Drug Substance Siegfried offers a combination of experience and proficiency in both the chemical and pharmaceutical segments. Siegfried’s chemical expertise centers on the development and production of active pharmaceutical ingredients and intermediates, thus making Siegfried the ideal partner for both cGMP and non-cGMP active pharmaceutical ingredients and intermediates.
The value we bring that you can expect more from includes:
Drug substance development and production is provided at our Zofingen (Switzerland), Evionnaz (Switzerland), St. Vulbas (France), Minden (Germany), Pennsville (USA) and Nantong (China) facilities. As part of our backward integration, we have made significant investments in the chemical development and production capacities at our new plant in Nantong (China), with parallel investments at our headquarters in Zofingen.
With Siegfried as your preferred drug substance partner, you benefit from custom development and manufacturing of both active pharmaceutical ingredients and intermediates on three continents. Whatever your specific drug substance product requirement may be, Siegfried will provide more to meet your expectations.
API / Intermediates
Siegfried offers experience and proficiency in the chemical and pharmaceutical industry. Siegfried’s chemical expertise centers on the development and production of APIs and intermediates, making Siegfried the ideal partner for both cGMP and non-cGMP active pharmaceutical ingredients and intermediates.
Both development and production of active pharmaceutical ingredients and intermediates is provided at our Zofingen (Switzerland), Evionnaz (Switzerland), St. Vulbas (France), Minden (Germany), Pennsville (USA) and Nantong (China) facilities. As part of our backward integration, Siegfried has made significant investments in the chemical development and production capacities at our new plant in Nantong (China), with parallel investments at our headquarters in Zofingen.
Expect more with Siegfried as your preferred partner. We provide expertise in the development and manufacturing of custom active pharmaceutical ingredients (API) and intermediates with specialized know-how from our portfolio products.
Process and Chemical Development
Siegfried’s Drug Substance process and chemical development services will assist you in achieving genuinely scalable, cost-effective and robust pharmaceutical manufacturing appropriate to your product’s market needs.
Our talented and innovative development chemists are well experienced either in the development of entirely new synthetic routes or adapting and optimizing an existing process (from Siegfried or our customers). With Siegfried as your drug development partner, you can expect much more refined and commercially viable manufacturing processes.
Siegfried will work closely with you to understand your needs, and will establish the development objectives and scope for process optimization you can expect. Depending on the relevant process status and clinical phase needs, we incorporate many of the following options for you:
| Option | Focus |
| Synthetic route investigation | Determining synthetic route viability |
| Process optimization | Robustness and cost reduction |
| Process implementation, Scale-up | Manufacturing preparation |
| Determining critical process parameters | Validation preparation |
| Salt screening / crystallization program | Interface for product formulation |
| Design of Experiment (DoE) approaches | Exploring process "design spaces" |
| Developing 2nd generation processes | Life cycle management/cost reduction |
Siegfried has development locations in Zofingen (Switzerland), Evionnaz (Switzerland) and Pennsville, (USA), bringing a wealth of experience through more than 1000 transformations in synthetic organic chemistry.
Siegfried efficiently addresses your development goals by employing a close working collaboration between Process & Analytical Development groups and our pilot plant & safety laboratory.
Technology
Siegfried labs and production plants are designed to carry out all typical organic chemical reactions and enzyme-catalyzed transformations. Reaction conditions range from -100°C to 300°C and from 1 mbar to 40 bar.
For synthesis, we use batch reactors and continuous flow technology (CFT). Depending on the relevant application, the appropriate equipment is chosen from reaction carousels, double jacketed reactors and even microreactors.
Using synthesis machines, such as LabMax, RC1, parallel synthesis (ChemSpeed ASW 2000P) and Crystal 16 ensures we generate process data and information in the most effective way, speeding up development lead times and gaining greater understanding of reaction parameters.
We conduct synthesis & analysis of high potency materials (with OEL down to 1 µg/m3) in specifically-built, segregated contained laboratory areas.
Siegfried pays special attention to crystallization & product isolation processes, as these are vital for product yield and purity. Manufacturing processes for clearly defined crystal modifications and particle size distribution are developed – aided by various analytical techniques – and complemented by milling processes. Further techniques to manipulate physical form include spray drying, micronization and pre-formulation mixtures.
Finally, our process and chemical development capabilities are fully supported through the regular use of an array of analytical techniques & equipment, including NMR, HPLC, UPLC, GC, LCMS, GCMS, DSC/TGA, and Malvern, Mictrotrac and Helos PSD equipment.
Analytical Development
Siegfried recognizes and understands the importance of requisite analytical parameters & controls, as they are vital for ensuring effective and robust processes.
