Making progress against persistent challenges

The analyzer market continues to be as impacted as the rest of the lab industry with the uncertainty and unpredictability that ensues with the current state of affairs. While the extent of the impact brings ambiguity, the need for clinical laboratory solutions to support medical professionals remains constant.

The strides in the hematology market have been catalyzed by multiple distinct factors. Advances in diagnostic technologies for hematologic malignancies and automation in devices have helped address current and emerging needs of patients in the hematology market.

Over the past 20 years, there has been a tremendous advancement in the technology of hematology analyzers and their availability to the general practitioner. New paradigms in medicine and healthcare have increasingly broadened the market potential. Hematology care encompassed by oncology, immunology, and molecular biology is opening new avenues in the hematology market. A case in point is through understanding of hematopoietic stem cells.

The strides in the global hematology market have been catalysed by multiple distinct factors. Advances in diagnostic technologies for hematologic malignancies and automation in devices have helped address current and emerging needs of patients in the hematology market. Over the past few years, new paradigms in medicine and healthcare have increasingly broadened the market potential. Hematology care encompassed by oncology, immunology, and molecular biology is opening new avenues in the hematology market. A case in point is through understanding of hematopoietic stem cells.

An understanding of success of specific treatments for haematological disorders has further enhanced the quality of care in the hematology market. Advances in cancer immunotherapy protocols play crucial role in shaping the contours of the market. Advances in cancer immunotherapy protocols play crucial role in shaping the contours of the market.

The Indian hematology instruments and reagents market in 2020 is estimated as Rs. 850 crore. Reagents constitute 62 percent of the market at Rs. 530 crore, and instruments, all fully automated.

The hematology instruments market may be segmented as 3-part and 5-part analyzers. Within the 5-part analyzers, the entry-level or standalone analyzers have been the preferred ones. However, as COVID-19 pandemic raged through the country, buyers preferred the 5-part high-end analyzers, and the 3-part dual chamber analyzers to the single chamber models. It has all become a function of affordability. Stringent manufacturing protocols are finally finding their place in the industry. Customers want to keep intervention of service technicians as minimum as possible.

Indian hematology instruments and reagents market

Leading vendors* – 2020

Tier I	Tier II	Tier III	Others
Transasia, Horiba, Mindray, Beckman Coulter, and Sysmex	Abbott and Nihon Kohden	Trivitron, Boule, Dymind, and Siemens	Agappe, CPC, Roche, Dirui, Meril, Beacon, Diatron, Shenzhen Prokan, Urit, LabIndia, and many small importers
*Vendors are placed in different tiers on the basis of their sales contribution to the overall revenues of the Indian hematology instruments and reagents market.
ADI Media Research

There are five dominant players in this market. Transasia, Horiba, Mindray, Sysmex, and Beckman Coulter, with the latter having restricted their offerings to the high-end range. Boule is gradually cementing its presence in the 3-part dual chamber segment. Abbott, Trivitron, Nihon Kohden, and Siemens give serious competition to these players. Many other players including Agappe, Beacon, CPC, Urit, and Meril are active in this segment.

COVID-19 hurt the hematology market considerably. The routine CBC tests have been on the backburner since March 2020. It is the in-patients that kept this industry going, as they had to be often tested twice a day, which gave impetus to the capillary testing procedure. It is estimated that the number of CBC tests done in 2020 were down to 110 million from 330 million tests in 2019. A back-of-the envelope calculation indicates that about 27 percent tests done are on 5-part analyzers; 65 percent are on 3-part dual chamber and 8 percent on 3-part single chamber.

While March-August 2020 saw an estimated 50 percent drop in vendor sales, the focus on COVID-19 situation was so much that the inquiries that had been received from various diagnostic centers did not convert to firm orders. 5-part high-end analyzers continue to be almost totally on rentals, while the other product segments have a mix between outright sales and placements.

As the Indian economy finds itself on the edge amid second wave, the lockdown declared by the government so far have been regional. The vendors are hopeful that if this remains the norm, the industry will revive itself. Elective surgeries will need to be done, OPDs will be held with some specified restrictions and routine tests will once again be recommended.

There are other challenges faced by the hematology community. Voluntary blood donation has dropped due to fears of contracting the SARS-COv-2. The ongoing pandemic will have consequences on the training of residents in hematology, who are now managing COVID-19 patients. Over the next year or more, this will affect a generation of clinical and laboratory physicians and scientists. Many clinical trials evaluating therapeutic discoveries for hematological disorders will suffer, as accrual to clinical trials has reduced while basic and translational research is hampered as resources are re-prioritized.

