5. Scientific and Technical Aspects of Extracellular Vesicles
Isolation Techniques
EV isolation methods can be categorised into conventional and next-generation approaches with unique advantages and applications.
Conventional methods include ultrafiltration (UF) and size exclusion chromatography (SEC), which rely on size differences, making them broadly applicable but often less specific. Centrifugation-based methods, such as differential centrifugation (DC) and density gradient ultracentrifugation (DG UC), are widely used for isolating EVs based on density. However, these methods can be labour-intensive and time-consuming. They are suitable for large-scale studies but may lack the specificity required for specific clinical applications.
Precipitation techniques are simple and cost-effective, though they may yield lower purity, making them less ideal for highly sensitive downstream applications. Immuno-affinity techniques use antibodies to capture EVs based on surface markers, offering high specificity but at a higher cost. These techniques are often used when specific markers are needed.
Next-generation methods, such as microfluidics, are highly efficient for high-throughput and specific isolation. Microfluidics utilises size-based and aptamer-based techniques, where aptamers (short strands of DNA or RNA) are engineered to bind with high specificity to EV surface markers, allowing for precise separation. This method is particularly suited for clinical diagnostics, where purity and speed are critical.
Researchers choose isolation methods based on a balance of throughput, specificity, and cost. For instance, microfluidics is preferred for precise diagnostic purposes, while centrifugation may be more suitable for exploratory research that requires larger EV yields.
Quantification and Characterization Techniques
Once isolated, EV quantification and characterisation are essential for assessing their properties and functionality.
Nanoparticle Tracking Analysis (NTA) and Dynamic Light Scattering (DLS) provide quantitative data on size distribution and concentration, offering a broad view of the EV population. These methods are relatively fast and suitable for routine analysis. NTA, in particular, allows direct visualisation, providing more nuanced size distribution data.
Transmission Electron Microscopy (TEM) provides high-resolution images for detailed structural analysis, making it ideal for studies that require precise morphological details. However, TEM is time-consuming and requires sophisticated equipment.
Tunable Resistive Pulse Sensing (TRPS) measures EV size and concentration based on electrical resistance changes as EVs pass through a nanopore. It offers high sensitivity and can detect smaller vesicles, making it particularly useful for high-resolution size distribution applications.
NTA and DLS are often chosen for general characterisation due to their ease of use and speed. At the same time, TEM and TRPS are preferred when detailed structural information or high
sensitivity is required, such as in therapeutic development where precise characterisation of EV size and purity is crucial.
Detection Techniques
EV detection focuses on identifying specific biological markers, critical for understanding their role in diagnostics and therapeutics. Flow cytometry and microfluidic chips allow for highthroughput detection and provide data on EV heterogeneity within a sample, making them suitable for biomarker discovery. Aptamer recognition or nucleic acid capture techniques detect specific EV nucleic acids, such as microRNA, which are valuable for diagnostic purposes. Aptamers are particularly useful due to their high specificity and versatility in detecting different biomolecules. Surface proteins are commonly detected using antibodies or aptamers, providing insights into EV function and origin.
Surface modification techniques, including radioactive labelling and nanoprobe detection, enable EV tracking in vivo, facilitating drug delivery studies. More advanced methods, such as Surface Plasmon Resonance (SPR) and Surface-Enhanced Raman Spectroscopy (SERS), are used for highly sensitive molecular detection and are often employed in the early detection of diseases like cancer. Flow cytometry and microfluidic chips are preferred for highthroughput applications due to their scalability and efficiency. In contrast, SPR and SERS are chosen for their superior sensitivity in detecting disease-specific markers, making them valuable in clinical research for early diagnosis.
Applications in Healthcare
EVs have significant potential in healthcare, particularly in disease diagnostics and therapeutic applications. They carry disease-specific markers in body fluids, enabling non-invasive diagnostics for cancer and neurodegenerative disorders.
Figure 3: Overview of EV isolation, detection, and characterisation techniques
Their natural properties biocompatibility, low immunogenicity, ability to cross biological barriers, and targeted delivery capabilities make EVs ideal candidates for drug delivery systems. For example, EVs can cross the blood-brain barrier, a significant advantage in developing treatments for neurological diseases. Advanced isolation techniques, such as filtration, acoustic waves, deterministic lateral displacement (DLD), and dielectrophoretic forces (DEP), further refine the purity of EVs for therapeutic applications. In clinical settings, detection methods like fluorescence, Surface Plasmon Resonance (SPR), and SurfaceEnhanced Raman Spectroscopy (SERS) provide the precision needed for molecular identification and quantification.
EV Components of Interest: RNA, protein, DNA, lipid and other components are being studied in EV research.
Component Description
RNA Includes miRNA, mRNA, lncRNA, tRNA, rRNA, piRNA, snoRNA, and Y RNA
Protein Surface proteins, cytosolic proteins, enzymes, receptors, and signalling molecules
Significance in EV Research Diseases Studied
Crucial roles in cell-to-cell communication
Cancer (various types
DNA Genomic DNA, mitochondrial DNA
Potential biomarkers for disease diagnosis and prognosis
Involved in regulating gene expression in recipient cells
Used as markers for EV identification and characterization
Neurodegenerative diseases
Cardiovascular diseases
Autoimmune diseases
Cancer metastasis
Lipids Phospholipids, sphingomyelin, cholesterol, ceramide
Involved in EV biogenesis, cargo sorting, and uptake by recipient cells
Potential therapeutic targets and biomarkers
Reflects the mutational state of origin cells
Potential for non-invasive cancer detection and monitoring
More stable compared to circulating tumor cell DNA
Form the EV membrane structure
Neurodegenerative diseases
Cardiovascular diseases
Infectious diseases
Various cancers
Autoimmune diseases
Cardiovascular diseases
Metabolic disorders
Involved in EV biogenesis and stability
Cardiovascular diseases
Metabolites Small molecules, ATP, ions (e.g., calcium)
Glycans Surface glycoproteins and glycolipids
May play a role in cargo sorting and EV uptake
Neurodegenerative diseases
Reflect cellular metabolic state Diabetes
Potential biomarkers for metabolic diseases Cancer
Cardiovascular diseases
Involved in EV-cell interactions and uptake Cancer
Potential targets for EV engineering and drug delivery
Table 1: Major EV components currently being profiled and reported
Inflammatory diseases
Infectious diseases
Emerging Technologies: Some of the advanced technologies for the characterisation of EVs that are gaining traction in Indian research labs are
Technology Description
Nanoparticle Tracking Analysis (NTA)
Visualizes and analyses light scattered by EVs in liquid suspension
Advantages Applications
- High sensitivity
- Direct visualization
- Size and concentration measurement
- Single-particle analysis
- Size distribution analysis
- Concentration determination
- Quality control
- Precise size determination
Resistive Pulse Sensing (RPS)
Raman Spectroscopy
Measures changes in electrical conductivity as particles pass through a nanopore
Surface Plasmon Resonance (SPR)
Analyzes molecular vibrations to provide a chemical fingerprint of EVs
- High-throughput
- Size and concentration measurement
- Label-free analysis
- Non-destructive
- Chemical composition information
- Real-time analysis
Measures changes in refractive index due to biomolecular interactions
- Label-free detection
- High sensitivity
- Concentration analysis
- Charge characterization
- EV content analysis
- Origin determination
- Purity assessment
- EV-protein interactions
- Quantification of surface markers
- Binding kinetics studies
Technology Description
Microfluidic Devices
Asymmetrical Flow Field-Flow Fractionation (AF4)
Utilizes small-scale fluid handling for EV isolation and analysis
Advantages Applications
- Rapid processing
- Low sample volume requirement
- Integration of multiple steps
- High resolution separation
Separates particles based on their diffusion coefficients in a fluid flow
- Minimal sample perturbation
- Compatible with various detectors
- Nanoscale imaging
Super-resolution Microscopy
Achieves resolution beyond the diffraction limit of light
- Single-vesicle analysis
- Structural details
- Point-of-care diagnostics
- High-throughput screening
- EV isolation and characterization
- Size-based separation
- EV subpopulation analysis
- Coupling with mass spectrometry
- EV morphology studies
- Protein localization
- Interaction analysis
- High sensitivity
Electrochemical Biosensors
Detects electrical changes due to EV-electrode interactions
2: Emerging technologies for EV characterisation
- Potential for miniaturization
- Rapid detection
- Point-of-care diagnostics
- EV quantification
- Specific marker detection
Standardisation and Reproducibility Challenges: Achieving consistent results across extracellular vesicle (EV) studies and complying with global standards such as MISEV 2023 involves addressing several key challenges. Standardising isolation methods is critical; combining different principles, such as size-based and density-based techniques, can enhance EV purity. Researchers must report detailed protocols, including centrifugation speeds and purification steps, to ensure reproducibility. Comprehensive characterisation using multiple complementary techniques, like Nanoparticle Tracking Analysis (NTA) and electron microscopy, can provide a complete profile of EVs. Ensuring proper quality control, such as monitoring for lipoproteins and platelets in plasma samples, is essential to differentiate EVspecific effects accurately. Adhering to MISEV 2023 guidelines requires using standardised terminology like "extracellular vesicle" unless specific biogenesis can be demonstrated, along with clear definitions and details on source and storage conditions. In functional studies, researchers should report the ratios of EVs to recipient cells and use appropriate controls to ensure that biological effects are specifically attributable to EVs. Transparency in data sharing through platforms like EV-TRACK can further promote reproducibility. Moreover, developing calibration and reference materials for EV measurements can enhance comparability, particularly in tissue-specific contexts where isolation methods must be adapted. Addressing these challenges will help researchers improve standardisation and reproducibility in EV research, meeting global standards like MISEV 2023 and enhancing their findings' reliability and clinical applicability.
