Company Presentation - Arevipharma€¦ · Company Presentation . ... High Potent Plant Pilot Plant...
Transcript of Company Presentation - Arevipharma€¦ · Company Presentation . ... High Potent Plant Pilot Plant...
AREVIPHARMA GERMANY 2017 | 2
AREVIPHARMA – WHO WE ARE
German API manufacturer offering … Generic APIs with a focus on narcotics and niche products
Process development and custom manufacturing of APIs
Custom synthesis of complex fine chemicals
Our Characteristics ± 200 tons of API production per year
Quality made in Germany + independent & flexible
inspected by global authorities + global distribution
AREVIPHARMA GERMANY 2017 | 3
ORGANIZATION
Managing Director Dr. H. Baumann
Marketing
Business Development
Process Development
Marketing & Sales
Production
Production
Environment/ Safety
Logistics
Quality
Quality Control
Quality Assurance
Regulatory Affairs
Finance/ HR
Site Development
Technology
Production Planning
Procurement
Administration/ Finance
AREVIPHARMA GERMANY 2017 | 4
ORGANIZATION
140 FTE Marketing & Sales / Development
Finance & HR
Quality
Production
40 university graduates
10 PhD
43,5 y average age
21 y average job tenure
14
23
29
74
AREVIPHARMA GERMANY 2017 | 5
KEY FIGURES
own products 80%
CMO 20%
Europe (other) 37%
USA 1%
Asia 2%
Germany 60%
narcotics 25%
Regular API 75%
AREVIPHARMA GERMANY 2017 | 6
1874 Foundation of the production site by von Heyden (salicylic acid)
1961 – 1990 Arzneimittelwerk (“drug factory”) Dresden (AWD) (development/production/FDF)
1991 – 2007 Degussa / Hexal / Novartis pharmaceutical production
since 2007 Arevipharma GmbH
140 years of Knowledge in Chemical Production / cGMP
WHERE WE COME FROM
AREVIPHARMA GERMANY 2017 | 7
Basic Chemicals
Complex Fine Chemicals
Regulated Starting Material
Advanced Intermediates
Finished Dosage Form
Studies with Patients
Active Pharmaceutical Ingredients
PROPRIETARY PRODUCTS Manufacturing of Generics Route Scouting & Process Development e.g. regulated APIs/Narcotics High Potent APIs up to OEL 4 (> 1 µg/m³)
EXCLUSIVE PRODUCTS Custom Manufacturing Upscaling New Chemical Entities Generic APIs Advanced Intermediates Process Optimization, cost-effective Route-Scouting Analytical Development Regulatory Support / Registration
High Quality Chemistry cGMP
OUR BUSINESS MODELL
AREVIPHARMA GERMANY 2017 | 8
OUR PRODUCT PORTFOLIO
Active Pharmaceutical Ingredients | Focus Products
NARCOTIC APIs
Amfepramon Hydrochloride/ Diethylpropione Hydrochloride CAS 616-91-1 (USP)
Buprenorphine * CAS 52485-79-7 (PhEur, USP)
Buprenorphine Hydrochloride * CAS 53152-21-9 (PhEur,USP)
Fentanyl * CAS 437-38-7 (PhEur)
Fentanyl Citrate * CAS 437-38-7 (PhEur)
Hydromorphone Hydrochloride* CAS 71-68-1 (PhEur)
Oxycodone Hydrochloride * CAS 124-90-3 (PhEur, USP)
Remifentanil Hydrochloride * CAS 132539-07-2 (PhEur, IHS)
Tilidine Hydrochloride Hemihydrate * CAS 27107-79-5 (PhEur)
REGULAR APIs
Amiodarone Hydrochloride CAS 19774-82-4 (PhEur)
Bisoprolol Fumarate CAS 104344-23-2 (PhEur, USP)
Carbamazepine CAS 298-46-4 (PhEur)
Carvedilol CAS 72956-09-3 (PhEur
Cetirizine Dihydrochloride CAS 83881-52-1 (PhEur)
Dimethylfumarate CAS 624-49-7 (IHS)
Ebastine CAS 90729-43-4 (PhEur)
Ketamine Hydrochloride CAS 1867-66-9 (PhEur, USP)
Memantine Hydrochloride CAS 41100-52-1 (IHS)
Moxonidine CAS 75438-57-2 (PhEur)
Phenprocoumon CAS 435-97-2 (IHS)
Pyridostigmine Bromide CAS 101-26-8 (PhEur)
Sotalol Hydrochloride CAS 959-24-0 (PhEur)
Sultiame CAS 6156-3 (PhEur)
Torasemide CAS 56211-40-6 (PhEur, USP)
* Controlled Substance in Germany
AREVIPHARMA GERMANY 2017 | 9
OUR SITE
Arevipharma Owns Three Production Units - and Builds Two More
Multi Purpose Plant (Multi Ton Production)
High Potent Plant (Multi Kilogram Production up to OEL 4 - Products)
Pilot Plant (Multi Kilogram Production)
Pilot Plant up to OEL 4 (Multi Kilogram Production)
starting in Q4/2017
Kilo Lab (Small Volume Production)
starting in Q3/2017
AREVIPHARMA GERMANY 2017 | 11
PRODUCTION
Multi Purpose Plant
High Potent Plant Pilot Plant Kilo Lab
API
± 200 tons in ± 500 Batches of 35 APIs
Intermediates
± 600 tons in ± 1.500 Batches of 68 Intermediates
Chemical production
± 360 tons in ± 100 batches of chemical products
1- to 10-step syntheses
APIs with up to 10 different customer-specific
quality grades
3 shift production with 45 shift workers
