W hen new assays or diagnostic tests are ready for commercialization, there can be tremendous benefits to outsourcing manufacturing to qualified contract providers. 
In doing so, assay developers can avoid significant investment in the infrastructure—automated equipment, highly trained personnel, high-end quality management systems—and the various certifications (FDA, ISO, GMP, etc.) required. 

The simplest of these arrangements involve outsourcing the manufacturing of an existing, established test that is already being manufactured. In many cases, this can occur when a company wants to downsize or shutter manufacturing operations altogether due to cost overruns. 

Still others have invested in developing the test and acquiring the required PMA or 510K approvals, but decide instead to keep focus on development of the next new test instead of entering the world of manufacturing. In this way, they can remain a lean organization with a limited staff and avoid large capital expenses.

Even large pharmaceutical companies sometimes choose to outsource manufacturing of smaller product lines that represent only a small part of the overall gross income.
However, the reality is that most opportunities in contract manufacturing do not fit neatly into a box. Instead, many assays arrive as “not-ready-for-prime-time” products that may not be fully developed, are still in the concept phase or proven in an R&D lab but not viable for scaled-up production.

When this occurs, contract manufacturers are often called on to provide assay development assistance. This can take many forms including making changes to format—i.e. IT to lateral flow—identifying alternative reagents/antibodies and changing the coatings applied to microtiter wells.

In addition, regulatory assistance is also a factor in most contract manufacturing situations. This includes receiving advice and guidance on how to meet the regulatory requirements of the FDA, but also achieve the required registrations required in other countries such as CE markings, Health Canada, and others.

Therefore, finding a qualified contract manufacturer that can also provide development and regulatory assistance is often a critical, even strategic, decision.

“Some of these new assays coming out of these labs are great products that are going to change the world, but the scientists that develop them have little understanding or background on the regulatory side, the quality side, or how to manufacture it on a large scale,” said Stephen Hall, chief financial officer, BG Medicine.

In addition to having worked for a contract manufacturer earlier in his career, Mr. Hall now works for BG Medicine, a company that licenses the Galectin-3 Test. 

The in vitro diagnostic device quantitatively measures galectin-3 in serum or plasma by enzyme linked immunosorbent assay (ELISA) on a microtiter plate platform. The results of the test are used to aid in identifying patients with chronic heart failure that are clinically stable but at a higher risk of hospitalization and mortality.

In his experience, Mr. Hall says there are some manufacturers that are willing to accept assignments for which they are not fully qualified. 

“I’ve had companies tell me they had all the capabilities, but when you start asking if they have any FDA products currently being manufactured in house, they say, ‘no, but we could get up to speed for that’ or ‘we’re not ISO certified, but if we had to be, we could be.’”

Hall says that when evaluating a contract manufacturer, he has a list of requirements that include ISO certification and a facility that is GMP and FDA-approved. In addition, he prefers to work with contract manufacturers with experience producing similar tests and formats.

Ideally, the company would also have all of the necessary instrumentation in-house to conduct any steps of the manufacturing process.  

“You’d rather have all the equipment and capabilities in house rather than having to ship items around,” said Mr. Hall.

In May 2007, BG Medicine entered into a biomarker product license and collaboration agreement with ACS Biomarker B.V. from The Netherlands. After licensing the intellectual property, the company decided to pursue 510K clearance from the FDA and did initial work with a Netherlands based developer of IVD immunoassays.

According to Mr. Hall, BG Medicine never intended to manufacture the product itself.  So, in 2009 the company engaged with contract manufacturer Corgenix to assist in final development and commercialization of the test kit. 

Corgenix of Broomfield, CO, operates in an FDA approved facility, is ISO-certified and operates under GMP conditions. For more than 20 years, the company has created and manufactured IVD tests, typically ELISA-based.

“When you don’t know if you have the volume to justify producing the test yourself, it just makes sense for a small company to use a contract manufacturer,” said Mr. Hall.
The first step in working with Corgenix involved a technology transfer, followed by optimizations and validations to determine compatibility with Corgenix manufacturing equipment and QC processes.

Although the assay was already developed, not all the test methods for manufacturing purposes had been developed. Corgenix had to develop the processes and the validations to create the gold standard tests to complete its in-process QC. 

In addition, some of the raw materials required validation to ensure availability and real-time stability to scale up for manufacturing. Because the assay was developed in the Netherlands, new sources for critical raw materials in the U.S. were also required.

Again stepping beyond its role as a manufacturer only, Corgenix also responds to customer service inquiries as needed, along with providing fulfillment and distribution services, including storing inventory, order processing and shipping to end users.

To manage inventory in a just-in-time fashion, Mr. Hall says there needs to be constant communication with the manufacturer to ensure production remains in line with variations in demand.

“When you are a small company you have limited resources and so you can’t spend a lot of working capital on inventory,” said Mr. Hall. “Therefore, you need to proactively know where you are with lead times from all the suppliers to ensure there is never an issue.”