Table
6. Impact Analysis of Scientific Publications Over the Last Decade
Extracellular vesicle (EV) research is rapidly expanding, with applications across key areas of science and medicine. The largest focus is Basic Research (34.6% of studies), which investigates the fundamental biology of EVs, including their production, release, uptake by cells, and role in cell communication under both normal and disease conditions. Biomarker Research represents 33.1% of studies, focusing on using EVs as non-invasive diagnostic tools for diseases like cancer and cardiovascular conditions due to the proteins, lipids, and nucleic acids they carry, which reflect their cell of origin. This makes EVs valuable for early disease detection and monitoring.
Drug Delivery accounts for 17.6% of research, exploring EVs as natural carriers for therapeutic molecules. Their ability to target specific cells positions them as promising vehicles for delivering drugs, RNA, or gene-editing tools, potentially improving treatment efficacy and reducing side effects. Therapeutics (14.7% of studies) uses EVs derived from stem cells to promote tissue repair, modulate immune responses, and treat conditions like autoimmune disorders and neurodegenerative diseases.
Basic Research has historically dominated EV studies, forming the foundation for more applied research. However, since 2018, clinical applications have been markedly increased, particularly in Biomarker Research, which has grown substantially, reflecting the rising interest in using EVs for non-invasive disease detection, especially in cancer. The growth in Drug Delivery and Therapeutics research also highlights the increasing potential of EVs in clinical settings, with implications for personalised medicine and advanced therapeutic systems.
Citations: The citation data for the analysed publications reveals a wide range of academic impact. On average, each publication received around 30.93 citations, although the median sits at just 6, indicating that half of the publications have fewer than six citations. A closer look at the distribution shows that 25% of the publications received one or fewer citations, while the top 25% garnered more than 21.5 citations. The maximum citation count for any single paper is an impressive 884, highlighting the substantial influence of some standout research. However, the standard deviation 86.99 points to significant variability, with a small number of highly cited papers skewing the average upward. While most publications have a modest citation count, a select few have significantly impacted their respective fields.
Figure 3: Scientific Publications Over the Last Decade in the different areas of EVs research
Figure 4: Impact factor analysis of the publications for the last decade
Impact factor: The impact factor analysis of the publications for the last decade reveals that the average impact factor is 5.29, indicating that the journals generally hold moderate influence in their fields. The impact factors vary widely, with a standard deviation of 5.61, suggesting that while many journals have an average impact, a few are significantly more prestigious. The median impact factor is 4.12, meaning half of the journals have an impact factor below this value. Additionally, 25% of the journals have an impact factor of 3 or less, while the top 25% exceed 5.12. The maximum impact factor is notably high at 50.5, reflecting the presence of a few highly influential journals. This data highlights a broad range of journal prestige, from niche publications to leading journals.
7. Scientific Overview of Extracellular Vesicles Isolation, characterisation and Application: Over the past decade, EV (Extracellular Vesicle) research in India has predominantly focused on human subjects, representing 69.6% of the total species studied. Rodents also play a significant role, accounting for 11.7% of research, followed by bovine studies at 9.5% and plants at 7.0%. Other species contribute a smaller portion, making up 2.2% of the research. Regarding the biological fluids from which EVs are isolated, cells are the primary source, used in 39.2% of studies, followed by blood at 33.6%, and urine at 15.2%. Other fluids contribute 12.0% to the overall studies. These figures highlight the central focus on human-derived EVs and the reliance on cellular and blood sources for EV isolation in scientific research.
Figure 5: EV sources from different biological sources
The three pie charts show the distribution of characterisation techniques used in extracellular vesicle (EV) research, categorised into biophysical, biochemical, and advanced methods.
Biophysical Characterization
Dynamic Light Scattering (DLS) is the most frequently used technique for biophysical characterisation, accounting for 28.4% of studies. Nanoparticle Tracking Analysis (NTA) follows closely at 25.7%, providing size and concentration data. Transmission Electron Microscopy (TEM), used in 17.6% of studies, offers high-resolution imaging of EVs. A combination of DLS and TEM is employed in 15.8% of studies, while other methods (e.g., atomic force microscopy) represent 12.6%.
6: Biophysical and Biochemical characterisation methods for EVs
Biochemical Characterization
For biochemical characterisation, the Bicinchoninic Acid (BCA) Assay dominates with 77.5%, as it is commonly used to quantify protein content in EVs. Other assays, like the acetylcholinesterase assay (4.6%) and ortho-vanillin assay (2.6%), are less common and used for more specific analyses. 6.6% of studies employ a combination of biochemical assays, reflecting the need for comprehensive molecular data.
Advanced Characterization
In advanced methods, Western blotting leads with 45.4%, which is widely used for identifying specific proteins in EVs. Polymerase Chain Reaction (PCR) (22.2%) and flow cytometry (21.1%) are also prominent, aiding in nucleic acid analysis and EV surface marker profiling, respectively. Other advanced techniques (11.3%) include mass spectrometry, which provides detailed molecular insights.
Figure
The pie chart illustrates the focus distribution among different extracellular vesicle (EV) components researchers are investigating. Proteins constitute the largest portion, making up 50.3% of the total research effort, highlighting the importance of proteins in EVs for cell signalling and communication. RNA components follow closely, accounting for 35.3%, reflecting the growing interest in RNA types like microRNAs and their role in gene regulation and potential as disease biomarkers. The remaining 14.4% is focused on other components, including lipids, metabolites, or other emerging areas of study within EV research. This distribution underscores the current emphasis on protein and RNA in EV studies, with other components receiving less but still significant attention.
Clinical areas: The field of Extracellular Vesicle (EV) biology in India is witnessing significant research and commercialization across multiple health domains. Key areas of focus for the past decade include neurodegenerative diseases, cardiovascular and metabolic diseases, and oncology and infective diseases. Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and epilepsy. Additionally, cardiovascular and metabolic diseases are being actively researched, with emphasis on myocardial infarction, coronary artery disease, diabetes, diabetic nephropathy, diabetic wound healing, and diabetic peripheral neuropathy. Cancer research also plays a pivotal role, covering gliomas, breast cancer, hepatocellular carcinoma, lung cancer, retinoblastoma, cervical cancer, and prostate carcinoma. Furthermore, infectious diseases are a major area of EV research, targeting HIV, COVID-19, hepatitis B virus, dengue virus, Japanese encephalitis, Mycobacterium tuberculosis, and Candida albicans. These diverse research areas reflect India's commitment to
Figure 7: Distribution of different components in EVs
Figure 8: Published therapeutic areas of EV research
advancing EV-based technologies for various health conditions, promoting innovation and commercialisation.
8. EV Ecosystem Overview: Academic Institutes, Industry, and Startups
Academic Research: The top institutes/hotspots in India engaged in Extracellular Vesicle (EV) research include the Apollo Hospitals Educational and Research Foundation (AHERF), All India Institute of Medical Sciences (AIIMS), National Dairy Research Institute (NDRI), Department of Biological Sciences and Bioengineering at the Indian Institute of Technology (IIT) Kanpur, Department of Molecular Medicine and Biotechnology at Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI), Lucknow and others. These institutes represent the key players advancing EV research across diverse fields such as healthcare, biotechnology, and agriculture.
