Plant Construction & Process Technology

Opportunities in Drug Development and Manufacturing

High-potency Manufacturing Continues to Attract Investment of CDMOs and CMOs

12.09.2016 -

Growth in the global oncology drug market is an important measure of opportunities in drug development and manufacturing, including for contract manufacturers of active pharmaceutical ingredients (APIs) and finished drug products. On the small-molecule side, whether as an API or finished drug product and depending on the product involved, growth in the oncology market is one indicator of potential opportunities in high-potency manufacturing.

Within the oncology market, a niche segment is antibody drug conjugates (ADCs), which consist of a cytotoxic small molecule linked to a monoclonal antibody (mAb). ADCs, certain oncology drugs, and other high-potency compounds (such as hormones) require high-containment manufacturing, which involve specialized approaches in facility design, equipment selection, and manufacturing processes to achieve the desired levels of containment and minimize operator exposure. Several contract manufacturers have recently invested in high-potency manufacturing. Below is a roundup of activity as announced in 2015 and 2016 to date.

ADC Biotechnology

In October 2015, UK-based ADC Biotechnology announced a $10-million plan to build a manufacturing facility in St. Asaph, North Wales, UK for advanced anti-cancer drugs. The two-stage expansion program marks the transition of ADC Biotechnology into GMP manufacturing of ADCs. Phase 1 of the project will come on stream in mid-2017, creating a 1,500-square meter dual-stream facility for process development, manufacturing, and quality testing of ADC drugs. The new facility will be able to produce clinical trial and low-volume commercial quantities. A projected second phase is planned to add another 2,500 square meters of manufacturing space for larger-scale clinical and commercial manufacturing. The company also invested £100,000 ($132,000) for an R&D lab, focused on bio-conjugation and payload-linker chemistry in early 2015.

Aesica Pharmaceuticals

Aesica Pharmaceuticals announced in April 2016 that it had doubled its development capacity at its facility in Queenborough, UK. With the addition of the new capabilities, Aesica can now develop and manufacture a customer product from early formulation development through clinical manufacture and into commercialization. The company’s highly potent and controlled drugs service offering was expanded at Queenborough as a result of the new center. The company previously only provided commercials-scale manufacturing capabilities for these drug classifications, but it now offers full formulation and development capabilities. The site handles highly potent drugs for any active up to SafeBridge Category 3, together with controlled drugs, with licenses for both Schedules 2 to 4. The SafeBridge Potent Compound Safety Certification program provides an independent assessment of a company's manufacturing capabilities for safe production of potent active pharmaceutical ingredients and drug products.

Alcami

In August 2016, Alcami announced plans to expand its manufacturing capacity for highly potent APIs at its facility in Germantown, Wisconsin. Alcami plans to invest in 2016 and 2017 toward enhancement of new and existing kilo labs to introduce the development and manufacturing of high-potency APIs. Two new cGMP-compliant production suites will focus on primary containment technologies with engineering controls designed to meet occupational exposure limits of minimally 0.03 μg/cubic meter (SafeBridge Category 3). The expansion will include a 5,000-square-foot renovation that will be operational by the first quarter of 2017.The newly designed space will include up to 150-liter reactor scale with cryogenic capabilities. These advancements follow operational and technology enhancements across development, clinical, and commercial manufacturing to increase overall production capacity by 50%. The company has global API operations in Germantown, and Weert, The Netherlands.

Cambrex

In July 2016, Cambrex announced that it had completed and validated a $50-million production and warehousing expansion for API manufacturing at its cGMP site in Charles City, Iowa. This facility sits on a 45-acre site and manufactures a wide range of APIs and pharmaceutical intermediates, including highly potent molecules and controlled substances. The new 7,500 square-foot multi-purpose manufacturing facility will initially add a total of 70 cubic meters of glass-lined and Hastelloy reactors ranging in size from 7 cubic meters to 16 cubic meters, along with Hastelloy agitated filter dryers for a multi-purpose configuration that will be capable of handling potent APIs at an occupational exposure limit of down to 1 μg/cubic meter. The facility complements the three existing large-scale manufacturing facilities at the Charles City site.

