Immunochemistry analyzers are rapidly gaining popularity as improved assays are being added to the test menus incrementally. There is a rising focus on biomarker development across the globe as they help in detection of various diseases in their initial stage. Immunochemistry plays a crucial role in the development of biomarkers; thus with the growing demand of biomarkers, the market for immunochemistry instruments and reagents will also flourish. Furthermore, government support in terms of funds and grants has also provided much-needed impetus to this market.
Indian Market Dynamics
In 2016, the Indian immunochemistry market is estimated at
1914 crore. The ELISA kits market in 2016 is estimated at 306 crore and rapid tests at 225 crore, both seeing a decline every year. Immunochemistry instruments and reagents market is estimated at 1383 crore. Reagents continue to account for 90 percent of the market.
Chemiluminescence immunoassay (CLIA) systems have been steadily gaining momentum, especially in Tier-I cities where the installation base and
replacement market is increasing, resulting in a decline in enzyme-linked immunosorbent assay (ELISA) tests. Rapid tests are also seeing a decline, particularly with blood banks, which are now being monitored more closely by the FDA (Food and Drug Administration). Facing stringent checks, they are gradually shifting to chemiluminescence.
The segment is receiving impetus with increasing awareness of tests as AMH (Anti-Mllerian hormone) and Vitamin D. The need for automation is now also being felt by laboratories in Tier-III and IV cities, perhaps being pushed by the opening of competitive labs by corporate chains.
Global Market Dynamics
The global immunochemistry instruments and reagents market is expected to
reach USD 24.5 billion by 2019 from
USD 19.8 billion in 2016, growing at a CAGR of 7.2 percent. North America dominates the market, with government funding being a major factor. Presence of advanced immunochemistry instruments is another major factor for the high share of the US market. The Asian market is poised to grow at the highest CAGR owing to increasing government investments in the life sciences sector and improving healthcare facilities in the region. The rising focus of prominent players on the Asian immunochemistry market is another factor driving its growth. Increasing number of baby boomers that require frequent health checkups is also a main driver for this market.
Automation and integration are driving the analyzers market. Offering a broad assay menu, including infectious diseases, is a central competitive factor for increasing installed base of analyzers. Consequently, market participants of this highly competitive market are expected to continue infectious disease immunoassay product development and menu expansion.
Reagent sales typically comprise approximately 85 percent of fiscal revenues from any single system. Instrument placement is necessary for reagent sales. Many competitive factors in the immunoassay testing market lie with the instrumentation platform. The installed base of an instrument allows for an increase in test sales. When deciding on a particular testing platform, central laboratories value integrated and automated solutions. The number of tests offered by an instrument promote the installed base and future reagent sales. A majority of testing platforms are closed systems in which the instrument does not facilitate tests of another provider. The competitive advantage in this market lies with companies that offer a broad testing menu on an integrated and automated system. Servicing the instruments installed in the laboratory is another significant part of the value proposition market participants should offer. Test performance is yet another competitive factor. However, it is becoming difficult for market participants to stand out on the basis of higher sensitivity or other testing characteristics.
As the market becomes highly competitive, it becomes essential for manufacturers to retain their installed base. This provides recurring reagent business, and hence, several market participants adopt various strategies with their customers.
Offering large discounts on the list price of the analyzer. As the market for immunoassay and clinical assay systems is enormously shrinking and eroding, companies are now adding immunoassay components or clinical chemistry systems to existing analyzers in order to make it an integrated analyzer. As a result, customers receive large discounts. This works in their favor when laboratories have stringent budgets.
Bundle reagent rental contracts. The tendency toward opting for reagent rentals varies from region to region. For example, laboratories in emerging markets opt for multiple reagent vendors, while established markets in the US and Europe prefer to select the instrument and the reagent from the same vendor, ensuring compliance and accreditation standards.
Offering upgrades and add-on analyzers and components. In order to retain their installed base, many vendors offer upgrades to existing analyzers at a very low cost to increase capabilities of existing outdated analyzers.