Figure 9: Word burst of major institutes involved in EV research
Industry and Startups: India's EV industry is rapidly advancing, with 14 specialised companies primarily concentrated in major hubs like Hyderabad and Bangalore. Hyderabad leads with six firms, including Urvogelbio Private Limited and Exomed Therapeutics, focusing on neurodegenerative disease diagnostics, diabetes treatment, and regenerative therapeutics. Bangalore hosts four companies, Stempeutics, Pandorum Technologies, Exygen and ExoCare, engaged in regenerative medicine, ophthalmology, and cancer diagnostics. Other cities like Bhubaneswar, Mohali, Noida, Ahmedabad, and Visakhapatnam also contribute to specialised firms addressing cancer detection, cosmeceuticals, and the supply of extracellular vesicles. These companies are actively involved in developing EV-based diagnostics and therapeutics for various conditions, including Alzheimer's, Parkinson's, multiple sclerosis, various cancers, and regenerative treatments for organs like the lung and cornea.
They also provide essential consumables, such as isolation reagents and extracellular vesicles, supporting research and clinical applications. Incubation support from institutions like AHERF in Hyderabad, KIIT in Bhubaneswar, and AMTZ in Visakhapatnam further bolster their growth
and innovation. The diverse applications and strong presence in key metropolitan areas, combined with robust incubation environments, position India as a significant player in the global EV market, driving innovative solutions in diagnostics and treatments. Following are the start-ups operating in EV space pan-India.
1 Urvogelbio Private Limited Hyderabad Neurodegenerative diseases (NDDs)Alzheimer's, Parkinson's, Multiple Sclerosis and other NDDs
therapeutics X
2 Exsure Private Limited Bhubaneswar X EV-based cancer therapeutics, drug-delivery vehicle Plant Exosure reagents for isolation
3 ExoCan Healthcare Technologies Mohali Early cancer detection EV precipatation reagents
4 Pandorum Technologies Bangalore X Regenerative therapeutics (lung, cornea, etc.) X
5 Advancexo Noida, X Cosmeceuticals and therapeutic Manufacturing X
6 ExoCure Bengaluru X uMSC and EV therapy for regenerative medicine Wharton's Jelly, Growth Media, Extracellular Vesicles
of
cell-based
Visakhapatnam X X Supply of EVs from different biological sources
13 Exegen Bangalore Glioma-based diagnostics X X
14 Wellness language Hyderabad Cosmeceuticals
Table 3: Major Indian EV startups
Incubators: India’s EV-based startups are well-supported by a network of key incubators spread across major innovation hubs. Apollo Hospitals Educational and Research Foundation (AHERF) in Hyderabad incubates companies like Urvogelbio, Exomed Therapeutics, and Sephirah Innovations, offering advanced research facilities, clinical expertise and collaborative medical expertise. KIIT-Technology Business Incubator (KIITTBI) in Bhubaneswar supports Exsure Private Limited with extensive laboratory spaces and is developing a manufacturing hub to enhance scalability. In Visakhapatnam, Andhra Pradesh MedTech Zone Ltd (AMTZ) incubates Akrivis Healthcare Private Limited, providing comprehensive facilities and specialised testing labs. National Chemical Laboratory (NCL) in Pune supports ExoCan Healthcare Technologies with access to cutting-edge scientific resources for developing EV diagnostics and therapeutics. AIC-CCMB supports Wellness language developing cosmeuticals using EV platform. These incubators provide crucial infrastructure, specialised resources, and collaborative opportunities, fostering innovation and accelerating the commercialisation of EV technologies in India’s growing biotech sector.
S.No Incubator
Place Companies
1 Apollo Hospitals Educational and Research Foundation (AHERF) Hyderabad, Telengana Urvogelbio , Exomed therapeutics, Sepharys biosciences
2 KIIT-Technology Business Incubator (KIIT-TBI)
Bhubaneshwar, Orissa Exosure Pvt Ltd
3 Andhra Pradesh Medtech Zone Ltd (AMTZ) Visakhapatnam, AP Akrivis Healthcare Private Limited
4 National Chemical Laboratory, India (NCL) Pune, MH Exocan
5 AIC, CCMB, Hyderabad Hyderabad, Telangana Wellness Language
Table 4: Major Indian Incubators hosting Indian EV startups.
9. PESTEL Analysis of Extracellular Vesicle (EV) Research in India
Political Factors: The Indian government and funding agencies, such as DST, DBT, ICMR, CSIR, and private organisations like AHERF, actively support biotechnology, especially EV research. Initiatives like "Make in India" and the National Biotechnology Development Strategy promote innovation and commercialisation, creating a favourable environment for biotech growth. These initiatives are crucial for driving long-term sustainability and positioning India as a global leader in EV research. Agencies such as BIRAC are instrumental in funding startups and nurturing biotech entrepreneurship. International collaborations, like those with Indo-French CEFIPRA and the NIH (USA), further strengthen India's position in
scientific advancements. Regulatory oversight by CDSCO ensures that EV-based therapies and diagnostics meet safety and efficacy standards.
Economic Factors: The Indian exosome research market was valued at $3.1 million in 2023 and is projected to reach $10.4 million by 2030, growing at a CAGR of 19%. Startups such as Urvogelbio, Exsure, and Pandorum Technologies are leading innovation in this space, supported by incubators like AHERF and KIIT. India's EV diagnostic and therapeutic market is expected to grow significantly, with the diagnostics segment alone projected to reach INR 750 crore (USD 90 million) by 2030, at a CAGR of 9.5%. Globally, the EV technologies market is expected to surpass $343.5 million by 2031, potentially reaching $6,848 million by 2032. India’s expanding biotech sector and its focus on healthcare innovation position it well to capture a significant share of this growth. However, high costs may limit accessibility in India’s price-sensitive market, but the strong ecosystem of startups and incubators positions the country as a key player with promising export opportunities.
Social Factors: The increasing prevalence of diseases such as cancer (106.6 cases per 100,000 people in 2020), diabetes, and neurodegenerative disorders drives demand for innovative diagnostics and therapies. EV research addresses critical healthcare challenges in oncology, neurological conditions, and post-COVID complications. EV Startups are developing noninvasive diagnostics, therapeutics and cosmeceuticals to meet the need for accessible healthcare. Additionally, the growing acceptance of personalised medicine is boosting demand for advanced EV-based solutions. However, limited public awareness may hinder the adoption of these therapies. Targeted awareness campaigns or partnerships with healthcare providers could help mitigate this challenge and improve public acceptance.
Technological Factors: Technological advancements in EV isolation, characterisation, manufacturing, and diagnostics are progressing rapidly, with EV start-ups at the forefront of technological advancements in EV isolation, characterisation, manufacturing, and diagnostics, integrating AI and cloud computing to enhance research efficiency and diagnostic precision. Specific AI applications, such as machine learning models for biomarker identification, predictive analytics for disease progression, and automated image analysis for EV characterisation, are enhancing the diagnostic capabilities of EV technologies. Emerging technologies, such as 3D cell culture, EV-based drug delivery, and cosmeceuticals, are expanding the scope of applications. While research infrastructure investments fuel technological growth, certain regions still face infrastructure limitations, which could impact the equitable spread of these advancements.
Environmental Factors: EV-based diagnostics, such as liquid biopsies, present more sustainable healthcare solutions by minimising resource consumption. The shift towards human-derived EVs aligns with ethical and environmentally conscious practices. Pandorum Technologies is developing EV-based therapies for ophthalmology and cardiology, addressing environmental health issues such as lung regeneration for air pollution damage. Moreover, the targeted nature of EV therapies could reduce the environmental impact associated with traditional pharmaceutical manufacturing. These sustainable practices could also be leveraged for marketing to environmentally conscious consumers, highlighting the reduced ecological footprint of EV-based solutions.
Legal Factors: Regulatory oversight by CDSCO and ICMR is crucial for approving and commercialising EV-based diagnostics and therapies. Intellectual property protection is vital for startups developing proprietary technologies. India's regulatory guidelines for biologics
could affect product approval timelines. Startups can proactively engage with regulatory bodies to streamline approval processes and expedite commercialisation. Legal frameworks concerning the ethical use of biological materials and data privacy will shape research practices. DSIR certification offers tax incentives for R&D activities, while regulations such as the Drug Price Control Order (DPCO) 2013 could influence the pricing and accessibility of future EV-based products.
10. Value Chain Analysis of India's (EV) Ecosystem: India's extracellular vesicle (EV) research value chain spans six key stages, from foundational research to post-institutions, startups, corporations, healthcare providers, regulatory entities, and other stakeholders to advance EV-based diagnostics and therapeutics.
