Technology for Life 1 Who we are Global supplier of custom - - PowerPoint PPT Presentation

▶
technology for life
SMART_READER_LITE
LIVE PREVIEW

Technology for Life 1 Who we are Global supplier of custom - - PowerPoint PPT Presentation

Jul 02, 2023 415 likes •687 views

Technology for Life 1 Who we are Global supplier of custom manufactured APIs and Intermediates Established in December 10, 1948 Turnover: USD ~80M [2014] 2 Locations Europe Office China Office Frankfurt, Germany

slide-1
SLIDE 1

“Technology for Life”

1

slide-2
SLIDE 2

Who we are

  • Global supplier of custom manufactured API’s

and Intermediates

  • Established in December 10, 1948
  • Turnover: USD ~80M [2014]

2

slide-3
SLIDE 3

Locations

3

San Diego Research Center

Hamari Chemicals USA Inc.

Europe Office

Frankfurt, Germany

China Office

Shanghai

Kobe Research Center

Hamari Chemicals, Ltd. Kobe Technolab

Head Office, R&D, Pilot Plant

Hamari Chemicals, Ltd. Osaka

Tokyo Office Commercial Plant

Yonezawa Hamari Chemicals, Ltd.

Commercial Plant

Chitose Hamari Chemicals, Ltd.

slide-4
SLIDE 4

Custom Chemical Manufacturing Technology

More than 60 different synthesis reactions at commercial scale Strengths: Unnatural Amino acids Long chain peptides Optically active compounds

4

slide-5
SLIDE 5

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

5

slide-6
SLIDE 6
  • 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.

6

slide-7
SLIDE 7

Sales in 2014

  • Sales volume: 80 million USD (Fiscal 2014)

7

Active Pharmaceutical Ingredients (57%) Cosmeceutical & Nutraceutical Ingredients (７%) Intermediates (30%) Others (6%)

slide-8
SLIDE 8

Our customers by region

8

Japan (93%) Others (2%) EU(1%) USA(4%)

slide-9
SLIDE 9

Product Name Manufacturing 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

9

slide-10
SLIDE 10

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.

10

slide-11
SLIDE 11

University • Technology Licensing Organization Nutraceuticals/Cosmeceuticals OTC Products/Natural Extracts Generic Pharmaceuticals Bio-Venture Novel Pharmaceuticals 11

slide-12
SLIDE 12

Yonezawa Plant

Hamari (Osaka)

12

Manufacturing Dept. President Board Members QAU R & D Dept. Sales &Marketing Dept. International Dept. Purchasing Dept. QA Section QC Section Shanghai

  • ffice

Group 1 Group 2 Group 3 Group 4 Kobe Lab. Section 1 Section 2

Hamari USA Europe

  • ffice

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.

slide-13
SLIDE 13

13

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 Transfer

Project 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

slide-14
SLIDE 14

Quality and R&D Employees

Research & Development Total Osaka Yonezawa Chitose New products 3 6 Process Chemistry 39 37 13 Quality Total Osaka Yonezawa Chitose QA 15 6 13 2 QC 29 9 25 5

14

slide-15
SLIDE 15

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)

15

slide-16
SLIDE 16

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)

16

slide-17
SLIDE 17

Yonezawa API Plant 3

Glass-lined 5 Stainless Steel 12 Vertical Dryer 2 Autoclave (1 MPa) SUS 2500 L

17

slide-18
SLIDE 18

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)

18

slide-19
SLIDE 19

Hamari USA Inc. San Diego Research Center

Synthetic 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…

19

slide-20
SLIDE 20

Reactor Osaka

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 SUS 0.49 MPa 0.2 MPa 2 Hastelloy 0.98 MPa 1

Yonezawa

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

SUS 1.0 MPa 1.0 MPa 1.0 MPa 0.2 MPa 6.8 MPa 5

Controlled areas

  • 1. GL1000L, SUS1000L
  • 2. GL200L, SUS200L

Controlled areas

1. SUS3000L, GL3000L 2. GL2000L, GL800L, GL200L 3. GL3000L, 2xGL2000L

Chitose

2000 1500 1000 800 750 500 300 250 30 Total Total (m3) Reactor GL 2 2 6 1 2 1 14 15.0 SUS 1 2 1 1 1 6 4.6 Autoclave Hastelloy 6.0 MPa 1

Controlled rooms

  • 1. GL1000L
  • 2. GL1000L

Reaction Vessels and Autoclaves

20

slide-21
SLIDE 21

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

21

slide-22
SLIDE 22

Analytical Equipment (1)

22

Equipment Type Osaka Yonezawa Chitose TOTAL QC 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 4 1 1

24

Test Chambers 25˚C / 60%RH 40˚C / 75%RH Yes Yes Yes Yes Yes Yes

YES

slide-23
SLIDE 23

Analytical Equipment (2)

23 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

slide-24
SLIDE 24

Audit Experience

(2012 - 2014)

59 9 12

from Japanese Clients from Non-Japanese Clients from Regulatory Authority

24

slide-25
SLIDE 25

Clinical Trial Products

(IND manufacturing in 2012 - 2014)

19 2

for Japanese Clients for Non-Japanese Clients

25

slide-26
SLIDE 26

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 1/14/2008 YONEZAWA HAMARI CHEMICALS CO LTD POLAPREZINC AS MANUFACTURED IN YAMAGATA, JAPAN DMF Number Status Type Submit Date Holder Subject 23196 A Ⅱ 10/18/2009 YONEZAWA HAMARI CHEMICALS CO LTD LULICONAZOLE AS MANUFACTURED IN YAMAGATA, JAPAN

26