A trend among major analytical instrument and lab product companies is the expansion into clinical diagnostic markets, both regulated products and, in the US, services based on laboratory developed tests (LDTs). Clinical diagnostics is a fast-growing market, with multiple opportunities due to the use of new research technologies for diagnostics, growth in emerging markets and applications in personalized medicine. This year, Agilent Technologies (see IBO 5/31/12), Illumina (see page 2) and Life Technologies (see IBO 7/31/12) each added to their diagnostic offerings through acquisitions. These purchases follow other diagnostic-related acquisitions in recent years by Danaher, PerkinElmer and QIAGEN, as well as other firms. Acquisitions and partnerships targeting diagnostic-development capabilities, as well as diagnostic techniques, have played a major role in companies’ development of their diagnostic businesses. Fields of interest include companion diagnostics, molecular diagnostics and pathology. In addition, companies are drawing upon their internal capabilities, especially as they seek to transition their genomic research technologies into the diagnostic field. All three components figure in companies’ diagnostic expansion, especially in the critical areas of informatics, clinical validation and sales channels.

PerkinElmer’s diagnostic business spans both traditional technologies, such as biochemical assays, and molecular diagnostic techniques, including xMAP technology and microarrays. The company has been offering regulated diagnostic products for close to 20 years, said Jim Corbett, president of PerkinElmer Diagnostics. “On the IVD [in vitro diagnostic] side, we offer a complete line of newborn screening assays. That’s been our core market for some time, along with prenatal screening,” he told IBO. These products include immunoassays and MS reagents. Diagnostic offerings also include services, including LDTs. “From a services perspective, we actually have three CLIA [Clinical Laboratory Improvement Amendments] laboratories in the US. We have one laboratory outside the US in India,” said Mr. Corbett. The company gained the labs, which include NDT Laboratories and Signature Genomics, through a series of acquisitions.

Taking a step that expanded its available technologies for diagnostics, PerkinElmer acquired Caliper Life Sciences last year (see IBO 9/15/11). Kevin Hrusovsky, president of Perkin­Elmer Life Sciences & Technology and former president of Caliper, highlighted three diagnostic applications of Caliper technology that Perkin­Elmer is developing. He told IBO the biggest priority for development is next-generation sequencing (NGS) for clinical diagnostics. PerkinElmer provides systems for all stages of the NGS sample preparation workflow, including liquid handling and microfluidics-based capillary electrophoresis (CE). Perkin­Elmer’s NGS offerings also include services and data analysis through its own lab, which gained a Connecticut state license and state CLIA registration in July. The company’s NGS solutions are also being used in other clinical labs. “We’ve made maybe 10 different installations at hospitals,” he said. “We have a lot of installations around sample prep for rare childhood diseases. That’s evolving now to most of the cancer hospitals, like Mass Gen, Dana Farber, Fox Chase. They now are going to want a profile of tumor samples with NGS,” he explained. “The sample prep is very important now because these are heterogeneous tumors. The repeatability is a real challenge if you don’t have pristine sample prep.”

Another facet of the company’s NGS offerings is informatics. Perkin­Elmer purchased Geospiza last year (see IBO 5/12/11), which makes Gene­Sifter Analysis for secondary and tertiary analysis of NGS data. Informatics capabilities are a crucial component in translating the use of NGS from research to diagnostics, according to Mr. Hrusovsky. “Over the years, that was one of the key learnings from these disruptive technologies is that it sometimes takes five years of installing the technology, but then the doctors don’t use it, and mainly because of the informatics to turn it into a medical report, versus a research report, were always at the end,” he noted. Last month, the company announced a collaboration with researchers at Massachusetts General Hospital’s Pathology Department and Cancer Center to develop an NGS information system for profiling tumors’ genetic changes.

A second diagnostic application highlighted by Mr. Hrusovsky utilizes the Vectra 2 automated slide imaging system for multiplexing tissue analysis. “[This is] looking at many different protein biomarkers on cancer tumor samples—these are solid tumors—and being able to better predict the prognosis and treatment options available for that particular patient,” he said. PerkinElmer offers the Vectra 2 with HistoRx’s AQUA technology for immunofluorescent imaging and analysis of proteins in tissue samples. Another application area he discussed was the analysis of circulating tumor cells in a patient’s blood for information about cancer progression. “We’ve got many different installations now with both our microfluidics and our imaging technology; being able to isolate as few as one circulating tumor cell in a billion normal cells, and being able to look at eight different biomarkers simultaneously on those particular tumor cells.”

Unlike PerkinElmer, Agilent is a newcomer to the diagnostics market. This year, the company entered the market with the $2.2 billion purchase of Dako to form the Agilent Diagnostic and Genomic Group (DGG). Prior to the acquisition, the company’s involvement in the diagnostic market had consisted primarily of OEM manufacturing agreements related to PCR and microarrays, as well as selling CGH (comparative genome hybridization) arrays for cytogenetic services. In addition, Agilent sample preparation reagents are being used in the development of clinical diagnostic NGS workflows.