The SARS-Cov-2 virus is not going to disappear soon. It may mutate and change in virulence, and eventually it will be contained through public health measures, vaccinations and therapeutic interventions. The hematology community will need to ensure optimal care for their patients by adapting to the challenges posed by this virus.

The global hematology analyzers and reagents market is expected to grow from USD 3.93 billion in 2020 to USD 4.31 billion in 2021 at a compound annual growth rate (CAGR) of 9.7 percent, estimates The Business Research Company. The growth is mainly due to companies resuming their operations and adapting to the new normal while dealing with from the COVID-19 impact, which had earlier led to restrictive containment measures involving social distancing, remote working, and the closure of commercial activities that resulted in operational challenges. The hematology analyzers and reagents market is expected to reach USD 5.69 billion in 2025 at a CAGR of 7.2 percent.

Automation of hematology diagnostics process has led to reduced turnaround time, thereby accelerating the overall treatment regimen. Furthermore, automation has also led to reduced administrative errors and overall costs of diagnostic tests. Thus, it is expected to boost growth of the hematology testing market in the forthcoming years.

Dominance of hematology analyzers can be attributed to the presence of fully-automated analyzers which are objective, have high-throughput, and are cost-effective. Furthermore, these hematology analyzers can also detect atypical results and can improve measurable parameters such as red cell distribution width, platelet distribution, reticulocyte (RET) counts, and nucleated red cells counts.

The advent of point-of-care (PoC) hematology testing devices has led to improved diagnostic and patient outcomes. These devices are user-friendly and are available for use outside the hospital settings. This is anticipated to increase the acceptability and accessibility of hematology testing which, in turn, is anticipated to propel market growth.

The rising number of blood donations globally is driving the hematology analyzers and reagents market as hematology analyzers are used to test and screen blood in blood banks. Blood banks are witnessing a huge outflow of blood to hospitals and other end-users and inflow of blood from blood donations on a daily basis. According to the WHO, there was an increase of 7.8 million blood donations from voluntary unpaid donors from 2013 to 2018. As the number of people donating blood increases, the demand for hematology analyzers and reagents increases, thereby driving market growth.

Recalls of defective hematology analyzers is acting as a restraint on the hematology analyzers and reagents market. A product recall is done by the manufacturer or developer of the product as a precautionary measure when safety issues or defects are discovered that can endanger the consumer. A faulty hematology analyzer may provide wrong results and may lead to misdiagnosis, affecting consumer confidence in the analyzers. Regulatory authorities caution healthcare professionals to be aware of the potential for inaccurate diagnostic results with these analyzers and to take appropriate actions including the use of alternative diagnostic testing or confirming analyzer results with manual scanning or estimate of cell counts.

Leading companies are working on making devices easier to use. Technological advancements include hemoglobinometers, a pocket-sized compact device that has patient data stored in it and has printable features. Many of the companies are developing a combined hematology and CPR system to improve functionality and features. The development of small and compact systems with high accuracy is increasing such as Cell-Dyn series from Abbott.

Over the years, interested stakeholders in the hematology market have benefitted from advances in understanding the biology of hematopoietic stem cells. An expanding cancer immunotherapy protocols have also expanded the potential of the market. Emerging area of induced pluripotent stem (iPS) cells will likely open new doors of opportunities in the not-so-distant future.

The advent of instruments that help clinicians’ measure patient-reported outcomes has taken the quality of care in the hematology market to a new trajectory. These outcomes are of vital prognostic value as they enable clinicians to incorporate patients’ perspective in the treatment process. Patient-reported outcomes assessments are gathering steam in clinical trials as well as clinical practice.

Manufacturers are increasingly investing in the research and development of analyzers with microfluidics technology that uses low volumes of sample and reagents. Microfluidics deals with the flow of liquids inside channels as small as a few micrometers. Low reagent consumption by hematology analyzers with microfluidics technology helps reduce operating costs significantly. For instance, the HA5 hematology system from BioSystems is based on microfluidics technology and uses approximately 75 percent less reagents compared to normal hematology analyzers. Also, the respons3H and respons5H hematology systems by DiaSys use microfluidics technology and consume 70 percent less reagents.

In January 2021, Beckman Coulter launched DxH 560 AL, a tabletop hematology analyzer designed to reduce the time and resource constraints faced by small- to mid-sized laboratories. In the same month, Roche signed a global business partnership agreement with Sysmex, renewing a long-standing arrangement allowing Roche to distribute Sysmex hematology testing products, including instruments and reagents, according to a press release from Roche. In 2019, Luminex Corporation had acquired flow cytometry portfolio of EMD MilliporeSigma..

