Services & Products
DOTTIKON provides chemical custom manufacturing services to scale up from grams to multi-tons, including routefinding, process design, process development, small-scale and pilot production, manufacturing, qualification and validation services.
DOTTIKON provides its customers with exclusive custom manufacturing services. The research and development efforts are optimized to allow for flexible and fast responses to customers needs. The streamlined decision process, the ability to ramp up production quickly and the state-of-the-art plants and equipment operated by highly-trained employees allow DOTTIKON to achieve its customers ambitious targets. DOTTIKON seeks to further expand on this platform by continuously improving the quality and efficiency of the production process based on the experience of a close exclusive interaction with customers, with whom DOTTIKON establishes unique and long-term relationships.
DOTTIKON is specialized in hazardous reactions. A 110-year history in handling explosives in the past makes DOTTIKON one of the most experienced partners in the industry for critical exothermal reactions such as nitrations, oxidations and azide chemistry, to name only a few. DOTTIKON's core technologies include hazardous, low-temperature and high-pressure reactions as well as continuous processing such as catalytic hydrogenations, alkylations, halogenations, Grignard and other metallorganic reactions.
DOTTIKON bases its operations on well-established and proven project management processes that are consistent with a sound quality management system.
Project/Product Managersare entrusted with the technical lead of the projects, while Business Development Managers take care of all commercial matters. The Steering Committee that involves the CEO and Senior Management regularly monitors and controls the progress of each project in order to ensure seamless project execution and the fulfillment of challenging customer requirements and high quality standards. This project governance structure in combination with highly skilled and experienced specialists ensures the safe and reliable achievements of project objectives.
Characteristics and benefits of DOTTIKON's project management
Active Pharmaceutical Ingredients
DOTTIKON has more than 40 years of experience in the production of active pharmaceutical ingredients (APIs). DOTTIKON is FDA and EMA approved. DOTTIKON's technology portfolio is built around APIs to enable scale-up, high-quality and cost-effective manufacturing under cGMP requirements from kilograms to multi-tons. The processes fulfill the ICH guidelines.
Experience and services
- Several API launches or post-launch transfers on production scale per year
- Preformulation and blending of APIs (e.g., nitrate esters)
- Quality management system in compliance with safety, health and environment (SHE) standards, ISO 9001:2015, including cGMP according to ICH Q10 guidelines
- Analytical method validation according to ICH Q2(R1)
- Process validation according to ICH Q10
- Submission and maintenance of Drug and Active Substance Master Files (DMF/ASMF)
- Stability testing according to ICH guideline Q1A(R2)
DOTTIKON develops and commercializes proprietary, high grade performance chemicals for a wide range of industrial applications in close partnership with its customers.
DOTTIKON Performance Chemicals platforms and selected applications:
Aromatic and Alicyclic Diamines for
- Polymers and composite applications
- High performance adhesives and resins
Bio-based Organosilanes for
- Polymer interfaces and surface modifications
- Reinforcement of polymer matrices
- Inorganic filler-polymer matrix coupling
Phlegmatized Azides as precursors for
- Crosslinking agents for polymer applications
- Coupling agents for carbon fiber composites
Nitrosamine Risk Assessment
The Nitrosamine Risk Assessment is based on a product specific and systematic theoretical evaluation of the nitrosamine risk level (EMA and FDA guidelines) including
- All stages of API manufacturing starting from RSM (registered starting material)
- Route of synthesis of RSM
- Starting materials, particularly when they are introduced late in the synthesis
- Reagents, solvents, water
- Recovered materials
- Process control
If the risk regarding the presence of nitrosamines in a particular API is found to be significant, confirmatory testing using state-of-the-art equipment is performed
- Quantification of volatile N-nitrosamines
- Determination using newest generation GC-MS-TQ with the option of headspace injection to allow quantification in complex sample matrix
- Highly selective and sensitive methods in place to quantify volatile
N-nitrosamines at or below concentrations according to ICH M7(R1)
- Methods originated from Ph. Eur. and Swissmedic
- Quantification under cGMP with validated generic methods, requalified for each individual sample and corresponding matrix
- Quantification of non-volatile and product-related
- Applying the most suitable instrument and technique
- Individual screening and analytical method development
- Method qualification and validation upon request
A detailed report is provided to support marketing authorization holder's obligation regarding assessment of nitrosamines in drug products
- LC-MS-SQ: Liquid Chromatography with Single Quadrupole Mass Spectrometer
- LC-HRMS-QTOF: Liquid Chromatography with Quadrupole Time of Flight High Resolution Mass Spectrometer
- GC-MS-SQ: Gas Chromatography with Single Quadrupole Mass Spectrometer
- GC-HRMS-QTOF: Gas Chromatography with Quadrupole Time of Flight High Resolution Mass Spectrometer
Different occupational exposure limits require different safety measures to handle APIs. DOTTIKON's experience ensures a safe handling of all processes involved.
