Small-Molecule Contract Services Update

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Small-molecule contract service providers have advanced their capabilities and offerings to help clients accelerate innovations and tackle industry challenges. This article will explore some recent small-molecule expansions and investments, as well as acquisitions.

New facilities and expansions

In May 2018, Cambrex completed its previously announced pilot plant expansion at its High Point, NC facility (1). The expansion includes the installation and commissioning of a fourth 400-ft² reactor suite with two 2000 L glass-lined reactors and a Hastelloy C22 filter dryer, allowing the manufacture of batch sizes ranging from 10–100kg under cGMP conditions for clinical-phase projects. According to a May 15, 2018 company press release, the installation increased the site’s reactor capacity by approximately 30%. Additionally, the company upgraded its analytical chromatography data systems for quality control and analytical R&D to Waters’ Empower 3 software. 

Also in May 2018, Cambrex shared progress on the construction of a $24-million facility at its Charles City plant for the manufacture of highly potent APIs (1). A 4500-ft² production area, which will have a reactor capacity of 2200 gallons and manufacture batches from 50–300kg, will operate to an occupational exposure limit down to 0.1µg/m³. The existing small-scale manufacturing area will be reconfigured, providing a single high-containment building to support early stage development and manufacturing. The company states that the facility is expected to be operational in the first half of 2019.

Cambrex will construct a new 150-m² R&D laboratory at its facility in Paullo, Milan, Italy (2). The laboratory will combine chemistry and analytical development capabilities and include 14 fume hoods, glass-lined reactors, and liquid chromatography and gas chromatography systems. In a June 12, 2018 press release, the company reported that construction will be completed by the end of 2018, with installation and validation of instruments to take place in the first quarter of 2019. 

The Milan site contains seven production departments, including a pilot plant, kilo-scale plant, and development and analytical laboratories. The company will also recruit additional scientists to increase the number of generic APIs in the company’s development portfolio.

In August 2018, Minakem, the contract development and manufacturing division of Minafin, will open a new, closed-controlled environment, high-containment production facility (3). The new facility, based at the Louvain-la-Neuve plant in Belgium, will extend the company’s capacity to develop and manufacture high potency API compounds, such as antibody drug conjugate toxins, from small-scale development to full GMP batch releases. According to the company, this high-class production facility is among only a dozen of its kind in the world; roughly half are located in Europe.

The facility will be equipped with a preparative chromatography system that allows the isolation and purification of target molecules at varying scales (milligrams to hundreds of grams) and suited to addressing a range of needs, from routine activity to analytics. Equipment includes nine fume hoods and new-generation glove boxes dedicated to dry powder handling and weighing, air locks, high efficiency particulate arresting air filters, and cascading flow. Minakem’s HPAPI production will be carried out with an occupational exposure limit below 0.1 g/m3/8h. Operations in the new high-containment facility will begin in September 2018.

Acquisitions

Catalent has agreed to acquire Juniper Pharmaceuticals to expand Catalent’s formulation development, bioavailability, and clinical-scale oral dose manufacturing services (4). The acquisition would also include Juniper’s Nottingham, UK-based Juniper Pharma Services division.

Catalent states that Juniper’s expertise in formulation development and supply will strengthen Catalent’s portfolio of solid-state screening, preformulation, formulation, analytical, and bioavailability capabilities including development of spray-dried dispersions, with integrated development, analytical, and clinical manufacturing at the Nottingham facility.

Under the agreement, announced in a July 3, 2018 press release, a subsidiary of Catalent will commence a tender offer to purchase all of Juniper’s shares for a price of $11.50, net to the seller in cash. Following the tender offer, Catalent plans to acquire the remainder of the Juniper shares at the same price through a merger with a newly formed wholly owned subsidiary of Catalent. The acquisition is subject to certain customary closing conditions and is expected to close in the first quarter of Catalent’s 2019 fiscal year, which Catalent states began on July 1, 2018.

Juniper provides bioavailability enhancement for poorly soluble compounds, including nano-milling, spray drying, hot-melt extrusion, lipid-based drug delivery, as well as cGMP clinical manufacturing for potent and controlled substances. Catalent will continue to support Juniper’s Crinone (progesterone gel) franchise marketed by Merck KGaA outside of the United States. Catalent also announced that the Nottingham facility will provide similar capabilities at its centers of excellence for early drug development in San Diego, CA and Somerset, NJ.

Recipharm is set to expand its presence in the respiratory drug market with the acquisition of Sanofi’s Holmes Chapel manufacturing site in Cheshire, UK, for £45 million (US$59 million) (5).

The 125,000-m² facility manufactures metered-dose inhalers and nasal sprays and develops dry-powder inhalation technologies. The site’s 450 employees will transfer to Recipharm, according to the company. The transaction is expected to close in the fourth quarter of 2018.

The acquisition provides Recipharm with additional inhalation commercial drug product manufacturing capabilities, adding to services already offered by Recipharm’s inhalation development facility in the US, as stated by the company in a June 13, 2018 press release. Sanofi has also entered into a long-term supply agreement for the products currently manufactured at the facility.

In July 2018, Cambrex announced it entered into a definitive agreement to acquire dosage form contract development and manufacturing organization (CDMO) Halo Pharma for approximately $425 million in total cash consideration (6). The acquisition will be funded with a combination of cash on hand and borrowings against Cambrex’s $500-million senior credit facility. Completion of the transaction is subject to customary closing conditions and is expected to occur during the third quarter of 2018.

With the acquisition of Halo, Cambrex will enter the finished dosage form CDMO market. Halo provides drug product development and commercial manufacturing services, specializing in oral solids, liquids, creams, sterile, and non-sterile ointments. Halo’s core capabilities include developing and manufacturing highly complex and difficult-to-produce formulations, products for pediatric indications, and controlled substances. 

Halo operates two state-of-the-art, GMP-compliant facilities located in Whippany, NJ, and Montreal, Québec, Canada, comprising of 430,000 ft² of plant space. Cambrex reports that Halo is currently engaged in more than 100 product development projects for over 70 customers and is expected to generate over $100 million in annual revenue in 2018. The release also states that Halo’s 450 employees will join Cambrex’s 1200 employees across the US and Europe.

References

1. Cambrex, “Cambrex Completes Pilot Plant Expansion at its High Point, NC Facility,” Press Release, May 15, 2018.
2. Cambrex, “Cambrex Expands Generic API Research and Development Capabilities at Milan, Italy Site,” Press Release, June 12, 2018.
3. Minakem, “Minakem Opens New High Containment Facility for Production of the Highest Class of HPAPI,” Press Release, June 19, 2018.
4. Catalent, “Catalent Signs Agreement to Acquire Juniper Pharmaceuticals, Inc.,” Press Release, July 3, 2018.
5. Recipharm, “Recipharm Expands Inhalation Capabilities with GBP 45 Million Acquisition of Sanofi CMO Business Located in UK,” Press Release, June 13, 2018.
6. Cambrex, “Cambrex to Acquire Halo Pharma, Adding Drug Development and Finished Dosage Capabilities to Global API Manufacturing Network,” Press Release, July 23, 2018.

Article Details

Pharmaceutical Technology
Supplement: Outsourcing Resources
Vol. 42
August 2018
Pages: s36, s38

Citation

When referring to this article, please cite it as A. Lowry, " Small-Molecule Contract Services Update," Pharmaceutical Technology Outsourcing Resources Supplement (August 2018).