An Overview of Dr Reddy\'s CPS Complete Product Development Capabilities and Service Provision

1. Rising to the Pharma Challenge
Introduction to CPS
(Custom Pharmaceutical Services)
For LinkedIn
Christian Jones
European Sales & Business Development Manager
30-Aug-11 1

2. Content
 Corporate Overview
 Custom Pharmaceutical Services (CPS) Overview
 API – Development Capabilities
 API – Commercial Manufacturing
 Dosage Form Capabilities
 Project Execution
2

3. Corporate Overview
Purpose:
“Providing affordable and innovative medicines for healthier lives”
Strategy:
Leverage industry-leading science & technology, product offering,
and customer service with execution excellence to provide affordable
and innovative medicines for healthier lives.
3

4. Dr. Reddy’s Today
Business Mix Size
•Pharma Services & Active •FY11 ~ $1.7 Billion in revenues
Ingredients contributing 1/3rd
of revenues
Business Size
•Global Generics contributing Mix
balance 2/3rd
•Proprietary products business
in incubation mode
$1.7 BN
People & Infrastructure Product Portfolio
•14,000+ employees; ~ 2,000 in •100+ APIs, 150+ Finished
in international workforce Dosages
Infra Product
•20 Billion units in finished structure Portfolio •2 biosimilars launched in India
dosage manufacturing
•69 ANDAs pending approval
capacities
•200+ DMFs filed globally
•16 manufacturing facilities (9
Chemicals, 6 Finished Dosages •8 biosimilars in development
& 1 Biologics)
•Over 200 projects under
development
4

5. Our Businesses
Pharmaceutical Global Proprietary
Services and Active Products
Ingredients Generics
• Active Pharmaceutical • Biologics
• NA
Ingredients
• Specialty Pharmaceuticals
• Custom Pharmaceutical • EU (Germany, UK)
Services (CPS)
• India, Russia, Ukraine/CIS
& Venezuela
5

6. The Last Decade:
Achieved Scale and Global Presence
Built the foundations for a strong business. Moved up the value chain. Strengthened capabilities.
Achieved scale and global presence. Growth aided by acquisitions.
1800
379 1,700
EBITDA ($ Mn)
1600 1,563
1,510
243
1400 1,365
351 369 1,250
121 285
1200 94
75 68
37 50 26
1000
FY00 FY02 FY04 FY06 FY08 FY10
800
600 546
463 447
380
400 338
234
183
200
0
FY00 FY01 FY02 FY03 FY04 FY05 FY06 FY07 FY08 FY09 FY10 FY11
6

7. Strong Product Development Platform
Strong and Growing Pipeline
Segment Pipeline
Total Filings 126 (including partnered ANDAs)
Pending ANDAs 69 (including partnered ANDAs)
US DMFs 176
EU DMFs 78
European Products >60
(pending registration)
Dossiers 150+ pending registration
(Rest Of the World)
Specialty (US 3 ready to market products +
Dermatology) several others in development
Biologics 8 in development
7

8. Track Record
2010 Agreement for acquisition of GSK’s Penicillin Facility (USA)
2009 Partnership deal with GSK in emerging markets
2008 Acquisition of BASF facility at Shreveport, US
Aquisiton of Dowpharma Small Molecules business associated with
2008
Dow’s Mirfield and Cambridge, UK Sites
World’s first biosimilar monoclonal anti-body ,Reditux (rituximab)
2007
launched
2008 2007 Fastest Indian Pharma Company to cross $1billion in annual revenue
2007 2006 1st Indian manufacturing company to be Sarbanes-Oxley certified
2006
2006 1st authorized generic deal with multinational pharma
2005
2001 2006 Key acquisition betapharm (Germany)
1997
2005 Key acquisition “Falcon” (Mexico)
1993
1st Indian pharma company to be listed on the New York Stock
2001
Exchange
1997 1st Indian company to out-license an NCE to a multinational pharma
8