Abbott to Acquire Alere – An Update
Alere and Abbott are both US-based companies active in in vitro diagnostics (IVD) systems. Their activities are largely complementary; Abbott has a broader portfolio of laboratory systems and Alere focuses on point of care. However, overlaps exist, in particular for point-of-care analyzers used in the testing of blood gases and cardiac markers.
On January 25, 2017, the European Commission approved the acquisition of Alere by Abbott Laboratories, subject to certain conditions. It also observed that the proposed merger might affect the ability of Danaher, another supplier of IVD systems, to compete for laboratory systems running B-type natriuretic peptide (BNP) tests.
In order to address the competition concerns identified by the Commission, Abbott offered the following commitments:
- lTo fully divest Alere's global Epoc business, including its manufacturing site in Ottawa, Canada;
- lTo fully divest Alere's global Triage business, including its manufacturing site in San Diego, USA; and
- lTo fully divest the Alere BNP reagents business that markets a BNP test with Danaher.
Following its assessment of Abbott's proposed commitments, the European Commission concluded that the acquisition could be implemented in light of the merger control regulation. This decision shows the complexity of merger control rules in the sector due to the very narrow markets and few active players in each individual market.
Competitors are certain to be closely following the sale of Alere's activities.
Drivers and Challenges
Under the strong rules and regulations, laboratories find it difficult to have good revenues. Thus it is very important to find ways to sustain in such a cost-crunched environment. Due to cost cutting in clinical lab fees, profitability per test is decreasing, which makes it necessary for the laboratories to focus on the volume rather than the value. There is also heavy pressure for quality, error-free results to ensure patient satisfaction. This forces labs to lean toward more automated systems with effective workflow solutions.
Globally, laboratories are encouraged for automation due to the heavy influx of patients with insurance coverage. But with limited workforce in the clinical lab, it is difficult to manage the huge inflow of patients. On the other hand, patients need prompt and error-free results. Thus this scenario demands laboratories to seek the help of systems that have a high accuracy, with managing high growing volumes and also offer remote data acquisition capabilities. Implementing informatics is critical, and the automated analyzers built today offer a full suite for barcode readers, rack detection systems, and sample/plate identification modules to avoid plate or sample switch.
The key challenge when building on installed base is the high cost associated with transition. Even when dissatisfied, most lab managers endure outdated instruments to avoid resource-intensive issues, such as the purchase process, staff retraining, protocol standardization, and data management system reevaluation. As labs consolidate, the immunochemistry analyzer market relies on instrument replacements to generate the needed revenue. Nearly all manufacturers rely on key strategies, such as offering replacements for old clinical chemistry and immunochemistry systems or acquiring clients from other vendors. Competition is stiffening as most vendors face difficulties increasing their customer base.
However, increasing focus on drug monitoring and growing incidences of various diseases will drive the growth of the market. In addition to this, technological advancement due to which automated and more accurate instruments are present in the market is another major factor that will propel the growth of the market in the future. Factors such as stringent regulations for the development and launch of immunochemistry products and low adoption rate of automated immunochemistry products in developing economies due to high cost can hinder the growth of the market in coming years.
The immunochemistry instruments and reagents industry is experiencing rapid technological developments. The need for highly accurate tests, ease of testing, wider test menu, flexibility of workload in individual parameters, demand for near patient testing, and difficulties faced in safe transportation of samples from distant places has led to ingress of companies offering solutions to this arena of diagnostic industry.
Many companies are manufacturing and marketing miniature instruments with highly accurate results. The quality results are being claimed owing to their cutting-edge luminescence-based technologies like fluorescence and chemiluminescence in miniaturized platforms. Some of these companies are offering specialized parameters like cardiac markers, others specializing in renal markers, while a few others are offering more demanded parameters like Hb1Ac, Vitamin D, Thyroid profile, and the like on a single platform machine. One such product has also been designed by Healthcare Technology Innovation Center, IIT Chennai, called i-Quant, keeping in view the demand of Indian healthcare industry. Some of these manufactures have even automated their manufacturing facilities to have consistency in their reagent quality.
