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Jubilant Drug Discovery Services Presentation
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• Jubilant Bhartia Foundation, a not for profit organisation is a social arm of Jubilant Bhartia Group
• The foundation is engaged in community development work focusing on primary education, basic healthcare, skill development through vocational training for youth & women
• Aims at long term sustainable social intervention by empowering communities through 4P model (Public‐Private‐People‐Partnership)
Pharmaceuticals & Life Sciences
An integrated global Pharmaceutical & Life Sciences Company
Life Science Ingredients: Life
Science Chemicals, Nutritional
Products Advance
Intermediates and Specialty Ingredients
Pharmaceuticals: APIs, Solid Dosage Forms, Specialty Pharmaceuticals, Drug Discovery Solutions and India Branded Pharmaceuticals
Revenues FY2015: US $ 953 Mn (Rs.5,826 Crs)
Listed on NSE & BSE, India
www.jubl.com
Diversified product portfolio includes
Agri products wide range of Crop Nutrition, Crop Growth and Crop protection products
Performance Polymers :
Consumer products :
Adhesives and Wood Finishes;
Food Polymers and Latex : Vinyl Pyridine, SBR and NBR Latex
Revenue FY 2015: US $ 140 Mn (Rs. 858 Crs) Listed on NSE & BSE, India
www.jubilantindustries.com
A master franchise of Domino’s Pizza for India, Bangladesh, Nepal & Sri Lanka and Dunkin’ Donuts for India
Domino’s: 1004 stores across 230 cities in India
Dunkin’ Donuts: 70 stores across 24 cities in India
Revenues FY 2015: US$ 339 Mn (Rs. 2,075 Crs)
Listed on NSE & BSE, India
www.jubilantfoodworks.com
Oil and Gas exploration and production activities with operating assets portfolio in North‐East India
3 key blocks at different stage of life cycle
Producing block ‐ Kharsang in Arunachal Pradesh
Appraisal and Development Blocks ‐ Deendayal block in KG and a block in Tripura
Listed in AIM market, London Stock Exchange
www.jubilantenergy.com
Aerospace : Sole
authorized
Independent Representative of Bell Helicopter in India for sales, marketing and customer support.
Also represent other international aerospace companies.
Oil & Gas Services Consultant to Transocean‐ offshore drilling company Manning and Marketing services for Tidewater Marine International etc
www.jubilantenpro.com
Agri & Polymers Food Service (QSR) Oil & Gas Services
One of the largest Luxury Auto Retail Company in India
Audi Dealership ‐ Bengaluru, Mangalore, Chennai and Pune
Porsche Dealership – Mumbai to cater to Maharashtra
Maserati Dealership‐ Bengaluru to cater to south India
www.jubilantmotorworks.com
Auto
www.jubilantbhartiafoundation.com
• Established in 2013 • Engaged in retailing of ready to use fresh produce like:
premium cut fruits, ready to cook portioned vegetables and gourmet salads
• Eminent among quick service restaurant chains, hotels, restaurants, variety of organized retailers and e‐commerce networks
Jubilant Bhartia Group - Snapshot
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Jubilant Life Sciences Business – A Snapshot
Pharma & Life Sciences
Life Sciences businesses
Drug discovery • Collaborative programs to clinic • Functional services to aid partner
API Contract manufacturing services Radiopharmaceuticals Sterile injectables
Largest CRAM Company, Leading Drug Discovery & Development
Solution provider in India
Revenue FY2014-2015–US $ 953 Mn
69%
31%
Revenue share
Life science products Life science services
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Company
Employees
Customers
Founded in 2000; part of Jubilant Life Sciences
Global Top 10, mid-size and virtual pharmaceutical and biotech companies
Noida, New Delhi Bangalore Malvern, PA, USA
~600 employees. Most PhDs have >10 years of US/EU Pharma experience
Jubilant Drug Discovery Services
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Therapeutic Areas