Carbogen Amcis

In May 2016, Carbogen Amcis announced the extension of its operations in Bubendorf, Switzerland. The company undersigned the acquisition of the land and buildings of GEA Pharma Systems in Bubendorf, close to the company's current headquarters. The space will allow the company to expand its laboratory capacity for highly potent development and small-scale production as well as analytical support. Operations are scheduled to expand into the new building in 2017.

Catalent

In January 2016, Catalent, through its wholly owned subsidiary, Redwood Bioscience, formed a research collaboration with Roche to develop molecules coupling different therapeutic modalities using Catalent's proprietary SMARTag technology, an ADC platform. Under the deal, Roche gains non-exclusive access to the SMARTag platform and will have an option to take commercial licenses to develop molecules directed to a defined number of targets. Roche pays Catalent an up-front fee of $1 million and will provide additional research funding during the initial phase of the collaboration. Catalent has the potential to receive up to $618 million in development and commercial milestones, plus royalties on net sales of products, if Roche pursues commercial licenses and all options are exercised. Catalent acquired an exclusive license to market the SMARTag technology in 2013 and subsequently collaborated with Redwood for the ongoing development and marketing of the platform. It later acquired Redwood in 2014. The SMARTag technology enables the generation of homogenous bioconjugates and is engineered to improve performance and manufacturing.

On the drug product side, in January 2015, Catalent expanded its potent handling and manufacturing capabilities at its facility in Somerset, New Jersey. The company completed the expansion of facility and engineering controls for its high-potency tableting and OptiMelt Hot Melt Extrusion operations in Somerset to supplement existing potent capabilities in oral solid and its Zydis Fast Dissolve manufacturing. The company invested in additional potent containment for large-scale blending, fluid-bed processing, and high-shear granulation. The expansion created a manufacturing Center of Excellence for potent handling across Catalent’s portfolio of oral solid manufacturing solutions, which includes hot-melt extrusion, high-shear and wet granulation processing, solvent-based capability, extrusion/spheronization, fluid-bed processing, Wurster coating, and compression and encapsulation. The company also invested in high-potency clinical packaging.

Cerbios-Pharma

In early 2016, Cerbios-Pharma opened a new R&D center for high-potency active APIs and mAb development. Cerbios is a privately held company located in Lugano, Switzerland, which specializes in the development and manufacture of both chemical and biological APIs. Exclusive, third-party manufacturing services are offered by the Chemical Division for high-potency APIs and by the Biological Division for mAbs, recombinant proteins, and pharma probiotics.

The construction of the investment was approved in November 2013 and started in April 2014. The new building consists of four floors of 280 square meters each. The second floor houses biological R&D, with three dedicated laboratories for the development of mAbs and/or recombinant proteins based on Chinese hamster ovary (CHO) mammalian cells and a large laboratory to develop pharmaceutical probiotics. The first floor houses a new additional GMP archive and offices for the directors and for the managers of R&D and quality assurance. The ground floor houses chemical R&D, doubling the capacity to develop highly potent APIs for contract manufacturing services, including Safebridge Category 4 products. Underground floors house two warehouses (one for R&D and one for production) and personnel services.

CMC Biologics and IDT Biologika

CMC Biologics, a contract provider of clinical and commercial manufacturing of mAbs and other therapeutic proteins, and IDT Biologika, a privately held life-science company with expertise in research, development and manufacture of biologics, formed a strategic collaboration in February 2016 for the manufacture of ADCs. Within this collaboration, CMC Biologics will perform process development and manufacture of the bulk mAb, and IDT Biologika will perform services from conjugation of the cytotoxic drug to the antibody substance through to the aseptic fill, finish, and packaging of the ADC final drug product. The joint manufacturing solution is intended to provide speed, reliability, quality ADC manufacturing, and a simplified supply chain, from DNA to finished drug product, for clinical trials through commercial manufacturing.