9. Care for Environment and Society
Triple Bottom Line Approach…
Society • Dr.Reddy’s Foundation – Livelihoods & Education
Communities • Community Development– Health/Education/Livelihoods/Employability
• Patient Assistance Programs & DRHFE
Business
Operations
• Employee Engagement- Volunteer Program & Power of Ten
• Environment: ISO 14001 & OHSAS 18001certified facilities;
Zero Liquid Discharge & SHE technologies
Core Purpose
• Customer: FDA approved, Product safety (Pharmcovigilance)
• Suppliers: Vikreta- B2B portal,GBS
• Corporate Governance
• Employees: Policies / Talent Mgmt Board / Leadership dev/ BPE
To help people lead healthier lives through Access & Affordability
9

10. Achievements
Aon-Hewitt 25 best Employers in India 2011 Dun & Bradstreet American Express
Business Leader in the Pharmaceutical Sector Corporate Awards 2007
Pharma Excellence Awards 2006-07 for
Forbes 2010 Asia Fab 50 companies 2011
sustained Growth
First time featured on the list
The Indian Express
Best Corporate Social Responsibility Initiative Asia-Pacific HRM Congress 2007
2007 Global HR Excellence Award for Innovative HR
BSE - India Practices
10

11. Overview – Custom Pharmaceutical Services
11

12. Background
 One of the largest Custom Pharma businesses from India
 End-to-end capabilities
Discovery Process Clinical Commercial
Chemistry Development Development Launch
Process Intermediates Intermediates
Development APIs & APIs &
Kilolab Dosage Commercial
quantities Supplies for drug product
clinical trials
 3 dedicated R&D facilities (2 in Hyderabad
and 1 in Cambridge)
 Broad Client Base: 39%
 Large Pharma – 10+
 Mid Sized Pharma – 5+
 Emerging Pharma and Biotech – 30+
12

13. Custom Pharmaceutical Services
To be the preferred supplier of APIs, Intermediates and
Formulations to ‘Innovators’ worldwide
Delivering cost-effective and cGMP compliant products and services
Managing intellectual property consistent with Global standards
Emphasizing safety, health and environment
cGMP Speed
Competitive
Innovation Pricing
13 13

14. History
2003 2004 2005 2006-7 2008-10
Expanded Acquired Dow
Technology Initiated customer base Pharma’s technology
Acquired
Development contracts with to about 30 platforms and facility
Business Roche’s
Centre Big Pharma with several in the UK, BASF
Facility in
commissioned repeat business Dosage site in the
Mexico.
US.
Manpower 70 110 800 950
Focus on API Integrated offer Offer contract Offer niche
Services Development of services with Development & technology
and scale up Dosage Form Manufacture of solutions in
Development Niche API’s (High complex Chiral
and Supplies Potent - Cytotoxic, molecules, PEG’s,
Hormonal etc) Peptides,
prostaglandins,
carbohydrates
14

15. Custom Pharmaceutical Services
A Global Organization
Custom Pharmaceutical Services
Sales & Marketing Technology Dev. Centers Manufacturing
North America R&D Chemical Plants
Hyderabad, India Hyderabad, India
Cambridge, UK Cuernavaca, Mexico
Europe
Mirfield, UK
Pilot Plant
Asia Pacific Hyderabad, India Formulation Plants
Mirfield, UK
Hyderabad, India
Louisiana, USA
15

16. CPS Value Proposition
Technology: Cost-effective:
► Chiral Capabilities – Chemo and Bio Catalysis ► Geographic advantage
► PEGylation Technology ► Fit-to-purpose scale of production
► Continuous Processing ► Global supply chain
► Steroid and HPAI capabilities
► Carbohydrate Chemistry (Ex.Fondaparinux) Track Record & Quality:
► Traditional Chemistry ► Large base of customers with several
► Peptide, Prostaglandins & Oligo building blocks repeat business
► High quality products and services
Manufacturing & Security of Supply: ► Corporate philosophy supports global
► Extensive, flexible capacity markets
► Geographical versatility -India/UK/Mexico ► cGMP compliant, USFDA inspected
► Large portfolio of DMF’s available off the shelf facilities
► More than 100 tech transfers of ► ISO 27001 certification (IP and
Innovator projects Documentation standard)
► Competent technical staff
► Dedicated project management teams through
product life cycle
16 16