Figure 11: PESTEL analysis of EV Research and market
1. Basic Research
Academic institutions, including IITs, AIIMS, IISERs, AHERF, CSIR, DBT, and NIPER, focus on elucidating EV biology, optimising isolation and characterisation methodologies, and advancing translational applications. Strengthening interdisciplinary collaborations incorporating computational biology, artificial intelligence, and advanced imaging technologies can enhance the predictive power of EV research. Improved mechanisms for technology transfer from academic research to industry are also crucial to expedite practical applications.
2. Applied Research & Development (R&D)
Startups such as Pandorum Technologies, Urvogelbio, ExoSure, and Exygen are pivotal in translating research findings into practical applications, including diagnostics and regenerative medicine. Partnerships with institutions and incubators like AHERF, KIIT, and AIMTZ accelerate product development. Structured mentorship programs involving experienced scientists, business strategists, and targeted funding and innovation hubs can optimize R&D and support startup scalability.
3. Clinical Trials & Validation
Institutions conduct clinical validation of EV-based products like Apollo Research and Innovations and SGPGI. These trials ensure product safety and efficacy, complying with CDSCO regulatory standards and ICMR guidelines. Standardised patient recruitment frameworks, diverse demographic inclusion, and international collaborations can enhance the scalability and credibility of EV-based diagnostics and therapeutics.
4. Manufacturing & Production
Companies such as Pandorum Technologies scale up the production of EV-based therapeutics while maintaining quality control. Manufacturing infrastructure provided by AMTZ supports these efforts. Expanding modular manufacturing systems that leverage automation and advanced analytics can improve production efficiency. Establishing GMP-compliant facilities is essential for meeting international standards and facilitating global market entry.
5. Commercialization & Market Entry
Commercialization of EV-based products is facilitated through strategic partnerships with hospital networks, pharmaceutical companies, and diagnostic labs. Effective market education, strategic consortia, and clear pricing and reimbursement strategies are essential for driving adoption and clinical integration. Strengthening these efforts ensures the clinical benefits of EV-based technologies are effectively communicated to stakeholders, enhancing market uptake.
6. Post-Commercialization Support
Continuous monitoring and feedback are essential post-commercialization to ensure product efficacy and safety. Systematic post-market surveillance, integration with digital health platforms, and AI-driven data analysis provide valuable real-world evidence for iterative improvements to EV-based products. This stage is critical for sustaining innovation and addressing emerging healthcare needs.
The value chain of EV research in India represents a well-integrated ecosystem that connects academic research, technological innovation, clinical validation, and commercial execution. Each stage is critical to ensuring that cutting-edge EV-based
Figure 12: Value Chain Analysis of India's EV Ecosystem
diagnostics and therapeutics are effectively brought to market, where they can address pressing healthcare needs. Indian institutions, startups, healthcare providers, and regulatory bodies all play essential roles in this process, making the EV research landscape in India a collaborative and dynamic field poised for significant advancements in personalised medicine and regenerative therapies.
11. Emerging Technology Trends in Extracellular Vesicle Research and Applications
Introduction
The extracellular vesicle (EV) research field is evolving rapidly, driven by advancements in isolation techniques, characterisation methods, and innovative applications in diagnostics, therapeutics, vaccines, and drug delivery systems. This section explores the most prominent technological trends shaping the future of EV research, categorised into five key areas: Isolation and Purification, Characterization and Analytical Technologies, Translation into Applications, Scaling and Production, and Manufacturing and Quality Control of EV therapeutics and vaccines.
Isolation and Purification
Efficient isolation and purification of EVs are foundational for all downstream applications and analyses. Advances in major technologies are transforming this critical step. Advanced microfluidic platforms enable rapid and efficient isolation of EVs from biological samples, reducing processing times and improving yield. New polymer-based enrichment techniques enhance EV purity and recovery, while refined immunomagnetic bead technology improves the capture of specific EV subpopulations, enhancing downstream analyses. Ongoing size exclusion chromatography (SEC) improvements deliver better EV separation while maintaining functional integrity.
Characterisation and Analytical Technologies
Comprehensive characterisation of EVs is essential to understand their properties and roles in various applications. Nanoparticle tracking analysis (NTA) is widely used to determine the size and concentration of EVs via real-time particle tracking. High-resolution electron microscopy provides detailed structural analysis, crucial for understanding EV morphology and composition. Improved flow cytometry techniques offer high-throughput characterisation of EV surface markers. Emerging systems like multi-color-emissive magneto-luminescent nanoarchitectures enable the simultaneous detection of multiple EV proteins, enhancing diagnostic capabilities. Surface-enhanced Raman spectroscopy (SERS) is utilised for EV analysis, providing enhanced sensitivity and specificity in detecting EV contents. Platforms that enable the screening of EVs for biomarkers are accelerating discoveries in diagnostics and therapeutics. Advanced proteomics and genomics methods provide a comprehensive analysis of EV cargo, offering valuable insights into disease mechanisms. The development of standardised EV analysis protocols and reference materials ensures consistency and reproducibility across laboratories.
Translation into Applications
The translation of EV biology into real-world applications is advancing in diagnostics and therapeutics. EV-based biomarkers are revolutionising liquid biopsy platforms, particularly for early detection and monitoring of cancer and neurodegenerative diseases. Integrating artificial intelligence (AI) with EV-based diagnostics allows for analysing large datasets and developing predictive models for disease diagnosis. EV-based diagnostic tools make diagnostics more accessible, enabling efficient, real-time testing. EV platforms are being developed for early detection of neurodegenerative diseases such as Alzheimer’s, utilising specific biomarkers. Research into outer membrane vesicle (OMV)--based vaccines leverages EV-like properties to stimulate immune responses against infectious diseases. Tumor-derived EVs are being developed as cancer vaccines to train the immune system to recognise and target cancer cells. EV-based mRNA vaccine systems are emerging as an alternative to traditional lipid nanoparticles, potentially offering more efficient vaccine responses and fewer side effects
Therapeutics and Drug Delivery
In therapeutics and drug delivery, cells are genetically engineered to enhance EV yield and modify their content for precise applications in therapy and diagnostics. Specific surface modification techniques improve the targeted delivery of EVs to specific tissues or cells. Techniques like electroporation, sonication, and incubation enable effective loading of therapeutic molecules (e.g., RNA, proteins) into EVs. Combining EVs with liposomes enhances stability and functionality for drug delivery. Engineered EVs can precisely deliver small molecules, proteins, and nucleic acids, minimising side effects. EV-based cell-free therapies show promise in tissue regeneration, especially in cardiac repair and wound healing. In cancer immunotherapy, EVs carry immune-modulating proteins to activate the immune
system against tumours. EVs are also being developed for treating neurological disorders, including Parkinson's disease and stroke, due to their ability to cross the blood-brain barrier. EV-mediated delivery of siRNA and miRNA holds potential for targeted gene silencing or modulation in gene therapy. EVs can cross biological barriers, such as the blood-brain barrier, making them suitable for treating brain diseases. Combining EVs with nanoparticles enhances drug delivery precision to specific tissues or cells.
Scaling and Production
Scalable and efficient production methods are crucial to meet the rising demand for EV-based products. Utilising 3D cell culture systems significantly increases EV yield, making production more efficient for therapeutic applications. Bioreactor-based methods offer scalable production, which is critical for clinical-grade manufacturing. Employing stem cells and immortalised lines ensures consistent and scalable EV production. Synthetic EV-mimetic nanovesicles provide customisable alternatives to natural EVs for scalable drug delivery. Manufacturing, Quality Control, and Regulatory Frameworks
Ensuring quality and regulatory compliance of EV-based products is essential for their clinical use. Implementing Good Manufacturing Practices (GMP) standards ensures that EVs are produced under stringent guidelines for clinical applications. Rigorous quality control protocols help EV-based diagnostics and therapeutics meet regulatory standards. Robust regulatory frameworks are needed to facilitate the safe and effective use of EV-based products in clinical practice. Developing scalable and reproducible production methods is vital to meet the growing demand for EV products.
Conclusion
Emerging technologies in EV research are transforming medicine and biotechnology. Significant advances in isolation techniques, characterisation methods, and the translation of EV research into diagnostics, therapeutics, vaccines, and drug delivery systems are driven by interdisciplinary collaboration in nanotechnology, biotechnology, and data science. These
Figure 13: Technological trends in EVs research
innovations are rapidly expanding the potential applications of EVs, particularly in personalised medicine, cancer treatment, and regenerative therapies, paving the way for more effective and targeted healthcare solutions.
