Helsinn Advanced Synthesis
Holding a GMP certificate since 1984, production has been completely dedicated to products requiring cGMP, with a clear focus on serving the Pharmaceutical Industry. HAS has also placed a high level of emphasis on our internationally renowned Quality System. HAS has also focused on sustainable production practices which protect the environment. Since early 2000, the plants have been ISO 14001 certified, as a part of Helsinn’s ongoing commitment towards international environmental protection. The continuous work on Health, Safety and Environment (HSE) also led to the OHSAS 18001 certification in 2005; we were one of the first chemical plants in Switzerland to achieve this status. In addition, the Helsinn Advanced Synthesis’ Sustainability report was approved by GRI (Global Reporting Initiative) and issued in 2012. Helsinn Group’s first Sustainability Report, approved by GRI and issued in December 2015, provides an updated situation of its production facilities in HAS. HAS has been successfully approved consecutively by the Swiss authorities and by the US, EMA and Japanese PMDA as well as by several other national boards, maintaining a flawless quality record. HAS has the capacity to produce a huge range of different batch sizes, from tens of tons to a few grams, depending on the requirements. Investment is ongoing to increase production capacity and more importantly, to add new capabilities increasing production flexibility.
Active Pharmaceutical Ingredients and Advanced Intermediates
Helsinn is able to take on a wide range of clinical and commercial projects due to the large flexibility in reactor sizes for small molecule classical APIs.
cGMP Process Scale-up:
- Kg quantities in our cGMP scale-up plant (100 and 250 L reactors)
- Stainless steel and glass-lined reactors
- Process verification and fine tuning
- Master formula preparation
- Demonstration batch
- Clinical batches
- Registration batches
- Process-validation batches
- Commercial supply
- Milling and micronization
- Flexible range of 1,000, 2,000, 4,000, and 6,300 L reactors including a (-80°C) reactor for metal-organic chemistry
- Stainless steel, glass-lined and Hastelloy Isolation
- Horizontal peeler centrifuges
- Basket centrifuges
- Pressure filter
- The final processing step in API manufacturing meets the conditions for final dosage form production
- Bi-conical rotary vacuum dryer (2,000 L and 4,000 L reactors) ISO 8
High Potency Active Pharmaceutical Ingredients (HPAPIs)
High Therapeutic Activity - Potent Low Dose compounds require product handling in containment facilities which provide the necessary protection for personnel, the environment and for the product itself. Helsinn’s expertise and reputation in this highly specialized area has been recognized worldwide by customers and agencies alike across the US, Europe, and Japan. Several HPAPIs have already been successfully produced in HAS' multipurpose production plant. With over 15 years of experience handling highly potent molecules (OELs ranging from 50 μg/m³ to 10 μg/m³), HAS' highly skilled team has produced numerous HPAPIs in therapeutic areas including: CNS, Cardiovascular, Respiratory, Dermatology, and Cancer Supportive Care.
- The Pilot Scale HPAPI Production Center, in operation since 2006, with 25 and 30 L reactors producing ~ 50 to 500 grams of material, process dependent
- The Small Scale HPAPI Production Center, in operation since 1999, is a multipurpose facility with 100 and 250 L reactors producing ~ 1 to 7 kg, process dependent
- The Large Scale HPAPI Production Center with 4000 L reactors is able to produce from ~ 25 kg up to hundreds of kgs, process dependent.
The chart below is the banding system that HAS has adopted. When working with highly potent and anticancer compounds, the first step is to define the containment level based on product characteristics.
HAS built a dedicated anticancer API plant in 2012 exclusively for the development, analysis and manufacturing of clinical and commercial anticancer APIs. The design of the facility offers complete independence from existing API and highly potent API areas to segregate production and anticipate pharmaceutical trends and future regulatory restrictions.
New dedicated laboratories have been constructed exclusively for R&D trials, design of experiment, initial process development, as well as QC activities.
The anticancer API Plant is segmented into three levels of production. Each production area is designed using state-of-the art closed system equipment with variable air pressure and engineering controls designed to protect HAS employees, the environment and the integrity of your product.
In terms of manufacturing, HAS can offer three levels of production dedicated to anticancer API compounds.
- The Pilot Scale anticancer API Production Center with 20 and 30 L reactors can produce ~ 200 grams to 3 kg of material, process dependent
- The Medium Scale anticancer API Production Center with 250 and 400 L reactors can produce ~ 3 to 20 kg, process dependent
- The Large Scale anticancer API Production Center with 630 and 800 L reactors can produce up to ~30 kg, process dependent
Facility Design Highlights
- Temperature range: -80°C up to +150°C; Pressure range: Up to 6 Bar
- Specific design and equipment to meet stringent OEL limits down to 50 ng/m3
- Additional safety measures for superior Health Safety & Environment (HSE) protection
- Closed system from raw material