent Cross-Contamination
Cleaning validation is an ongoing process that involves setting acceptable limits, proving that those limits can be met consistently, and routinely re-evaluating performance. This might include setting specific thresholds for TOC levels, microbial counts, or rinse conductivity. All of this will help confirm whether a vessel is clean enough for the next batch.
Regulatory bodies often ask not just for proof that your cleaning process works but for evidence that it has worked every time. A big benefit of a GMP cleaning system is that its routine checks and records can support long-term consistency.
Operator Training and SOPs: Human-Centric Ways to Prevent Cross Contamination
Even the best cleaning systems vary in effectiveness depending on how they’re used.
Operator error remains one of the most common sources of cleaning-related compliance issues. Your personnel need to be trained in how to perform the cleaning tasks, with SOPs that are clear, role-specific, and regularly reviewed. If your facility has a high staff turnover; you should place extra emphasis on retraining.
You’ll also want to check routine performance checks for employees, operator sign-offs, and peer verification systems that help build accountability into your daily routines. Preventing contamination goes beyond your equipment – the people operating that equipment also need to be continuously using it correctly.
Choosing the Right Equipment Partner to Support Compliance
Ultimately, controlling the ways to prevent cross contamination is only as effective as the humans behind it. Selecting a partner that understands the realities of GMP design, validation, and lifecycle support can make a lot of difference to your cleaning systems.
Suncombe’s cleaning solutions for the GMP vessels meet strict pharmaceutical and biotech standards. Our extensive product line of GMP Washers, GMP Process Skids and Systems, and GMP vessels is fully validated and follows GMP guidelines in pharma. We help facilities implement all systems, from CIP integration to compliance documentation that supports production and inspection readiness.
To discuss how our GMP vessels and cleaning systems can help reduce cross-contamination risk in your facility, contact us at +44 (0) 203 089 0280 or email [email protected] today.
