“Technology for Life”

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Who we are

Global supplier of custom manufactured API’s

and Intermediates

Established in December 10, 1948

Turnover: USD ~80M [2014]

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Locations

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San Diego Research CenterHamari Chemicals USA Inc.

Europe OfficeFrankfurt, Germany

China OfficeShangha i

Kobe Research CenterHamari Chemicals, Ltd. Kobe Technolab

Head Office, R&D, Pilot PlantHamari Chemicals, Ltd.

Osaka

Tokyo Office

Commercial PlantYonezawa Hamari Chemicals, Ltd.

Commercial PlantChitose Hamari Chemicals, Ltd.

Custom Chemical

Manufacturing Technology

More than 60 different synthesis reactions at commercial scale

Strengths: Unnatural Amino acids

Long chain peptides

Optically active compounds

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A look back to the beginning…

1948 Hamari’s first product: Saccharin

1950 first API: Quinine Ethylcarbonate

1957 first custom synthesis: Orotic acid

1961 first Amino acid: DL-Methionine

1962 first Amino acid derivative: Methyl Methionine Sulfonium Chloride

1966 first peptide in laboratory: L-Leucyl L-Leucine

1968 first peptide on commercial scale: L-Glycyl L-Glycine

1970 first peptide on a multi-ton scale: β-Alanyl L-Histidine

1970 first contract manufacturing: protected Amino Acids

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1976 first contract manufacturing with multi-step synthesis

1985 first FDA approved product: Ibuprofen

1997 FDA inspection of the Yonezawa facility (Yonezawa Hamari Chemicals, Ltd.)

2001 ISO 14001 Certification of the Yonezawa facility

2002 launch of Zinc Carnosine on the US market

2006 two separate FDA inspections at the Yonezawa facility

2008 establishment of a high-potency laboratory and a kilo-scale laboratory at

the Osaka facility (Hamari Chemicals, Ltd.)

2008 founding of the Hamari Chemicals, Ltd. Kobe Technolab

2011 founding of Hamari Chemicals USA Inc. San Diego Research Center

2013 FDA inspection at the Yonezawa facility

2013 acquisition of Chitose Hamari Chemicals, Ltd.

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Sales in 2014Sales volume: 80 million USD (Fiscal 2014)

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Active PharmaceuticalIngredients (57%)

Cosmeceutical & NutraceuticalIngredients (７%)

Intermediates (30%)

Others (6%)

Our customers by region

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Japan (93%)

Others (2%)EU(1%) USA(4%)

Product NameManufacturing

Site

Annual

Production

Amount

Delivery Location

Polaprezinc /

Zinc Carnosine Yonezawa 11 t Japan and USA

Benfotiamine Yonezawa 50 t Worldwide

Tamsulosin HCl Osaka 26 kg Japan

API Examples (Commercial Products)

* Final intermediate * Final intermediate

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Chemical Name Brand name Trademark

Zinc Carnosine PepzinGI

(L-Carnosine Zinc complex)

Benfotiamine BenfoPure

(Vitamin B1 derivative)

L- Carnosine CarnoLife

(β-alanyl-L-histidine)

Food Supplement Products Sold in the US

Hamari has been supplying food supplement ingredients

to the US market for over than 20 years.

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University •Technology Licensing Organization

Nutraceuticals/CosmeceuticalsOTC Products/Natural Extracts

GenericPharmaceuticals

Bio-Venture

NovelPharmaceuticals

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Yonezawa Plant

Hamari (Osaka)

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Manufacturing

Dept.

President

Board Members

QAU

R & D

Dept.

Sales &Marketing

Dept.

International

Dept.

Purchasing

Dept.

QA Section

QC Section

Shanghai

office

Group 1

Group 2

Group 3

Group 4

Kobe Lab.

Section 1

Section 2

Hamari

USA

Europe

office

Project

Management

Office

Plant Manager Plant Manager

Chitose Plant

QA Dept.

Manufacturing

Dept.

No.1

Section

No. 2

Section

No. 3

Section

QA

Section

QC

Section

Production

Management Dept.

Technology

Dept.

Packaging & Labeling

Section

Engineering &

Maintenance Section

QA Dept.

QA

Section

QC

Section

Manufacturing

Dept.

Engineering &

Maintenance Section

The organizational chart of Hamari Group

Material Management

Section

EHS

Office

Environment Control

Dept.

