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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!