17. API – Product Development Capabilities
17

18. Technology Development Center (Hyderabad, IN)
Dedicated R&D facility for CPS with ~300 chemists and engineers
Kilo Lab / Pilot Plant with about 10,000 sq ft
Class 100,000 clean room
Discovery Chemistry & Process R&D
21 Chemistry Labs
5 Analytical Labs
Class 100, 000 Cytotoxic suite
18 18

19. Analytical Capabilities
Method development and validation
Impurity profile: Established expertise in isolation, identification and
characterization
Certified, qualified and validated equipment: DSC/TG, GC/LC-MS, LC-MS-
MS, powder XRD, single crystal XRD, NMR, LC-NMR, FT-IR, CHN analyzer
19 19

20. Technology Development Center (Cambridge, UK)
Biocatalysis
• Discovery and development of Industrial biocatalysts and their
application in bio-catalytic manufacture of fine chemical intermediates
• In-house culture collection of more than 2000 microorganisms in 96 well
plate format
Chemocatalysis
Mirfield
• Technologies with utility in large scale manufacturing
• World leader in asymmetric hydrogenation
• Other capabilities for fine chemical applications such as Cambridge
• Achiral
• Asymmetric hydro-formylation
Complex Synthesis
• Have experience of more than 120 customer projects over
the last 12 years
• Capability to develop efficient processes to manufacture
complex target molecules including
• Sugars
• Prostoglandin analogues
• Oxa-prostoglandins
20 20

21. Activated PEG Offering
► mPEG-X
–Linear architecture
–Molecular Weights: 5, 10, 20, 30, 40, 60 kDa
–Narrow polydispersity
–Low levels of difunctional PEG: < 1-5% depending on MW
► Functional Groups
–p-nitrophenyl carbonate
–propionaldehyde
–Maleimide
–Amine
► Custom PEGs
21
21

22. API – Commercial Manufacturing Capabilities
22

23. API Production Facilities - India
Six commercial production units – All inspected by USFDA
Six Pilot Plants, Two Kilo Labs
Over 2 million liters of reaction volume
Over 500 GL and SS reactors that can handle temperature range
of –75 to 300 oC
Operations fully integrated through SAP
and global supply chain practices
23 23

24. Highly Potent API Production Blocks - India
Contained Blocks 1&2:
► Fully contained cGMP compliant facility
► Range of reactor capacity – 63 L to 630 L, 250 L to 2000 L
► Occupational Exposure Limits (OEL) 0.2µg/m3 for 8 h TWA
► Containment practiced through Air Handling, Pressure Zoning, Isolators
and Personal Protective Equipment
24 24

25. API Manufacturing Network: India
CTO IV – 1984 CTO V – 1987
CTO III – 1995
Vizag
Hyderabad
Miryalguda
CTO II – 1986
CTO VI – 1990
CTO I – 1985
25

26. Regulatory Experience
Type Number
USDMF 176
EDMF 78
CEP 22
Canada 51
Japan 18
Korea 23
China 14
Turkey 12
Singapore 5
26

27. USFDA Inspections
Unit Date Unit Date
Unit II & III March 2003
Unit IV November 1987
Unit VI May 2004
Unit IV March 1996
Unit V March 2005
Unit V March 1997
Unit I & II Nov 2005
Unit I & IV June 1999
Unit III & IV March 2007
Unit II, III & VI February 2000
Unit VI April 2008
Unit V November 2000
Unit I & Unit 5 Feb 2009
Unit IV November 2002
Unit III September 2010
27 27