12. Evolving Regulatory Landscape of Extracellular Vesicle (EV) Research in India
India's regulatory framework for extracellular vesicle (EV)-based products is rapidly evolving to ensure these innovative therapies and diag safety, efficacy, and quality. The framework encompasses several key areas: regulatory oversight, standards development, lab-based testing requirements, clinical trial protocols, ethical considerations, international alignment, and future developments.
Regulatory Oversight
The Central Drugs Standard Control Organisation (CDSCO) is India's primary regulatory authority overseeing EV-based products. These products are expected to be classified as "new
drugs" under the New Drugs and Clinical Trials Rules, 2019, which mandates that EV-based products undergo rigorous clinical trials and receive CDSCO approval before marketing. This classification ensures that EV-based therapies and diagnostics meet stringent safety and efficacy standards before reaching the public.
Standards Development
In parallel, the Bureau of Indian Standards (BIS), specifically through its Medical Biotechnology and Nanotechnology sectional committee, Working Group 2(MHD 20), is actively developing guidelines for EV standards. These standards focus on quality control, safety, and alignment with international benchmarks, ensuring that EV-based therapies and diagnostics adhere to high regulatory and scientific standards. The ongoing efforts by BIS aim to establish comprehensive guidelines that govern the production, characterisation, and use of EV-based products, facilitating their integration into the healthcare system.
Lab-Based Testing Requirements
Figure 14: Regulatory framework for EVs based therapy
Although specific guidelines for EV-based products are still being formulated, several labbased testing requirements are anticipated to be integral to the regulatory process for both therapies and diagnostics:
1. Characterisation: This involves size distribution analysis using techniques like nanoparticle tracking analysis and tunable resistive pulse sensing, morphological assessment through high-resolution imaging such as electron microscopy, and protein marker analysis to confirm EV characteristics and purity.
2. Purity and Safety: Ensuring the purity and safety of EV preparations includes contaminant analysis to eliminate non-EV structures, sterility testing to verify the absence of microbial contamination, and endotoxin testing to assess bacterial endotoxin levels.
3. Functional Assays: Functional assays are crucial for evaluating the biological activity of EV preparations through in vitro potency assays and determining shelf life and optimal storage conditions via stability studies. Additional validation studies may be required for diagnostics to ensure the reliability and accuracy of EV-based diagnostic tests.
Clinical Trial Requirements
It is assumed that Clinical trials for EV-based products in India are expected to follow a pathway similar to other biological therapies:
1. Preclinical Studies: These studies establish EV-based products’ safety and potential efficacy through laboratory and animal research.
2. Phase I Trials: Focus on assessing the safety and appropriate dosing in a small group of healthy volunteers or patients.
3. Phase II Trials: Evaluate preliminary efficacy and assess safety in a larger patient population.
4. Phase III Trials: Confirm efficacy and monitor adverse reactions in large-scale patient populations to ensure comprehensive safety and effectiveness.
Clinical validation studies will be necessary for EV-based diagnostics to demonstrate the diagnostic accuracy, sensitivity, and specificity of the tests in relevant clinical settings.
Ethical Considerations
The Indian Council of Medical Research (ICMR) is expected to provide ethical guidelines for EV research and clinical applications. These guidelines will parallel those established for stem cell research, ensuring that ethical standards are maintained in EV studies and therapies and in developing and implementing EV-based diagnostics. This includes considerations related to informed consent, patient safety, data privacy, and the responsible conduct of research.
International Alignment
India's regulatory approach is being shaped by established frameworks from leading global regulatory bodies to ensure international compatibility and recognition:
• United States (FDA): EV-based products are regulated as biological products in the USA, requiring an Investigational New Drug (IND) application to initiate clinical trials.
• Europe (EMA): The European Medicines Agency (EMA) classifies EV-based products as Advanced Therapy Medicinal Products (ATMPs), subjecting them to
similarly stringent approval and testing requirements as other biological therapies and diagnostics.
Drawing inspiration from these established frameworks, India aims to harmonise its regulations with international standards, facilitating global collaboration and acceptance of EV-based therapies and diagnostics.
India is diligently developing its regulatory framework for EV-based products, encompassing innovative therapies and diagnostics. This framework incorporates stringent lab-based testing requirements, robust clinical trial protocols, and comprehensive ethical guidelines. By aligning with international best practices, India aims to ensure that EV-based therapies and diagnostics are safe, effective, and high-quality. This proactive approach fosters innovation and advances healthcare outcomes, positioning India as a key player in the global landscape of extracellular vesicle-based technologies.
13. Market Definition and EV Product Segmentation
India's Extracellular Vesicle (EV) research market is an emerging biotechnology and healthcare sector focusing on diagnostic, therapeutic, and drug delivery applications. Driven by technological advancements, increasing disease prevalence, and a shift towards precision medicine, the market presents significant growth potential despite facing several challenges.
Product Segmentation in the Indian EV market highlights a limited availability of specialised instruments for EV isolation and characterisation. Current tools, such as ultracentrifuges and nanoparticle tracking analysers, are often repurposed for general biological applications. There is a pressing need for EV-specific microfluidic devices and advanced imaging technologies to enhance research precision and throughput. Companies like Exsure Private Limited provide basic isolation reagents, while global firms offer more advanced solutions. The market would benefit from standardised quality control materials and diverse biofluid sources to improve reproducibility and expand biomarker discovery.
Indication Segmentation reveals that Indian companies leverage EVs for early cancer detection, neurodegenerative disease diagnostics, diabetes management, and regenerative medicine. ExoCan and Sephirah Innovations focus on tumorderived EVs for cancer diagnostics, while Urvogelbio targets neurodegenerative diseases like Alzheimer’s and Parkinson’s. Exomed Therapeutics is exploring EVbased insulin delivery systems for diabetes, and companies like Pandorum and Stempeutics utilise stem cell-derived EVs for tissue regeneration and wound healing.
Application Segmentation demonstrates that EVs are being developed into diagnostic platforms for detecting disease-specific biomarkers and as vehicles for targeted drug delivery,
Figure 15: Dynamics of India's EVs Research market
particularly in oncology and regenerative medicine. Innovations include EV-mediated delivery of siRNA, miRNA, proteins, and potentially gene-editing tools like CRISPR-Cas9, aimed at overcoming biological barriers such as the blood-brain barrier. Opportunities lie in advancing EV-specific technologies, scaling up manufacturing capabilities, and establishing robust regulatory standards. Investment in microfluidics, affinity chromatography, and other innovative isolation techniques can enhance EV research and application. Collaborations with regulatory bodies like CDSCO and ICMR are crucial to developing comprehensive guidelines that support the safe and effective use of EV-based diagnostics and therapeutics. Challenges facing the Indian EV market include limited market maturity, technological gaps in EV isolation and purification, scalability issues, and the absence of clear regulatory frameworks. The lack of GMP-compliant production facilities hinders the clinical translation of EV-based products, while undefined regulatory guidelines pose safety and efficacy concerns.
The EV research market in India holds substantial promise, with diverse applications in cancer diagnostics, regenerative medicine, and drug delivery, positioning it as a key player in the global precision medicine landscape. Addressing technological, manufacturing, and regulatory challenges will be essential to fully realise the potential of the Indian EV market, enabling significant contributions to advanced healthcare solutions and non-invasive diagnostics.
14. Market Landscape and Growth Potential of Extracellular Vesicle (EV) Research in India
Market Overview
India's extracellular vesicle (EV) research field is nascent but exhibits significant growth potential. While specific market data for India remains limited, the global EV technologies market is anticipated to expand robustly, with projections varying from US$ 211.6 million by 2034 at a CAGR of 9.10% to USD 6,848 million by 2032 at an impressive CAGR of 81.2%. Specifically, the global EV technologies market is expected to reach over US$ 343.5 million by 2031, growing at a CAGR of 24.8% from 2023 to 2031.
Key Market Segments
• Diagnostics: Currently the dominant application, accounting for approximately 68% of the market share in 2024. EVs are leveraged as biomarkers for early disease detection, particularly in oncology.
• Therapeutics: Expected to experience rapid growth with potential product launches anticipated from 2029 onwards. EV-based therapies are being explored for targeted drug delivery and regenerative medicine.
Indian Market Specifics
The Indian EV diagnostic and therapeutic market is projected to grow at a CAGR of 9.5% over the next decade. India's diverse genetic pool presents unique EV research and development opportunities, potentially leading to breakthroughs tailored to the local population.
