STEM/CAR-T CELL & GENE THERAPY INDIA SCENARIO

CELL & Gene therapy is a promising field of biomedical research and improving the safety and efficacy of gene therapy is the need of the hour. The United States and Europe are the pioneers in this field with clinical trials being carried out for more than two decades and India has stepped into it with much more awaiting results. Recently, here has been a surge in the number of gene therapy research activities in India. Ethical issues observed in the past related with the use of gene therapy technologies led to the development of stringent guidelines and regulations to avoid its misuse and premature commercialization. Hence, it is the responsibility of all the stakeholders to develop the strategies for adhering to the national guidelines to make gene therapy a reliable treatment option in future. These guidelines and regulations are dynamic and will have to be looked upon from time to time as per the changing global standards. Elaboration of strategies based on specific genetic diseases will also be a welcoming adds on to the update of the current guidelines.

The gene and cell therapy field saw its first approved treatments in Europe in 2012 and the United States in 2017 and is projected to be at least a $10B USD industry by 2025. Despite this success, a massive gap exists between the companies, clinics, and researchers developing these therapeutic approaches, and their availability to the patients who need them. The unacceptable reality is a geographic exclusion of low-and middle-income countries (LMIC) in gene therapy development and ultimately the provision of gene therapies to patients in LMIC. This is particularly relevant for gene therapies to treat human immunodeficiency virus infection and hemoglobinopathies, global health crises impacting tens of millions of people primarily located in LMIC. Bridging this divide will require research, clinical and regulatory infrastructural development, capacity-building, training, an approval pathway and community adoption for success and sustainable affordability.

After three decades of research and clinical evaluation, the last 5 years in the gene and cell therapy field has witnessed the approval of multiple gene therapies for inherited and malignant diseases receive for drug status in Europe and the United States (U.S.). With hundreds of gene therapy clinical trials currently in progress for nearly as many diseases, the approval pipeline is expected to grow exponentially in the coming decade .Dr. Scott Gottlieb, U.S. Food and Drug Administration (FDA) Commissioner from 2017 to 2019, predicted that as many as 10–20 new gene therapies could be approved per year by 2025, and the Massachusetts Institute of Technology predicts as many as 40 gene therapies approved by 2030 .

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Indeed, 206 investigational new drug applications for gene therapy products were submitted to the FDA in 2018, an increase of 94% from the previous year. Unsurprisingly, financing in the regenerative medicine sector, which includes gene therapies, has seen an exponential increase from $6B U.S. in 2019, to $19.9 B U.S. in 2020.

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At the forefront of reservations are the widely acknowledged high costs of approved gene therapy treatments, which range from $373 K U.S. to $2.1 M U.S. While these price tags reflect the incredible efforts undertaken by gene therapy pioneers to achieve initial approvals, they are not sustainable for developed countries, let alone low- and middle-income countries (LMIC), defined by the World Bank as those nations with a gross national income of less than or equal to $12,535 USD per capita.

This affordability gap underscores the need for more cost-effective strategies to deliver gene therapy to make curative treatments accessible to all who need them.?A?query for interventional clinical trials with the search term “gene therapy” retrieves a total of 849 trials, while only six include sites in southeast Asia, and only four include sites in Africa. Sites in southeast Asia include India, where three trials for Gaucher’s disease, inherited retinitis or non-small cell lung cancer are registered, and Thailand, where three trials, two for beta-thalassemia and one for metastatic prostate cancer are registered.

For the first time in pharmaceutical drug discovery and development ?the patient is part of the whole manufacturing and development process and, therefore, also part of the logistics supply chain when we are talking about so-called autologous therapies where the patient is really donating its own cell/gene ?and then the therapy is made out of that .

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In this ?treatment, first is ?collection, that have to do the infusion later on, for those that have to bring the product through a warehouse, bring the cryo-storage, do the transportation, and ultimately for those that are in need of the therapy: the patients.

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In this rapidly expanding era of biomedical research and appraising burden of genetic disorders, India has become one of the few countries to formulate the guidelines on research involving clinical trials of gene therapy products (GTP). In November 2019, “National Guidelines for GTP Development and Clinical Trials” has been released by the Indian Council of Medical Research (ICMR) in collaboration with Department of Biotechnology (DBT). This document broadly specifies the ethical, scientific, regulatory procedures, and requirements to be followed for developing and conducting clinical trial on GTP in India. The Indian guidelines were framed with reference to (United States-Food and Drug Administration) and European Union guidelines on gene therapy. This document provides an overview of the Indian regulatory guidelines on GTP.