28. API Production Facilities – Cuernavaca, Mexico
USA
Mexico City
Toluca
Belize
Cuernavaca
Guatemala
28

29. Quality
Centre
Incinerator
Main Tank Farm
Offices
Warehouses
Utilities
Production
29

30. API Production Facilities – Cuernavaca, Mexico
Installed production capacity : 3350 MT
7 Reactor Bays with reactor volume ranging from 100L to 20KL
1000L and 3000L Cryogenic reactors capable of -110 oC
20 Steroidal API’s and several Steroid Intermediates currently produced
Unit audited by FDA
125 Multi-disciplinary professionals
• 25 post-graduates (Ph.D. and Masters)
• 100 graduates (chemists, engineers, accountants)
30 30

31. Product Lines - Mexico Facility
Naproxen:
• 32 Years of experience in producing Naproxen
• Installed capacities: Naproxen & Naproxen Sodium – 1000+ TPA History of
Supplying of Naproxen globally including USA, EU and Japan
• Inspected & approved by USFDA
Steroids:
• Expertise in development of NCE steroids
• Dedicated, refurbished bay at a cost of ~ $29 M
• 3 Flexible manufacturing trains
• Containment for Offloading & Milling
• Class 100,000
• More than 20 DMF’s,
80% on exclusive basis on behalf of customers
31

32. Dosage Form Capabilities
32

33. Seamless Formulation Services
Covering the Entire Product Development Chain
Analytical Preformulation Formulation CT Commercial
Development Development Development Manufacturing Manufacturing
Preclinical Clinical Supply Market Launch
• Preformulation
• Analytical and Bioanalytical Development
• Formulation Development
• Pilot Scale-up
• Clinical Trial (CT) Supplies Manufacturing
• Commercial Scale Contract Manufacturing
33

34. NCE Product Development - Capabilities
Preformulation Studies:
Solution stability studies
Chemical Physical properties
Solid-state characterization
Solubility and reactivity and forced degradation studies
Formulation Development;
Formulation development for safety assessment studies
Prototype formulations for clinical evaluation
Process development
Formulations for comparator studies
Commercial formulation development
34

35. NCE Product Development - Capabilities
Clinical Trials Supplies Manufacturing and Packaging:
 Process optimisation, scale-up and technology transfer
 Clinical trials supplies manufacturing and release testing
 NDA stability and registration batches
 CMC documentation for IND submission
Analytical Development:
 Method development and validation
 Cleaning method development and validation
 Dissolution and drug release profiling
 Forced degradation studies
 Specification development
 Stability studies per ICH guidelines
35

36. Clinical Trial (CT) Supplies Manufacturing
 cGMP Manufacturing of CT supplies for Phase I, II and III.
 Scales of 1/100, 1/10 and 1 in similar equipment.
 Seamless scale-up and technology transfer to commercial site.
 Drug product supplies for comparator trials (DB encapsulation).
 Packaging for clinical studies, comparator trials and commercial supplies.
 IND and NDA support documentation.
 Experienced Product Development teams
36

37. Product Registration Support
Support Includes:
 Manufacturing, packaging and release testing of registration
batches
 Stability studies per ICH guidelines and monitoring
 Process validation plan, protocol and validation reports
 Documentation:
• CMC for IND and NDA
• Technical reports
 Experienced PAI teams
37

38. NCE Product Development - Experience
 Rapid prototyping for “quick” first time in human (FTIH) studies
 Clinical product development integrating formula, process and analytical
development minimizing costly reformulation
o Solubilization Technology;
 Nanoparticulate Formulations
 Cyclodextrin-based Formulations
o Injectables:
Small volume parenterals
Lyophilization
o Cytotoxic Product Development;
IV
Oral
o CMC for Regulatory Submission
38

39. Product Development Capabilities
New Drug Delivery Systems
39

40. Drug Delivery Technologies
Apart from standard oral solid dose formulations, specialized
technology platforms and IP have been developed to target:
 Delivery of drugs with tailored release profile
 Combination product with multiple incompatible DS
 Combination product with sequential release
 Solubility, dissolution and bioavailability
enhancement
 Taste masking and stabilization
40 40