Drivers
1. Increased Healthcare Demand: The rising prevalence of chronic diseases, especially cancer, in India is driving the need for advanced diagnostic and therapeutic approaches.
2. Government Initiatives and Funding: Enhanced government support through initiatives like the National Biotechnology Development Strategy is fostering research and development in EV technologies. Increased government funding for biotech research further propels market growth.
3. Rise of Personalized Medicine: The growing demand for targeted and personalised therapies is fueling interest in EV-based approaches, which offer precision in treatment modalities.
4. Technological Advancements: Progress in EV isolation and characterization techniques enhances the feasibility and efficiency of EV-based applications.
Restraints
1. Technical Challenges: Current methods for isolating and purifying EVs face issues related to consistency, reproducibility, and yield, hindering widespread adoption.
2. Regulatory Hurdles: The absence of specific regulatory guidelines for EV-based therapies in India poses significant challenges for product development and clinical translation.
3. Limited Research Infrastructure: India operates on a micro-scale for EV research activities, indicating a need for more robust infrastructure, specialized equipment, and resources to support large-scale research and commercialization efforts.
4. High Costs and Affordability Concerns: The high costs associated with EV-based technologies may hinder their widespread adoption and accessibility.
Opportunities
1. Cancer Diagnostics and Therapeutics: EVs show considerable promise as biomarkers for early cancer detection and as vehicles for targeted drug delivery, offering more efficient and less invasive diagnostic and therapeutic options.
2. Regenerative Medicine: EVs derived from mesenchymal stem cells (MSCs) have potential applications in tissue regeneration and wound healing, opening avenues for innovative treatment modalities.
3. Drug Delivery Systems: The development of EV-based drug delivery systems presents opportunities for creating more efficient and targeted therapies, enhancing treatment efficacy and reducing side effects.
Figure 15: Dynamics of Indias's EVs research market
4. Collaborations with Global Entities: Partnerships facilitated by the IEVS with international societies can lead to significant knowledge exchange, joint research initiatives, and accelerated advancements in the field.
Challenges
1. Lack of Standardization: The absence of standardised protocols for EV isolation, characterisation, and quality control hampers reproducibility and clinical translation, making it difficult to ensure consistent results across studies and applications.
2. Limited Awareness: There is a need for increased education and awareness among healthcare professionals and the public regarding the benefits and applications of EVbased technologies.
3. Clinical Trial Bottlenecks: The complex nature of EV-based therapeutics presents challenges in designing and conducting clinical trials, including determining optimal dosing and administration routes and ensuring patient safety.
4. Analytical Limitations: The size and complexity of EVs make detailed characterisation challenging, particularly from a production and quality control perspective, limiting the ability to understand and optimise EV-based products fully.
5. Scaling Up Production: Developing cost-effective, large-scale production methods for clinical-grade EVs remains a significant challenge, essential for meeting the growing demand and ensuring the feasibility of commercial applications.
Though still developing, India's EV research landscape holds substantial promise fueled by increasing healthcare demands, government support, and technological advancements. Addressing technical, regulatory, and infrastructure challenges is crucial for unlocking the full potential of EV-based diagnostics and therapeutics. Establishing research societies like the IEVS and fostering collaborations with international entities will be pivotal in advancing EV research and its applications within the Indian context. With strategic investments and focused efforts, India can be a significant player in the global EV technologies market.
15. Government Funding and Investment Landscape in the EV domain
Key Funding Sources: The funding landscape for EV research is a well-balanced mix of public and private sector support, with significant contributions from major government agencies and private institutions. The Department of Biotechnology (DBT) leads the way, frequently funding EV research projects to advance biotechnology and life sciences. Similarly, the Indian Council of Medical Research (ICMR) plays a crucial role by financing research exploring EVs' medical applications, particularly in diagnostics, therapeutics, and regenerative medicine. Department of Science and Technology (DST) and its autonomous body, DSTSERB (Science and Engineering Research Board), contribute significantly, supporting basic and applied EV science. Apollo Hospitals Educational and Research Foundation (AHERF) is a key player in the private sector. Its strong involvement shows the healthcare sector’s growing interest in EVs for clinical applications such as drug delivery, diagnostics, and therapeutic innovations. AHERF’s focus on applied research highlights the potential for EVs to make a real-world impact, especially in healthcare and personalised medicine. Several smaller funders add diversity to the ecosystem. ICAR (Indian Council of Agricultural Research) supports interdisciplinary EV research, indicating that EVs have potential uses beyond medicine, including agriculture and food sciences. Other contributors, like SERB/Shiv
Nadar Institution of Eminence and DBT/Ministry of Science and Technology, fund specialised and collaborative projects, further enriching the research landscape.
Overall, this comprehensive funding ecosystem ensures EV research is supported from multiple angles. Government agencies back fundamental and applied research, while private institutions like AHERF drive efforts toward practical, clinical applications. The combination of major and minor funders guarantees a wide range of research topics, from basic science to cross-disciplinary innovations, positioning EV research for continued growth and real-world impact across healthcare, agriculture, and biotechnology.
Private Sector and Collaborations:
As depicted in the chart, the funding scenario for EV research derived from publications for the past decade is predominantly supported by government funding, which makes up the largest share at 46.5%. This highlights the crucial role that public institutions and national research agencies play in advancing the field. Institutional grants account for 17.4% of the funding, indicating strong support from universities and research centers that drive academic and exploratory research. Private sector funding contributes 11.6%, reflecting the growing interest of businesses, especially in the healthcare and biotechnology sectors, in the commercial applications of EVs. International collaborations, representing 7.0% of the funding, point to the global nature of EV research, with partnerships across borders
Figure 17: Word burst of Government Funding and Investment Landscape in the EV domain
Figure 18: Funding contributions for EV research in India
fostering innovation. Though smaller at 5.8%, public-private partnerships show efforts to combine resources and expertise from both sectors to accelerate research and development. Lastly, the "Other" category, at 11.6%, likely includes various smaller funding sources, such as non-governmental organisations and charitable foundations, contributing to the diversity of financial support for EV research. This comprehensive funding landscape ensures that EV research is well-supported by a mix of public, private, and international contributors.
16 Limitations of the study: Given that the data for this analysis comes from publications reported in PubMed, Scopus, internet sources, and secondary research, it is important to acknowledge several limitations specific to this dataset and the Indian context of EV research. Publication bias may cause an overrepresentation of successful research outcomes, as studies with positive results are more likely to be published and indexed, potentially skewing the perception of progress in Indian EV research. Significant delays between research completion and publication indexing mean the dataset may not fully reflect recent advancements or the most cutting-edge developments, especially those not yet published. Incomplete funding information is another concern, as many publications lack comprehensive details about funding sources, which could lead to underestimating private sector involvement or contributions from smaller agencies. The limited coverage of non-academic research such as studies by private companies or institutions that do not regularly publish in academic journals may result in underrepresentation in this dataset. Variations in how research methodologies and results are reported can lead to a lack of standardisation, making it challenging to compare studies directly or draw definitive conclusions about EV research in India. The reliability of information from internet sources may vary, introducing inaccuracies or biases into the analysis. Secondary research may not capture the full nuances of primary data and could be influenced by previous analysts' interpretations. Assessing the quality and impact of research-based solely on publication data is difficult, presenting challenges in quantifying research quality. Inconsistencies in how funding sources are reported across different publications can make it difficult to assess the relative contributions of various funding agencies accurately. These limitations should be considered when interpreting the findings of this analysis. Future studies could benefit from incorporating a wider range of data sources including direct surveys of Indian research institutions, clinical trial registries, and patent databases to provide a more comprehensive picture of the EV research landscape in India.
17. Strategic Recommendations for Developing EV-Based research and outcomes
Infrastructure and Policy Support
1. Establish National EV Research Centres
o Set up specialised centres of excellence for EV research across India, equipped with advanced infrastructure for EV isolation, characterisation, and analysis. These centres can be funded through a mix of government grants, industry partnerships, and international collaborations to ensure sustainability over the long term. These centres will serve as hubs for collaborative research, integrating fields like nanotechnology, medical devices, vaccines, and regenerative medicine to foster innovation and standardise methodologies.
2. Develop Standardized Protocols
o Collaborate with global EV labs and societies, such as the International Society for Extracellular Vesicles (ISEV), the American Society for Exosomes and Microvesicles (ASEMV) and 33 global EV societies, to develop and implement standardised protocols for EV isolation, characterisation, and analysis.