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INDIAN SCENARIO

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Unlike other countries, the prevalence of inherited genetic disorders and its associated morbidity and mortality have not been fully established in India. Based on the data reported from tertiary care hospitals genetic diseases such as haemophilia, thalassemia, sickle-cell anaemia, certain forms of muscular dystrophies, retinitis pigmentosa, primary immunodeficiency in children, lysosomal storage disorder, and cystic fibrosis were the most common monogenic genetic disorders affecting the Indian population. Despite the growing burden of genetic diseases in India, most of the clinical trials on gene therapy are currently being conducted in other countries such as USA, Europe, and other Asian countries such as China, Japan, and South Korea. Hence, the recently released national guidelines on GTP clinical trials might help to streamline this evolving field of gene therapy which can cater to the large unmet medical needs in Indian patients.

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Permissible Area of Research

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Basic Research

Approval of IC-SCR and IEC

Clinical Trials

Clinical grade cells/derivatives?that are processed in CDSCO certified GMP Facility .Approval of IC-SCR and IEC and CBBTDEC (CDSCO) .

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Restrictive Area of Research

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Additional Approvals are required from

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NAC-SCRT and IAEC/CPSCEA

Research involving introduction of human ESC/iPSC/SSCs into animals.

Studies on chimeras including primates.

RCGM

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Genome modification including gene editing.

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Funding Agency and HMSC

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International collaboration.

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Prohibited Areas Of research

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Human germ line gene therapy and reproductive cloning

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In vitro cultures of intact embroyo

Clinical trials involving transfer of xenogeneic cells into human host

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Clinical trials on xenogeneic -Human hybrids

Use of genome modified human embryos ,germ line stem cells, gametes for developmental propagation

Implantation of human embryos after in vitro manipulation at any stage of development into uterus in humans and in primates.

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Breeding of animals in which any type of stem cells have been introduced.

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Challenges in SCR&T

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Minimal Manipulation -Processing neither alters the number nor the biological characteristics and functions of cells (or tissues )?.

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Clinical application using such cells need regulatory approvals if these are meant for homologous use for?unapproved indications.

If the minimal manipulated cells are to be used for non homologous purposes approval form CDSCO is mandatory before initiating any clinical application.

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If cells/tissues are removed and implanted into the individual during the same surgical procedure within a single operation it should not undergo processing steps beyond centrifugation/rinsing/cleaning/sizing .

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Need for regulation

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Desperate vulnerable population falling prey

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Financial toxicity

Internationally being criticized

No systematic study to understand safety and efficacy .

False promise or hope to cure incurable disease condition

Several complains from patients/NGO/Patients Advocacy groups

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Keeping minimally manipulated cells out of the preview of definition of new drug means legitimizing its use .

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Gene therapy Advisory & Evaluation Committee

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Mandate

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Provide handholding ,pre-IND consolation for investigators and industry .

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ROBUST evaluation of GTPs and GT-Clinical Trials .Providing technical and scientific acumen to CDSCO-SEC facilitating and expediting regulatory process.

Formulation and periodic updating of guidelines .

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Education and Awareness of stakeholders.

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MISSION

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Streamline regulatory framework in coordination with various government agencies .

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Scientific and ethical conduct of R&D of GTPs .

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Safety of human participants .

Facilitate indigenous development of affordable GTPs.

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Do Stem Cells fall under the Category of Drug ?

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Stem cells and their derivatives fall under the definition of “Drug” as per the Drugs and cosmetics Act 1940 and are categorized as “Invetigational New Drug “(IND) or?“ Investigational New Entity (INE) “

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New Drugs and Clinical Trials Rule 2019 (NDCTR) for Stem cells and other cell based products including GTPs.

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Clinical trials are a must before they can be used for any indications.

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Specific Considerations:

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A structured multilayered monitoring involving IBSC,RCGM,CDSCO and GTAEC.

For SC products ICSCR,IEC,CBBTDEC,NAC-SCRT(ESCs/iPSCs).

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Germ line or in utero GTP is prohibited in India .

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Somatic cell gene editing is permissible but need to ensure no biodistribution to gonads.

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Therapeutic use of stem cells for unapproved indications is not permissible ,only to be done under the realm of clinical trials with necessary approvals .

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Investigators have domain expertise and involved in clinical trials must and CGMP training .

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Infrastructure has to be CGMP Certified by CDSCO.

