How to find a cleanroom-production goldilocks zone

Wouter Geurts, technical business development manager, TekniPlex Healthcare, shares how finding a film’s sterility ‘sweet spot’ will expedite speed to market and mitigate cost.

As medical products manufacturing continues to evolve, the heights to which cleanroom technology has soared is, in a word, incredible. For the most sterility-stringent medical apparatuses, such as implanted devices and certain microchips, the simplest metaphor to convey current purification capabilities involves a really large lake and a really small coin.

Picture Lake Ontario, all 7,300 square miles of it. Now picture 40 penny-sized flecks floating in that lake. That’s equivalent to the level of purity that today’s-controlled environments can achieve when producing medical products.

Meanwhile, another ever-progressing field is diagnostics, which has continued to become more exacting even as application flexibility and durability have expanded in tandem. For example, recent years saw the pioneering development of accurate COVID-19 tests with a shelf life lengthy enough to serve less developed, hard-to-reach locales. Here, success hinges on one inevitability: As diagnostics tools like microfluidic cartridges get more precise and sophisticated, so must the components that comprise and contain them.

The regulatory effect

Regulatory agencies have taken notice – and acted accordingly. A nod to both increased cleanroom capabilities and more exacting sterilisation needs, the European Union’s Medical Device Regulation published a set of elevated guidelines in 2017 that officially took effect in May 2021. Similar laws exist in the United Kingdom and United States, whose FDA is especially rigorous in regulating medical devices and diagnostics tools. Crucially, these directives impose stricter monitoring of quality and safety during a product’s lifecycle, starting at the inception of component production. These regulations insist that the sum must not be less sterile than its parts.

Among these key components is diagnostics films. Typically composed of cyclic olefin copolymer (COC), such films are critical to the overall viability of a diagnostics assay device, insomuch as they enable PCR multiplexing with low-noise signal readout and an optimal seal. In other words, COC films simultaneously keep diagnostics tests free of contaminants and, by remaining glass-clear, optimise analysis instrument precision by avoiding accuracy-degrading autofluorescence issues. Another benefit of COC diagnostics films is their versatility, as they can incorporate value-added features such as conductive printing, PCR thermocycling, laser welding and ultrasonic sealing.

For as vital as they are to diagnostics, it’s fortunate that such films require substantively less purification than our Lake Ontario anecdote. If adequately sterilising diagnostics films required such infinitesimal particulate tolerances, producing such films simply wouldn’t be economically viable. We’d still have diagnostics tools, yes – but they’d be neither as promising nor as prolific.

If you’re familiar with controlled environments, you’ll know that cleanrooms are designated with internationally recognised numbers based on their particulates tolerances. The lower the number, the lower the tolerance.

Assembled in a cleanroom

Most diagnostics kits are assembled in an ISO 5 setting. Not quite the equivalent of 40 pennies per 7,300 nautical square miles, but incredibly sterile, nonetheless. Creating and maintaining a controlled environment of that calibre is expensive, and acquiring the regulation-mandated production data is laborious. So, while it’s medically necessary to do some of the kit-building work in ISO 5, it’s not ideal to do all of it there.

To meet the latest, more stringent regulations, it is preferred that COC diagnostics films be produced in ISO 7 Cleanrooms, eliminating the need for post-production web cleaning – which adds both time and money to the overall process. That might not seem impressive by comparison, but considering the relative simplicity of a film structure this is exceptionally strong. In fact, it’s a level at which exceedingly few producers are currently providing diagnostics films.

The reasoning behind the ISO

From a cost-benefit standpoint, then, an ideal diagnostics tool kit process might assemble at an ISO 5 level, but source components may be produced at individually recommended sterility levels. This is crucial, because the ability to reliably source films produced at an ISO 7 is significantly cost-effective compared to post-production web cleaning alternatives, which in addition to adding cost and time can also result in a percentage of film being damaged during this tension-heavy process.

This sort of “building block” approach to cleanroom production also can expedite regulatory approvals, and therefore reduce time to market. This is because sourcing cleanroom-produced components means those items come pre-certified – a big plus given the escalated data acquisition, analysis and reporting requirements placed on manufacturers of medical device and diagnostics tools.

This is where the sweet spot lies – one that keeps the pace of production up while keeping costs down. Sourcing materials and components produced in cleanrooms suitable for their own specific needs blends fiscal responsibility with rapid repeatability…all without sacrificing device efficacy or diagnostics accuracy.

The Goldilocks Zone

What’s more, diagnostics tools suppliers sourcing specialty films like COC constructions often will find that dedicated vendors – themselves specialists – can cater to customisation and small quantity requests in ways that are both medically sound and economically attractive.

For diagnostics films, the cleanroom-production Goldilocks Zone does indeed exist. However, kit manufacturers will seldom find it in their own backyards. Through a hub-and-spoke, source-and-assemble approach, cleanroom-produced diagnostics devices can meet the economic, regulatory, and high-volume needs of today’s tightly controlled medical products landscape.