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CodeLink s Chandler, Ariz., Fab Facility Gears up for Rat ADME Array Rollout

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The next product to come off the assembly line of the CodeLink fabrication facility in Chandler, Ariz., is a 16-chamber rat genome catalog microarray for ADME applications. The chip, which will hit the market within the next 60 to 90 days, is not just significant for its content: It will be the first CodeLink product released after the completion of the $10.3 billion acquisition of Amersham, the UK-based life science giant, by General Electric, and its transformation into GE Healthcare.

Last week, BioArray News met with management, public relations representatives, and quality-assurance specialists of GE Healthcare, and toured the GE Healthcare CodeLink microarray fabrication facility. This was the first time the company gave independent media a tour of the new plant where the CodeLink products are manufactured.

Trevor Hawkins, vice president for development and new business initiatives for discovery systems in GE Healthcare Bio-Sciences, provided BioArray News with an overview of the company’s strategy in the CodeLink area and beyond. For GE Healthcare, he said, the target is personalized medicine, which may take as long as 15 years to evolve.

“We are attempting to do something a lot bigger than gene expression,” Hawkins said. “Gene expression will play a major part in our vision moving forward. It is one in a number of cogs moving forward. What is clear to us is there are now major transformational moves that GE Healthcare can make — because it is the combination of GE Medical Systems and Amersham — that we weren’t able to do before.”

In the short term, he said success will be measured by a growing customer base, and a customer base that comes back for repeat orders. That is the No. 1 goal, he said. “You get there by developing the right products at the right time for the right price.”

Within the Discovery Systems unit of GE Healthcare, formerly Amersham Biosciences, CodeLink is the fastest growing business area, Hawkins said.

CodeLink, which positions itself in the market on its performance and sensitivity, is regarded as the No. 3 player in the preprinted microarray market, following Affymetrix and Agilent Technologies, respectively. CodeLink’s position in the marketplace is derived somewhat anecdotally as the company does not provide details on its installed base of customers, or the revenues derived from the sale of the hardware, software, and reagents, as well as the bioarrays that, together, form the CodeLink product line.

This market landscape with three major players has shifted, however, with the first-quarter entry of sequencing giant Applied Biosystems into the field, and the expected arrival of Taiwan’s Phalanx Biotech Group, which says it will enter the market in the fall, bringing online a production facility that can manufacture as many as 50,000 microarrays per day.

Of course, the microarray market, which is estimated to reach $1 billion in revenues this year, is nowhere near consuming 50,000 microarrays a day, or even a month. And it is unclear whether this emerging market can support multiple providers of what might well soon be a commodity product.

But it is clear that competition is ratcheting up in a dynamic marketplace where competitive conditions are rapidly changing from quarter to quarter.

Hawkins said the company is addressing this competitive climate by going forward into proteomics and diagnostics. “This is becoming a crowded market with four companies launching products into the research space,” he said. “We believe that quality, reproducibility, and sensitivity will be cornerstones in the proteomics market and will be critical in the diagnostics market as the FDA gets into this area. We certainly believe that quality attributes that are central to CodeLink are going to be critical in this space.”

Under GE Healthcare

The company is also banking on the GE umbrella to provide it with needed leverage in this competitive market.

“I don’t know of any competitors of CodeLink who can jump across Applied Materials [GE’s plastics company], a multibillion business, to apply things from completely different segments,” Hawkins said. “There is a wealth of skills.”

Within GE, a company with more than 330,000 employees, the CodeLink line will have access to resources and the 2,000 scientists within the company’s global research centers in China, India, Germany, and Albany, NY, he said.

“The vast majority of R&D gets done at the global research centers,” he said. “We were there last week, spending two days, really just going through what we are doing, what are challenges are. They service all of the businesses. A fair fraction of money is available for new programs and new projects. Those have to be prioritized, obviously, because there are all of those businesses vying for those slots. When you suddenly realize there are thousands of incredible engineers who have systematically developed some of the world’s greatest tools and devices over the years, and have them get excited about CodeLink and where it can go, that’s one of the greatest things about GE.”

Inside the Facility

Meanwhile, at the manufacturing level, the company is focusing on quality control as the tour given to BioArray News indicated.

In Chandler, Ariz., Tom Wetteroth, a process engineer wearing a white “bunny suit,” sat before a workbench in one corner of the 8,000 square-foot, Class 1000 CodeLink clean room, which is set up in an open “ballroom” configuration.

With gloved hands, he used a vacuum instrument to pick up an array and load it into a device, which attaches a 16-chamber black silicon gasket onto a 1-inch-by-3-inch microarray slide. Sometimes his efforts were rewarded with the click of a perfect fit; other times he had to repeat the process to get a precise alignment between the slide and the accessory, which would fit onto a microtiter plate. It was one of the few places for hands-on labor in a room full of robotic, climate-controlled devices.

The manufacturing area is an ultraclean facility where technicians work 8-hour shifts wearing garments that are designed to contain particulate matter, like skin and hair, which might interfere with the purity of the products.