Oncology • 16 Programs
• 2 IND’s •12 Kinases
•2 each of GPCR & Lyase
CNS
• 8 Programs
• 2 Candidates •3 Kinases
•3 Ion Channels
•1 each of Secretase & Transcription Factor
Metabolic Disorder
• 13 Programs
• 1 IND
• 1 Candidate • 5 GPCR’s
• 2 Kinases
• 1 each of 6 others
Pain & Inflammation
• 12 Programs
• 2 Candidates •8 Ion Channels
•3 GPCR’s
•1 Hydrolase
• Also working on areas like Anti-infectives, Ocular diseases, Cardio Vascular, Gastro-Instestinal etc • 53 programs in 10 years; 6 optimised leads, 5 preclinical candidates and 3 INDs delivered
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Target Identification & Validation
Target to
Lead Generation
Lead Op. &
Preclinical Dev (IND)
Bioinformatics
Target proposal (line-of-
sight to IND)
Target Validation (siRNA,
tool cmpds, expression)
HTS
Structural Biology
(protein, X-ray
crystallography)
Med / Comp Chem
E-phys screening
in vitro ADME
hERG
in vitro / Cell biology
Med / Synth / Process Chem
(GMP)
DMPK
In vivo PD & disease models
scale-up & API
Preformulation
non-GLP Tox (14d, mice,
rats)
GLP Tox (rodent)
Genotox
D2M predictions
Target engagement models
Our Drug Discovery Capabilities
Serv
ices
Support
Project Management IPR & Legal Info security Mgmt.
ISO270001 cert. (BSI)
Supply Chain Mgmt
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Past Collaborative Programs – Highlights
S. No Collaborator Target
Validation
Target to
Hit Hit to Lead
Candidate
Selection IND Phase I
1 ENDO
2 ENDO
3 Top 15 Pharma
4 Top 15 Pharma
5 Top 15 Pharma
6 Top 15 Pharma
7 Top 15 Pharma
8 Top 15 Pharma
9 Top 10 Pharma
10 Top 10 Pharma
11 Top 15 Pharma
12 Small Pharma
Oncology
Oncology
Inflammation
Oncology
Metabolic Disorders
Metabolic Disorders
Metabolic Disorders
Pain
Pain
Oncology
Metabolic Disorders
Pain
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Current Integrated Programs
S. No Collaborator Target to Hit Hit to Lead Candidate
Selection IND
1 Mnemosyne
2 Orion
3 Top 10 Pharma
4 Top 10 Pharma
5 Top 10 Pharma
6 Sanofi
7 Sanofi
8 Small Pharma
9 Small Pharma
10 Virtual Pharma
11 Virtual Pharma
12 Virtual Pharma
13 Virtual Pharma
CNS
Pain
Metabolic
Disorders
Metabolic
Disorders
Oncology
CNS
CNS
CNS
Anti-Infectives
Oncology
Oncology
Oncology
Oncology
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Endo Pharmaceuticals Collaboration – Case Study
To collaborate and discover molecules that will address unmet needs in oncology therapeutic area Program Objective
1) Target to Hit 2) Hit to Lead
3) Pre-clinical Candidate Deliverables
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Target to CS (Contracted) Target to Hit (10 mths) Hit to Lead (12 mths) Candidate Selection
Target to CS (Actuals) Target to Hit (9 mths) Hit to Lead (10 mths) Candidate Selection Development IND, Ph I/II
Year 1 Year 2 Year 3 Year 4 Year 5
Target to IND in less than 3 years
Candidate in clinical trials
4 Milestones achieved till date
A good example of Collaborative Drug
Discovery
Dr Sandeep Gupta, SVP, Endo
Pharma “I congratulate the Jubilant
and Endo teams on achieving this
important milestone. It was their
outstanding collaborative work and
ingenuity that enabled the successful
filing and acceptance of an IND in less
than three years
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Why Jubilant
More than a decade of experience as Drug Discovery Service Provider and a track-record of
working on 50+ integrated programs
Jubilant Innovation demonstrating capabilities to innovate and provide starting points for
integrated programs
Flexible/ Customized business models and team composition
Diverse experience in working on collaborations with Big, Medium and Small pharma/
biotechs
Long term collaborations of more than 5 years due to consistent and high quality delivery
Niche capabilities include Ion channel screening