CordenPharma

In March 2016, CordenPharma announced the completion of expanded development capabilities for mid-scale (up to 20 kg) contained capacity of highly potent and oncology oral dosage forms in its CordenPharma Plankstadt manufacturing facility in Germany. The new and expanded capability provides contained manufacturing of oral dosage forms from grams to 150 kg.

Goodwin Biotechnology

In May 2016, Goodwin Biotechnology, a CDMO based in Plantation, Florida, expanded its bioconjugation capabilities by adding a dedicated suite for developing and manufacturing cytotoxic antibody drug conjugates up to Safebridge Level 4/5.

Johnson Matthey

In March 2015, Johnson Matthey, a provider of pharmaceutical services, APIs, and catalyst technologies, announced the completion and commissioning of a new high containment facility for potent product manufacture at its Edinburgh, UK site (Macfarlan Smith). 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 meter. Johnson Matthey also manufactures highly potent products through its facilities in West Deptford, New Jersey and Devens, Massachusetts.

Infa

In November 2015, the Milan Italy-headquartered Infa Group, now part of Olon, reported that Labochem received cGMP certification for its new multipurpose highly potent API plant. The new kilo laboratory has capacity of up to 2.5 kg/batch size and manufacturing capabilities ranging from hundreds of grams to tens of kilograms for advanced intermediates and APIs, classified from Occupational Exposure Band 3 to 5.

MilliporeSigma

In May 2015, SAFC Commercial, Sigma-Aldrich's custom manufacturing services business unit, completed the expansion of its St. Louis, Missouri facility to support commercial-scale ADC manufacturing. In 2015, Merck acquired Sigma-Aldrich for $17 billion and later rebranded its life-sciences business as MilliporeSigma in the US. The expanded capabilities in St. Louis were further enhanced by expanded commercial capacity for highly active manufacturing and storage at the company’s facility in Madison, Wisconsin.

Novasep

In June 2015, Novasep announced the addition of a fully integrated ADC facility at its site in Le Mans, France. The new facility will enable Novasep to complement its current ADC offering with full bioconjugation services. The facility was planned to be commissioned in the second quarter of 2016 and will provide contract manufacturing in batch sizes from a few milligrams to 600 g to ADC drug developers during clinical trial and commercial development phases. The expansion is part of Novasep’s €10 million ($11 million) investment in clinical and commercial-scale ADC conjugation.

Piramal

In August 2016, Piramal, through its wholly owned subsidiary in the US, agreed to acquire Ash Stevens, a Riverview, Michigan-based CDMO of APIs for $42.95 million plus an earn-out consideration capped at $10 million. The transaction was expected to be completed by the end of August 2016. The acquisition provides Piramal with 60,000 square feet of facilities, eight chemical drug development and production laboratories, and six full-scale production areas, which includes highly potent API manufacturing. Ash Stevens’ facility in Michigan has engineering and containment controls for the safe handling and cGMP manufacture of small- and large-scale high-potency APIs, with occupational exposure limits ≤0.1 µg/cubic meters.

Also, In November 2015, Piramal Healthcare opened a new £2 million ($2.2 million) ADC manufacturing suite at its facility in Grangemouth, Scotland, according to the Scottish Enterprise, the economic development arm of Scotland.

Regis Technologies

In August 2015, Regis Technologies, a contract provider of custom synthesis and separation services, started up a new potent compound suite (PCS) at its 36,000 square foot, cGMP facility in Morton Grove, Illinois. The PCS addition provides for small-molecule cGMP manufacturing of potent compounds up to about one kilogram per batch. Regis’ new PCS includes isolators, laminar flow hoods, and local exhaust ventilation appropriate for potent compound handling.

This article first appeared in the April 20, 2016 edition of DCAT Value Chain Insights, an information resource from the Drug, Chemical & Associated Technologies Association (DCAT), and was updated for publication in CHEManager.