41. Novel Drug Delivery Systems (NDDS) - Capabilities
• Explore drug delivery approaches for life cycle management
(LCM) to enhance therapeutic outcome and improve patient
compliance.
• Delivery System Based:
• Gastro-Retentive Systems
• Colon Specific Drug Delivery systems
• Small Drug particles
• Solid-Lipid particles
• Orally Disintegrating Tablets
41

42. Technologies practiced at Dr Reddy’s…..
 Pellets/ beads
 Gastro-retentive
 Zein Coating
 Muco-adhesive
 Combination product
 Liquid API in solid dosage form
 Nanotechnology
 Cyclodextrin Complexes
 ODT
 Ion exchange resins
 Ultra sound particle sizing
42 42

43. Dosage Forms Commercial Manufacturing Sites
• FTO 1 - Bollaram, Hyderabad
• FTO 2 - Bachupalli, Hyderabad
Vyzag
Hyderabad
• FTO 3 - Bachupalli, Hyderabad
Yanam
including R/D and pilot plant
• FTO 4 - Yanam
Baddi
• FTO 5 - Recently divested
• FTO 6 - Baddi (started up April 1 2006)
• FTO 7 - Vishakapatanam ~800km from
Hyderabad (Vyzag)
43

44. FTO-3 Capabilities
Main site for the development and manufacturing
of standard oral dosage forms and specialized
dosage forms
Modular concept - All batches follow linear
flow movement and one product at a time
Total of 11 modular manufacturing suites:
•9 Modules for Tablet Manufacturing
~ 4’750 mn units/year
•2 Modules for Hard Gelatin Capsules
Manufacturing ~ 650 mn units/year
•3 Pilot Plants (10 suites + 2 pkg)
Integrated development services
44

45. Processes and Equipments:
Fully aligned from Laboratory to Pilot Scale
Process Equipment Make Capacity
Solubilization Bead Mill Netzsch 100 mL – 2 Ltr
Labstar
Granulation High Shear Kevin 100 mL – 250 Ltr
Fluid Bed Glatt 1 Ltr – 125 Ltr
Blending Double Cone and Adams 1 Ltr – 425 Ltr
Octagonal
Compression Rotary Compression Cadmach 8 – 20 Station
Press
Pelletization Extruder Fuji Paudel 1 kg/hr – 20 kg/hr
Spheroidizer Fuji Paudel 1 kg – 2.5 kg
Drug Layering Glatt 150 g – 35 kg
Coatings (Tablets Side Vented Pans Gansons 500 g – 30 kg / lot
and Pellets) Fluid Bed (Wurster) Glatt 1 Ltr – 125 Ltr
Coater
Capsule Filling Tamp Filling Machine PAM 5 K/hr – 40 K/hr
Lyophilization Lyophilizer Vertis 200 – 2000 vials
Spray Drying Spray Dryer Buchi / Hemraj 100 mL – 5 Ltr / hr
45 45

46. Granulation, Blending and Tablet
Manufacturing Capabilities
Different batch sizes (20 kg – 1800 kg)
Granulation (low and high shear, FBP)
Aqueous-based
Solvent-based (x-proof)
Blending (60 L to 5000 L)
Compression: Sejong, Cadmach, Manesty (8 – 75
stations), bi-layer- tablets
Coating: Accela-cota equivalent (24’’ up to 66” from
15 kg – 450 kg)
Fluidized Bed Coating (125 to 500 Liters)
Aqueous coating (Functional and non-functional
coating)
Organic solvent-based coatings
46

47. Capsule Manufacturing
• Different Batch Size
• Bead Manufacturing (Pelletization or non
pareil seeds, dry powder loading).
• Fluid Bed Drying (15 kg – 300 kg)
• Blending (60 L – 5000 L)
• Coating (24’’ up to 66” from 15 kg – 450 kg)
• Encapsulation tamping and dosator - from
40 K/hour up to 120 K/hour
47