GMP facility enables us to collaborate all the way up to Ph-I clinical material supply
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Business Models
FFS
Functional Services/PO
FTE
• Function specific FTE
• Hybrid FTE
Shared Risk
Discounted FTE &
Milestone payments
Licensing/ Partnering
Upfront and Milestone payments
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Oncology - Capabilities
Disease area expertise in terms of disease pathways /mechanisms Large panel of human tumor cell lines and established xenografts Broad capabilities in enzyme, cell based, PK-PD, efficacy models Built fully integrated target to candidate drug discovery engine Executed around 20 targets and delivered 2 pre-clinical candidates and several leads/optimized leads
Cell / Ex-vivo assays Target modulation: Target Autophos, modulation of substrate proteins, etc using ELISA, alpha-screen, MSD,
western, flow cytometry Cell Cycle: FACS analysis Cell Migration: Boyden chamber, Wound healing; Matrix Invasion: Matrigel and HUVEC tube formation assay Proliferation & Apoptosis assays: Alamar blue, Annexin V, caspase activation, PARP cleavage Others: FLIPR assays for GPCR, Immunocytochemistry, 3-D culture in soft-agar, Cell Adhesion
In vivo models Xenograft (Subcutaneous) models for PK-PD or efficacy: Lung (NCI-H82, HCC827, Calu-6); Breast (MDA-MB-231); Colon (HT-29, Colo-205, HCT116; LoVo); Prostate (PC3,
DU-145); Gastric (MKN-45); Ovarian (A2780); Pancreatic (PANC-1; Bx-PC3); Melanoma (A375); Others (A431, U-87 MG); Hematological cancers (MV-4-11, Pfeiffer, CCRF-CEM, MM1.S)
Orthotopic (Breast, Prostate, SCOT, glioblastoma) Syngeneic models (B16-F10, CT26 and 4T1) Matrigel plug angiogenesis model
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Metabolic disorders - Capabilities
Fully integrated target to candidate drug discovery engine; Team with rich drug discovery experience – have run several programs with big pharma/ biotech
Ability to think through the problem and quickly establish in-vitro assays & disease models Broad capabilities in cell based assays, PK-PD, efficacy models Availability of panel of cell lines to jump start research programs [Min6; STC-1; 3T3L1; C2C12; L6] Delivered 1 IND; 1 pre-clinical candidate and several leads/optimized leads
In vivo models Streptozotocin-Type 1 diabetic model; STZ-induced diabetic neuropathy model DIO mouse: weight, glucose, insulin, lipids, and pair-fed studies Expertise in genetic models of diabetes (ZDF, ob/ob, db/db) Acute model of Incretin and endocrine secretion- [GLP-1] in mice Acute and Chronic OGTT, IPGTT (Glucose & Insulin) in mice and rat Acute model for malonyl CoA lowering in rats Lean diabetic model(STZ + Nicotinamide) NASH model: DIO plus methacholine deficient
Cell / Ex-vivo assays Assays: Insulin secretion, glucose uptake, glucagon secretion, incretin release [GLP-1, CCK, PYY, GIP] assays beta cell protection; Adipogenesis, adipolysis assays; Apo B secretion, fatty acid oxidation; membrane potential assays; Transporter assays; assessment of Gene/ Protein modulation Cells: Islet cells, Hepatocytes and muscle cells Platforms: High Content Imaging; MSD; ELISA; Western Blot; Immunocytochemistry
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CNS/Pain Capabilities
Disease area expertise in terms of disease pathways /mechanisms Broad capabilities in enzyme, cell based, PK-PD, efficacy models Executed around 15 targets and several leads/optimized leads
Cell / Ex-vivo assays Cytokine panel assays: Cytokine release assay in cell line, primary cells, and tissues using ELISA and MSD. Ex-vivo assay: Neurotransmitter release assay, biomarker release analysis, receptor occupancy assays. Secondary Functional Assay: IP1 assay – HTRF, cAMP assay – HTRF, Ligand Binding assay, specific p-Ser Assays, B-