Some of the leading players in the international market are Abbott Laboratories, Sysmex Corporation, Danaher Corporation, Siemens Healthcare, Sigma Aldrich Corporation, Drucker Diagnostics, Bio-Rad Laboratories, Roche Diagnostics, Mindray Medical International Limited, and Horiba Ltd. Sysmex Corporation, Beckman Coulter, and Horiba account for more than 90 percent of the market. The majority of the company’s manufacturing units are based in the Asia-Pacific region. The companies are increasingly focusing on the launch of advanced products to expand their market share.

Among the various regions, North America has been showing vast revenue generating potential. Rising concern of blood-related disorders, notably in the US, and constant research for developing cutting-edge instruments have reinforced the prospects of the region. Meanwhile, Europe and Asia-Pacific are potentially promising regional markets, with the latter showing considerable appetite for growth. Growing awareness of hematologic disorders and improving oncology care are aspects augmenting prospects. Advances made in transplant biology and immunology in Europe will help open numerous lucrative avenues in the region in the coming few years.

Laboratory automation has been for long limited to clinical chemistry and immunochemistry platforms. The major hurdle encountered in developing models of automation for laboratory hematology is represented by the peculiar sample type, which is whole blood anticoagulated with dipotassium ethylenediaminetetraacetic acid (EDTA). The presence of EDTA in the sample, which irreversibly sequestrates ionized calcium and many other metal ions, makes EDTA plasma an unsuitable sample matrix for clinical chemistry and even for coagulation testing, thus generating considerable obstacles for consolidation of laboratory hematology with other branches of laboratory medicine.

Nevertheless, a number of technological solutions have been developed for laboratory hematology in recent times. These basically include commercialization of modular, high-throughput, and versatile analyzers, which can be easily interconnected by means of sample conveyers, and can fit the organization of small, medium, and large facilities; integration of pre-analytical workstations, which can be identical to those included in models of total laboratory automation, or can be specifically designed to suit hematological testing; connection with automated slide strainers, which help improving the entire slide making process; as well as integration of automated image analysis systems.

Throughout the relatively long history of laboratory hematology, the only reliable means for identifying, enumerating, and sizing blood cells has been for long represented by optical microscopy of peripheral blood smear. This practice carries many drawbacks, since it is inevitably time-consuming, vulnerable to high inter- and intra-observer inaccuracy and imprecision, needs specific education and training of microscopists, and poorly suited for rapid diagnostics as otherwise needed in patients with many acute hematological disorders.

Recent technological advances have led to development and commercialization of innovative automated image analysis systems, which are suited for automation and can hence be directly connected (in series) with hematologic analyzers. These innovative platforms scan the slides (usually at a picture of ×100 objective), and store digitalized images of blood smears at high magnification. The images are analyzed by artificial neural networks based on a preexisting database of blood elements (thus including RBC), which can be locally customized or updated by the users. The images can be transmitted to, and displayed on, computer screens, which can be even placed at long distances from the scanner, for analysis and potential reclassification of blood elements. The operator can also increase the size of the images, or expand single sections of the scan, so obtaining a more accurate view. The operator can then accept and conserve the automatic classification, or move elements from one cell category to another, thus improving the final reclassification. Albeit these automated image analysis systems have been originally developed for analysis of white blood cells (WBC), specific information can also be garnered on erythrocyte morphology, thus including the presence of anysocytosis, hypochromia, microcytosis or macrocytosis, spherocytosis, elliptocytosis, ovalocytosis, stomatocytosis, acanthocytosis, echinocytosis, polychromasia, poikilocytosis, and abnormal erythrocytes. Recent data showed that the diagnostic sensitivity of these systems for identifying some critical categories of abnormal erythrocytes is excellent, typically higher than 80 percent, thus making the use of digital image analysis a highly valuable, and probably more accurate and reproducible alternative to optical microscopy.

Notably, the use of these systems may also enable an efficient recognition of parasitoid infections such as malaria, as well as the reliable identification of intravascular and spurious hemolysis, which would be otherwise undetectable on whole blood specimens. Interestingly, most of these automated image analysis systems are also capable of optimizing the identification of rare RBC abnormalities, since morphological erythrocyte alterations can be more efficiently visualized on the computer screen. Finally, the creation of a large personalized database of images of suggestive RBC abnormalities, represents a valuable resource for education and training of students and laboratory professionals.