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Major Challenge is to curb unethical use of stem cells and cell-based products .

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CART-Cell Therapy India Scenario.

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Overview

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current status and?existing challenges .

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On going activity in India is divided into 2 parts

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a)Industry driven

b) Academic center driven

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Need for loco regional program .

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Local vector development and manufacturing .

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Local expertise in cell manufacturing and delivery ..

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Our experience with regulatory process

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Possible strategies to improve access and goal of equitable health care distribution .

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SCIENCE magazine in December 2013 mentioned CART Cell therapy as “Breakthrough of Year”

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“CAR T-Cells have produced dramatic improvements when tested in clinical trials -in one early phase trials more than half of Leukemia patient went into complete remission” .

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FDA Approvals brings First Cell based Gene therapy to USA KYMRIAH by Novartis august 2017 for adult patients with multiple myeloma .

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YESCARTA by Kite (A Gilead Company ) in October same year 2017 brought Cell based Gene therapy?for DLBCL,PMBCL.

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KYMRIAH from Novartis or the Yescarta from Kite or now Gilead, these are really niche therapies. They require a very special infrastructure, being shipped at -196 degrees Celsius with liquid nitrogen, being it really this B2B supply chain, this closed-loop B2B supply chain.

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Common Themes

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Industry driven

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Centralized manufacturing process

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Costs US $373,000 to a Million $

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Cost of Allogenic Stem cell transfer

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Major cost drivers

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Donor source??????Cost India (INR)???????????Cost USD ($)

MSD???????????????????????????1400000?????????????????????????20000

MUD???????????????????????????4000000?????????????????????????55000

Haplo??????????????????????????2500000?????????????????????????32000

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Rs 74=1$US

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Other important drivers

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Graft rejection

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GVHD

Infection

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Some go out of the country to access this therapy .

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INDUSTRY

Following 3 companies are actively involved and pursuing the CGT in India .

INTAS

Immuneel

Aurigene (A Dr Reddys Laboratories Company )

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Dr Reddys In CAR T-Cell Therapy

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In -Licensed DRL-1801 a BCMA Nanobody based CAR T for development in India.

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In the process of building GMP CAR-T Facility

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Clinical trials will be done in r/r Multiple myeloma patients ,post CAR-T facility establishment and regulatory approval .

Pregene and Dr Reddys announce license agreement for Anti-BCMA CAR-T PRG1801 IN India.

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Shenzhen Pregene Biopharma and Dr Reddys Laboratories announces a license agreement whereby Dr Reddys?will acquire the exclusive rights in the Republic of India for PRG1801 an Anti-BCMA CAR-T Cell therapy based Injection based on single domain antibody technology from Shenzhen Pregene Biopharma.

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EYESTEM

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Cell and gene therapy is going to lead to a paradigm shift in healthcare. Diseases that were deemed incurable will start getting treatment because of this, say experts. Indian patients can benefit if a base is created here for these new platforms. Currently, such treatments are not sustainable due to the astronomical costs — a therapy for spinal muscular atrophy can cost Rs 16 crore per patient.

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Eyestem intends to change that by keeping the cost low.

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This cell therapy company was founded by a group of doctors and management consultants whose vision was to create a cell therapy platform to treat incurable diseases and make these technologies accessible to everyone.

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Big challenges

Eyestem treats incurable diseases by replacing the cells that are lost to conditions such as idiopathic pulmonary fibrosis, age-related macular degeneration and retinitis pigmentosa.

Age-related macular degeneration (AMD) is a leading cause of incurable blindness in the industrialised world. About 170 million people suffer from this disease; 40 million in India. It presents as two variants: wet and dry. Wet AMD is treatable and the global market value?..

These diseases have an individual market size of $20 billion annually, say the experts at Eyestem. The global prices of these treatments would be more than $250,000. Eyestem hopes to bring the prices down by 80%.

A question of affordability

The company claims to be capital efficient and aims to get each product from concept to human trials in under $4 million. Most pharma companies spend 10 times this number to reach this stage, claims co-founder and Chief Executive Officer Jogin Desai

On how soon the treatments can be commercialised, he says, “Our treatment of dry AMD will go through first human trials by Q4 2022 and each new product to treat incurable diseases will be deployed 12 months after that.

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INDIA ?JOURNEY SO FAR IN ?CAR-T CELL CLINCIAL TRIALS

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(1)TMH(Tata Memoria Hospital ) in Mumbai .