Various test parameters, which were earlier required to be performed on different machines based on different technologies, are now converging to such single platforms through these miniaturized machines. This is not only helping labs and hospitals having moderate workloads to save on huge investments in capital equipment but also recurrent maintenance cost of the multiple machines.
As majority of immunoassay workload is carried out by high-end national laboratories and second-tier regional laboratories, these labs often get stuck with the companies which have installed the equipment on lease basis. With the advent of these miniaturized, state-of-the-art technology instruments and their availability at a fraction of the cost, not only the large laboratories but even smaller labs and nursing homes will have the option to install these instruments and switch to most competitive reagent manufacturers and suppliers.
J. Mitra & Co. Pvt. Ltd.
Meeting the Need for Safe Blood
The immunochemistry market in India is growing at a CAGR of 15–16 percent annually and the trend is expected to continue till 2018. The Indian market has metamorphosed over the past couple of decades. Many of the testing formats like radio-immunoassays and the latex agglutination tests have made way for newer formats that better address the needs of clinicians and patients. Test menus now offer better sensitivity, specificity, accuracy, and precision.
Over the years, there is a sea-change in the testing menu across various formats. In the current scenario, there is an increasing trend for testing of hormone levels and other non-infectious bio-markers like assays for autoimmune diseases, oncology and cardiac markers, and tests for vitamins. This is in addition to the focus on diagnosis of infectious diseases like hepatitis, HIV, dengue, and malaria
Immunochemistry testing is widely used by lab chains, government, corporate and private hospitals, nursing homes, labs attached to clinics as well as blood banks to screen transfusion-transmitted infections.
The product segment mainly comprises immunoassay analyzers and reagents for chemiluminescence, fluorescence immunoassays, immuno-chromatography tests, and the latest generations of ELISA tests.
Some of the important decision criteria in choosing an immunochemistry testing system are: reliability of results; cost effectiveness; time to results; test menu; regulatory approvals; ease of performance; quality control and quality assurance; and service and application support.
In the near future, chemiluminescence assays seem to be headed for an even better growth trajectory, primarily owing to the broad menu offered with excellent sensitivity and specificity. Newer testing formats include point-of-care testing as well as microarrays in appropriate settings.
Manufacturers are focusing on meeting the laboratory needs for innovative test formats and systems that can adapt to the workflow of their setup, ensure reliable results consistently, and are affordable. Immunoassays for transfusion-transmitted infections need to be designed on parameters such as early detection, reduction in infection rates, affordability, etc.
Transasia Bio-Medicals Ltd. has been identifying and catering to the growing needs of blood banks by providing solutions for reliable screening of transfusion-transmitted infections, thereby ensuring safe blood.
Sr. Business Development Manager-Immunology,
Transasia Bio-Medicals Ltd.
Meeting the Need for Safe Blood
Immunochemistry reagents and instruments have the highest share in the Indian IVD industry. It is estimated at
1800 crore in the year 2017. Reagents account for 90 percent of the market. The major tests in this segment include the blood screening tests, hormones, specific protein testing, TDM, infectious disease testing, and tumor markers.
With technological advances in this field, the hormone analysis, once considered as the rare and specialty tests, has become routine and affordable to the common laboratories. With the new-generation bench-top analyzers with small foot print and cartridge-based testing, this segment witnessed an exponential growth in the installation base. It is estimated that more than 700 units are installed annually in this segment and majority of the instruments installed are on rentals. In the routine hormone testing, thyroid panel has a share of 50 percent, followed by infectious panel at 28 percent. Vitamin-D testing has shown an increase in the last few years and is with a share of 10 percent. The other testing panels include Fertility panel followed by Anemia. With multinationals entering into this segment directly with highly attractive prices, the cost of performing the tests has dropped down drastically.
With the introduction of affordable and easy-to-use rapid tests, the blood screening segment has shown an increase of 25 percent on the annual tests vis-a-vis last year.
