Overview

DOTTIKON offers full-scale chemical cGMP production, specialized in hazardous reactions, low-temperature and high-pressure chemistry as well as continuous processing.

DOTTIKON's equipment includes

  • Small-scale and pilot plant reactors with a total volume of 10 m3 ranging from 15 to 1'000 l in stainless steel, glass-lined, and Hastelloy C22 with pressure filters and centrifuges for separation
  • Production equipment with a total volume of 300 m3 and a reactor range of 4'000 to 12'500 l in stainless steel, glass-lined, and Hastelloy C22 as well as pressure filters and centrifuges for separation
  • Dedicated equipment for explosives, low-temperature, and continuous processing
  • Drying capabilities including a vacuum tray dryer (520 l, Hastelloy C22), paddle dryers (1'000 to 6'000 l in stainless steel and Hastelloy C22), and state-of-the-art spherical dryers (100 to 3'000 l in Hastelloy C22)
  • Batch distillation capacity with up to 40 plates under vacuum conditions
  • Thin film evaporator
Full-scale chemical cGMP Production

Process Development

DOTTIKON dedicates significant resources for rigorous R&D, routefinding and process development.

30 Project teams

  • 22 Process lab teams
  • Hazardous Reactions lab
  • High-pressure lab
  • Low-temperature lab
  • Continuous processing lab
  • 4 Route and process design teams
  • 10 Analytical development teams
  • Safety lab

 

Main process development equipment

  • Automated synthesis apparatus
  • 0.2 to 10 l double-jacketed reactors
  • Low-temperature reactors
  • Hastelloy, glass-lined and glass autoclaves
  • 1 l glass spherical dryer
  • Screening tools
  • Flow reactors: tube-, corning- and chemtrix-reactors
  • Lasentec(R) / turbidity probes
  • Online FT-IR
  • Off-gas IR determination
  • Crystal16 (R) automated solubility determination
  • Wet mills
  • Analytical preparative HPLC
  • Digital microscope
  • DynoChem (R) simulations

 

Kilo lab (30l)

 

Over 3'300 projects

  • 30 Development projects simultaneously
Process DevelopmentMultiple Autoclave

Small-scale

DOTTIKON offers small-scale production capabilities to quickly respond to the demand for smaller quantities and scale-up development needs (1 to 50 kg).

DOTTIKON's facilities are suited to the manufacturing of chemical intermediates and active pharmaceutical ingredients (APIs) in clinical trials, as well as for marketed small-volume APIs. The small-scale facilities are equipped to handle high-potency products.

 

Experience in over 130 different chemical reactions enable DOTTIKON to deliver new complex organic compounds within weeks instead of months.

 

The stand-alone facility is coordinated by our pilot plant and is operated by qualified staff dedicated specifically to the unit. The two small-scale plants operate according to cGMP guidelines.

Small-scale Production Capabilities

Pilot

A trend towards high-potent and therefore low-dosage drugs is a key challenge for suppliers of intermediates and active pharmaceutical ingredient.

DOTTIKON meets this demand with three stand-alone, fully qualified cGMP pilot/small-scale plants, equipped to handle high-potency products. DOTTIKON has experience in over 130 different chemical reactions and is scaling up over 80 reaction steps per year using its portfolio of core technologies, low-temperature, high-pressure, wet milling, and continuous processing.

 

DOTTIKON's modular approach to tailor the equipment to specific needs enables these facilities to handle small- to medium-scale production on one hand, and process and technology transfer as well as scale-up to feed our large-scale multipurpose plants on the other hand.

Pilot Plant Reactor

Production

DOTTIKON has nine cGMP multipurpose and specialized multi-ton production plants handling hazardous reactions, high-pressure (50 bar), low-temperature (−100°C), and continuous processing.

As part of DOTTIKON's full volume range manufacturing and scale-up services, versatile large-scale capabilities are offered for the production of up to several 100 tons per product and year, e.g.

  • 300 m3 capacity
  • 9 cGMP multipurpose and specialized multi-ton production plants
  • Dedicated plants for
  • Over 100 different chemical reactions
cGMP Production Plant

Isolation & Drying

Isolation and drying equipment is available on all scales and in different materials. All equipment is compliant with cGMP and other higher industry standards.

Isolation equipment for small-scale, pilot and large-scale production

  • Pressure filters (mobile and fix, clean rooms)
  • Inverted bag and peeling Centrifuges (clean rooms)
  • Clean rooms (Class 100'000)
  • Dedicated filtration rooms
  • Containment (endless liners, DoverPac system, Glove Box)

 

Drying equipment (cGMP)

  • Vacuum tray dryer (520 l, Hastelloy C22)
  • Spherical dryer (0.1 m3, Hastelloy C22)
  • Paddle dryers (1 to 6 m3, stainless steel/Hastelloy C22)
  • Spherical dryers (0.1 m3 to 3 m3, Hastelloy C22)

 

Special equipment

  • Fine impact mill
  • Jet mill
Isolation and Drying Equipment

Quality Control

The quality control unit of DOTTIKON ensures compliance with cGMP guidelines using validated analytical methods on qualified instruments.

 

As part of DOTTIKON's quality management, the quality control unit is responsible for testing raw materials, intermediates and final products to ensure compliance with specifications. For each material an approved testing procedure is available which defines the different analytical methods, and their acceptance criteria. The tests are carried out according to cGMP standards on qualified instruments that were calibrated in defined intervals. Method validation is performed according to the actual ICH guidelines.

The quality control consists of three laboratory teams for liquid chromatography, GC and non-chromatographic methods including spectroscopic methods as well as pharmacopoeia tests with 40 analysts. Validation of analytical methods is performed in a separate group, Analytical Quality Assurance.

Main analytical methods are

  • Liquid chromatography (HPLC/UHPLC)
  • Gas chromatography (GC)
  • Ion chromatography (IC)
  • Capillary electrophoresis (CE)
  • Thin layer chromatography (TLC)
  • IR-Spectroscopy
  • UV/VIS spectroscopy
  • High-resolution continuum source AAS
  • X-ray fluorescence (XRF)
  • Spectral colorimeter (e.g., Apha color scale)
  • Titration (including Karl Fischer)
  • pH
  • Melting point
  • Loss on drying
  • Differential scanning calorimetry (DSC)
  • Other gravimetric and thermogravimetric methods
  • Total organic carbon (TOC)
  • Particle size (Malvern 3'000)
  • X-ray powder diffraction (XRPD, service)
  • Specific pharmacopoeia tests
  • ICP-MS
  • Microbiological testing (service)
  • Nuclear magnetic resonance
    (400 MHz, 1H-, 13C-NMR, 15N-, 19F-)
     

Analytical techniques regarding Process Analytical Technology (PAT)

  • Online FTIR
  • Lasentec/FBRM

 

Analytical techniques for structure elucidation

  • Liquid chromatography with mass spectrometry detection (HPLC-MS, LC-MS-SQ, LC-HRMS-QTOF)
  • Gas chromatography with mass spectrometry detection (GC-MS, HS-GC-MS-TQ, GC-HRMS-QTOF, GC-MS-SQ)
Quality Control