48. Dosage Forms Primary Packaging
Conversion of dosage forms to finished packs of
HDPE Bottles, Blisters (PVC/Alu, PVC-PVdC/Alu,
Alu-Alu, including cold form, PVC/ACLAR or
Aluminium Pouches
Total of 10 Lines
 4 Bottle Lines
 6 Blister-cartonators
48

49. Dosage Form Secondary Packaging Capabilities
Automated equipment designed and constructed as
per cGMP requirements
BossPack (Aus), Swiftpack(UK), Countec (Korea)
BQS, BP-602, Cartonator (IMA)
49

50. Highly Potent Formulation Facility
• Will comply with USFDA and MHRA requirements
• Containment practiced through Air Handling, Pressure Zoning,
Isolators and Personal Protective Equipment
• Three modules for
• Hormonal Tablets – 40 mn units/yr
• Cyto Capsules – 15 mn units/yr
• Cyto Injectable (Liquid/Lyophilized) – 3 mn units/yr
• Being commissioned
50

51. Project Execution
51

52. Well Knit Support Structure
Regulatory Affairs
QA
Supply Chain
Management Planning QC
Project Management
Capacity & Infrastructure
Process &
Production
Formulation R&D
52

53. Confidentiality
• Global Standards practiced for Confidential Disclosure Agreements
• IP ownership and rights clearly defined at project initiation
• Complete data protection for customers. Firewalls within various Project Teams
• Non disclosure and confidentiality agreement executed by all employees
• ISO 27001:2005 certified for information security management
©
53

54. R&D Support for R&D Work
CHEMISTRY FORMULATION
350 Chemists and Engineers across 3 Preformulation
centers Analytical & Bioanalytical
Access to Kilo-Labs for piloting development
Multiple Analytical Labs for process Formulation development
research support Pilot scale-up
DSC/TG, GC/LC-MS, LC-MS-MS, LC-MS/MS, Prep-HPLC, Capillary-HPLC,
powder XRD, single crystal XRD, NMR, GC, FTIR, NIR, p-XRD, Photo Stability
LC-NMR, FT-IR, CHN analyzer, ICP-MS Chamber , Dissolution Apparatus (Type
I, II, III & IV)
54

55. Project Path – Functional Involvement
Feasibility Optimization Hazop Studies Lab Validation Piloting Trial Production Comm.
Production
R&D
AR&D
PE
QA
QC
MFG
55

56. Communication Process
 Project manager is single point of contact
 Communication between functional departments of CPS & clients
 Regular e-mail updates & periodic progress reports
 Use of web-based communication channels like Groove
 Weekly / Fortnightly teleconferences & videoconferences
 Face to face meetings
 Proactive communication of deviations for joint problem solving
 Campaign reports
 Reduces re-work leading to better control on cost, quality and time
 Establishes strong customer orientation
56

57. Uniquely Positioned to meet pharma challenges…
Assets
(Dossiers, DMFs, IP,
Manufacturing)
Life Cycle Mgmt
Service Portfolio Mgmt Niche
Orientation Capabilities
Tech-Transfer
Niche Offerings
57

58. CPS uniquely poised to meet pharma challenges…
58

59. …By leveraging organizational strengths
59

60. CPS Group in Dr. Reddy’s – A Summary
• Wide experience and use of several Technology solutions
• Breadth of experience in process R&D, scale-up and commercial contract
manufacturing
• Intellectual property managed as per global standards
• Well-trained man power, quality systems and excellent infrastructure
• Well-versed with API & Formulation development, scale up, technology transfer,
Regulatory requirements and CMC Documentation needs
Our Value Proposition: Excellent speed and cost
advantage without compromising quality
60

61. For more information or to discuss your specific interest please
contact:
Christian Jones
European Sales and Business Development Manager
Dr Reddy’s CPS
ChiroTech Technology Limited,
410 Cambridge Science Park,
Cambridge, UK
CB4 0PE
T:+44(0)1223 728 030
M:+44(0)7827 157 247
E: cjones@drreddys.com
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