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Bench to Bed side Translation -The first Clinical Trial Phase I for CAR-T Cells in India was successfully conducted?on October 2021 where 5 patients were infused and collaborators were for ?Product and technology contributed ?by IIT Mumbai and Clinical Trials/Studies at TATA ?Memorial hospital Mumbai ,Knowledge partners (Subject matter experts ) were National Cancer Institute USA and Clinical translation was done by Immuno ACT PVT Ltd .

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(2)The Christian Medical College (CMC) in Vellore, India, represents a clinical research center and regional training center of excellence with bone marrow transplant service capable of performing 200 transplants per year and the capacity for manufacturing blood cell gene therapy products locally . Half of the world’s beta-thalassemia carriers and affected births reside in South-East Asia.

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This outlined the need for a NATIONAL PROGRAM .

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Technology development .

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Program for indigenous vector development and large scale manufacturing .

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Reduction on cost of cell manufacturing -Decentralized CAR-T Cell manufacturing .

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Harness higher national purchasing power /parity /lower labour cost .

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Harness scale of production and numbers to reduce costs .

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Actively increase the number of products ,industry involvements and centers delivering care-COST will further reduce .

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CAR-T Cell manufacturing .

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Automated cell processing provides options for manufacturing of patient specific cell therapies .

They can be divided into Centralized,Regional or Local?Point-of -care .

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The Cell processing laboratory at CWRU is ISO7 Controlled laboratory .

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Prodigy is not housed in the clean room since the device is a closed system.

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Point-of-Care Manufacturing

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The major challenge has been the cost of therapy .

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Cost dictated to a large extent due to industry and centralized manufacturing process.

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Centralized manufacturing process is also a logistics challenge in our country .

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Requires a minimum Class 100,000(ISO8) Facility .

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CliniMACS Prodigy?system housed in CGMP.

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Approvals needed to progress to a clinical trial :

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IRB/IEC (Institutional Research and Ethics Committee) approval to be obtained -this is then submitted to the IBSC.

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IBSC(Institutional Biosafety Committee ).This is an institutional committee but has members from the central?government department of biotechnology (DBT).Once IBSC (approves ) next step is to submit to RCGM.

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RCGM(Review committee on Genetic Manipulation ) .RCGM is central government organization that oversees all research and development and import of genetically modified cells or plants .

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All after getting the RCGM can either you do the research involving genetic manipulation or import vectors or other reagents that are involved in genetic manipulation .

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RCGM approval is also required for all pre-clinical studies, In-vitro ,In -Vivo and for pre-clinical validation studies .

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GTAEC (Gene therapy advisory and evaluation committee ) is an advisory body to which the clinical trials protocol can be submitted prior to obtaining license to do the study .A body of experts will advise on additional regulatory requirements e.t.c.

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Once pre-clinical validation of?manufacturing process complete will need to submit to CDSCO (Central Drugs Standard Control Organization ) under Drug Controller General of India (DCGI) .

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CDSCO will inspect the facilities and evaluate manufacturing processes and issue the license to do the trials and where appropriate to market a product ( if INDUSTRY ) .

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YOURWAY OFFERINGS FOR CELL & GENE THERAPY SUPPLY CHAIN MANAGEMENT

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Yourway is an integrated biopharmaceutical supply chain solutions provider offering a full range of primary and secondary packaging, logistics, storage and distribution services for the global pharmaceutical and biotech industries.

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Much of the investment and investigation in today’s market is going into biologics, sometimes for orphan drugs and rare disease therapeutics, or new frontiers like cell & gene therapy.

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As medicine becomes increasingly personalized, so too does the clinical supply chain. The focus is more and more on patients, including the shift toward virtual and home-based trials. In this changing landscape, outsourcing clinical supply chain logistics services to an integrated, global solutions provider like Yourway is a logical pathway to increasing speed-to-market, mitigating risk and optimizing overall supply chain efficiency.

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Full Clinical Trial Supply Chain Support Worldwide

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Yourway is one of only a small handful of global supply chain partners able to independently support all aspects of clinical trials. We combine years of know-how, unrivaled responsiveness and our global network of GMP depots to support the full scope of your clinical supply chain needs. We are the only truly integrated partner, offering a single-source solution for clinical packaging, storage and distribution, and premium courier services.