arrestin recruitment assay. Alzheimer specific Assay: Abeta and Tau Assays. Electrophysiology: medium throughput automated palanar patch and manual patch ion channel screening
assays Others: FLIPR assays for GPCR
In vivo models Nociceptive & Inflammatory Pain Models: Formalin induced behavioral model, Acetic acid induced writhing test
model, hot plate / Tail flick, Carageenen induced inflammation, thermal hyperalgesia (rat), CFA induced thermal / mechanical allodynia model in rats, Collagen Induced Arthritis model in DBA mice
Neuropathic Pain models: CCI induced neuropathic pain , L5/L6 ligation(SNL) model, Cisplatin induced pain (cancer), Bone cancer pain model, STZ induced Diabetic Neuropathy (mechanical allodynia) Acute and Chronic
Target Engagement Models in Brain for Neurodegenerative and Psychiatric Disorders Partnership with Psychogenics
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Inflammation - Capabilities
Disease area expertise Ability to think through the problem and quickly establish in-vitro assays & disease models Broad capabilities in cell based assays, PK-PD, efficacy models Fully integrated target to candidate drug discovery engine Delivered 2 pre-clinical candidates and several leads/optimized leads
Cell / Ex-vivo assays Assays: Cytokine Release; T-cell proliferation; T- cell migration; IKK and NF-kb reporter assays; JAK-STAT pathway
assays; Kinase assays [PI3k, AKT, P38; MAPK, JNK]; Primary leukocyte; Chemotaxis; Platforms: FACS; High Content Imaging; MSD; ELISA; Alphascreen; HTRF; Western Blot; Beta-complementation;
FLIPR; Immunocytochemistry; Cells: Primary cells (mouse, human, rats) and cell lines
In vivo models Inflammatory Pain: Formalin, CFA, Carageenan, Capsaicin-induced nociception Arthritis: Collagen induced arthritis Inflammatory Bowel Disease: DSS, TNBS and oxazalone-induced colitis in mice (acute and chronic) Respiratory and Atopic Allergy Models: Steroid sensitive and resistant asthma in mice; LPS-induced neutrophilia in rats Fibrosis Models: Lung, liver, skin, kidney, NAFLD and NASH Others: Psoriasis, EAE (MS model), anterior and posterior Uveities in rabbits, rats and mice (ocular models)
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E-Phys and HTS Capabilities
Integrated Robotic Deck
Fully Equipped Cell Culture Facility
Port-a-patch, Q- Patch
(Planar Patch Clamp Ephys)
ICR 12000 Ion Channel
Reader (Atomic Absorption
Spectrometry)
FDSS 6000
(Fluorescence and
Luminescence reader for
kinetic assays)
Envision
(Multimodal optical plate
reader for end point assays)
HTS Capable for Voltage and ligand gated ion channels, Enzymes and GPCRs REMP compound management system (Bangalore)
Profiling ( 7000 data points / day)
15,000 wells/day • Li detection for Na
channels • Rb detection for K+
channels
50,000 wells per day Ca++ flux
(fluorescence; aequorin)
Membrane potential assays (VSP dyes)
50,000 wells/day • Absorbance, FI, FP,TR-FRET,
HTRF, HitHunter, PathHunter, assays
Jubilant Malvern, PA 3 Electrophysiologists 2 cell biologists
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Bio- Chemi Informatics
Structural Biology
Functional Capabilities
Discovery Chemistry DMPK
Toxicology
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Structural Biology
Cloning
>400 clones
• 7.5 kb gene cloned
• SDM
• Vector Design
RACE
• Validated Porcine sequence
qPCR
• Tissues & Cell lines
Expression
Bacterial cell
• Chaperons
• Auto Induction
Insect cell
• Secretion
• In presence of Glyco-inhibitor
Mammalian cell
• CHO, HEK293, Freedom CHO-S
• BacMam
Cell lines
Patch derived stable cell line
Single cell derived stable cell line
(ion channels, GPCR)
Large scale Transiently
transfected cells
Protein purification
>300 Proteins
~80 targets
Recombinant proteins
Endotoxin free protein
Protein extraction
Protein Characterization
Conventional
•SDS-PAGE
•Native
• Immunoblot
Biophysical
•TSA
•CD/MassSpec*
• ITC/BLI/SPR*
Biochemical
•Enzymatic
•Binding
