Contamination Is a System Problem: Designing for Biological Risk in Product Development

Why managing biological risk requires joined-up scientific thinking

In a biological lab or cleanroom environment, contamination does not usually mean something visibly dirty or obviously wrong. Most biological contaminants are microscopic: bacteria, fungi, spores, or biological residues that cannot be seen, smelled, or detected without specific testing.

Contamination can enter a system through contact with people, surfaces, liquids, air, or tools, and once introduced it can persist silently. A system may continue to function, sometimes for weeks or months, while contamination subtly alters results, interferes with biological behaviour, or compromises repeatability. By the time contamination is detected, it has often been present for some time and influenced far more than the single test or batch in which it is discovered.

Contamination is often referred to as if it was an event. A failed sterility test. An unexpected organism. A batch that cannot be released. In many product development environments, the response is immediate and reactive: investigate the failure, identify a cause, fix the issue, and move on.

But contamination is rarely that simple.

Over nine years of my career as a Cell/Molecular Biology Scientist, time and time again I have seen contamination identified only at the point of the symptoms being detected, long after the underlying conditions were established. By the time it shows up in a result, the system has usually been compromised for some time.

Detection is far more often the visible outcome of invisible system behaviour than observing a single event. The contamination emerges from the interaction between design decisions, human practices, process maturity, environmental controls, and the assumptions made along the way. Treating contamination as a single failure risks solving the wrong problem - and worse, repeating it.

To manage biological risk effectively, teams must move away from event based thinking and towards a system level perspective

The myth of the isolated contamination event

When contamination is framed as a discrete incident, the analytical focus naturally narrows. Investigations often look for a moment of error: a handling lapse, a procedural deviation. While these factors may be present, they are rarely sufficient explanations on their own.

I have witnessed investigations stop once a clear deviation is found, even when it does not fully explain the risk. The surface issue is fixed, but the system that made it possible is often left unchanged.

Biological systems are inherently complex. Microorganisms respond to surfaces, fluids, temperatures, and time in ways that are not always intuitive. A positive result at the end of a process is usually the final signal in a long chain of interacting influences.

By focusing only on the point of detection, teams risk overlooking upstream decisions that enabled contamination to occur - problems that may be repeated again and again.

Start with intent: defining contamination risk early

Some of the most significant contamination risks are introduced long before any biological testing of a product takes place. Early design choices, often made for speed or convenience, can unintentionally create environments that favour microbial persistence or transfer, including:

• Material selections that interact poorly with biological media
• Interfaces that are difficult to clean or validate
• Geometries that trap fluids or create dead volumes

We regularly find that these choices, made with the intent to accelerate learning, simplify building, or enable rapid iteration, are made without biological behaviour being part of the initial decision.

At OPD, systematic control begins with intent. Before testing strategies or protocols are defined, we establish what “contamination risk” actually means for the specific product or process.

Early development includes a clear understanding of where biological interaction is expected, tolerated, or unacceptable. We agree how much variability the product/process must withstand and recognise of which assumptions are being made due to incomplete data.

We have worked with teams who engaged us assuming that contamination was something to manage later, once functionality was proven. In reality, early prototype handling, shared test rigs, or informal cleaning steps had already introduced biological variability into the system. When results later became difficult to reproduce, the issue was not the design itself - it was that contamination had quietly influenced the data from the start.

At this stage, the goal is not compliance, but risk visibility. Making biological risk explicit early allows create activities that meaningfully reduces uncertainty rather than simply advancing functionality of the product.

At early stages, these decisions may appear insignificant. However, once a product or process begins to mature, these same choices can become significant biological liabilities. Contamination control, therefore, is not something that starts in the laboratory or clean space. It starts in design intent and assumption management.

Contamination control is a lifecycle adaptation, not a facility feature

One of the most persistent misconceptions in development programmes is that contamination is “solved” once work enters a controlled facility. In reality, contamination risk evolves across the lifecycle of a product or process.

I have seen projects move into controlled environments with a sense of relief, only to discover later that immature processes or inconsistent behaviours have been carried straight through with them.

Another common misunderstanding is that contamination originates from one domain alone. In practice, it emerges at the intersection of people, process, and environment.

Even highly skilled teams introduce variability. Differences in training, interpretation of procedures, manual skills, and informal workarounds all influence biological risk. When engineering teams and biological specialists operate independently - important risk signals can be missed.

Immature or evolving processes are a common source of contamination vulnerability. Unvalidated steps, undocumented adaptations, and process drift during the scale-up, all increase risk. Pilot and pre production builds expose weaknesses in repeatability and transferability while verification phases introduce tighter controls. Processes that “work” in early development often lack the robustness required for repeatable, controlled outcomes.

Controlled environments such as Containment Level 2 lab and clean room at OPD are powerful tools but they are not absolute barriers. Without appropriate process discipline and behavioural controls, they can offer false reassurance. Environmental control must be seen as one layer of defence, not the defence itself.

At OPD, we consider these domains together, because that is how contamination truly arises. Our contamination control approach is therefore continuously adaptive, with controls maturing alongside the product and informed by data, experience, and evolving risk profiles. Treating contamination as a static problem ignores this dynamic reality.

From reaction to design: building contamination-resilient systems at OPD

Contamination cannot be managed effectively through reaction alone. It must be designed out, constrained, and monitored through a connected system of product design, process development, environmental control, biological understanding, and measurement integrity.

Our teams approach contamination as a system problem, so we gain the ability to control it systematically - throughout development and into the final product.
Our contamination strategies are not reactive. They are built in.

This means:

• We verify assumptions early, before they become embedded
• We design processes that tolerate biological variability
• We use biological insight to inform engineering decisions
• We follow quality rules that maintain alignment without stifling learning
• We progressively strengthen the system as contamination risks become better understood

The result is not just cleaner outcomes, but more predictable development, stronger verification, and greater confidence at every stage of progression.

When contamination is approached as a system property, teams shift their focus. Instead of asking “what went wrong?”, we ask “how do we design this, so it is hard for things to go wrong at all?”

That change in mindset is where real resilience is built.