A decade ago, approximately 35 percent of specific proteins were done by latex testing, which were either qualitative or semi-quantitative tests in nature. This was one of the limiting factors where there was always uncertainty of results in the borderline areas of reference ranges. These tests were affordable to the rural population because of the low cost per test but due to the low specificity and sensitivity, the purpose of testing was eluded in many cases. Approximately 45 percent of the tests were performed in turbidimetry assays either in fully automated or semi-automated systems with a higher cost. Nephelometry, the gold standard for protein testing, was unreachable to the common laboratories because of the very high cost of the automated instruments and high cost of reagents and consumables.
Semi-automated nephelometry systems were introduced in India in the last decade and became the game changer in the specific protein testing. It is estimated that approximately 2500 nephelometric analyzer units are installed in India annually accounting to
25 crore. With increase in the number of parameters, these systems are gaining wide acceptance among the customers. The latest entrant in nephelometry segment is cartridge-based fully automated system with wide testing menu.
With the current CAGR of 16 percent, the immunochemistry market in India is expected to reach
2650 crore by the year 2020.
Laboratory Size Should Not Correlate with Quality
Small privately owned laboratories make up more than 80 percent of India's vast clinical diagnostic laboratory network, yet most IVD products are designed for consolidated centers or the largest and richest facilities that are also the most likely to afford voluntary accreditation. Any approach to improving laboratory quality in India must include the implementation of reagents and instruments specifically designed to improve quality in lower throughput settings.
Such test systems require durable affordable automation in a small footprint, ease-of-use, reduced consumption of consumables including DI water, and built-in quality-control programs. Often poor quality is associated with a lower level of training and expertise available in rural towns and villages, yet because of costs these are the laboratory settings where technicians are most likely to perform biochemistry and immunology tests using manual methods that require a higher level of skill and understanding.
Chennai-based CPC cooperated with USA-based Awareness Technology to develop a line of top-quality biochemistry reagents manufactured in India (i-chem, Jeev Diagnostics) and a dedicated instrument (Turbochem-100) designed in every detail to meet the needs of the lower throughput lab. CPC installed more than 500 systems in India proving that laboratories formerly using manual methods were able to earn and save enough money by reduced reagent requirements, reduced training requirements, reduced error and re-work, and improved competitiveness to lease or buy the dedicated systems.
Although basic automation offered these labs many time-saving conveniences, perhaps the greatest value was overall quality improvement. Each chemistry analyzer was also installed with a remote surveillance and service system called i-track that allowed CPC's in-house quality experts to monitor system performance. Pipetting precision, temperature and timing control, tracking patient information, and reagent stability were among the immediate improvements. Technicians were free to spend more time and attention on pre- and post-analytic aspects of quality control and on continuous education.
Growing competition forces Indian laboratories to work hard to distinguish themselves by maintaining reliable reputations, using better reagents, instruments, skills, and quality practices. As the industry adds new technologies and expands test menus, it will do well to specifically address the practical, financial, and quality requirements of this very significant sector.
Awareness Technology Inc., USA
Integrated System to Become the Trend
With the combination of basic principle of radioimmunoassay, high-sensitive chemiluminescence, and high-specific immunoassay, the year 1977 saw the emergence of a new technology –chemiluminescence immunoassay (CLIA) – which provided one of the best solutions for the quantification of specimens from a complex mixture with non-radioactive nature, making it an advantage to replace RIA in multiple immunoassay applications in IVD industry. Multiple factors have constituted the vast and rapid development of chemiluminescence immunoassays in the global IVD industry.
High Technical Barrier
The priority of in vitro diagnosis lies on the accuracy of a test result which attributes to the integration of instrument, reagent, and international standard reference materials. Any difference among them could lead to the discrepancy of test results. CLIA, given the nature of the active proteins such as antigen and antibody in reagent components, has to be used with the corresponding reagents manufactured by the same manufacturer. Therefore, most of automated CLIA systems are closed systems. As closed systems, the integration of interdisciplinary disciplines including biomedical science, engineering, automation, immunology, and the vast investment and quality control in instruments as well as reagents sets an extremely high technical barrier for research and development of CLIA systems. As a result, relatively fewer manufacturers command the market share of CLIA market.
