Molecular diagnostics is a rapidly advancing area of research and medicine, with new technologies and applications being continually added. In the current medical diagnostics market, molecular diagnostics for cancer testing offers one of the brightest areas for growth and innovation. The confluence of breakthroughs in genomics, proteomics, and the development of microarray devices to measure analytes in the blood and various body tissues, has led to this revolutionary market segment offering the power of advanced analytical techniques to the diagnosis and treatment of cancer.

The technologies that come under the umbrella of molecular diagnostics include first-generation amplification, DNA probes, polymerase chain reaction (PCR)-based technologies, fluorescent in situ hybridization (FISH), peptide nucleic acids (PNA), electrochemical detection of DNA, sequencing, mitochondrial DNA, biochips, nanotechnology, and proteomic technologies. These technologies are improving the discovery of therapeutic molecules for cancer, the screening, diagnosis and classification of cancer patients, and the optimization of drug therapy. In the past few years, this rapidly evolving field has seen several fascinating developments. Major developments include the integration of specialty labs and gene-expression profiling into clinical practice, the introduction and rapid growth of cell-free fetal DNA prenatal testing, the advancement of companion diagnostics for drug development, the widespread installed base of automated instruments for molecular testing, and the development of personalized medicine. The genetic testing space is one of the most profitable sectors of molecular diagnostics and is expected to be an area of high growth and corporate change over the next 6 years.

Indian Market Dynamics

The Indian molecular diagnostics market is estimated at Rs. 104 crore, with reagents contributing 100 percent to sales. Analyzers are totally being placed. The revenue generation takes place from the reagents procured for the closed systems supplied by the vendors or some plastic consumables.

Automation is the foundation of clinical molecular laboratory to report patient results with confidence. We have confined our study to extraction analyzers used for clinical applications. In many areas of infectious diseases, classical detection methods have been replaced or supplemented by PCR. Large buyers continue to be premium laboratories as SRL Diagnostics, Dr Lal PathLabs, Metropolis India, Suburban Diagnostics, PGI-Chandigarh, and Institute of Liver and Biliary Sciences (ILBS).

Roche and Qiagen offer extraction analyzers, real-time PCRs and a combination of both. Abbot's m2000 real-time system automates steps to perform nucleic acid amplification assays from sample processing through amplification, detection, and data reduction.

2015 saw increasing reliance on Cepheid, for its Xpert MTB/RIF test, which detects Mycobacterium tuberculosis complex DNA and, in positive specimens, provides simultaneous identification of rifampin-resistance associated mutations of the rpoB gene. Bio Rad's real-time PCRs and droplet digital PCR systems are also increasingly being used for molecular diagnostics by smaller laboratories; it no longer being the exclusive prerogative of large labs, smaller laboratories are also now conducting these tests.

Last year, Tulip Group entered the world of molecular diagnostics with the launch of its portable Truela real-time micro PCR system. It expects this portable system, which gives results in less than 30 minutes, to be a game changer in the diagnostics field. In 2015, it had success in the Indian market. Danaher India is planning an aggressive entry in this segment this year. bioMérieux India has some presence with its molecular biology solutions covering extraction, amplification, and detection. Beckman Coulter too is moving medicine forward by bringing 75 years of automation and innovation history in the clinical diagnostics lab to the molecular diagnostics arena.

Molecular diagnostics performed at the point of care (POC) are regarded as a leading expansion market. Molecular POC diagnostics are able to improve the sensitivity and specificity of existing near-patient and rapid tests and also expand the diagnostic capabilities at points of care such as hospital critical care units, physician offices, outpatient clinics, and community health posts in the developing world. Soon, portable, hand-held, inexpensive POC test devices, equivalent to currently offered full-size systems, will become available to aid in detection of mutations or in identification of infectious agents.

Technological advancements are coming hard and fast in the molecular diagnostics market. The integration of diagnostic methods with advanced IT and data analytics is minimizing the complexity of assays and further analysis, and the use of nanotechnology for developing molecular diagnostic products will help increase the efficiency of diagnostic methods and results. One of the most promising applications of molecular diagnostics is oncology - it is used for screening, therapy selection, diagnosis, and relapse monitoring of cancer.

Global Market

The global oncology molecular diagnostics market was valued at USD 1.48 billion in 2015 and is expected to reach USD 2.86 billion by 2019, growing at a CAGR of 17.8 percent, and in India it is rapidly gaining traction. India adds 6-7 lakh cancer patients every year, who require monitoring after diagnosis.

Growing base of geriatric population globally, and rising prevalence of infectious diseases and hospital-acquired infections are pivotal factors driving the molecular diagnostics market size. Estimates as per World Health Organization (WHO) imply that the fraction of geriatric population is anticipated to grow by 8 percent by 2050 forming over 16 percent of the total population According to the Centers for Disease Control and Prevention (CDC), every year there are approximately 19 million new STD infections, around half of which is found in people of the age group 15 to 24.

The market is witnessing rising instances of external funding to conduct clinical studies in the molecular diagnostics field. This has accelerated new product development, boosting global molecular diagnostics market growth. For instance, Merck's venture capital arm led a USD 12 million financing for AdvanDx to conduct R&D on pathogen screening for major hospital-acquired infections.

