Adoption of Apheresis Equipment to Intensify

To strengthen the blood transfusion services, the Metro Blood Bank Project has been conceived by the Health Ministry to set up Centers of Excellence in Transfusion Medicine with state-of-the-art technology for component separation and processing of blood.

Since the separation of red and white blood cells was first reported in 1974, the technology has become fundamental in the biomedical sciences. The separation of a unit of whole blood into its constitutive components – red blood cells (RBCs), platelets, and plasma soon after donation is required in order to maximize its clinical value to future transfusion recipients. The technology of apheresis has had a major impact upon the practice of blood transfusion over the past 15 years. The first introduction of equipment to perform apheresis procedures was in blood transfusion centers as they held responsibility for supplying blood products for transfusion to patients, and the development of apheresis equipment was primarily to obtain blood components for transfusion. The collection of blood components for transfusion led to development of apheresis units outside the blood transfusion center to meet demands for blood components. Blood also contains massive information about the functioning and status of the body, making separation of blood cells a requisite and critical step in many research applications and therapeutics.

Current methods for blood cell separation require complex and expensive equipment. Centrifugation, the gold standard and the most common method for blood cell separation, is labor-, energy-, and time-intensive and relies on well-trained operators. To address the limitations of conventional, centrifugation-based blood processing, several groups have explored alternative technologies, such as hollow fiber filtration that is capable of extracting RBC products from whole blood, with minimal labor or equipment requirements, but requires relatively expensive membranes; single-stage microfluidic arrays have typically been able to handle very dilute blood samples; and devices employing fluorescence-activated cell sorting (FACS) or magnetic separation (MACS) can sort up to 50,000 cells per second, with higher rates achievable at the cost of purity.

Market players are presenting shrewd stage plans that fuse, for example, particular hemoperfusion, twofold filtration with adsorption, plasma trade, and twofold filtration which helps blood refinement solutions. Additionally, players are making propelled gadgets that have mechanization features and are outlining propelled equipment that have computerization highlights, and these apparatuses have broad request in national blood transfusion focuses. The developing acknowledgment of dispensable apheresis packs because of their generally low costs, has made bounteous open doors for little producers.

Governments Role
India collects about 11 million blood units every year. Nearly 71 percent of these blood donations are collected through voluntary non-remunerated donors. A recently concluded assessment of licensed blood banks of India revealed that the average blood donation rate in India is 0.8, which is lower than many high income countries leading to a shortfall in quantum and access to safe blood in select hard-to-reach areas of the country. Rational use of blood also needs to be ensured to enhance utilization, as one unit of blood can benefit more than one beneficiary through separation into red cells, plasma, platelets. To strengthen the blood transfusion services, the Metro Blood Bank Project is conceived as a Central Sector Scheme by the Ministry of Health and Family Welfare (MoHFW) to set up state-of-the-art centers of excellence in transfusion medicine in the four metro cities of Delhi, Mumbai, Chennai, and Kolkata. These centers are high-volume blood collection centers where there is state-of-the-art technology for component separation, processing of blood, and quality systems. Approval of the Union Minister has been accorded for the first phase, wherein these facilities are to come up in Chennai and Kolkata. National Blood Transfusion Council under National AIDS Control Organization (NACO) will be the implementing division of the ministry for this project.

Furthermore, as India is home to an extraordinary variety of climatic regions, there are always cases of vector-borne diseases such as dengue that lead to increased demand of platelets and apheresis machines is the only hope. Also, increasing number of road accidents and cancer cases require blood and its various components. However, the country lacks proper functioning and adequate amount of equipment. Recently, a tender has been finalized by the Bihar Medical Services and Infrastructure Corporation Ltd (BMSICL) for setting up blood component separators in all the district hospitals of Bihar. With patients struggling to get blood components, especially platelets and frozen plasma in rural areas of Karnataka, as there are not many blood component separation units, the Health Department will soon start 40 new blood separation units in the state. The Health Department has also revised prices of blood units and its components in all the 134 private blood banks in Karnataka. Additionally, soon, HIV-positive patients in the state will get blood and its components free of cost in both government and private blood banks that was as of now restricted to those with Thalassemia, hemophilia, and sickle cell anemia.