•Potency
X-rayŦ
Hanging drop/ Sitting drop
Crystallization
200 co-crystal structures
9 Novel structures
5 FAb complexes
Refinement & Annotation
4000 structures
Ligand fitting
~60 million images
Expertise & team:
Collectively > 50 years of industrial experience
Team of 2 Ph.Ds and 12 MS Scientists
Differentiation Multi construct approach for structural studies, Three expression systems, Co
expression, Protein Characterization, Endotoxin free proteins, Secretory
proteins, Gene expression profiling of cancer tissues, In-house X-Ray facility,
Expertise in structure refinement & Image annotation, off-the-shelf proteins
for assay and structures
Capabilities headlined, additional bullets describe project experience *Outsourced to IISc; ŦAustralian Synchrotron Access
In-house X-ray Diffraction Facility
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Discovery Chemistry Capabilities
Hit / Lead identification
Lead optimization
SAR development
SPR-guided analogues design for better drug-likeness
Cheminformatics, Computational chemistry and
structural biology support
Target landscape analysis and scouting
IP analysis
Scaffolds, Building blocks, Intermediates, Reference
compounds
Library design and synthesis
Asymmetric Synthesis (Stereo-selective, enzymatic and resolution techniques)
Impurity / Metabolite synthesis
10 mg to 100 g
Process design, development and optimization
Salt screening and polymorph studies
Capability to scale from grams to 10 kilograms
Process safety studies
Tech Transfer
GMP and Non GMP Material supplies for Tox, Pre-clinical,
Phase 1 / 2
IND filing support
GLP Method Developments
Purifications (including chiral compounds)
Dedicated support to synthetic group
Stability Studies (ICH)
Physical characterizations (DSC, TGA, XRD)
Impurity profiling
Experienced CQA support
Medicinal Chemistry Custom Synthesis Process Research/GMP Analytical Research
250 Chemists (30) 50 Chemists (5) 25 Chemists (5) 40 Analysts (5)
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DMPK Services
Absorption Permeability – Caco-2 (AB and BA); – PAMPA; MDCK-MDR-1
Solubility – Aqueous (various pH) – SGF and SIF
Log D, pKa and Log D Pharmacokinetics – Mice; Rats; Rabbits – Dogs and Monkeys (outsourced) – Bile duct cannulated rat PK – Portal vein and urinary bladder
cannulation in rats – Lymphatic vessel cannulation – Cassette dosing – Microsampling in mice – Dose escalation studies – DBS (dried blood spot)
Distribution Protein binding – Equilibrium dialysis (ED) – Ultra filtration – Tissue distribution in Rats (using cold
compound) – ED method to determine fu in plasma, tumor & brain
Excretion – Mass balance (metabolic cages) – Biliary and Urinary excretion
Metabolism Metabolic stability – Liver microsomes; S-9 fractions and Hepatocytes
CYP and FMO profiling – CYP inhibition – CYP induction
Metabolite ID – In vitro using liver microsomes,
hepatocytes – In vivo from plasma, bile, urine and
feces – Glutathione trapping – Blood/plasma partitioning – Time dependent inhibition – Plasma and Chemical stability
Cross functional activities – PK-PD – Toxicokinetics – D2M prediction
Instrumentation – 6 LC-MS/MS (API-6500, 5500, 4000 and 4000 Q-Trap) and 2 HPLC units
Software – WinNonlin – GraphPad prism
Turn around time – 5-6 Days most of the in vitro studies – 6-7 Days for IV and oral PK study
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Laboratory Animal Facility
The Animal Facility is registered with:
“Committee for the Purpose of Control and Supervision of Experiments on Animals”
(CPCSEA) Reg. no: 1029/PO/RcBi/07/S/CPCSEA (Ministry of Environment, Forest
and Climate Change, Govt. of India)
IAEC (Institutional Animal Ethics Committee) monitors activities related to animal
facility & ensure that all animal experimentation procedures are carried out
strictly as per the guidelines and approved study protocols.
