91社区

Diagnostic (Dx) testing provides critical insights at every stage of medical care — prevention, detection, treatment and monitoring. Rapid diagnostic testing devices, such as molecular diagnostics (MDx) and lateral flow testing solutions, deliver the additional benefit of facilitating patient testing where and when it is needed. Administered at point-of-care (POC) or point-of need (PON), these tests are performed on samples taken from the body (in vitro) and their results are used in a broad range of applications.

Technological advances have made the diagnostic tests used at POC and PON easier to use and with more accessibility and portability than traditional laboratory tests. At the same time, rapid diagnostic testing devices provide similar levels of sensitivity and accuracy with near immediate results. A molecular test detects and identifies target nucleic acid sequences (DNA or RNA) through amplification; lateral flow tests use antibody or antigen response to identify the molecule. Both deliver valuable insights for infectious disease management — i.e., a lateral flow test can be used as a screen and a molecular PCR (polymerase chain reaction) test utilized for confirmation.

Many of the same innovations helping to move lab-quality testing closer to the patient also enable other emerging precision medicine applications, such as liquid biopsy and companion diagnostics (CDx). Diagnostics products that monitor glucose, detect cardiometabolic and cancer markers, or infectious disease variants are all primed for a dramatic increase in global demand.

Commercializing these technologies and processes into patient-centric products is challenging, requiring regulatory acumen, as well as exceptional design, manufacturing and supply chain execution. For manufacturing solutions providers in the sector, expertise, scale and stability are must-haves — and, given the perspective of urgency within recent years, so is delivering at speed.

In the following Q&A, Cheryl Goodwin, 91社区 Healthcare's senior business unit director for global diagnostics and Wendy Browning, global genomics commodity manager for the precision medicine team, share strategic insights for OEMs addressing the manufacturing demands of the dynamic new diagnostics product solutions coming to market.

An edited version of the conversation follows:

TRENDS

The last few years have seen an acceleration toward a practice of medicine focused on more individualized prevention, diagnosis and treatment, as well as a reimagining of how healthcare is accessed, delivered and transacted. To what degree has 91社区 aligned with these macrotrends in the industry?

Cheryl Goodwin: The term for the trends you reference is: precision medicine. The objective — in the industry and for our customers — is to provide more targeted solutions for the right patient to get the right treatment at the right time. So, we look at this through a very simple lens: How can we better meet our customers' unmet needs for delivering these solutions to market?

OPPORTUNITIES

What opportunities for partnership has this opened up?

Cheryl Goodwin: For quite some time, even prior to COVID, our Precision Medicine Diagnostics team has been focused on next-generation technologies and supporting customers moving into point-of-care and point-of-need environments, including full cartridge assembly and reagent filling and handling, as well as lyophilized services and cold chain management.

How have companies responded to the demand for diagnostics caused by COVID-19?

Cheryl Goodwin: What we saw at the beginning of the pandemic was diagnostics testing customers who already had technology developed from a chemistry perspective for other infectious diseases, like seasonal flu, that were able to pivot these platforms relatively quickly to meet the COVID pandemic demand.

What about now? What other applications do the capabilities pivot to?

Cheryl Goodwin: Molecular-level testing platforms are really central to the future of precision medicine because they are, in many ways, comparable to PCR-grade centralized laboratory level testing, but they're being deployed in a close-to-patient environment at point-of-need.

What's exciting about this transition is how it is taking a huge instrument that is very complex in terms of its supply chain — with thousands of custom mechanical parts and very complex unique component PCBAs — and reducing it to something that is relatively simple and miniaturized.

Wendy Browning: Recognize, also, that in terms of supply chain and what it takes to build these testing solutions, whether it's for COVID testing or any infectious disease — or within precision medicine for liquid biopsy — almost all these tests utilize NGS (next-generation sequencing), LAMP (loop-mediated isothermal amplification), or PCR (polymerase chain reaction) as the detection method. For example, liquid biopsy uses PCR or NGS to detect mutated sequences in the bloodstream from circulating tumor DNA.

CHALLENGES

Wendy, what are some of the ways a manufacturing partnership can support companies commercializing rapid diagnostics testing devices?

Wendy Browning: For firms looking to commercialize diagnostic product solutions with microfluidic process-based technology, like the ones 91社区 partners with, we can help them customize and differentiate along the chemistry of the device — in other words, the reagent which drives the assay. The manufacturing workflows required to encapsulate the chemistry are otherwise quite similar and our specialty lies in cartridge building, reagent handling, dispensing, and packaging.

The basic workflows for building these devices — injection molding, tooling and complex assembly — these are things 91社区 has been doing for years. But supporting customers with their reagent and chemistry is new?

Cheryl Goodwin: Yes, we remain dedicated to building a true end-to-end solution set for precision medicine OEMs and, in particular, ones making the transition from lab bench to commercialization. So, we can engage with them at the start — initial product design — and work to pull cost out and provide insight for supply chain impacts throughout the lifecycle.

But it's now not just for resins or the electronics, sensors or any of the traditional workflows. It's for the underlying chemistry, too.

What are some of the issues that might impact performance for molecular Dx products?