The central machine, which actually spots oligonucleotides onto glass slides covered with a 3D matrix, is a piezo-electric ink jet, which was developed by Motorola and then transferred to Amersham. At one end of the production line is a machine that prepares concentrated oligonucleotides for application onto arrays. They go from concentrated form to 96-well plates, to 384-well plates. Another machine uses a pulsing laser to etch serial numbers onto slides at the very beginning of the assembly process, creating a digital identity so that the product, and every step of a well-monitored and highly engineered process, can be recorded and documented.

In another area, a large box holds dispensing plates of oligonucleotides. Each set undergoes mass spectrometry analysis to verify the sequences. A rotating red laser beam points to the next plates required in the process of building arrays. Some 150 separate plates of 30-mer length oligos are required to build whole genome human microarrays. The laser beam helps reduce the possibility of a mistake.

On a computer screen, each slide is analyzed against specifications with the readout showing a linear graph, bouncing between boundary bars indicating standard deviations above and below the data points being displayed. “That’s Six Sigma,” Jeff Leaf, CodeLink’s director of manufacturing said, pointing to the graph on the screen.

Six Sigma is a method of manufacturing developed by Motorola and General Electric. While other units of Amersham may have to adopt Six Sigma methods, this method has long been in place at this factory. [For GE’s explanation of Six Sigma, visit http://www.ge.com/sixsigma/keyelements.html]

“It’s just a number, but it’s also a philosophy,” said Leaf. “Six Sigma is not the end-all: why not go to Nine Sigma? It’s relentless pursuit of perfection.”

On another computer screen, Chris Becher, a project engineer, looks at an image from a whole-human-genome array. One spot is red, indicating it will be flagged for potential analysis. On this slide, some 80 spots out of the 58,000 spots appear blue (control) or to a much lesser extent, red (quality flag). Each slide shipped is scanned and the images are stored for quality control. “We use what our customers use,” Becher said.

The penultimate step in the process rinses the chemistry used in the block and wash process. The final step is the attachment of the hybridization chamber that envelops the product.

“You take any one of our arrays,” said Hawkins. “You can trace back the material that is on that particular array, how much product is in any one of the spots, all of the QC and data, which individual worked on it, and on what day, under what conditions. This is where a lot of the Six Sigma approaches and methodologies come into play. We spend a huge amount of our time on this.”

High-Tech Neighborhood

The CodeLink manufacturing facility, which employs some 200 people, operates on three eight-hour shifts, five days a week. Workers can park their vehicles under carports to deflect the piercing desert sun that boosts daytime temperatures to well above 100 degrees in the summer.

The fab and offices are located in a location called the Silicon Desert, a rural area where massive steel- and glass-box buildings rise above corn fields and cattle feedlots. The anchor of this high-tech collection of companies is Intel’s $2-billion Fab 12 silicon chip fabrication facility. Orbital Sciences and Boeing Iridium are located nearby with their own manufacturing facilities. The city of Chandler, which is south of the Phoenix area, is in what it calls an industrial build-out phase, in which it is encouraging industry to locate there. A residential build-out is the next phase in the city’s long term planning.

The CodeLink facility was purchased from Amkor Technology of Westchester, Pa., a contract semiconductor assembly and test services provider to the semiconductor industry. Today, a sign in the black and orange colors of the Amersham logo hangs from the top of the building. Soon that will be replaced by the GE logo, as will the unit’s business cards, stationary, websites — all the trappings of a corporate identity.

Amersham purchased the four-year-old CodeLink product line from Motorola in 2002 for some $20 million, with Hawkins, who was then a consultant to Amersham, leading the negotiations. Many of the employees in Chandler are holdovers from Motorola who have stayed through the transition to Amersham, and now the transition to GE Healthcare, after the April 8 close of the acquisition.

Going Forward

After the purchase, the new owners had to move the production facilities from Motorola’s fabrication facilities in nearby Tempe to a new manufacturing facility. Although the company doesn’t divulge the cost of the new facility, which opened in February 2003, Chandler city documents pin a $5 million cost on the plant.

The factory achieved ISO 9000:2000 certification in December. ISO is an international quality standards group.

The company has also been working with independent auditors to study its manufacturing processes to prepare for regulatory compliance in the context of the molecular diagnostics market, said Sam Raha, who oversees the CodeLink product line.

CodeLink will release a whole-rat-genome catalog array this summer. A whole-mouse-genome array is scheduled for a late third-quarter or early fourth-quarter release. Additionally, the company is developing product concepts for clinical diagnostics.

“We have been working with our pharmaceutical strategic partners on how to take CodeLink forward,” said Hawkins. “We have now begun to work with our new GE colleagues to look at specific examples of how we can develop clinical in vitro diagnostic products that complement our products in the in vivo space. We see CodeLink as one of the central platforms.”

“Our mission might take us three to five years to accomplish,” said Raha. “The microarray industry is very young. We have a long-term perspective to be successful.”

—MOK

 

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