To handle active substances, DOTTIKON has state-of-the-art containment concepts on all scales (e.g. closed charging / handling / discharging, full protection suit, monitoring, WIP/CIP cleaning, and cleaning validation). These concepts are applied by highly skilled and regularly trained staff.
cGMP and other higher industry quality standards are an integral part of the comprehensive quality system of DOTTIKON's independent Quality Management department.
DOTTIKON meets the high quality requirements of its customers thanks to the strict adherence to a quality system based on the process approach of ISO 9001:2015, which includes cGMP according to ICH Q7 as well as safety, health and environmental (SHE) protection.
DOTTIKON is authorized by Swissmedic (Swiss Agency for Therapeutic Products) to manufacture and sell active pharmaceutical ingredients (APIs) including liquid and solid dosage forms. It is subject to regular inspections by the Regional Medicines Inspectorate of North-Western Switzerland. The most recent audit was completed in February 2022.
The Quality Management system is based on a 3-level hierarchy
- Quality manual with a general overview and the perspectives of quality management
- Processes and general instructions for the main business processes
- Standard operating procedures with detailed description of each operational step
As part of the company's Quality Management, the Quality Control unit is responsible for testing raw materials, intermediates and final products to ensure compliance with specifications. The process analytics unit is responsible for in-process tests as well as release of cleaning results. The Quality Assurance unit monitors compliance with cGMP requirements such as review of batch records. Activities such as cleaning and process validation are performed by the responsible Quality Management project manager.
Active Substance Master Files (ASMF) or Drug Master Files (DMF) are prepared in the new eCTD format and are registered with the respective authorities worldwide
- In Europe with the EMA (European Medicines Agency) in the 'centralized procedure' and with the several national authorities in the 'national procedure'
- In USA with FDA as Drug Master File Type II
- In Japan with PMDA (Pharmaceutical and Medical Devices Agency)
- In several other countries such as Australia, New Zealand and Canada
DOTTIKON's most recent FDA inspection was completed in December 2022.
Recycling & Waste Treatment
Recycling & Waste Treatment includes recycling, thermal recovery, and high-temperature incineration of waste streams, as well as waste water treatment and purification.
The high-temperature waste processing plant is one of the most modern incineration plants in the world.
It was built to incinerate waste that cannot be treated in any other type of plant
- Incineration of 8'000 to 9'000 tons of waste per year (solid, liquid, and gaseous waste)
- Continuous plant operation (24 hours per day, 7 days per week)
- Computer-assisted operation and control of all process parameters
The on-site waste water pre-treatment plant consists of activated carbon adsorption of organic impurities, followed by neutralization and sedimentation. The used carbon is reactivated for reuse.
Based on the quality management system according to ISO 9001:2015, DOTTIKON ensures that the safety, health and environmental requirements of authorities and customers are consistently met.
Broad process development experience and technological expertise enables DOTTIKON to offer high-quality chemicals and intermediates, including
- Benzoic acid derivatives
- Benzyl compounds
- Boron building blocks
- Chiral compounds
- Cyclohexane derivatives
- Cyclopropyl building blocks
- Nitrate esters
- Nitroaromatic compounds
- Phenols and anisoles
- Pyridine building blocks
High purity, non-GMO isosorbide dimethyl ether (CAS 5306-85-4)
- Non-GMO statement available upon request
- Drug Master File type IV, "Letter of Access" available upon request
- Dottisol is a registered trade mark
Solubility enhancer in
- Skin whitening
- Skin cleaning
- Pharma grade excipient
- Accelerated topical delivery of actives
- Accelerated penetration
- Formulation and stability enhancer
- Dental tartar rehydratizing/softening agent
- Miscible with water
- Color- and odorless
- Among best-in-class leaf penetration promoters
- High water retention rate
- No phytotoxicity observed
Performance additive in
- Phase transfer reagent
- FDA and EU food regulations compliance
- Water-based formulations
- Improved adhesive properties
Article on isosorbide as renewable platform for novel applications
Spec. Chem. Mag. 34, 24 (2014)