Our well-experienced Drug Substance Analytical Development team works closely with their Process Development counterparts to ensure our customer’s product is fully supported at every phase of the development process. Modernly equipped, we provide the following range of analytical services to help bring your drug substance development project & cGMP manufacture to fruition:
Siegfried works closely with you to understand your needs and establish the analytical objectives and development scope you can expect. Our shared goal is to develop routine procedures and efficient analytical testing methods packaged together with specifications suitable for Quality Control.
Depending on the relevant process status and a project’s clinical phase needs we incorporate many of the following development options:
| Offer | Focus |
| Method development | Product quality and process control procedure |
| Method optimization | Robustness and cost reduction |
| Method transfer | Production preparation according to the cGMP-guidelines |
| Method validation | Production preparation according to the cGMP-guidelines |
| Stability studies support | Durability regulations according to the ICH guidelines |
| Optimization of the routine method | Life cycle management and cost reduction |
Siegfried has analytical development locations in Zofingen (Switzerland), Evionnaz (Switzerland) and Pennsville, (USA), bringing a wealth of experience with more than 500 method validations in accordance with ICH Guidelines.
Having vast experience in cGMP compliance, we are able to support and advise our customers on relevant analytical aspects in the pharmaceutical sector (purity profiles, impurity tracking, establishing limits, structure determination, genotoxic contamination, heavy metal determinations, etc.).
Development Team
Siegfried employs close collaboration between Process & Chemical Development, Siegfried’s pilot plants and Quality Control to ensure overall analytical development goals are met.
For projects involving both Drug Substance and Drug Product, we similarly operate in close cooperation with Drug Product Analytical Development for characterization of the active ingredient and generation of specifications.
Technology
Modern analytical instruments available:
The analytical data, standards, specifications and testing guidelines are managed using a validated LIMS system.
Analytical Project Management
With Siegfried’s approach to project management, you can expect your own dedicated analytical project manager who coordinates the project’s internal analytical aspects with your analytical department and external service partners.
Once method development is complete, Quality Control puts a well-defined process in place to ensure smooth method transfers for routine operation.
Pilot Manufacturing and Scale up
Siegfried can help you save time & accelerate your drug development via our versatile cGMP pilot manufacturing & scale-up capabilities. Our core strength is taking a chemical process from development and scaling it up into a cost-effective & robust manufacturing process.
For drug substance pilot manufacturing Siegfried offers four production sites: Zofingen (Switzerland), Evionnaz (Switzerland), Nantong (China), and Pennsville (USA).
With Siegfried you are able to profit from a vast knowledge acquired from over 1,600 chemical development projects. Over the last ten years alone, Siegfried’s chemists have commercialized over 50 New Chemical Entities (NCEs) and applied a range of chemistries.
Whether it is a new or modified process generated from our chemical development or an existing process received directly from our customers, we are able to quickly and efficiently take the process to the next manufacturing stage required. We are able to support your various material needs from early clinical trials through to commercial launch and routine manufacturing.
Pilot Plant (Zofingen, Switzerland)
Kilo Lab & Pilot Plant (Evionnaz, Switzerland)
Pilot Plant (Pennsville, USA)
Pilot Plant (Nantong, China)
Manufacturing
Siegfried, as a flexible partner, provides reliable and consistent commercial supply combined with good quality product and performance. We do this by providing our customer’s versatile cGMP manufacturing capability and robust manufacturing processes suitable for specific market needs.
For drug substance manufacturing, Siegfried offers six production sites: Zofingen (Switzerland), Pennsville (USA), Nantong (China), Minden (Germany), Evionnaz (Switzerland), and St. Vulbas (France). All sites are fully cGMP compliant with an outstanding inspection history.
Siegfried offers extensive experience & expertise in manufacturing Active Pharmaceutical Ingredients (APIs) and key intermediates for exclusive customers, and an independent know-how through a portfolio of non-exclusive products. Also, we offer an extensive range of chemistries & process capabilities at production scale to efficiently manufacture demanding drug substances, intermediates and complex synthetic processes. Among the range of materials produced are controlled substances and high potency materials.
In addition to the synthetic chemistry, Siegfried ensures that the final isolation & finishing processes (crystallization, drying, milling, blending and packaging) are performed in separately controlled areas. Siegfried has applied drying units which utilize the latest double air-lock systems available. When possible, solvents are recycled using our extensive rectification capacity.
Whatever your production requirements may be, please contact Siegfried, as we would be delighted to service your needs.