Standardisation will enhance reproducibility, enable robust multi-centre studies, and ensure data comparability.
3. Enhance Regulatory Framework
o Develop clear regulatory guidelines for EV-based diagnostics and therapeutics. Implement a phased approach, beginning with initial consultations with stakeholders within the first year, drafting guidelines in the second year, and finalising and rolling out these guidelines by the end of the third year. Strengthen institutions like ICMR and DCGI to support EV development and regulation.
4. Increase Targeted Funding
o Allocate dedicated funding for EV research through national funding agencies like DBT, DST and others. Clarify if existing funding streams can be reallocated or if new funding mechanisms need to be established. Create targeted grant programs focused on translational EV research to bridge the gap between basic discoveries and clinical application.
Market Expansion Strategies
1. Foster International Collaborations
o Encourage partnerships with leading global institutions in EV research, such as the International Society for Extracellular Vesicles (ISEV) and other global societies. Establish joint research initiatives and exchange programs to facilitate knowledge transfer and capacity building and enhance the international visibility of Indian EV research.
2. Develop EV Biobanks
o Create a network of EV biobanks across India to collect, store, and distribute high-quality EV samples. These biobanks can be funded through government grants, public-private partnerships, and user fees to ensure long-term sustainability. These biobanks will support large-scale studies and attract international collaborations by providing standardised resources.
3. Focus on India-Specific Applications
o Prioritize EV research areas that address health challenges unique to India, such as tropical diseases, cancers, neurodegenerative diseases, endocrinology, and region-specific genetic disorders.
4. Leverage India's Diverse Genetic Pool
o Use India's genetic diversity to develop personalized therapies and diagnostic tools. This strategic advantage can help position India as a leader in precision medicine solutions in the global EV market.
o
Collaboration Across Ecosystems
1. Implement Industry-Academia Partnership Programs
o Develop initiatives to incentivize collaborations between academia and industry. This can include providing tax breaks, grants, shared intellectual property (IP) rights, or joint funding mechanisms to encourage meaningful partnerships. This can include joint funding mechanisms, shared facilities, or industry-sponsored doctoral programs to translate academic research into commercial applications.
2. Support EV-Focused Startups
o Establish incubation centres to support EV-focused startups, leveraging existing centres such as the Biotechnology Industry Research Assistance Council
(BIRAC) and Startup India, and expanding upon their capabilities, offering mentorship, seed funding, and access to research facilities. Implement policies that facilitate technology transfer from academia to startups, reducing commercialisation barriers.
3. Organize Regular Symposia and Workshops
o Host annual conferences and symposia focused on EV research to facilitate networking and collaboration. Conduct regular workshops to train researchers and clinicians in the latest methodologies and advances in EV science.
4. Develop Interdisciplinary Research Programs
o Encourage interdisciplinary research teams, integrating experts from fields like nanotechnology, artificial intelligence, and materials science, to drive innovation in EV research. Interdisciplinary efforts are crucial for advancing the translational potential of EV technologies
By implementing these strategic recommendations, India can enhance its EV research ecosystem, strengthen its global position, and expedite the translation of EV research into clinical and commercial applications. These efforts will advance scientific knowledge, address critical healthcare challenges, and create significant economic opportunities in the biotechnology sector.
18. Conclusions:
In conclusion, scaling EV technologies in India requires a concerted effort that builds upon the strategic recommendations outlined. Establishing national EV research centres, developing standardised protocols, enhancing the regulatory framework, and securing targeted funding are foundational steps for building a robust EV ecosystem. Expanding domestic and international collaborations will bolster research capabilities and foster innovation. A key focus on Indiaspecific healthcare challenges and leveraging the country’s diverse genetic pool will ensure that EV-based solutions are relevant and impactful.
Figure 19: Roadmap for Scaling EV Technologies in India
The success of EV technology scaling also hinges on skill development and clinical translation. By building a skilled workforce and fostering strong academia-healthcare partnerships, India can expedite the transition of EV research from laboratory settings to clinical applications. Supporting EV-focused startups and leveraging existing infrastructure will accelerate scientific growth, leading to commercialisation. A unified effort involving regulatory bodies, research institutions, industry, and international partners will help India become a global leader in EV research and applications. This comprehensive approach will advance scientific knowledge, address critical healthcare needs, and create economic opportunities, ultimately positioning India at the forefront of EV research and translation.
19. Appendices
Abbreviation Description
AF4 Asymmetrical Flow Field-Flow Fractionation
AHERF Apollo Hospitals Educational and Research Foundation
AI Artificial Intelligence
AI-ML Artificial Intelligence and Machine Learning
AIIMS All India Institute of Medical Sciences
AMTZ Andhra Pradesh MedTech Zone
ATMP Advanced Therapy Medicinal Product
BIRAC Biotechnology Industry Research Assistance Council
BIS Bureau of Indian Standards
CDSCO Central Drugs Standard Control Organisation
CMDO Contract Manufacturing and Development Organizations
CSIR Council of Scientific & Industrial Research
DBT Department of Biotechnology
DC Differential Centrifugation
DG UC Density Gradient Ultracentrifugation
DLS Dynamic Light Scattering
DST Department of Science and Technology
EMA European Medicines Agency
EV Extracellular Vesicles
EV-TRACK Extracellular Vesicle Transparent Reporting and Centralized Knowledge base
GMP Good Manufacturing Practices
IIT Indian Institute of Technology
ICMR Indian Council of Medical Research
IND Investigational New Drug
JNU Jawaharlal Nehru University
KIIT-TBI KIIT-Technology Business Incubator
MHD 20
WG2
Medical biotechnology and medical nanotechnology sectional committee – Bureau of Indian Standards – Working group 2
MISEV2023 Minimal Information for Studies of Extracellular Vesicles 2023
MSC Mesenchymal Stem Cell
NCL National Chemical Laboratory
NIPER National Institute of Pharmaceutical Education and Research
NTA Nanoparticle Tracking Analysis
OMV Outer Membrane Vesicle
PCR Polymerase Chain Reaction
PI Principal Investigator
R&D Research & Development
SEC Size Exclusion Chromatography
SERS Surface-Enhanced Raman Spectroscopy
SGPGI Sanjay Gandhi Postgraduate Institute of Medical Sciences
SPR Surface Plasmon Resonance
TEM Transmission Electron Microscopy
TRPS Tunable Resistive Pulse Sensing
UF Ultrafiltration
Glossary of Technical and Important Terms
1) Asymmetrical Flow Field-Flow Fractionation (AF4): A technique used for separating particles based on their size and molecular weight, often used in the analysis of extracellular vesicles.
2) Apollo Hospitals Educational and Research Foundation (AHERF): An organization involved in healthcare research and education in India.
3) Artificial Intelligence (AI): The simulation of human intelligence by machines, especially computer systems, used in data analysis and diagnostics.
4) Artificial Intelligence and Machine Learning (AI-ML): Technologies involving AI with a focus on improving systems through learning from data, widely applied in healthcare for predictive modeling.
5) All India Institute of Medical Sciences (AIIMS): A premier medical institute in India focused on higher education and research.
6) Andhra Pradesh MedTech Zone (AMTZ): A medical technology park aimed at promoting the production and research of medical devices in India.
7) Advanced Therapy Medicinal Product (ATMP): A medicinal product based on cells, genes, or tissues used for regenerative purposes.
8) Biotechnology Industry Research Assistance Council (BIRAC): A public sector enterprise that supports the biotechnology industry in India.
9) Bureau of Indian Standards (BIS): The national standards body of India, responsible for developing standards for various sectors, including healthcare.
10) Central Drugs Standard Control Organisation (CDSCO): The national regulatory authority for drugs and medical devices in India.
11) Contract Manufacturing and Development Organizations (CMDO): Companies providing services to pharmaceutical and biotech firms for product development and manufacturing.
12) Contract Manufacturing Organization (CMO): An organization that serves other companies in the pharmaceutical industry to provide comprehensive services from drug development through drug manufacturing.
13) Chemistry, Quality, and Analysis (CQA): The quality characteristics for a pharmaceutical product.
14) Contract Research Organization (CRO): A company that provides support to the pharmaceutical, biotechnology, and medical device industries in the form of research services outsourced on a contract basis.
15) Council of Scientific & Industrial Research (CSIR): An autonomous body that conducts scientific and industrial research in India.
16) Department of Biotechnology (DBT): A government department in India responsible for biotechnology policy and funding.
