Genzyme case study

Sanofi Genzyme

Genzyme, one of the world’s leading biotechnology companies, was contemplating the production of a new active ingredient for its new phosphate scavenger, an important treatment for patients suffering kidney failure. Unlike many of its competitors at the time, Genzyme was prepared to consider stepping out into the higher-risk area of the product / process matrix – i.e. a new product produced by a novel process.

Genzyme was tempted by the potential for significant capital and operating savings offered by NiTech’s continuous manufacturing technology. It therefore started work with NiTech just two years after the latter’s spin-out from Heriot Watt University, and the companies soon embarked on an 18 month collaborative development programme.

NiTech initially demonstrated the feasibility of the approach by testing the chemistry in one of its batch Oscillating Baffle Reactors (OBRs).  This gave the partners the confidence to proceed with the development programme (the first Stage Gate). The process was then moved to a continuous pilot unit, a Tubular Baffled Reactor (TBR) with 25 litres of working volume, to demonstrate the concept in equipment configured similarly to the target commercial system (second Stage Gate).

A series of trials was conducted, during which the reaction time was reduced by a factor of 60, and Genzyme was satisfied that the process could deliver significant benefits. “The NiTech folks were great to work with during this intense phase of the project, having a clear understanding of the capability of their technology in this new reaction system, and sharing our commitment to achieving a compelling outcome from the work” said Genzyme’s Senior Technical Director of Chemistry & Biotechnology Development.

Genzyme had been considering using two 150m3 pressurised stirred tank reactors to make the required API in volumes of hundreds of tonnes per year.  Now it was able to look at the possibility of incorporatinga single reactor – which would be less than 3m high and with reactor volume of less than 1m3 . “With the capital savings alone offered through performance like this, it was not difficult to sell the project internally”, added the Senior Technical Director.

The NiTech reactor® created uniform mixing throughout the solid / gas / liquid system (the gas introduced needed to react to a precise degree with the solids in an aqueous slurry feed) and offered predictable scale-up and plug flow conditions. The team was therefore confident that the performance demonstrated in the pilot plant could be duplicated in the commercial scale plant, and Genzyme proceeded to gain internal approval to build its new plant at its Haverhill, UK, site, with the NiTech TBR® at the heart of the design.

The plant needed only 20% of the space required for conventional technology, with knock-on implications for civil, structural, vessel and piping costs. The plant was up and running, with FDA approvals in place, within two years of the first engagement between the companies!

Today the plant has been in operation for over seven trouble-free years, and the performance has been outstanding. It is now producing product at twice the rate originally assumed in the design, thus eliminating the need for debottlenecking capital and costly shutdown time to install such upgrades.  This performance makes the economics of the original investment even more compelling in retrospect:

  • The technology is extremely robust, with maintenance levels a fraction of those needed  by pressure vessels
  • The fact that processing is continuous means that the need for auxiliary feed and collection vessels is eliminated
  • The use of sophisticated process analytics enables extremely good control of quality, as sampling rates are 100% and in real time, allowing the control system to make adjustments according to variations in flow rate, concentration, etc. This level of control would not be possible in conventional batch reactors
  • The TBR has enabled all of the manufacturing steps to be conducted continuously with no intermediate testing other than data from the control system
  • High levels of automation have enabled the TBR process to operate without operator supervision, in marked contrast to the alternative batch process.

Today, with Genzyme a part of the larger Sanofi group, the Haverhill site has become a disciple for the NiTech technology: “These benefits have made a major contribution to Genzyme’s business in the UK. We look forward to seeing further examples of this exciting technology commercialised within Sanofi in the coming years – continuous manufacture of APIs is the way ahead.  We look to produce smaller quantities of a larger variety of drugs in many different parts of the world – with a high quality threshold and at competitive costs. NiTech Solutions has a significant contribution to make in this transition to distributed manufacturing.

NiTech has now developed its pilot offering to include a range of professionally-built commercial units.  These are being sold to companies keen to exploit the benefits of this innovative continuous manufacturing technology (see other parts of this website for details).  Of course, not everyone wants to follow the Genzyme route and introduce a new product made using a novel process.  But there are still countless opportunities to use NiTech continuous technology to replace batch processes.

The proven operating efficiency gains described above can make a significant impact to the profitability of a business by utilising a smaller footprint.  The technology can therefore be retrofitted to existing plants to enable rapid de-bottlenecking and optimisation.

Sanofi Genzyme continuous pharma API plant