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Hamari -Osaka

R&D Dept. (37)

Manufacturing Dept.(1３)

Domestic Sales &

Marketing Dept.(11)

International Dept.(6)

QA Dept.(6)

QC Section (9)

Manufacturing gram to 100 kg

(Lab, Pilot, Pre-clinical，PhⅠ，PhⅡa)

Scale-Up

TransferProject Management (7)

Yonezawa Hamari

Technology Dept.(14)

Manufacturing 50 to 200kg

(PhⅡb, PhⅢ, Validation, Commercial)

QA Dept.(13)

QC Section (25)

Manufacturing Dept.(74)

Project Management (2)

Chitose Hamari

Manufacturing 50 to 100kg

(PhⅡb, PhⅢ, Validation, Commercial)

QA Dept.(2)

QC Section (5)

Manufacturing Dept.(8)

Hamari USA Inc.

San Diego

Research Center

Synthesis

Transfer

Quality and R&D EmployeesResearch &

Development Total Osaka Yonezawa Chitose

New products 3 6 0 0

Process

Chemistry39 37 13 0

Quality Total Osaka Yonezawa Chitose

QA 15 6 13 2

QC 29 9 25 5

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Osaka Size: 1970 m2

Work Shift: Daytime (adjustable)

Waste Water: incineration, public sewage treatment

Water: potable, deionized

Low Temperature cooling system

Total Reactor Capacity: > 21 m3

Reactors: 50L to 2000L, 17 GL, 10 SUS

Low Temp.: -20˚C

High Temp.: 150˚C

Autoclaves: 3 reactors at 0.96 MPa (SUS 100L, 500L, Hastelloy 500L)

Controlled Areas: 2 lines (200L, 1000L)

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Yonezawa Size: 52,806 m2

Initial Production Date:1981

Work Shift: Daytime (some evening shifts)

Waste Water: incineration, self-process

Water: potable, purified, deionized

Total Reactor Capacity: >270 m3

Reactors: 50L to 5000L {72x GL(148m3); 75x SUS(123m3 )}

Low Temp.: -90˚C

High Temp.: 150˚C

Autoclaves: 1 reactor at 0.2 MPa (SUS 1000L); 4 reactors at 0.96 MPa (300L to 2500L); 1 reactor at 6.8 Mpa (SUS 500L)

Controlled Areas: 4 areas (200L, 800L, 1000L, 2000L, 3000L)

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Yonezawa API Plant 3Glass-lined 5

Stainless Steel 12

Vertical Dryer 2

Autoclave (1 MPa) SUS 2500 L

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Chitose

Size: 8,000 m2

Land Size: 56,760 m2

Initial Production Dates: Pharmaceutical 1999, Nutraceutical 1990

Acquisition Date: 2013

Total Reactor Capacity: >20 m3

Reactors: 14 x GL (15 m3); 6 x SUS (4.6 m3)

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Hamari USA Inc. San Diego Research

CenterSynthetic Route Scouting

Size 307 m2

Seven 8’ hoods

Two 12’ walk-in hoods

5 to 50 L jacketed reactors

Parr hydrogenator and autoclave

Onsite LC/MS, HPLC and NMR

CHIRALPACK 1A, 1B, 1C, 1D and 1E columns

Combi-Flash automatic chromatography

Access to FTIR, TGA, DSC, XRD…

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ReactorOsaka 2000 1500 1200 1000 500 200 100 75 50 Total

Total

(m3)

Reactor

GL 1 3 5 3 2 2 1 17 12.75

SUS 1 2 2 2 2 1 10 8.5

Hastelloy 1 1 0.5

Teflon-lined 1 1 0.075

Autoclave

SUS0.49

MPa

0.2

MPa2

Hastelloy0.98

MPa1

Yonezawa 5000 4500 4000 3000 2500 2000 1800 1700 1600 1500 1200 1000 800 500 200 50 TotalTotal

(m3)

Reactor

GL 2 5 14 1 19 3 11 4 2 2 5 3 1 72 145.4

SUS 1 6 5 20 3 1 1 12 14 5 6 1 75 122.9

Autoclave SUS1.0

MPa

1.0

MPa

1.0

MPa

0.2

MPa

6.8

MPa5

Controlled areas

1. GL1000L, SUS1000L

2. GL200L, SUS200L

Controlled areas1. SUS3000L, GL3000L

2. GL2000L, GL800L, GL200L

3. GL3000L, 2xGL2000L

Chitose 2000 1500 1000 800 750 500 300 250 30 Total Total (m3)

