Cambrex, which describes itself as a small molecule innovator and maker of generic APIs, and Axyntis, France’s largest producer of fine chemicals, have both taken steps in the direction of becoming true CDMOs in the past few months. This clearly follows a general trend towards CMOs enhancing their capabilities to offer more complete packages to customers.
October saw Cambrex’s $25 million acquisition of North Carolina-based PharmaCore and the opening of a new pilot plant at a site in Italy, following on from major expansions at the company’s two main multi-purpose manufacturing sites in the U.S. and Sweden. In all, the company expects to have spent over $200 million in capital projects within its existing facilities, nearly 30% of it in the recent expansions.
Now renamed Cambrex High Point, after its location, PharmaCore specializes in developing, manufacturing and scaling up small molecule APIs for clinical phase projects. It has sales of about $15-17 million/year.
Cambrex said that this deal would enhance its portfolio of small molecule API services for both pharmaceutical and biotech customers, while complementing its existing large-scale facilities by helping to develop early clinical phase products and new technologies. “We expect PharmaCore’s substantial customer base and robust project pipeline to broaden our potential late stage clinical development and commercial manufacturing opportunities,” commented CEO Steven Klosk.
PharmaCore’s 35,000 ft2 (3,250 m2) GMP facility, including a 15,000 ft2 (1,390 m2) chemistry laboratory and a 13,000 ft2 (1,200 m2) pilot plant, with reactor capacity ranging from 20 to 2,000 litres. It develops and produces complex APIs and multi-step intermediates at up to 100 kg scale in Phases I-III. The company also has a U.S. DEA license to make Schedule II-V controlled substances. There are about 60 employees, including 40 lab-based process and analytical chemists.
The pilot plant at Cambrex’s cGMP manufacturing and R&D site at Paullo, near Milan, has now been validated and ISO-certified. This plant can produce batch sizes in the 1-15 kg range and was built to meet growing demand for small-volume API volumes, both for validation to support a DMF filing for ANDAs or generic registrations, of which Cambrex has over 70 in its portfolio.
The plant will also supply niche APIs, notably ophthalmic drugs, and custom manufacture NCEs and intermediates for early stage drug development and clinical trials. Key features include a hydrogenator that can operate at 30 bar, two separate lines of 150 liter glass lined and stainless steel reactors, a static dryer, milling and micronization capabilities. A further upgrade is planned in 2017 to support the production of Class 3 and 4 high potency products.
Shortly beforehand, Cambrex had completed a $9 million investment to expand large-scale manufacturing at the site at Karlskoga, Sweden, which carries out development projects from R&D to commercial scales. This included new 4-13 m3 multi-purpose reactors and upgrading the control room within an existing plant. Following validation and cGMP qualification, operational start-up is expected shortly.
In July, Cambrex had announced the completion and validation of a $50 million production and warehouse expansion at its main cGMP site in Charles City, Iowa, which already houses three large-scale facilities. A similar-size shell building is also ready for further expansion.
Undertaken because of strong demand for small molecule APIs, this investment included 70 m3 of glass-lined and Hastelloy reactors, plus 6 m2 Hastelloy agitated filter dryers, all in a 7,500 ft2 (700 m2) multi-purpose manufacturing facility. The facility will be able to handle high potency APIs down to an occupational exposure limit of 1 μg/m3. Charles City is also DEA authorized to import narcotic raw materials at commercial scale.
Axyntis, meanwhile, finalized the acquisition of 3M’s API production unit at Pithiviers, central France, on undisclosed terms. This unit is located alongside Axynti’s Orgapharm subsidiary – the two already share water reserves for fire-fighting. Axyntis said that the deal will strengthen Orgapharm’s resources at R&D and pilot level and the group’s ability to offer CDMO services.
3M has been withdrawing from APIs and this was its last site in the field. Although it only recently confirmed its interest in selling up, the two companies had been talking ever since Axyntis came into being in 2007. The site was no longer making drugs and the number of employees had fallen from 250 in 2009 to 60. There had been sporadic unrest at the site, including strikes; at one point a manager was held hostage after closures were announced.
The 6.5 hectare site will bring 200 additional tonnes/year of manufacturing capacity and about €10 million/year in sales to Axyntis, whose employment base has now risen from 330 in 2013 to about 500. The company had expected to have sales of €82.4 million this year prior to the acquisition and now expects to grow to €95 million next year.
Director-general David Simmonet said that bringing together two neighbouring sites in this way will create a technology platform that “will help to improve group competitiveness by exploiting economies of scale to absorb costs better … We have about 20 R&D projects going on with high potential, half in pharma and half in cosmetics. These additional capacities will enable us to accelerate their development significantly.”
Production at the site, Simmonet added, will be geared towards projects for Axyntis’s part-owner, the Japanese silica manufacturer Fuji Silysia, with the regional pharmaceutical cluster Polepharma in biopharmaceuticals and continuing the supply of existing molecules to 3M on a multi-year contract. Production systems will not be changed but there will be a project to bring their activities into closer alignment.
The company will also reactivate parts of the site that had been mothballed since 2009. François Baduel, the director taking charge of fine chemicals, remarked at CPhI Worldwide that the site has unused cytotoxic capabilities and devices had been left behind that could make high potency formulations and Axyntis is now working out what it can do with this unexpected bonus.