AREVIPHARMA GERMANY 2017 | 12
PRODUCTION
Multi Purpose Plant High Potent Plant Pilot Plant
reactors 7 reactors (250 L – 630 L)
glass-lined & stainless steal
3 reactors (2,5m³) glass-lined (SiC/glass) & equipped with condenser
36 reactors (1,6m³ - 6,3m³)
glass-lined & stainless steal
temperature -20°C – 160°C -60°C – 200°C -10°C – 160°C
pressure 1 mbar – 15 bar 1 mbar – 15 bar 1 mbar - 6 bar
equipment
centrifuge connected with dryer (closed discharging system)
closed containment system (air, waste, safety)
emergency shut down system packaging area
centrifuges receivers tanks various filters filter dryer (stainless steel and
hastelloy)
specialities
Bromination hydrogenation with H2, NaBH4,
LiAlH4 gaseous reactions Grignard Friedel-Crafts Cyanation handling of corrosive substances
Hydrogenation with H2 or LiAlH4 reactions with NaCN, SOCl2 or
POCl3
Reduction with NaBH4, LiAlH4, BRCN
cyanation
centrifuges dryer various filters filter dryer
AREVIPHARMA GERMANY 2017 | 13
Aldol Condensation
Alkylation / Acylation
Amidation / Amination
Boronic Acid Chemistry
Condensation
Cyanation
Cryogenic reactions (pilot scale)
Decarboxylation
Diels-Alder reaction
Esterification / Saponification
Friedel-Crafts reaction
Grignard reaction
Halogenation (Cl, Br, I)
Handling of controlled and highly potent compounds
Handling of corrosive and toxic compounds, e.g. POCl3, SOCl2, NaCN, HBr, BrCN, Methylvinylketon, Ethylchlorformiate, Epichlorhydrine, N-LOST-Derivatives
Hydrogenation with H2-gas at up to 15 bar (catalysts: Pd/C, RA-Nickel, Pt)
Oxidation (e.g. Oppenauer)
Racemat Separation
Reduction with NaBH4, LiAlH4
Reactions with gases
Ritter reaction
Strecker reaction
Suzuki Coupling
von Braun reaction
Milling, micronizing, sieving
OUR TECHNOLOGY PORTFOLIO
Technologies for Custom Synthesis
of APIs, Advanced Intermediates and other Complex Fine Chemicals
AREVIPHARMA GERMANY 2017 | 14
Finishing Area closed system
class 100.000 (ISO 8)
Milling, Micronizing, Sieving particle size design
measurement with malvern
Jet mill, Hammer mill, pin disk mill
vibrating sieves ø 1m
Health, Safety, Environment highly controlled incineration of waste gas and
liquid waste (incl. chlorinated solvents)
waste water evaporation
Warehouse 2000 qm storing areas
separate cooling area 2-8 °C
high security storage of controlled substances/narcotics
INFRASTRUCTURE
AREVIPHARMA GERMANY 2017 | 15
Quality Control/ Assurance
Quality Control of final product and IPCs
13 analysts
Analysis of 5.000 batches p.a.
60.000 test parameters
Development of 30 in-hose methods incl. full validation (ICH Q2)
cGMP, Pharmaceutical Manufacturing License
QUALITY
Major Equipment
24 HPLC systems
Equipped with wave length, DAD, mass & corona detectors
18 GC Systems
Equipped with FID,NPD, TCD, ECD & mass detectors
Several injectors: headspace, on-column, cold
Spectrometers
500 MHz NMR, UV-Vis, IR
AAS & ICP-MS
AREVIPHARMA GERMANY 2017 | 16
Inspections by Authorities
REGULATORY AFFAIRS
United States US FDA (2009, 2012, 2016)
Brasil ANVISA (2012, 2015)
Japan PMDA (2012)
Korea KFDA (2012)
Germany GMP inspection (2014, 2016)
US-DMF E-DMF
CEP
J-DMF
6 32 23 2
Registrations
more than 150 global DMF approvals g
(e.g. Australia, Canada, Russia, Brazil, Taiwan,
South Korea)
AREVIPHARMA GERMANY 2017 | 17
Main Tasks of the Process Development Upscaling of (laboratory) processes Documentation, literature- and patent check Process optimization and trouble shooting Safety check (i.e. calorimetry etc.) Development of analytical methods and validation Synthesis of reference standards and impurities
PROCESS DEVELOPMENT
Process Development Industrial Production Pilot Production Process R&D
Head of Process Development
Process Development
Team 3 (Chemist)
Pool of Laboratory Technicians
Process Development
Team 1 (Chemist)
Process Development
Team 2 (Chemist)
AREVIPHARMA GERMANY 2017 | 18
Claudia Böttcher Europe +49 351 8314-1238 [email protected]
Marketing and Sales Team:
FROM GERMANY TO THE WORLD
Carsten Schröpfer +49 351 8314-1121 [email protected]
Dr. Hendrik Baumann +49 351 8314-1124 [email protected]
Business Development:
Kerstin Dreissig Overseas, Agencies +49 351 8314-1120 [email protected]
Arevipharma GmbH Meißner Str. 35 01445 Radebeul Germany Tel: +49 351 8314-0
Fax: +49 351 8314-2100
Web: www.arevipharma.com
Mail: [email protected]
CEO: