Manufacturing Trends: Fine Chemicals and Chemical APIs

By Patricia Van Arnum - DCAT Editorial Director

October 7, 2015

Small molecules still constitute the majority of commercial drugs, but biologics' inroads into the pharmaceutical market is growing both on developmental and commercial levels. So what has been the impact of pharmaceutical manufacturing investment? DCAT Value Chain Insights (VCI) takes an inside look.

Recent large-scale manufacturing investment by pharmaceutical companies has largely centered on biologics manufacturing as companies have aligned their supply networks to meet growing product demand in this area. But how about chemical production capacity? DCAT Value Chain Insights (VCI) looks at manufacturing investment for small molecules.

On the CMO side  
High-potency manufacturing continues to be an active area of investment for contract manufacturers, which includes investment in manufacturing cytotoxic small molecules as part of antibody drug conjugate development and commercialization. On the API side, in March 2015, Johnson Matthey, a provider of pharmaceutical services, APIs, and catalyst technologies, announced the completion and commissioning of new high-containment facilities for potent product manufacture at its Edinburgh, UK site (i.e., Macfarlan Smith site). The self-contained facility meets existing demand for potent products and also provides additional capacity for anticipated future requirements. It features isolators containing a range of hastelloy and glass vessels, with powder transfers being mediated through split butterfly values with active valve wash stations. It also contains a dedicated finishing room, quality control laboratory and control room. The facility has the necessary manufacturing controls and procedures in place to produce compounds with occupational exposure limits of less than 30 ng per cubic Johnson Matthey also manufactures highly potent products through its facilities in West Deptford, New Jersey and Devens, Massachusetts.

Earlier this year, Patheon closed on its previously announced acquisition of IRIX Pharmaceuticals, a Florence, South Carolina.-headquartered company that specializes in making difficult-to-manufacture active pharmaceutical ingredients (API) for drugs from early and late development, through commercial launch. With the acquisition, Patheon secured additional API development and manufacturing services in the US, including high-potency (SafeBridge Class IV certified) and controlled substances (Schedule 1-4) IRIX has commercial API manufacturing at sites in Greenville and Florence, South Carolina.

Other companies also recently invested in high-potency manufacturing. In 2014, Lonza started up its second-large scale ADC facility in Visp, Switzerland. Since 2010, Lonza has validated large-scale commercial manufacturing of platform ADC technologies primarily used by ADC drug developers in conjunction with novel linker/payload platforms. Also in 2014, Carbogen Amcis, the Swiss-based pharmaceutical process development and API manufacturing company, agreed to take over the operations of a high-containment facility located in Vionnaz, Switzerland. The high-potency facility in Vionnaz opened in December 2005 and was formerly managed by Bachem as an integrated part of its site in Vionnaz. In 2014, Carbogen Amcis also constructed a cleanroom dedicated to conjugation projects at its site in Bubendorf, Switerland, and said at the time of the investment, that it plans to introduce additional capability for highly potent drugs at its site in Neuland (Hunzenschwil), Switzerland. In May 2014, Novasep completed an EUR 4 million ($5.5 million) investment to expand its highly potent API manufacturing capabilities at its facility in Le Mans, France. The Le Mans production facility combines chemical and purification capabilities to manufacture ADC payloads at commercial scale. In May 2014, WuXi PharmaTech (Cayman) Inc.'s manufacturing subsidiary, Syn-The-All Pharmaceutical Co., Ltd. (STA), began operation of a high-potency API laboratory in Shanghai, thereby adding high-potency API processing to its portfolio of services. The laboratory supports process development and clinical-trial supply of high-potency small molecules at kilogram scale. In 2014, Cerbios-Pharma SA invested in a cGMP atomization plant for particle engineering using super critical fluid technology capable of generating micro and nano API particles with very narrow particle size distribution. By the end of 2015, the plant will be fully operative for the handling of high-potency APIs at 200 grams cGMP scale.

In a move to integrate ADC API and drug product manufacturing, in September 2014, Baxter's BioPharma Solutions business and Sigma-Aldrich Corporation's SAFC Commercial custom manufacturing services business unit have established a collaborative manufacturing agreement for ADC. SAFC is contributing expertise in conjugation and the manufacture of drug linkers while Baxter BioPharma Solutions is offering sterile fill/finish services for final filling of ADC products. Dedicated project managers at each site will work closely together to help ensure a consolidated timeline and a transparent transfer, with a primary project lead identified as the main contact as mutually agreed. The bulk drug substance conjugated by SAFC will be transferred directly to Baxter's project management team using established protocols. The Baxter team will then work to provide the correct filling, regulatory testing and validation, packaging, and import/export paperwork processing as well as product lot approval for distribution.