ReactorGL 2 2 6 1 2 1 14 15.0

SUS 1 2 1 1 1 6 4.6

Autoclave Hastelloy6.0

MPa1

Controlled rooms1. GL1000L

2. GL1000L

Reaction Vessels and Autoclaves

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Osaka

Filter Centrifuge Dryer Milling and Packing room

1 GL Nutsche 1 SUS (30 inch) 1 DBL Cone 2 Milling and Packing Room

4 SUS Nutsche 4 SUS (36 inch) 3 Tray Dryer 2 Cutter Mill

1 GL Vacuum 4 Vacuum Tray Dryer 1 Pin Mill

4 SUS Vacuum 1 Electric Sieve

1 Teflon-lined

1 Hastelloy

Yonezawa

Filter Centrifuge Dryer Milling and Packing room

3 GL Nutsche 1 SUS (30 inch) 7 Double Cone Dryer 8 Milling and Packing Room

12 SUS Nutsche 22 SUS (36 inch) 5 Tray Dryer 5 Cutter Mill

1 GL Vacuum 1 SUS (40 inch) 6 Vacuum Tray Dryer 1 Pin Mill

8 SUS Vacuum 2 SUS (42 inch) 7 Vertical Dryer 2 Hammer Mill

6 Plate and Frame Presses 1 SUS (48 inch) 1 Spray Dryer 4 Electric Shifter Sieve

2 Rubber-lined (36 inch) 1 Supersonic Wave Sieve

2 Teflon-lined (36 inch)

Chitose

Filter Centrifuge Dryer

1 SUS Nutsche 4 SUS (30 inch) 1 DBL Cone

1 Teflon-lined 1 Hastelloy (36 inch) 1 Tray Dryer

1 Filter Dryer

Other Equipment

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Analytical Equipment (1)

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Equipment TypeOsaka Yonezawa Chitose

TOTALQC R&D QC R&D QC

HPLC

PDA or UV

UHPLC

Ion Chromatography

7

1

1

34

4

19

7

10

1

2

1 87

GC

FID

TCD

ECD

Head Space Sampler

5

1

2

1 6

2

0

4

1

124

Test Chambers25˚C / 60%RH

40˚C / 75%RH

Yes

Yes

Yes

Yes

Yes

YesYES

Analytical Equipment (2)

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Equipment Osaka Yonezawa Kobe Chitose TOTAL

Atomic Absorption Spectrophotometer 1 1

LC/MS 1 1

Laser Diffraction Particle Size Analyzer 1 1

Potentiometric Titrator 1 2 1 4

FT/IR 1 2 1 4

Karl Fischer Titrator 1 3 2 6

NMR 200 MHz 1 1 2

Polarimeter 1 1 1 3

UV Spectrophotometer 1 1 1 3

Total Organic Carbon (TOC) 1 1 1 3

GC/MS 1 1

Conductivity meter 1 1 1 3

Fluorescence Spectrophotometer 1 1

Differential Scanning Calorimeter (DSC) 1 1

TG-DTA (Thermogravimetric Analysis) 1 1

X-Ray Diffraction (XRD) 1 1

Color Differential Spectrophotometer 1 1

Audit Experience(2012 - 2014)

59

9

12

from Japanese Clients

from Non-Japanese Clients

from Regulatory Authority

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Clinical Trial Products(IND manufacturing in 2012 - 2014)

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2

for Japanese Clients

for Non-Japanese Clients

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Type Ⅱ 2

EDMF 1

Korea 1

Client’s DMF 6

CEP 1

DMF’s Held by Hamari

DMF Number Status Type Submit Date Holder Subject

21259 A Ⅱ 1/14/2008YONEZAWA HAMARI

CHEMICALS CO LTD

POLAPREZINC AS

MANUFACTURED IN

YAMAGATA, JAPAN

DMF Number Status Type Submit Date Holder Subject

23196 A Ⅱ 10/18/2009YONEZAWA HAMARI

CHEMICALS CO LTD

LULICONAZOLE AS

MANUFACTURED IN

YAMAGATA, JAPAN

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