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Intelligent solutions for the pharmaceutical industry.
The special demands of the pharmaceutical industry require specific knowledge, know-how and experience. We are familiar with the specific features and regulations in this industry. This is particularly important for pharmaceutical plants.
Our great knowledge of the requirements for the synthesis of active pharmaceutical ingredients is revealed not only in the design of the processes and plants, but also by the integration of pharmaceutical standard automation systems. This facilitates a discontinuous or continuous synthesis stage, the implementation of safety functions by means of redundant, safety-oriented PLCs, provides the flexibility to change products quickly, and also allows reproducible batch processing to ensure consistent product quality.
Effectiveness and optimal tolerability are the main key points by which the products of our customers are judged in the pharmaceutical industry. This also involves the ability to respond quickly to the results of research and development.
- Optimization of synthesis processes in the production area
- Technical support for product development processes (preliminary stage and final stage products)
- Development of processes for manufacturing new active ingredients and their precursors
- Purification and preparation processes
- Synthesis and distillative ultrapurification
- Implementation of plants (turn-key or engineering support for preparation and implementation)
EPC Exclusives Engineering
- Multistage rectifications with diverse cycles (for example rectification and purification columns for producing ultrapure monosilane)
- Recalculation of columns for use with other substance systems (alcohols, tensides, etc.)
Hydraulics in interconnected networks for central supply systems (cold water, etc.)
The standard configuration of an organic synthesis module for special chemistry, fine chemistry and pharmaceutical substance chemistry can be described in simplified form as follows:
- Feeder system for solvents (central or decentralized preparation, buffer container, avoidance of incompatible media)
- Dosing system for reaction partners (portioning or continuous feeding)
- Agitated, temperature-controlled reactor with distillation system (jacket/half-coil pipes, additional internal and external heat transfer surfaces, central media supply or assigned heating/cooling units, cool/cold/cryogenic)
- Vacuum condensation system (dry-running vacuum pumps, liquid-ring pumps; condensers cool/cold/cryogenic)
- Co-reactor for phase separations
- Separation and drying of solids (either separate process stages or a filter-dryer combination)
In the case of multi-purpose plants, either reference syntheses and their minimum requirements are defined, or the limit values for using the plant are derived from the configuration.
Examples taken from requirement specifications:
- The plant is designed for largely automated operation. This means that the technical field conditions have been implemented for complete recipe control. The subsystems are operated and monitored by a central process control system. The elements relevant to GMP are qualified.
- Only some individual phases (such as dosing) run automatically. Batch logs are generated from the registered process variables and events that document the batch production.
Examples taken from requirement specifications:
The plant uses hazardous substances subject to the Hazardous Substances Order, which have the following properties: extremely flammable, highly flammable, very toxic, toxic, harmful, irritant, corrosive, sensitising, an occupational exposure limit value. Notices are available that describe the CMR properties of the substances used: EU category 2 or 3 (GHS category 1B or 2). A hazardous explosive atmosphere can develop in the plant area as per (TRBS (German Technical Rules for Operational Safety) 2152 Part 1. Liquids subject to the German Water Ecology Act are used in the plant (plant for producing, treating and using substances).
EPC Exclusives Process Technology
Special plants for producing pharmaceutical ingredients: Design compliant with Food and Drug Administration and GMP requirements
The following are integrated in the planning of pharmaceutical projects to comply with Food and Drug Administration and GMP requirements:
- Implementation of user requirements
- Risk assessment by means of an FMEA
- Qualification plans with acceptance criteria
- Qualification logs in the form of check point lists
- Qualification reports with assessment
- Change control management
- High pressure polymerization to produce polyethylene waxes
- High pressure polymerization to produce polyethylene vinyl acetate copolymers
- Polymerization in an agitator vessel to produce norbornene ethylene copolymers
- Synthesis in an agitator vessel to produce formaldehyde reducing agents
- Synthesis in an agitator vessel to produce bleach activators
- Synthesis in an agitator vessel to produce trimethylolpropane
- Continuous gas/liquid reaction to produce hexamethylenetetramine
- Rotary, thin-film evaporator and spray tower to produce granulated paraformaldehyde
- Catalytic gas phase reaction to produce dimethyl ether
- Continuous gas/liquid reaction to produce dimethyl formamide
- Synthesis in an agitator vessel to produce glycidyl ether
- Synthesis in an agitator vessel to produce epoxy resin
High pressures and temperatures are also used to control reactions effectively in the field of special chemistry
(Hydration reactor for synthesizing hexenol at 100 bar(g) in a salt bath reactor at +400 °C)
On the other hand, diverse reactions are controlled in a low temperature range
(Highly reactive substances, selective isomerisation, etc.)
- Alcohols, alcohol mixtures (e.g. methanol, ethanol, ethylene glycol, isobutylol)
- Aromatics, phenols (e.g. benzene, ethyl benzene, cumene, phenol, xylenes)
- Amines, amides (e.g. dimethylamine, trimethylamine, monomethylamine, formamide, methyl formamide, dimethyl formamide)
- Monomers for polymer production (e.g. norbornene, dicyclopentadiene)
- Chlorinated hydrocarbons (e.g. dichloromethane)
- Ketones (e.g. cyclohexanone)
- Carboxylic acid derivates (e.g. fatty acid methyl esters, fatty alcohols)
- Extractive distillation (e.g. butene-butadiene separation)
- Dehydration of products
- Separation of solvents from substances with relatively high boiling points (e.g. epoxy resin)
- Thermally gentle rectificative processes
- Reactive distillation (chlorosilanes)