Global Market
In the past few years, apheresis procedures have witnessed a stark rise in the number and areas of applications and the global market for these procedures continues to rise at an excellent pace. Presently, a variety of apheresis procedures are widely used as a part of treatment in various renal, neurology, hematology, cardiovascular, and autoimmune diseases. According to Transparency Market Research, the global apheresis market was valued at USD 2.04 billion in 2017 and is projected to reach USD 4.33 billion by 2025, expanding at a CAGR of 10.2 percent.

The plasmapheresis segment dominated the global market in terms of revenue contribution, chiefly owing to high number of donor plasmapheresis procedures undertaken every year globally and the vast number of applications of therapeutic plasma exchange. The segment is also projected to expand at a CAGR of 8.9 percent. However, the segment of photopheresis is expected to lead in terms of rate of growth as the segment is projected to exhibit an excellent 12.2 percent CAGR from 2018 to 2025. The vast technological advancements observed in the field of photopheresis in the past few years have led to a vast rise in the procedure’s vast applications in areas such as cancer and hematology disease treatment.

From a geographical standpoint, North America dominates the global apheresis market owing to its well-established healthcare infrastructure and high demand for plasma for production of plasma-derived medicines. Disposables products segment is anticipated to contribute the largest share in the North American apheresis market. Asia-Pacific, with its considerably established apheresis market in countries such as Japan and emerging economies such as India and China, is projected to witness exponential growth. The regional market is expected to exhibit an excellent CAGR of 11.2 percent from 2018 to 2025. Factors such as the vast rise in the prevalence of chronic diseases, high geriatric population, and increasing healthcare expenditure in this region will play a key role in upping the demand for apheresis procedures in the next few years.

The global apheresis market is consolidated and highly competitive. Some of the leading players operating in this consolidated market are Asahi Kasei Medical, Terumo Corporation, Haemonetics Corporation, Fresenius Kabi, Cerus Corporation, B. Braun Melsungen, Kawasumi Laboratories, Nikkiso, Therakos, and Medica. A majority of the leading players in this market are based in developed countries across North America and Europe. Industry experts are heavily involved in strategic mergers and acquisitions and novel product launches to sustain the competition. Recently, Terumo, a world leader specializing in cellular and apheresis technology, announced the launch of an innovative apheresis device to treat Myasthenia Gravis (MG) disease and Guillain-Barré syndrome. This device, named Spectra Optia Apheresis System is the first and only device of its kind in Europe which is enabled to treat the aforementioned disorders by means of therapeutic plasma exchange.

Technological Advances
There have been many attempts to develop cell separation technologies that are affordable to buy and use, do not require labels, and are able to retain significant numbers of cells. An alternative separation technique to FACS and MACS is dielectrophoresis (DEP). DEP can be used both to characterize and separate cells according to the passive electrical properties. The technology has a capacity and throughput comparable to the fastest MACS and FACS, requires no chemical labels, has significantly lower cell loss, and significantly lower capital and running costs.

Differential centrifugation. This makes use of differences in density of various blood components. Mature red cells have the greatest density, while plasma has the least. The donor or patient blood is separated into layers of components based on density detected by sensors. In the intermittent-flow method, the centrifuge container is filled and emptied and the same venous line is used for both withdrawal and return of blood. The major advantage is that it is one-arm procedure, hence convenient. In the continuous-flow method, two venous access sites are used, one for removal of the whole blood and the other for return of the unwanted portion back to the donor. The advantage of continuous-flow method is its speed and small extracorporeal volume.