17) Differential Centrifugation (DC): A method used to separate cellular components by spinning them at various speeds.
18) Density Gradient Ultracentrifugation (DG UC): A technique for purifying extracellular vesicles based on their density.
19) Dynamic Light Scattering (DLS): A technique used to determine the size distribution of small particles, including extracellular vesicles.
20) Design of Experiment (DoE): A systematic method to determine the relationship between factors affecting a process and the output of that process.
21) Department of Science and Technology (DST): A government department in India promoting science and technology activities.
22) European Medicines Agency (EMA): An agency of the European Union responsible for the evaluation and supervision of medicinal products.
23) Extracellular Vesicles (EV): Small membrane-bound particles released by cells, playing a role in intercellular communication and diagnostics.
24) Extracellular Vesicle - Transparent Reporting and Centralized Knowledgebase (EV-TRACK): A platform for reporting and sharing information about extracellular vesicle research.
25) Field Development Services (FDS): Services that involve the development and validation of technologies in field conditions.
26) Food and Drug Administration (FDA): A federal agency of the United States Department of Health and Human Services responsible for protecting public health.
27) Full-Time Equivalent (FTE): A unit that indicates the workload of an employed person.
28) Good Distribution Practice (GDP): Quality assurance system that includes requirements for purchasing, receiving, storage, and export of drugs intended for human consumption.
29) Good Laboratory Practice (GLP): A quality system concerned with the organizational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived, and reported.
30) Good Manufacturing Practices (GMP): Guidelines that ensure products are consistently produced and controlled according to quality standards.
31) Good Practice Quality Guidelines and Regulations (GxP): General term for Good Practice regulations and guidelines.
32) High-Performance Liquid Chromatography (HPLC): An analytical technique to separate, identify, and quantify components in a mixture.
33) High Throughput Screening (HTS): A method for scientific experimentation especially used in drug discovery and relevant to the fields of biology and chemistry.
34) International Council for Harmonisation (ICH): An initiative that brings together regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of drug registration.
35) Indian Institute of Technology (IIT): A group of autonomous public technical and research universities in India.
36) Indian Council of Medical Research (ICMR): The apex body for the formulation, coordination, and promotion of biomedical research in India.
37) Investigational New Drug (IND): A drug that has been approved by a regulatory authority for clinical trials.
38) Intellectual Property (IP): A category of property that includes intangible creations of the human intellect.
39) International Organization for Standardization (ISO): An international standardsetting body composed of representatives from various national standards organizations.
40) Jawaharlal Nehru University (JNU): A public university in India known for its emphasis on research.
41) KIIT-Technology Business Incubator (KIIT-TBI): An incubator that supports startups and innovations, especially in the technology and healthcare sectors.
42) Laboratory Information Management System (LIMS): A software-based solution with features that support a modern laboratory's operations.
43) Limit of Detection (LOD): The lowest quantity of a substance that can be distinguished from the absence of that substance.
44) Limit of Quantification (LOQ): The lowest amount of analyte in a sample that can be quantitatively determined with suitable precision and accuracy.
45) Medical Health Department 20 (MHD 20): A department of the Bureau of Indian Standards (BIS) focusing on medical health regulations.
46) Minimal Information for Studies of Extracellular Vesicles 2023 (MISEV2023): Guidelines for reporting studies on extracellular vesicles.
47) Mesenchymal Stem Cell (MSC): A type of stem cell that can differentiate into a variety of cell types and is used in regenerative medicine.
48) National Chemical Laboratory (NCL): A research, development, and consulting organization with a focus on chemistry and chemical engineering.
49) New Drug Application (NDA): An application to the FDA for approval to market a new drug.
50) National Institute of Pharmaceutical Education and Research (NIPER): An institute in India offering higher education and research in pharmaceutical sciences.
51) Nanoparticle Tracking Analysis (NTA): A technique for visualizing and analyzing particles, such as extracellular vesicles, in a liquid suspension.
52) Outer Membrane Vesicle (OMV): A type of vesicle derived from the outer membrane of bacteria, used in vaccine development.
53) Patent Cooperation Treaty (PCT): An international treaty that allows for a single patent application to be filed for protection in multiple countries.
54) Polymerase Chain Reaction (PCR): A laboratory technique used to amplify DNA sequences.
55) Principal Investigator (PI): The lead researcher for a particular research project.
56) Quality Assurance (QA): A way of preventing mistakes or defects in manufactured products and avoiding problems when delivering solutions or services to customers.
57) Quality Control (QC): A process by which entities review the quality of all factors involved in production.
58) Quality Management System (QMS): A formalized system that documents processes, procedures, and responsibilities for achieving quality policies and objectives.
59) Qualified Person for Pharmacovigilance (QPPV): A role responsible for ensuring the company's compliance with pharmacovigilance regulations.
60) Regulatory Affairs (RA): A profession within regulated industries that ensures compliance with regulations and standards.
61) Research & Development (R&D): The work a business or organization conducts toward the innovation, introduction, and improvement of products and processes.
62) Return on Investment (ROI): A measure used to evaluate the efficiency of an investment.
63) Real-World Evidence (RWE): Clinical evidence regarding the usage and potential benefits or risks of a medical product derived from real-world data.
64) Serious Adverse Event (SAE): An undesirable experience associated with the use of a medical product in a patient.
65) Size Exclusion Chromatography (SEC): A method used to separate molecules based on their size.
66) Surface-Enhanced Raman Spectroscopy (SERS): A technique that enhances Raman scattering, used for molecular detection and analysis.
67) Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI): A medical institute in India offering higher education and research.
68) Standard Operating Procedure (SOP): A set of step-by-step instructions compiled by an organization to help workers carry out complex routine operations.
69) Surface Plasmon Resonance (SPR): A technique used to measure molecular interactions in real-time.
70) Strengths, Weaknesses, Opportunities, and Threats (SWOT): A framework for identifying and analyzing the internal and external factors that can impact an organization's viability.
71) Transmission Electron Microscopy (TEM): A microscopy technique in which a beam of electrons is transmitted through a specimen to form an image.
72) Technology Readiness Level (TRL): A system used to assess the maturity level of a particular technology.
73) Tunable Resistive Pulse Sensing (TRPS): A technique for measuring the size and concentration of particles, including extracellular vesicles.
74) Ultrafiltration (UF): A membrane filtration process used to separate particles from a liquid.
75) United States Pharmacopeia (USP): A scientific, non-profit organization that sets standards for the identity, strength, quality, and purity of medicines.
76) Validation Master Plan (VMP): A document detailing the principals involved in the qualification of a facility, defining the areas and systems to be validated, and providing a written program for achieving the facility's validation.
77) World Health Organization (WHO): A specialized agency of the United Nations responsible for international public health.
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Acknowledgements
AHERF
Prof. NIRMAL KUMAR GANGULY President AHERF
Ms. ISHITA SHIVELY Sr. Vice president
Dr. JAYANTHI SWAMINATHAN Secretary, Governing Board and Clinical Director
Dr. M.V. SASIDHAR Chief Scientific Officer
Mr. PATNAM. SREEKANTH Scientist
Dr. S. KARTIK KUMAR Scientist
Ms.SHAYANTANI PAUL
Project associate
Ms.SUPRIYA THALAKANTI
Project associate
MsMEGHANA HANAGODU Project associate
IEVS
Dr. M.V. SASIDHAR, President Chief scientific officer, AHERF
Dr. SAROJ KUMAR, Vice President- Research Additional Professor at AIIMS, New Delhi
Dr. MADHAN JEYARAMAN, Vice PresidentEducation Assistant Professor at ACS Medical College, Chennai
Mr. PATNAM. SREEKANTH, General Secretary Jr. Scientist, AHERF
Dr. ANULA DIVYASH SINGH, Joint Secretary Sr. Scientist, Sapien Biosciences
Dr. GANJI PRAVEENA, Treasurer Scientist, Urvogelbio Pvt Ltd
Dr. SURAJIT PATHAK, Committee Chair Head Professor, Chettinad Academy of Research and Education
Dr. JOVEETA JOSEPH, Communications Head Head of Microbiology Services, LV Prasad Eye Institute
Dr. ANBARASU KANNAN, Membership Head Scientist, CFTRI, Mysore
Dr. MAIRAJ AHMED ANSARI, Education Head Assistant professor, Jamia Hamdard University
Dr. S. KARTIK KUMAR, Industrial Communication Scientist, AHERF
Dr. KRISHNA K INAMPUDI, Events Head Additional Professor, AIIMS, New Delhi
