New From Old Flexibility is Everything in the New cGMP-Compliant Active Pharmaceutical Ingredient (API) Plant for Saltigo
Lanxess subsidiary Saltigo has increased production capacity by converting an old fine chemicals plant into a new multipurpose facility. Join us on a tour of the new plant. Gleaming boilers and shiny-clean tiles— even at first glance, you can tell that Saltigo’s new API plant is no chemicals plant in the traditional sense.
Active pharmaceutical ingredients and their precursors—around 200 tons per year—are set to be prepared here, thereby contributing to the success of the Pharma Business Line. Currently, the company’s pharmaceutical business line contributes a quarter of its annual turnover of € 400 million, with another quarter being contributed by Specialty Chemicals and half from its Agrochemical business. But if the company’s managing director Wolfgang Schmitz has his way, the Pharma business line is set to expand. “It is a key cornerstone of our business,” he emphasizes.
Saltigo was not an instant success story. In mid-2006, Lanxess certainly helped along the birth of its subsidiary with a start-up dowry of € 50 million. But in the fact of profitable competitors such as the BASF subsidiary Orgamol, life is tough in the fiercely-contested fine chemicals sector. And business involving exclusive syntheses in the customer order is a separate story again: falling margins, an internationally-saturated market with few innovations, competitive pressure from Asia and customers who had not waited for a new player to emerge. Accordingly, the newcomer first had to fight for its place in the rankings, and it did not grow up unscathed.
Five hundred posts were shed, unprofitable operations were closed down, levels of hierarchy were stripped out and structures streamlined. Its strong links with the Bayer Group also proved to be an unexpected obstacle, as some customers feared that there might be know-how seepage, despite confidentiality agreements. But over the intervening period the share controlled by Bayer has fallen from 70 to 40 per cent, and with it the reservations of potential customers have been alleviated. Now it seems that the most difficult days are behind the company. “We have proved that custom synthesis and manufacture can also be operated successfully and profitably in locations with high wage cost levels,” Schmitz emphasizes.
Plant with tradition
The company committed € 10 million to convert the plant in Building O10 and to adapt it to the requirements for GMP-compliant manufacture of APIs and pharmaceutical intermediate products. The plant in the old brick building could already look back on a rich manufacturing tradition. Initially it was a site for producing dyes, and later quinolones, a first-generation group of antibiotics which also includes the Bayer preparation Ciprobay. “At the outset, we examined various options for using the plant,” recalls Dr. Karl-Heinz Duchene, Head of Manufacturing Business Line Pharma at Saltigo. Converting to an API plant seemed a demanding undertaking at first sight: after all, it involved converting a mono-operation plant with dedicated equipment into a multi-purpose plant. But on closer inspection the project team determined that the lion’s share of the equipment could continue to be used without major modifications. Collaborating with companies from the chemical park, such as the former Bayer workshops Tectrion on pipe construction, accelerated the work of the internal project team.
Now the blueberry-colored Saltigo logo of the Lanxess subsidiary is proudly illuminated, and inside the building a multi-purpose plant is in place representing a mix of old and new, with existing plant equipment being brought together with newly-acquired machines. Walking through the plant causes the heart of every true chemist to beat that bit faster: filters, centrifuges and reactors on a scale of between 2.5 and 8 cubic meters—this is pure chemistry. But even at first glance, the finer details of a GMP-compliant plant are revealed: for instance, looking at the filling aspect. Here, enclosed filler cabins prevent cross-contaminations. And the materials entry area on the ground floor is equipped with a pressure zones design and has Class D clean rooms (100,000 particles). Even the unit for producing super-clean water is unusual for a chemicals plant, but is necessary for the APIs being manufactured, which are in part administered orally and intravenously and therefore need to be of high purity.
Production in modules
Production takes place from top to bottom—in other words, the chemicals move under the force of gravity, in four mixing lines, one of which is completely new. One module is specially reserved for manufacturing registered intermediates, while the other three can be used to produce intermediates and active ingredients. The ‘brains of the plant’ is the control center, from where the employees control the entire plant using a validated process control system which was formerly used to manage the quinolone plant. One of those involved in the project recalls that “the challenge here was to enable the new package units to communicate with the existing ones”.
The reactors, with the boilers made in various materials, are a key equipment component: in addition to stainless steel and alloys, there is hastelloy for temperatures down to –120 °C and steel enamel for reactions involving hydrochlorides. In line with the trend in the pharmaceutical industry towards manufacturing active ingredients and intermediates as solids, which can be stored more easily and are more stable, the plant is equipped with funnel filters, two centrifuges and filter-driers. For instance, the inverting filter centrifuge in Module 2 can isolate up to 75 kg of moist product on each run, and the filter-drier in Module 4 uses a filter area of four square meters.
Duchene takes the view that this multi-purpose plant is well-equipped for the fine balancing act to be performed by all service providers, namely that of offering high flexibility with regard to customer requirements whilst also ensuring high capacity utilization on production plant. The plant configuration can be altered in accordance with the synthesis task, and the boiler pipe-work can be adjusted to the tubular track heights.
Typical of the custom manufacturing operation is its project business. Schmitz confirms that “80 percent is attributable to customer projects, and the rest to the broader customer base.” It is for good reason that he wants to further develop the Pharma side in particular. “The outsourcing market for patent-protected active ingredients and intermediates has a global volume of around US$ 12 billion,” explains Ann Gidner, Head of Marketing and Sales Business Line Pharma. Schmitz adds that Saltigo now already ranks amongst the top five custom manufacturers for pharmaceuticals. A key regional focus is the USA, which is why active pharmaceutical ingredients through to clinical phase IIa are being manufactured in a new plant in Redmond. Via this facility, Saltigo is looking to offer capacity to the flourishing pharmaceutical industry on the West Coast in particular, for fast and flexible small volume production. The new plant in Leverkusen now supplements the service offer by producing larger volumes of substances, as are required to supply the market. Overall, these moves see Saltigo boosting existing production capacities in Redmond and in the Leverkusen ZeTO (Central Organics Pilot Plant) by a quarter. “If we support an active ingredient as the synthesis partner from development in the laboratory through licensing and on to market, this opens up considerable value-adding potential for us,“ is how Gidner sums up the position.