Next-generation centrifuges. The next-generation system includes advanced features such as automatic electric brakes, solid-state speed control, electronic tachometer, and safety cut-off switch to stop the system if the lid is open. They are microprocessor-controlled smart centrifuges, which provide high efficiency with more memory storage. These centrifuges provide precise temperature control, wide range of RCF, acceleration, and time. These centrifuges also allow network and PC connectivity which helps in data management.

Microfluidic separation. Thanks to the developments in the lab-on-a-chip technologies, novel diagnostic methods intended to quantitatively characterize specific cell types in a fast and efficient way, directly from blood. Integration of microfluidics with micro-electro mechanical systems (MEMS) provides portable, low-cost, high-throughput, fast, and precise tools for medical diagnostics and biological sciences. Miniaturized dimensions in microfluidic systems allow mimicking natural interactions of cells either with other cells or their microenvironments while providing high-resolution data at single-cell resolution. Precise, low-volume liquid handling features of microfluidics have been incorporated with sensitive and specific DEP manipulation techniques; as a consequence, DEP methods have again become one of the powerful methods for biological and clinical applications.

3D-printed microfluidic chip. It is capable of continuously sorting cells by their densities, without using a centrifuge or other significant hardware. The chip contains several fluids with different densities forming a continuous-flowing density gradient. In this miniaturized density gradient, cells with different densities collect in different outlets, ready for enumeration or further analysis. This technique can continuously sort a stream of cells by their densities alone (without being influenced by the cells’ other physical properties) and can isolate cells of interest from other cells with higher throughput and gentler conditions than existing tools. The density-based cell sorter offers several advantages over existing techniques like density gradient centrifugation. As a continuous-flow technique, the cell sorter eliminates virtually all of the manual labor associated with transferring samples into and collecting fractions out of density gradients.

DEP-based cell-separator using 3D electrodes on disposable chip. Using a simple electrical charge, one cell type is allowed to pass through the chip and the other is retained and subsequently recovered. It causes the cell separation to be done 10,000 times faster by using this device which resembles an electric sieve and acts like a force field, by catching objects which are polarizable. Thanks to the new design of these cell separators, they can used in vital therapies for life-threatening diseases, can be carried out at a fraction of the usual cost, and can be used for therapeutic as well as research purposes. This offers significant promise as a new standard benchtop laboratory technique, and can provide major benefits in health and other fields.

Sound waves technology. Researchers have developed a highly accurate single cell sorting technology using focused sound waves. This new technology enables rapid and accurate isolation of single cells from complex blood samples, which will facilitate the broad application of single cell analysis toward precision medicine. Microfluidics technology capable of precise cell manipulation has great potential to reinvent the next-generation cell sorting technology. Compared to conventional FACS systems, the merits of this cell sorting technology include a substantially simplified sorting mechanism that shrinks the instrument size, reduces its complexity, and substantially lessens costs. Not only that, but it also enables more accurate single cell level sorting and leaves no damage on target cells because sound waves are much gentler than electric fields widely used in conventional FACS systems.

The Future
Growing awareness regarding the technology is anticipated to bolster the market for blood separating equipment in the coming years. The extending recurrence of various blood-related messes has enlivened the enthusiasm for platelets and plasma. Joined with this, learning concerning apheresis blood gathering frameworks, machines, and units has incited capable improvement of the equipment. The growing number of causalities requiring surgeries and increase in geriatric masses will also strengthen the interest for these equipment and packs. Moreover, the rising rate of blood-related sicknesses united with progressions in innovation of contraptions is depended upon to help the development of the advanced equipment.

Nearly all of the >100 million individual blood components transfused each year worldwide are first produced by multi-stage centrifugation of freshly-donated WB units, or through apheresis collection of a larger amount of a specific component from a willing donor. In India, the 11 million blood collection in a year is estimated to be a USD 50 million market for blood and related products. International entrants in the Indian market, high purchasing power, awareness toward product innovation, pricing policies, and judicious use of components will provide growth opportunities in the market. Interaction between blood bankers and clinicians backed by government support promise a movement toward a goal for safe blood supply.

Second Opinion