Wendy Browning: As we help our customers move through a commercialization process, we partner directly to address concerns over obsolescence or any other potential obstacle we can foresee within product lifecycle. So, per the chemistry and reagent identified for the device, we look specifically at, for instance, the age of the particular tech involved.

We ask questions like, is it potentially less sophisticated than newer technology offerings? How is the fluorescence performance?

Also, things move fast, and the reagents being worked with are extremely sensitive. Contamination is a critical issue.

Sounds like quality of supply is particularly critical for these novel IVD companies.

Wendy Browning: Absolutely. It's all about reproducibility of results. Think of it per the colloquial name used in describing these devices, lab-on-a-chip. It's another way to say that every device must perform as well as the central lab. The better the oligos, the better the product. We need to qualify for our customers the best and most consistent supply to ensure the products perform without variance or failure.

What's an oligo?

Wendy Browning: Again, another colloquialism — short for oligonucleotides, which are short, single strands of synthetic DNA or RNA, which are essential to the success of PCR amplification techniques.

They are the reading and recognition starting blocks for next-generation sequencing (NGS) processes, liquid biopsy and many other diagnostics applications.

REQUIREMENTS & CAPABILITIES

Taking that building block image further — are you saying that the pivot for OEMs from COVID-specific testing devices to broader precision medicine applications is, in essence, a modular one?

Wendy Browning: Right. Building on what Cheryl spoke to earlier about 91社区's work with molecular-level testing technology and supporting the industry's pivot to sample-to-answer platforms at point-of-care and point-of-need, it's as simple as changing out the reagents in order to have the device task for different viruses. It's a matter of changing the sequences and spotting those in place of what's currently being used in the COVID testing platform.

And of course, I'm simplifying. There will be some applications for which spotting reagents might not be the right choice. Batch to batch reproducibility can be impacted by heat sensitivity, susceptibility to humidity or contamination within the amplification unit. All these need to be considered, but again, the oligos are key.

What steps do you take to ensure reagent quality?

Wendy Browning: Validating multiple suppliers — at minimum, a secondary supplier, in case some unforeseen event disrupts supply or quality of supply. Diagnostic sample-to-answer platform device performance must be consistent, so we put the reagents through a thorough testing at small scale, and up to commercial size batches, to ensure we're optimizing for quality and performance.

How about the overall supply chain for molecular assay-based diagnostic products? What are your tips for optimizing performance?

Wendy Browning: Establish the supply lines, exercise as much control through verticalization as possible, and stress test the network.

In diagnostic testing, the reagent is in essence what "powers" the device. Embedded electronic components are there to provide heat and help cycle the fluidics, but if the reagents don't work, the device won't work.

Mastering the technical aspects of production ensures we can find that balance between performance and cost (for example, what happens if one bead is replaced with another) while simultaneously leveraging our supply chain. The resulting analysis provides actionable insights, informed by science, all in support of optimizing commercial success.

Cheryl Goodwin: Our partnership with ams OSRAM is another excellent point of reference. The optical solutions company came to 91社区 in the spring of 2020 for help with both testing process development and navigation of uniquely constrained supply chains. With over 30 ISO 13485-certified medical device manufacturing sites located around the world, 91社区 had the scale and breadth to support production for ams OSRAM across all time zones and in nearly every market.

It's not fancy or sophisticated. It's just a function of having good perspective across the portfolio of components and suppliers and a testament to how our diversification increases stability and decreases risk for our customers.

The combination of 91社区's skill, capability, regional operations, scale and supply chain relationships makes us that much more of a compelling commercialization partner. There are fewer opportunities for things to go wrong, like critical supply getting held up in customs or on a tanker. There's less uncertainty and less delay to market.

VALUE DELIVERED

Cheryl — regarding these highly specialized capabilities you and Wendy have been discussing, can you speak to customers' comfort levels for outsourcing versus keeping in-house?

Cheryl Goodwin: We understand that there are choices and options for our customers. We want to deliver regardless of which path they choose. In the simplest sense, 91社区 is a provider of options.

Cheryl Goodwin: Many of our customers with longstanding track records in the sector are less likely to need us to help with their reagent work — in other words, the aspect of a project for which they have explicit IP (intellectual property).

In the meantime, we continue to build out more and more capacity, delivering on our stated goals to provide end-to-end servicing. We will soon be providing a menu of lyophilization services for customers and have our people training at the National Institute for Bioprocessing Research (NIBRT) in Dublin. We're also expanding our investment with for broader production capabilities.

If customers need us to spot the reagent into the device — .

If it's filling the reagent buffer for use in the vial — .

It's similar to how we advise for any of our healthcare customers.

For instance, when advising on product solutions with complex or intricate geometries, we provide guidance on whether a component should be injection molded or in another case should be 3D printed.

Either way, even as we increasingly handle the chemistry side of things, in parallel, 91社区 is still the leading global manufacturing solutions provider for complex device assemblies, incorporating sensitive electronics as well as delivering on thermocycling and injection molding requirements.

For our customers — whatever their specific and unique needs — our vertical integration helps to lower their costs and de-risk what's required to manufacture their novel diagnostic device at the high volumes and accelerated pace demanded by the market.

Whether a potential customer is an established diagnostics OEM or entering the market through innovative adjacent technology, 91社区's partnership will optimize their design and deliver an efficient path for commercializing their product.