Technological advancements in terms of accuracy, portability, and cost effectiveness should act as a catalyst for market growth. The increasing demand for POC diagnostics in order to curb the healthcare expenditure by minimizing hospital stays should propel the growth of global POC diagnostics market.

Moreover, the changing trend of healthcare practitioners toward increasing their dependency on the usage of POC diagnostic-enabled medical devices and consumables should drive the market demand.

Product analysis. Sexually transmitted diseases (STDs) dominated the overall molecular diagnostics market size in 2015, by infectious diseases, with revenue close to USD 1 billion, followed by HIV. HIV and STD demonstrate maximum penetration due to increasing occurrence and ease of diagnosis.

In terms of technology, PCR is identified to be the largest segment grabbing up to 46 percent molecular diagnostics market share in 2016. However, this share is expected to decline in the coming years due to the fact that other technologies such as in situ hybridization and genetic sequencing are expected to experience an increase in demand over the next seven years.

A Paradigm Shift

With the entry of molecular diagnostics into the clinical laboratory, beginning in the 1990s, however, additional requirements became evident. Due to the innate complexity of molecular medicine, it was apparent that relying on a laboratorian to do the processing and hardware to do the analytics was not going to be sufficient. The use of heavily multiplexed panels that could provide a clinically actionable result required the simultaneous analysis of multiple analytes, each requiring multiple reactions. It quickly became apparent that the biggest issue that needed to be addressed in every molecular diagnostic laboratory was how to automate or simplify the DNA testing process.

This need led to the first true evolution of the molecular diagnostic analyzer. Previously, laboratory technicians relied on a combination of manual preparation steps with a thermal cycler and crude data capture systems to generate a usable result. The changing need led to the emergence of two kinds of instrumentation.

Automated liquid handler platforms, which can be integrated onto a singular automated platform that can automate most of the manual preparation steps and thermal cycling. By adding a data analysis platform to the back end, the system is able to achieve a high degree of semi-automation for a completely manual lab testing process. The automated liquid handlers, with their open architecture, help to automate the entire test process, no matter what the test process is, as long as it can be split into logical steps.

Commercial analyzers, which use manufacturer specific reagents, mostly on a closed mechanical analytics system. These resemble the analyzers for other areas of the clinical lab but with a key, distinct feature. Rather than improving upon speed or throughput, the core enhancement made was with regard to ease of use - how much the system can automate in order to minimize user intervention. For the molecular diagnostics laboratorian, running a singular sample for a panel of 20 mutations manually in the "old way" is a monumental task; each mutation can require as many as 10 pipetting steps, which means nearly 200 manual processes for just one sample. But with the new automated analyzers, running a test becomes as simple as adding the sample and loading the analyzer with consumables, and clicking the start button.

With the arrival of automated molecular diagnostic analyzers, the molecular laboratory underwent rapid growth and expansion. Automated analyzers provided a number of benefits - ability to process a large number of samples simultaneously; elimination of human error to increase accuracy and reliability of results; reduction in labor costs to enable the performance of "complex" genetic testing.

Sample-to-result and high throughput. Responding to the new requirements linked to the types of testing outlined above, the evolution of the molecular analyzer has continued, and two additional types of analyzers have emerged. The first is the sample-to-result analyzer, which can take any test from primary sample tube to result without the need for any operator manipulation of the sample. The second new development is the emergence of the high-throughput systems. These new workhorses can provide an output of several thousand (or more) sample results in the same amount of time. In most cases these benchtop factories are not as automated as any of their ancestors, but their ability to run at rapid speeds compensates for their higher manual requirement.

The Road Ahead

So, now market has four distinct types of analyzers that can populate a modern molecular diagnostic clinical laboratory to meet the needs of multiple forms of testing - automated liquid handlers, ease-of-use commercial analyzers; sample-to-result analyzers; and high-throughput systems. What's next? Currently, laboratories are observing two new trends:

Consolidation of testing. As many smaller labs are joining forces, and large labs are looking to absorb smaller regional players, there is a need for analyzers to not only be high-throughput but to have sufficient automation to handle the more complex panels and the ability to perform different kinds of tests in the same system.

Rapid point-of-care testing. Many physician offices and small clinics are gearing up to provide rapid genetic testing to their patients. They require analyzers that are fast, easy-to-use, and have small footprints.

However, these new trends reflect the increased rate of adoption of molecular medicine in the clinical lab. Molecular diagnostics is transforming healthcare, and analyzers with novel technologies may soon emerge to push the molecular diagnostics laboratory into yet another stage of evolution.

