Life Technologies division Applied Biosystems said today that it plans to launch a new low-to-medium-throughput capillary electrophoresis sequencer this summer. A version of the instrument will comply with the European Union's in vitro diagnostic medical devices directive, the first of its CE systems to do so, the company said.
The launch of the 3500 Dx "will be the first move into the European Union diagnostic market for Applied Biosystems' capillary electrophoresis system," Andrew Felton, product line manager for ABI's CE business, told In Sequence last week.
ABI believes this market has a similar growth potential for its CE business as the "applied markets", which include forensics and quality and safety testing, he said. Last year, the company said sales of CE systems in applied markets grew in double digits (see In Sequence 2/17/2009).
The launch of a Dx CE instrument "builds on the success" of the company's 7500 Fast Dx system real-time PCR system, he added. Last fall, ABI received 510(k) clearance from the Food and Drug Administration to use that instrument with a flu test.
The 3500 Genetic Analyzer -- which comes in two versions, with eight or 24 capillaries -- will be for research use only and is intended to replace the 3130 Genetic Analyzer, which comes in two models with either four or 16 capillaries.
The 3500 Genetic Analyzer Dx, which has the same basic features but offers additional software, will comply with the EU's IVD medical devices directive, also referred to as being CE IVD-marked. In contrast to the research-use-only instrument, which will be sold globally, the Dx version will only be sold in certain European countries, including France, Germany, Italy, the Netherlands, Spain, Sweden, and the UK.
Both instrument lines are scheduled to be released in August. Pricing information for the instruments is not yet available.
Initially, ABI will continue to sell the 3130-type instruments along with the 3500, but the company may decide to phase out the 3130 at a later point, according to Felton.
ABI decided to seek compliance with the EU directive because it believes diagnostic laboratories that have been using its capillary electrophoresis instruments -- up until now, the research-only versions, such as the 3130 Genetic Analyzer or the 3730 DNA Analyzer -- will increasingly demand CE IVD-marked instruments in the future.
"We see the market as changing," in the EU, Felton said. "We see that the European Union is going to become stricter in its interpretation of that regulation, and we think laboratories that are operating in a clinical environment will need the added quality and assurance of a CE IVD-marked instrument and consumables."
He said hospitals and diagnostic laboratories are already requesting that systems they use comply with the IVD medical devices directive, and ABI "is responding to the demands of these customers in providing a set of products that these labs can use."
According to Emiliano Giardina, a professor of medical genetics at the University of Rome Tor Vergata, there is no requirement in Europe right now to perform genetic tests on a CE IVD-marked instrument. However, he said, working groups in Europe are currently writing guidelines "to provide the essential requirements for labs to perform [genetic] tests," and he said he believes that compliance with the directive may become mandatory in the future. Giardina provided ABI researchers with samples from patients with a chromosomal disorder for testing on the 3500 Genetic Analyzer.
The In Vitro Diagnostic Medical Device Directive, 98/97/EC, took effect in 1998 and regulates such devices in the member states of the European Economic Area, which includes countries of the European Union as well as Iceland, Liechtenstein, and Norway.
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Under the directive, an IVD medical device is defined as one that is "intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information" about medical issues.
Products for general laboratory use are excluded, "unless such products, in view of their characteristics, are specifically intended by their manufacturer to be used for in vitro diagnostic examination," according to the directive.
Companies wishing to sell IVD medical devices in the EEA need to gain CE-marking for their instrument, meaning they have to declare that they comply with the requirements of the directive.
For ABI, this meant changes in the manufacturing, quality control systems, and complaint handling operations for the 3500, according to Felton, a "pretty significant effort." Last year, the company received ISO 13485:2003 Quality System certification for its Singapore manufacturing facility, awarded by the British Standards Institution Americas, enabling it to CE-mark products that comply with the EU directive.
The company has not yet decided whether to pursue IVD use of its sequencer in the US. "We are looking at our options for that, but that regulatory environment is different" from Europe, he said.
Other sequencing vendors are also eying the European diagnostic market. For example, Roche's 454 Life Sciences is working on a version of its Genome Sequencer FLX system that will be CE-marked. "We are confident that the speed, accuracy, and depth of analysis provided by the platform make it ideally suited for diagnostic applications," Mort Minaee, head of regulatory affairs at 454, told In Sequence by e-mail.
3500 Genetic Analyzer
Besides a higher throughput, the main difference between the 3500 and the 3130 Genetic Analyzer is improved data quality, according to Felton.
The new instrument uses a different laser, which reduces the heat output and the overall footprint. The new design "improves the precision and accuracy of the results, and generally, the performance of the system," he claimed.
In addition, the software has been redesigned to now include both data collection and primary analysis such as base calling or size calling. Previously, those steps were performed by separate pieces of software.
Users can also now normalize the signal intensity between runs as well as between different instruments. "That's really going to help in an in vitro diagnostic environment where labs want to do studies across different laboratories, or within laboratories across different instruments," Felton said.
Also, consumables are formulated differently for the new instrument, and they are now labeled with radio frequency identification tags for tracking.
The Dx version of the instrument has essentially the same features, but a portion of its software has been specifically developed for in vitro diagnostics, Felton said. The platform, software, and key consumables all comply with the IVDMD directive.
While the research platform is geared at basic and clinical research as well as applied markets like quality control of manufacturing processes, the Dx version will have a specific usage, for the analysis of human DNA or RNA to detect genetic changes that indicate disease or disease susceptibility.
Like ABI's other capillary electrophoresis instruments, the 3500 will be able to run both DNA sequencing and genotyping applications. Generally speaking, about a third of the company's installed capillary instruments are used for sequencing, a third for genotyping, and a third for both applications, according to Felton.
Michael Friez, director of the diagnostics laboratories at the Greenwood Genetic Center, a non-profit institute in Greenwood, SC, that provides a variety of genetic testing services, mostly in South Carolina, has sent ABI DNA samples to validate the new instrument. He has also seen the instrument but has no experience running it.
His lab has developed a test to detect X-linked mental retardation that involves sequencing a panel of nine genes, which the lab runs on a 3730 Genetic Analyzer. Using samples that Friez had already analyzed, ABI ran the same test on the new 3500 instrument and obtained the same test results, he said.
"It appears to be a more intuitive, user-friendly platform," Friez said, allowing users, for example, to monitor the status of runs more flexibly.
Overall, the improvements appear to be incremental rather than a technological leap. "The 3130 they are replacing is already considered a very sophisticated instrument, so a lot of the upgrades to the new instrument are really just to make it even that much easier to use, and that much more efficient," he said.
"At some point" over the next few years he said he will consider replacing his lab's 3130s with the new instrument, though not immediately.
Giardina's lab in Rome, which performs a variety of genetic tests, including peri- and postnatal diagnostic, disease susceptibility, and forensic tests, also provided ABI researchers with samples for testing on the 3500, which his lab had already tested in-house on its 3130 instrument. The samples were of patients who have inherited two copies of chromosome 15 from one parent and none from the other.
He said that "specific technical artifacts of PCR are less evident in the new instrument," whereas the overall test results were the same with both instruments.