Zofingen (Switzerland) Facilities
Annual output
Approx. 1,500 metric tons final APIs
Output range per product
0.5 – 900 metric tons
Total multi-purpose reactor volume
350 m3
Range of reactor volumes
800 – 5,000 liters (stainless steel, glass-lined, Hastelloy C22)
Number of reactors
120
Temperature range
-90 to 250°C
Pressure range
1 mbar to 40 bar
Product isolation
Centrifuges, nutsch filters, filter press, Titus-type centrifuge dryer
Drying capacity
25 m3 (10 dryers 200 - 2,500 liters)
Services
Custom manufacturing, full-scale validation, DMF, COS
Special equipment
Mills and sieves, KD 10 short path distillation, efficient Biazzi high pressure hydrogenation reactor, special bromination, chlorination unit
Pennsville (USA) Facilities
Annual output
300 metric tons final APIs
Output range
5 kg – 150 metric tons
Total multi-purpose reactor volume
233 m3
Range of reactor volumes
100 – 7,600 liters (stainless steel, glass lined, Hastelloy C22)
Number of reactors
52
Temperature range
-15 to 180°C
(special equipment up to 350°C)
Pressure range
1 mbar to 8 bar
Product isolation
Centrifuges, filter presses, Heinkel inverting basket centrifuge
Drying capacity
23 m3 (13 dryers 100l – 4.5m3) including a pilot and a commercial spray dryer
Special equipment
Sieves, mills and micronizer in IH class 1µg/ m3
Nantong (China) Facilities
Annual output
2,500 metric tons final APIs and intermediates
Output range per product
0.1 - 500 metric tons
Total multi-purpose reactor
175 m3 for API and 175 m3 for intermediates
Range of reactor volumes
1,600 – 10,000 lieters (stainless steel, glass-lined, Hastelloy C22)
Number of reactors
58
Temperature range
-100 to 250°C
Pressure range
1 mbar to 65 bar
Product isolation
Centrifuges, nutsch filters
Drying capacits Services
36 m3 (9 dryers 2,000 – 6,000 liters)
Custom manufacturing, full-scale validation
Special equipment
Mills and sieves, short path distillation, high pressure hydrogenation reactor, special bromination, chlorination unit, high and low temperature
Minden (Germany) Facilities
Annual output
Approx. 4,000 metric tons final APIs
Output range per product
2,500 metric tons
Total multi-purpose reactor volume
185 m3
Range of reactor volumes
800 – 10,000 liters (stainless steel, glass-lined)
Number of reactors
64
Temperature range
-15 to 260°C
Pressure range
1 mbar to 10 bar
Product isolation
Distillation columns with approx. 40 and 94 theoretical plates, Centrifuges (horizontal, vertical, inverting) nutsch filters, filter dryer, paddle dryers
Drying capacity
8.6 m3 (5 dryers 800 – 2,400 liters)
Services
Exclusive and portfolio APIs and Intermediates
Special equipment
Evionnaz (Switzerland) Facilities
Total multi-purpose reactor volume
315 m3
Facility lay out concept
Flexible set up tailored to meet any process
Stand-alone units are connected at will with flexible hoses to build production trains
Range of reactor volumes
2,000 – 8,000 liters (stainless steel, glass-lined, Hastelloy C22)
Number of reactors
75
Temperature range
-20 to 150°C (200°C on specific reactors)
Pressure range
1 mbar to 6 bar (12 bar on specific reactors)
Product isolation
32 theoretical plate distillation columns, thin layer evaporators (stainless steel and glass-lined)
Centrifuges, nutsch filters, filter dryer, tumble dryer
Drying capacity
36 m3 (14 dryers 1,000 – 4,000 liters)
Services
Exclusive and portfolio APIs and Intermediates
Special equipment
4 segregated chambers for hazardous reactions cGMP Phosgen generator (200 kg/Hr) secured bunker for Azide chemistry special bromination and hydrogenation units Mills and sieves
St. Vulbas (France) Facilities
Total multi-purpose reactor volume
141 m3
Facility lay out concept
Flexible set up tailored to meet any process
Stand-alone units are connected at will with flexible hoses to build production trains
Range of reactor volumes
2,500 – 8,000 liters (stainless steel, glass-lined, Hastelloy C22)
Number of reactors
28
Temperature range
-100 to 140°C (200°C on specific reactors)
Pressure range
1 mbar to 6 bar
Product isolation
16 theoretical plate distillation column
Centrifuges, nutsch filters, filter press, filter dryer
Drying capacity
31 m3 (8 dryers 3,500 – 4,000 liters)
Services
Exclusive and portfolio APIs and Intermediates
Special equipment
3 segregated chambers for hazardous reactions cryogenic reactors (4,000 and 6,000 liters) cGMP Phosgen generator (160kg/Hr – up to 300kg/Hr) special bromination and hydrogenation units
Portfolio API/Intermediates and Controlled Substances
With Siegfried as your partner for active pharmaceutical ingredient needs, your business can expect more value through:
Whatever your requirements are with regards to active pharmaceutical ingredients and intermediates, Siegfried will deliver more value for your business.
Marianne Spaene
Chief Business Officer