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Temperature-Controlled Needs for Advanced Therapies

Emerging cell and gene therapies (CGTs) are showing enormous potential for treating cancer, neurodegenerative diseases, and a wide range of other conditions. The CGT industry is expected?to grow 30% between 2019 and 2025, and the transition from clinical trials to commercial-scale production is now seen as inevitable.1

Pharmaceutical companies are addressing the challenges that CGTs present for?temperature-controlled logistics. Unlike traditional biological therapies requiring temperature control, CGTs (as well as some biological samples) require ultra-cold temperatures, ranging from –4 °C and –20 °C to –80 °C, –120 °C, –150 °C, and beyond.?

Despite this, investment in the CGT market is strong. Between January and June 2020, CGT?developers raised $10.7 billion?from IPOs, venture capital, and other sources.2?This is a 120% increase from the first half of 2019. Noting the upswing, the?U.S. Food and Drug Administration (FDA)?released a statement in January 2019 stating that it expects more than 200 investigational new drug (IND) applications a year through 2025.3

Because of their potential to cure disease, CGTs are seen as potentially disruptive to traditional therapies. Thus, pharmaceutical companies are making CGT an important part of their growth strategy. Amid the continued growth of these markets, temperature-controlled logistics account for nearly 18% of all biopharma logistics spending, according to the?2020 Biopharma Cold Chain Sourcebook?published by Pharmaceutical Commerce.?

The ultra-cold storage requirements of these products, their personalized nature, their direct patient involvement in a circular supply chain ("vein-to-vein"), and limited industrial capacity are challenges to achieving an efficient supply?chain. Pharmaceutical companies are having to outsource ultra-cold-chain services to third-party companies, including outsourcing temperature-controlled storage to biorepositories. Biorepositories are primarily collections of human specimens and associated data, but their functions have expanded to include specimen processing, information management system, storage, and preparation for distribution.

Biorepositories Maintain the Chain of Identity

With today's CGT?products, other biologic therapies, and several COVID-19 vaccine candidates currently in clinical trials,?there is increasing demand for storing product at deep frozen temperatures?(on the order of –40 °C to –80 °C), and cryogenic for living cells (requiring liquid nitrogen; –160 °C to –196 °C).2

In contrast to traditional medications, the patient is part of the manufacturing process in the CGT supply chain, donating and/or receiving a live therapy. This vein-to-vein supply chain means that biorepositories need to create logistics platforms that will connect therapies to the correct?patients.

As a result,?CGT?biorepositories have become not just storage facilities but information management systems that coordinate closely with manufacturers, providers, and distributors to ensure that therapies are in good shape and are delivered to the right patients. The chain of identity must be maintained and verified throughout the entire supply chain.

All the relevant information, as well as data concerning the study participant and laboratory analyses, must be properly stored in a biorepository's interoperable information management system. With this patient identity information also comes the?responsibility of protecting personal health information.??A biorepository must be compliant with?Health Insurance Portability and Accountability Act (HIPAA)?and?General Data Protection Regulation (GDPR)?health privacy regulations in the United States and the European Union, respectively.???

Unlike conventional, large-batch drugs, each CGT patient requires his/her own manufacturing batch. The patient is literally the first step of the supply chain. Few manufacturers have the systems in place to track the condition of the cells from the moment of apheresis until re-infusion of the therapy. Data tracking and verification capabilities must?preserve?the chain of identity. This is more complex and nuanced than simply tracking a consumer. This demands an infrastructure that can track and verify that CGTs get to patients efficiently and compliantly to drive the best possible outcomes and potentially save lives.

Multiple Storage Sites

Multiple storage sites at dispersed locations becomes an expensive but often necessary reality. This is partly due to the ongoing impacts of the COVID-19 pandemic, which has led to even further decentralization of the vein-to-vein supply chain. Fear of infection forced apheresis centers and facilities to close or decentralize and collect specimens closer to or at patients'?homes.?

Biorepositories –– and integrated outsourced providers that provide such services –– must now coordinate with a wider network of apheresis centers, clinical sites, patients, logistics vendors like distributors, and biopharmaceutical partners. This decentralization will likely last after the pandemic. Patients have come to enjoy less commute time to collection sites, and the added comfort associated with the increased patent-centric practices resulted from the decentralization of clinical services.

Multiple storage sites become even more important when one considers remote locations or developing countries. It is not always possible to have access to liquid nitrogen, ultra-cold freezers, or even electricity in some situations. In situations where freezer systems may not be available, lower-cost options include saliva filter cards, certain branded collection tubes, and tissues fixed in formalin and embedded in paraffin blocks.??Biorepositories can work with pharma companies to assess the best collection and storage options.

