One Size Fits One - Advancing Infectious Disease Diagnostics With Custom Molecular Reagents

Understanding the application

Fortis’s custom approach focuses on partnering with clients by developing a thorough understanding of the customer’s technology or product performance requirements, the unique challenges that the customer is facing with their product, and the economics of their product and market cost parameters. The team uses their toolbox and expertise to produce custom products that solve the customer’s problem.

Considering quality

Every project initiated at Fortis is performed under the strict requirements of their quality system from day 1, starting with early-stage project design, feasibility, and specification development and into high volume manufacturing. "Another differentiator for us is that everything we do from the beginning is under our ISO 13485 Quality System— we're also an FDA registered contract manufacturer —and everything that we do is compliant with the appropriate regulatory requirements," Kuiper noted. "So whether it's a catalog item, or a custom reagent project, everything is under our strictest requirements of the quality system, reducing the risk for any project that a client considers taking on with us and assuring long term consistent quality over the life of the product."

Manufacturing custom enzymes

An example of a recent project brought to Fortis by a client was a need to produce a specific proprietary enzyme for use in their IVD application. The client required it to be developed and manufactured under a Quality System, at production scale. For this project, early engagement with the customer’s development, manufacturing, and quality teams was critical. The Fortis team first undertook learning what the end application was, gathering inputs and identifying the performance requirements, product specifications, and also understanding the customer’s manufacturing and quality system requirements. Where appropriate during development, Fortis also performed rigorous testing to ensure that the reagents met the functional requirements of the application.

In this specific case, the client previously had another contract provider that could not meet the quality, volume, or cost requirements for their program. They engaged with Fortis to optimize the product and processes to scale up enzyme production. The Fortis team worked closely with the client to explore potential alternative solutions, getting better product performance, at a lower total cost, while being manufactured in compliance with the Quality System requirements. Over a six-month period, working in close partnership with the customer, an alternate approach to both the product construct and the manufacturing process was developed while completing product and process validations. The validated process is now yielding almost 10-times more enzyme per manufacturing run compared to the previous supplier. This provides cost savings, minimizes lot-to-lot variability, and relieves supply-chain and quality system stress for the client with regards to a key reagent in their workflow.

As Kuiper noted, even if standard manufacturing processes for this particular enzyme had been used, Fortis would have been able to scale it appropriately to meet the customer’s needs. By using Fortis’s know-how, the company was able to significantly increase yield to reap the associated downstream benefits. "If we can squeeze more ‘juice’ out of every batch it saves cost, reduces the manufacturing scale requirements, reduces lot-to-lot variability, and dramatically improves turnaround time. There are benefits in all key areas: quality, cost, and delivery."

To ensure successful scale up from small quantities to full manufacturing, Fortis ensures every product that comes into its pipeline goes through a rigorous development and product launch process culminating with a three-lot validation process.

Creating a master mix

While some clients leverage Fortis’s capabilities to develop and manufacture custom enzymes, each will typically need buffers and ancillary reagents, and these will quite often end up as components in a more complex master mix solution. "We’re happy to provide the enzymes, buffers, and reagents separately. We just think it makes the end-user’s job easier if we can formulate it into the end master mix," Kuiper said.

However, doing this often requires a better understanding of how the test sample will be collected and processed. A good example of this is the development over the past two years by the company’s customers of a range of RT-qPCR reagents to detect SARS-CoV-2.

Many of Fortis’s reagent customers use different sample types (saliva, nasopharyngeal swab sample, etc.) and have unique sample collection and transport medias. They often have unique workflows and protocols that are specific to their assay or to their equipment.

Considerations for how to design a buffer or master mix solution include what kind of sample would be used, reaction volume, if it needs to be an ambient stable (e.g., lyophilized or air-dried) mix, if the sample would be run through a purification and extraction process first, or if it would be processed directly. Each component introduces unique requirements necessary for creating a functioning mix solution.

Fortis has optimized and currently manufactures multiple reagent mix solutions, at scale, for various RT-qPCR tests from unique high-concentration lyophilized reactions used in single-use, point-of-care cartridge devices, all the way to bulk reagents that are used in high-throughput laboratory applications that are amplifying RNA direct from crude samples, such as saliva, nasal, or nasopharyngeal swabs. Creating the best master mix is often an iterative process to discover those that work better than others to finally pinpoint and optimize the one that works best, at the best price, for a particular test.

Kit solutions

Since the custom solutions team at Fortis becomes so familiar with assays their clients are developing—to the extent that they will often bring a client’s platform in-house to develop an intimate understanding of what is required to optimize the diagnostic—it only makes sense that the company also offers a service to produce the entire test kit.

In some cases, a client may buy the amplification components (e.g., enzymes or master mixes) from one supplier, buy the primers and probes from a second supplier, and maybe buy the controls from a third vendor. That is a model that has worked for many companies, but which involves supply chain and logistics complexity, introduces quality risk, and increases the total cost. But for customers who want a one-stop solution, Fortis’s quality systems and certifications provide the foundation to bring the entire kit manufacturing under one roof.

"If it seems to make sense to bring those components in under our contract manufacturing and quality systems and to put all of the components together into one kit, we're happy to do that as well," Kuiper said. "Any kits that we put together could range from just the enzymes, and master mixes, all the way through to a complete kit solution containing the enzymes, the oligos, controls, et cetera." For further customer convenience, Fortis will work with clients on the label and packaging approval processes. As a contract manufacturer, Fortis can manufacture, label, warehouse the kits to customer specifications, and dropship them straight from their facility.

When choosing to work with Fortis on a project, whether it is the development and manufacturing of a unique enzyme or the assembly of a customers’ complete kit, clients can expect to benefit from their scientific and process expertise, their certified manufacturing and quality systems, and their commitment to customer support.

The Fortis team has an unmatched depth and breadth of scientific and process know-how. This, in combination with its portfolio of enzymes and proteins and years of learned experience supporting commercial life science customers enables Fortis to rapidly develop and manufacture the unique products that meet its customers’ requirements.

Contact an Expert

At Fortis Life Sciences, we know that effective molecular diagnostic assays require enzymes, reagents, master mixes and kitted solutions that meet strict quality systems produced by experts you can trust.