With the R&D of more and more immunoassay markers, the comprehensive test menu and various applications boost the rapid development of CLIA systems in the IVD market. At present, the applications of CLIA consist of tumor markers, infectious diseases, endocrines, and so forth. The number of assays available so far for a CLIA system with the largest test menu is more than 120. There is no denying that with such varied applications in one automated system, CLIA systems are rather appealing to all sorts of laboratories and hospitals.
With a higher demand for an integrated system to process a vast quantity of samples for tests of biochemistry, immunoassay, and electrolytes, integrated systems with the combination of biochemistry, CLIA, and electrolyte modules are appealing in large-scale laboratories. The emerging need for sophisticated integrated system urges the research and development of CLIA systems, which are able to integrate with other modules and have a larger test menu, to become trending in the IVD market.
Overseas Technical Director,
SNIBE Co. Ltd.
Integrated System to Become the Trend
The growing need of IVD testing arises due to increasing incidences of chronic and infectious diseases and growing geriatric population prone to immunological disorders. Moreover, increased application of personalized medicines and widespread knowledge of rare diseases are boosting the growth of IVD market. Another such rise has been observed in testing of specific proteins for infectious diseases, cardiac diseases, diabetes, autoimmune disorders, inflammatory markers, and others.
Immunoturbidimetric methods have become the main technique for performing specific protein tests. The transition from nephelometry has been cautious but is increasing as laboratories enjoy the comparability and flexibility of immunoturbidimetry. Immunoturbidimetric and nephelometric techniques measures turbidity of a sample to determine the level of analytes. It is also observed that specific proteins have traditionally been analyzed using methodologies, such as immunonephelometry on specialized analyzers. Although, immunonephelometry is a well-recognized and accepted methodology, yet it requires a specialized analyzer that performs a limited menu of tests. In addition, nephalometers are slow with expensive consumables cost and requires trained and experienced person to run the assay.
A variety of immunoturbidimetric assays are now available, and can be adapted to general-purpose clinical chemistry analyzers that are open systems. Immunoturbidimetric assays have been improved considerably over time. These improvements include advances in antibody purification techniques, enhancements in instrument design, function, and production of new reference materials based on global standardization initiatives. Additional practical advantages of immunoturbidimetric protein assays include random access analysis instead of batch testing, relatively rapid turnaround time, high volume testing capability, cost reduction through consolidation of testing on a single platform, elimination of standalone specialized analyzers, and time and effort required to maintain them. Collectively, these characteristics of immunoturbidimetric assays have resulted in more reliable tests and reduced laboratory variances to help the clinicians.
DiaSys Diagnostic Systems immunoturbidimetric test portfolio offers more than 20 ready-to-use, stability optimized reagents for routine and special diagnostics with outstanding performance. DiaSys immunoturbidimetric tests are available in different vials and kit sizes for manual and automated use in various common clinical chemistry analyzers. DiaSys reagents, in combination with DiaSys instruments, optimized applications, calibrators and quality control material form a harmonized system for highest laboratory demands.
Head-Strategic & Operational Marketing,
DiaSys Diagnostic India Pvt. Ltd.
Immunohistochemistry – 21st Century Updates
The identification of protein expressed in the tissue of interest is the central domain of research, which can be done using mass spectrometry or Western blotting. But to determine the exact location of protein in the tissue, visualization in its cellular context is critical, which is possible with Immunohistochemistry (IHC). IHC is a practical tool for identifying the type and stage of diseases, particularly in cancer diagnosis and scientific research. IHC dates back decades, but that does not mean it is stagnant. Automated sample processors, digital slide scanners, image analysis software, and much more have given this aged procedure decidedly a 21st-century flair.