Dako, a supplier of immunohistochemistry products for anatomical pathology, immediately gave Agilent a position in the diagnostics market. The company also provides companion-diagnostic development in partnership with pharmaceutical companies. “The combined Agilent DGG brings to market strong and complementary capabilities within diagnostics, including more than 40 years of protein and molecular techniques for tissue-based diagnostics that remains the backbone of cancer diagnostics today, as well as SureFISH [fluorescent in situ hybridization] and leading cytogenetic research applications based on CGH,” said Lars Holmkvist, president of DGG and CEO of Dako. “Agilent has the capability to combine these traditional technologies with our expertise within target selection and enrichment for NGS for the development of the next-generation diagnostics applications. In addition, Agilent has a strong position within automation, bioinformatics and a market leading position in clinical research, an important validation domain for new diagnostic technologies and solutions.”

The Dako acquisition also supplied Agilent with diagnostic expertise. “In addition to the tissue-based cancer diagnostic capabilities, the acquisition of Dako has provided Agilent DGG with a worldwide clinical channel into cancer diagnostics, as well as expanded worldwide development and regulatory expertise required to bring IVD-class products to market,” explained Mr. Holmkvist. “Agilent DGG has a very broad range of regulated clinical products with six PMAs [premarket approvals] (Class III) products, 60 FDA 510(k)s and more than one thousand IVD Class I products—covering the full-solution requirements from reagents to instruments and software.”

Agilent has further positioned itself in the diagnostic market by expanding its cytogenetics product line with the March introduction of SureFISH probes, which are Class I Analyte Specific Reagents. “Our comprehensive cytogenetics portfolio includes SureFISH probes, CGH and CGH+SNP arrays, a scanner and Agilent CytoGenomics software. Customers now have a single source for all their cytogenetics needs,” said Robert Schueren, Agilent vice president and general manager, Genomics, at the time. In May, the company expanded the SureFISH product line to 425 probes. As Mr. Holmkvist explained, “The new unit has the capability to cover the full set of FISH applications, ranging from Dako’s solid tumor applications over leukemia and lymphoma to the original Agilent genomic focus on cytogenetics and congenital abnormalities in clinical research.” As he explained, NGS products also fit with this market. “In addition, NGS supported by our target enrichment capabilities is emerging as a new application for cancer diagnostics and clinical research within pathology labs, complementing the traditional Dako protein and FISH-based tests on biopsy tissue.”

Life Technologies has taken a different route to the diagnostic market. The company has sold products into the diagnostic market for years, including PCR and CE-based sequencing assays and instruments, as well as Dynabeads magnetic beads for IVD assays and CISH (chromogenic in situ hybridization) probes for anatomical pathology. Last year, the company valued its diagnostic sales at $300 million. Earlier this year, it named Ronnie Andrews, former CEO of molecular diagnostics firm Clarient, president of its Medical Sciences business. “Over time, we plan to offer a full range of products to diagnose, aid in therapy selection, and treat and monitor these complex diseases,” said Mr. Andrews on a July conference call. “The important point here, though, is that our placements span across our CE, qPCR, SOLiD, FISH, immunohistochemistry and Ion PGM [Personal Genome Machine] technologies and platforms. Life’s global channel access is a powerful advantage as we build out our molecular diagnostics business.”

This year, the business has purchased two diagnostic companies. It acquired Navigenics, a provider of genetic testing services, giving Life Technologies a CLIA lab that is approved in all 50 states and an informatics platform for communication with physicians and patients. To add content, the company acquired Pinpoint Genomics, whose Pervenio Lung RS risk-stratification test for early-stage lung cancer debuted this month as a service offered through the CLIA lab. Life Technologies also plans to commercialize a regulated version of the test. As Mr. Andrews explained on the conference call, “[W]e will launch through our global channel, allowing us to access our large installed base of qPCR platforms currently being used in clinical labs outside the US today.” Another piece of Life Technologies’ diagnostic strategy is its partnership to distribute diagnostic assays. The company has agreements in place with Quidel, China’s DaAn Gene, and Gen-Probe.

The firm’s established resources are also being utilized, according to Kim Caple, head of Molecular Medicine Products at Life Technologies. “Life Technologies has an R&D organization devoted to development of IVD products, a global regulatory team capable of product registrations/submissions anywhere in the world and a current clinical customer install base of over 7,500 platform placements,” she said.

Life Technologies’ senior manager of Public Relations for Regulated Markets, Suzanne Clancy, PhD, told IBO that among markets the company is prioritizing oncology and companion diagnostics. The company has agreements in place for companion diagnostic test development with GlaxoSmithKline and Bristol-Myers Squibb.

Life Technologies is also working to transition newer research technologies to diagnostics. Most notably, its efforts have focused on NGS. The firm plans to submit its Ion PGM and Ion Proton systems for FDA clearance. Among Life’s partnerships for developing NGS diagnostic applications are one using the Ion Proton for HLA (human leukocyte antigen) analysis and one for developing a lab infrastructure protocol for a CLIA sequencing facility. Dr. Clancy said that the firm also plans to seek FDA clearance for its QuantStudio Real-Time platform, which offers qPCR and digital PCR.