Experiences in the industry with spoiled product have led biorepositories to rely heavily on the use of data-collection tools, such as advanced monitoring systems and telemetry, to reduce the frequency and likelihood of delays and temperature excursions.?

Temperature-Sensitive Packaging

Temperature-sensitive packaging is essential for the preservation of CGT products. Along their journeys through production, storage, and shipping, specimens are exposed to extreme temperature that can fluctuate anywhere from –190 °C to 37 °C.?Biorepositories need to supply appropriate packaging for storage (primary) and shipping (secondary).?

Packaging also needs compliant chain-of-identity?labelling, unique?National Drug Code codes for various dosing kits, and additional labeling text statements, which may impact label size and placement. Adding country-specific requirements in multiple languages can further complicate the development of product labeling. Biorepositories and integrated logistics providers must have excellent information management systems and knowledge of country regulations to make sure no labeling errors are made.

Outsourcing Temperature-Controlled Storage

With so many variables to consider, it's no surprise that pharmaceutical companies are increasingly outsourcing their temperature-controlled ––including ultra-cold –– storage needs to providers with biorepository capabilities. Outsourcing to third party temperature-controlled services occurs at every development phase, especially phase II.?

Pharma companies would rather focus on research and development. They know that?logistics companies tend to be more experienced?at engineering solutions that reduce costs, such as?creating warehouse space by building giant freezer farms, holding temperature-controlled inventory, providing CGT on a just-in-time basis, expanding use of preconditioned shippers, reducing the multi-step process to just two or three steps, and tightening process integration.2

As the number of approved?CGT?products continues to grow, there is more demand for cryogenic storage systems that can maintain internal temperatures between –150 °C and –180 °C for extended periods of time. Biotech companies need to grow their cryogenic storage infrastructure, especially liquid nitrogen cryogenic storage (–180?°C).

This is especially difficult for small biotech companies that lack hard assets like cryostorage but are conducting clinical trials. They need CGT-experienced biorepositories that use a?logistics-by-design?approach to tackle temperature-controlled storage and provide other services.1??For example, some biorepositories can go beyond informatics, storage, and packaging by taking on tasks like aliquoting (dividing) specimens for further analysis.

Yourway?Biopharma Services offers the storage needed to service the CGT temperature-controlled chain no matter how complex a project and its needs may be. With a robust and advanced temperature-controlled global GMP deport network, Yourway provides storage at 21 depots around the world, as well as integrated primary and secondary packaging services. Yourway can store material within hours or even minutes of its destination.

Yourway also provides clients with the ability to seamlessly manage inventory through our easy-to-use customer portal. Our warehousing and logistics services are fully automated, allowing you to monitor your inventory 24 hours a day, seven days a week. Simply call in your orders and they will be immediately dispatched by next-flight-out (NFO) or ground transport. Partnering with Yourway means minimized overhead, field inventory levels, and?—?most importantly?—?faster turnaround time, enhanced quality/compliance, and reduced costs.

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REFERENCES:

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(1)??https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323560/ National guidelines for gene therapy product (2019): A road-map to gene therapy products development and clinical trials in India .

(2)??https://economictimes.indiatimes.com/small-biz/entrepreneurship/eyestem-has-a-visionary-approach-to-make-cell-therapy-affordable-in-india/articleshow/90388616.cms

(3)??Dr Vikram Matthews -Professor of Clinical hematology ,Christian Medical college Vellore ,India?Presentation to ASGCT (American Society of Gene & Cell Therapy ) on October 9th 2021 .

(4)??Dr Geeta Jotwani- Senior Deputy Director General & Scientist ICMR presentation to ASGCT (American Society of Gene & Cell Therapy ) on October 9th 2021 .

(5)??https://asgct.org/research/news/september-2021/global-gene-therapy-initiative Global Gene Therapy Initiative Aims to Bring Gene Therapy Trials to India and Uganda.

(6)??https://www.nature.com/articles/s41434-021-00284-4 Towards access for all: 1st Working Group Report for the Global Gene Therapy Initiative (GGTI) .

(7)??https://www.yourway.com/biopharmaceutical-services/clinical-supply-chain OSD, Biologics and Cell & Gene Therapy

(8)??https://www.biopharmadive.com/spons/cell-and-gene-therapies-evolving-temperature-controlled-requirements-call/605732/ Cell and gene therapies' evolving temperature-controlled requirements call for specialized logistics solutions by Leandro Moreira SVP Yourway Inc.