Conventional IHC requires long, laborious process times and high costs. Automation in staining has reduced the cumbersome procedure with an added advantage of streamlining the quality and decreasing the stain variability.
Another transformative development in IHC is the advent of so-called digital pathology, wherein the systems scan the stained slides in their entirety, store in a digital format that can then be viewed and manipulated on a computer, with possible telepathology consultations. An additional benefit of digital pathology is the ability to perform sophisticated image analyses, which identifies cells and subcellular compartments.
Microfluidic IHC platforms have been developed to reduce the cost of antibody stains, but coming with a disadvantage of expensive equipment. Manual pipettes have been deployed in microfluidic platforms to curtail the equipment and reagents costs. Tissue microarray is a last-decade innovation in the field of pathology. A microarray contains many small representative tissue samples from hundreds of different cases assembled on a single histologic slide, and therefore allows high throughput analysis, even IHC, of multiple specimens at the same time.
Recently, we have seen introduction of combination of mass spectroscopy with immunohistochemistry allowing highly multiplexed, direct quantitative imaging of tissue samples for both basic and clinical research. Multiplex IHC (mIHC) allows for the simultaneous detection of multiple targets of interest in a single tissue section. Using this method, it is possible to evaluate several effectors of a signal transduction pathway at one time, co-localization of markers, or distribution of molecules relative to one another within tissues.
Rapid advances in technology in identification of proteins or molecules, causing disease or cancer, with precise quantification will help the treating doctor to move toward the personalized medicine or targeted therapy in eligible patients.
Dr Mahesh H. Karigoudar,
Professor-Department of Pathology, BLDE University,
Consultant-Dr. Karigoudar Diagnostic Laboratory, Vijayapur
Immunochemistry analyzers have proved to be an effective tool in endocrinology, oncology, cardiology, therapeutic drug development/monitoring, infectious disease testing, drugs of abuse testing, autoimmune diseases, etc. In the corporate sector, medical diagnostic laboratories are encouraged for immunoassay automation due to the heavy influx of patients with insurance coverage, limited technical workforce in the clinical laboratories, and requirement of authentic – error-free results to the patients. Thus this scenario demands laboratories to seek highly sophisticated systems that can match augmented workloads with remote data acquisition capabilities.
Today, immunochemistry represents 40 percent of the global in vitro diagnostics (IVD) market showing strong segmental growth of immunoassay technology in developed and developing countries. The immunochemistry market segment comprises manufacturers of immunoassay analyzers and reagents – the key players being Siemens, Abbott Diagnostics, Beckman Coulter, Ortho Clinical Diagnostics, Thermo Fisher Scientific Inc., F. Hoffmann-La Roche Ltd., etc., and a few autoimmune diagnostics include Inova Diagnostics, SQI Diagnostics, Euroimmune, Aesku Diagnostics, etc.
The automated unit has an autosampler, a reagent dispenser, a washer, and a detection system. Configuration and sophistication vary according to the needs of the laboratories – low-end discrete batch-mode analyzers to random-access high-throughput integrated analyzers. 85 percent of fiscal revenues are generated by immunochemistry reagent sales through open or closed platforms (depending on the instrument and the reagent from the same or different vendor). Closed platform ensures compliance to accreditation standards for the labs and augments immunochemistry reagent sales for vendors. Value propositions by IVD vendors include servicing of equipment, automation, integration to clinical chemistry, upgradation of existing outdated analyzers at a very low cost to increase capabilities, and the like.
Major challenges a laboratory shall face in immunochemistry are to ensure patient satisfaction despite increasing cost per reportable rate (CPRR), reduced profitability per test, quality, and expenses to deliver accurate, error-free results. With advancing transition from wet to dry toward nanotechnology, immunochemistry is evolving to be more customer-friendly through increased compliance and lab-at-doorstep strategies in this digital era. For organizational success, “Quality is the best business plan."
Dr Suresh DR,
HOD-Laboratory Services & Consultant Biochemist,
Elbit Medical Diagnostics Ltd., Bangalore