Indian GLP certified facility (June 2015)
Full accreditation of AAALAC since 2012
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Pre-formulation & Toxicology Services
Toxicology
Pre-formulation
Preclinical Formulation • Solubility (different media) • Formulation Development • Formulation Strengths & stability • Formulation Homogeneity
hERG (binding, ephys) Genotoxicology (GLP/non- GLP)
• Ames test / Mini-Ames study
• Micronucleus test
• Chromosomal aberration test
General toxicology (GLP/non- GLP)
• Acute toxicity studies
• Dose range finding study
• Repeated dose toxicity studies (4, 7, 14
and 28 day)
Compound Characterization • Stability (Sol & Soild state) • Salt & Polymorph screening • Solid State Characterization • Bulk Properties Characterization
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PathArt (> 3000 pathways) enables study of therapeutic targets through their biomolecular interactions, signaling and metabolic pathways in disease conditions, captured in the database
Additional custom curation and analysis for clients
PathArt™
Analysis of Pathways in Disease Conditions
MolSign (> 10,000 biomarkers and > 100,000 records) enables study of disease biomarkers in Cancer, Arthritis and Diabetes
Data analytics services using MolSign™ help in pre-clinical target identification, validation and Clinical Theranostics
MolSign™
Analysis of BioMarkers in Health and Disease
ChemBiobase (~2.5 million molecules) enables study of literature information on therapeutic targets of interest. For active molecules, biological and physicochemical properties can be accessed via user-friendly interface
Chem BioBase™
Analysis of Known Medicinal Chemistry for
therapeutics
Pre-clinical/Clinical Informatics Services Analysis & reports of targets, pathways, biomarkers and biologically active small molecules Informatics Target Analytics Services: curation & reports associated with therapeutic targets Virtual Lab for Computational Support: molecular modeling associated with drug discovery projects Collect, analyze and present data on Pharmacogenomics and Pharmacovigilance
Jubilant Proprietary Informatics Databases
Informatics Services
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Key Support Functions
Project Management
• Dedicated Project Management Team
• PM coordinates the logistics for project planning through the process of initiating the projects, follow-up the project implementation process for the successful execution
Intellectual Property
• Robust IP process of safeguarding and maintaining the client’s IP through a technically skilled team
• SOP driven IP and LNB audit procedures are in place
• IP & R&D teams up to improve and protect the IP assets of the client
Data security
• Jubilant Proprietary Software
• Chemical Tracking System (CTS)
• Compound Management System (CMS)
• Projects are blind coded and used for communication tracking
• Information flow is strictly on a need to know basis
Supply Chain Mgmt & Logistics
• Procurement timeline:
• Aldrich – 4 d
• Alfa – 5 d
• Local – 1-2 d
• Rare RM –15 d
• Shipment delivery
• US - 96 h
• Europe – 72 h
• Local – 24-48 h
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Environmental Health and Safety
Dedicated safety officer in charge of EHS
Dedicated safely committee :
– Devising and implementing EHS SOPs
– Review of safety performance and safety audit
– Investigation of any incident and taking necessary corrective and preventive actions
Organizing training session for the new joiners before assigning any lab work
Routine audit on:
– Chemical labs
– Other hazardous areas
– Night safety
– Usage and storage of pyrophoric/poisonous chemicals
Hazardous chemical waste management – segregation and proper disposal
Onsite emergency and business contingency plan
– Organizing regular mock drills
Compliance with all EHS related law of land
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Certified ISO 27001:2013 (By British Standards Institution, India)
•Recognized Globally – Verifiable on publicly available database •Endorses JBL as a business with risk based information security management system •Doorway to future business development
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Thank You!