Albeit the laboratory diagnostics of anemia remains a rather simple enterprise, accurate disease characterization has emerged as a mainstay in the era of precision (laboratory) medicine, even for RBC disorders. The many technological advances occurred in laboratory medicine over recent times have enabled the introduction of a vast array of innovations, which have led the way to more efficient patient care and more convenient organization of resources and workflows within the laboratory. In the foreseeable future, the better understanding of phenotypic heterogeneity of RBC disorders, also supported by IT tools such as expert diagnostic systems or artificial neural networks, will predictably enable to improve the global management of these disorders at multiple levels. Yet, some additional issues will need to be addressed, on top of it all the current lack of harmonization in laboratory hematology.

Considerations when buying a hematology analyzer. When purchasing a hematology analyzer or cell counter, the following may be key considerations:

Parameters. Cell counters may report on ranging from the classic 8 parameters to 36 parameters and 2–6 histograms and scatter diagrams. The decision on number of parameters required generally depends on the type of test needed, which in turn depends on case mix and load. Look at the size, type of facility, and testing capability needs. Is your facility a large multi-specialty hospital with an active inpatient population, mix of all types of cases, and high throughput requirement? If yes, one probably needs a fully automatic 5-part differential (Or even 6-part) hematology analyzer. If there is frequent need for stat testing due to high number of critical cases, then a back-up semi-automatic 3-part differential cell counter may also be required. Small and medium secondary care hospitals can opt for 3-part differential cell counters. They are mostly less automated, have less throughputs and limited test menus, but would suffice for their requirements. Less frequent, specialized test requirements can be outsourced.

Current and future throughput. Analyzers come with throughput ranging from 40 to 200 samples per hour. One may decide based on hospital throughput requirements.

Sample volume and mode. Generally hematology analyzers support 3 modes-Pre-diluted mode, whole blood mode, and capillary whole blood mode for various test requirements. Capability to work with smaller volumes is useful, especially for pediatric tests. There are some cell counters supporting as low as 9µl samples also.

Data storage. Cell counters offer storage capacity starting from 35000 to 100,000 results, including histograms, scatter diagrams etc.

Dimension and weight. If buyers are concerned about the space they have for the laboratory, then the compactness of the system may be important to them.

Efficiency and cost. Check the number and quantity of reagents that need to be used as well as their shelf-life. Ask for per test cost that one may incur based on the present and future volumes of samples.

Touchscreen and LCD display. Modern analyzers come with extensive touchscreen and large, convenient LCD displays for all operations, including inventory management system, thereby eliminating the need for a separate computer system. On the flip side, if staff is not properly trained and careful in using touchpads, one may require touchscreen replacement or unnecessary frustrations with faulty touchpad/keys, even though the analyzer functions are all intact.

Closed tube sampling or open tube sampling? A critical factor for any type of hematology analyzer instrument that analyzes potentially infectious body fluids is automation that eliminates or minimizes contact between the user and the specimen so as to ensure user safety. In this regard closed tube sampling is considered safer than open tube sampling devices. Also check how the device deals with waste management.

Maintenance support. In case of fault or failure, quick and efficient service by the seller is critical because the blood samples deteriorate quickly. This is the reason most labs opt for reagents based rental systems, rather than outright purchase. In case of rentals, it is up to the seller to repair or replace the system within the promised SLA. However, a rental model works only for regular and higher volumes. If volumes are smaller than planned it may turn out to be costlier per test.

Trained staff. Carefully assess the staff’s capacity or training to use the new system. Some specific blood analysis testing may be high in complexity and may require extensive training for procedures requiring a high degree of operator preparation, calibration, intervention, and analysis.

Digital connectivity. Another important factor to consider when purchasing a hematology analyzer is the system’s digital/computer interface capabilities. Number of ports available, printer systems, LAN/wireless connectivity, HL7 compliance, and barcode scanner interface are all important. Seamless integration with hospital information system, lab information management systems, and/or electronic medical records may be required based on the systems the hospital already has.

Budget. Last but not the least — techno-commercial evaluation needs to be done based on the budget of the hospital.

The analyzer market continues to be as impacted as the rest of the lab industry, with the uncertainty and unpredictability that ensues with the current state of affairs. While the extent of the impact brings ambiguity, the need for clinical laboratory solutions to support medical professionals remains constant.

Regardless of what the future holds for the clinical lab analyzers market, the one thing that remains constant is change. And as changes in disease detection and management keep coming, the lab industry and its analyzers will keep meeting the challenges that the new trends present.