Dr Rajas V. Warke, Director-Molecular Biology and Virology, HiMedia Laboratories Private Limited
Industry Speak
Simplicity and Speed

"Simplicity and Speed" is going to define the success of molecular diagnostics in the coming decades where the past years have already seen a vast advancement with PCR-based methods emerging as the most rapid and accurate diagnostic procedures. Because of the ability to exponentially amplify both RNA and DNA, quantitative PCR can be highly specific and sensitive, which enables the identification of a pathogen as well as the genetic screening of an inheritable disease. However, much of the world's population which lives in developing countries cannot access these requisite technologies mainly due to the cost, and the equipment required. Acquaintance to appropriate molecular diagnostic tools is the biggest challenge faced for the improvement of global health. In the developing countries, with a very limited access to professional labs, efforts are being made to explore the diagnostic devices that are free of dedicated instrumentation and are affordable too. Today's molecular diagnostic systems are designed for use in professional labs and the requirements of these laboratory-based tests are often incompatible with the constraints of resource-limited settings, which include a lack of cold chain for proper storage of sensitive reagents. A huge population in the developing countries is still dwelling with inadequate resources, which renders Earlier Is Better elusive. Therefore, there is an enormous push for a portable system-based molecular diagnostic method for rapid and accurate detection of infectious diseases at the point of care (POC). An appropriate POC diagnostics development for high-impact diseases could significantly reduce the global disease burden. The World Health Organization has come up with an acronym for the characteristics of POC diagnostics that are appropriate for even the lowest-resource global health settings: ASSURED (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverable to users).

In our opinion, based on these requirements, the industry should focus on developing small and portable molecular diagnostic devices for PCR along with stable reagents at the point of care worldwide, which would enable rapid, on-site diagnosis of infectious diseases.

Dr Rajas V. Warke
Director-Molecular Biology and Virology,
HiMedia Laboratories Private Limited

Dr Shelly Mahajan, Research Scholar, Penn Medicine, University of Pennsylvania
Second Opinion
Targeted Therapy - Where Diagnostics and Therapeutics Meet

As we move toward an era of molecular diagnosis and personalized medicine, targeted therapies are becoming a promising concept in the treatment of diseases, ranging from metabolic disorders all the way to cancer. The ongoing quest of identifying genes involved in the pathogenesis of these diseases and of finding potential targets for treating these diseases is providing new opportunities to develop more effective and personalized treatment protocols.

Targeted therapy, in a nutshell, is the concept of identifying specific mutations generally associated with cancer, developing molecular tests to help diagnose these mutations, and then creating drugs that attack these specific "molecular targets." This is a paradigm shift in cancer treatment from general cytotoxic treatment that attacks the entire body causing severe side effects, to individualized "targeted treatment" that is specific down to the level of cancer sub-types. Not only does this produce a more effective therapeutic outcome but also implies lesser adverse reactions and side effects.

Even though today personalized medicine is majorly comprised of pharmacogenomics, where patients' genetic information helps a clinician decide how the patient will respond to a drug, the field of targeted therapy is bound to grow by leaps and bounds in the next year or so just based on the amount of research happening in the field. For example, currently I am part of a team that is working on developing new molecular diagnostic markers for prostate cancer. Imagine having a drug that attacks the exact mutation that caused the cancer in the first place - this is targeted medicine!

Dr Shelly Mahajan
Director-Molecular Biology and Virology,
Penn Medicine, University of Pennsylvania

Suresh Chandrasekaran, VP-Marketing & Knowledge Management, CPC Diagnostics Private Limited
Industry Speak
Sachika - Enhancing Skill Sets through Empowered Training

Sachika was conceptualized by CPC as a first of its kind innovative training institute in medical diagnostics industry. Training at Sachika provides laboratory professionals in in vitro diagnostics (IVD) an opportunity to learn and upgrade their skills.

Sachika conducts exclusive residential programs catering to the following disciplines.

Clinical chemistry: Sachika provides training on entry level automation. This is a two-day residential program module, which covers all the aspects related to laboratory automation. This is complemented by a wet lab on handling automated chemistry systems like Turbochem 100 and Turbochem 240.

This module also covers key aspects in good lab practices. Sachika has conducted more than 25 entry-level automation training programs. More than 250 laboratory professionals have benefited from this program.

Immunology: Sachika provides training in autoimmune diagnostics and allergy diagnostics.

A Guide to Autoimmune Diagnostics is a 3-day residential program module, which provides the lab professionals An Insight into invasion by Internal Invaders.

The course covers basics on autoimmune diseases, all aspects on immunofluorescence microscopy, pattern identification for key autoimmune diseases like ANA, ANCA, autoimmune liver diseases, neuroimmunology, nephrology, and the like using EUROStar III plus microscope. The module also includes a hands-on wet lab apart from a special focus on trouble shooting.

The above sessions are complemented by a session on recombinant immunoblot assay processing, which includes hands-on wet lab for EUROLine profiles on automated line immunoassay processor PlexMat and interpretation using Linescan software.

Sachika also provides a tailor-made training program for allergy diagnostics, which covers all aspects of allergy testing apart from the importance of India-specific allergy profiles. This is also complemented by hands-on wet lab for EUROLine profiles on the dedicated line immunoassay processor AllerMat and quantitative results using Linescan software.

Sachika has conducted more than 35 programs covering the above modules of immunology and close to 200 laboratory professionals have benefited from this program.

We look forward to include newer programs in Sachika, which will further support the lab professionals in future.

Suresh Chandrasekaran
VP-Marketing & Knowledge Management,
CPC Diagnostics Private Limited


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