Tracking the Expansion Activities of Contract Service Providers

Bjorn Holland/Getty ImagesThe investment activity of CDMOs and CMOs reveals the broader business and technical trends of the pharmaceutical industry.

The author examines recent expansion activity. Some key areas of investment are technologies for bioavailability/solubilization enhancement, formulation and manufacture of high-potency drugs, and modified-release applications.

Contract service providers offering formulation-development, drug-delivery, and manufacturing services are an important part of the value chain for pharmaceutical companies. Recent expansion activity of CDMOs and CMOs reflect the business and technical trends in the pharmaceutical industry as a whole. Key areas of investment include capabilities to support bioavailability enhancement, modified-release applications, parenteral-drug manufacturing, and high-potency drugs.

Building the toolbox

Thus far in 2013, Catalent Pharma Solutions has made several moves to strengthen its position globally as well as to strengthen its toolbox. Earlier this year, the company formed two joint ventures in China, one for its softgel technologies business and one for its clinical-supply-solutions business. In softgels, Catalent agreed to acquire, pending regulatory approvals, a majority share in the Haining-based and privately held Zhejiang Jiang Yuan Tang Biotechnology, which produces nutritional softgel products for the Chinese and Asia Pacific markets. In a separate move, Catalent, and ShangPharma Corp., formed a new joint venture, which includes a new 31,000-ft² facility in Shanghai. The facility, currently under construction, will offer capabilities in clinical-trial supplies, including comparator sourcing, primary and secondary packaging and labeling, storage, and distribution. The facility is scheduled to open later this year.

On an organizational basis, in July 2013, Catalent created a new business unit, Advanced Delivery Technologies, which aligns the company’s existing modified-release and

medication-delivery businesses. The company’s business units now include Catalent Softgel Technologies, Advanced Delivery Technologies, and Development and Clinical Services. Additionally, Catalent is investing $35 million to expand its controlled-release manufacturing facility in Winchester, Kentucky. The 100,000-ft² facility is expanding by almost 80,000-ft². Catalent expects the expansion to be completed by October 2014.

Earlier this year, Almac’s Clinical Services business unit expanded its services for dispensing and bottling solid dosage products with new enhanced containment equipment and processes at its EU and US headquarters, respectively in Craigavon, the United Kingdom and Souderton, Pennsylvania. Additionally, Almac is expanding its commercial-manufacturing capacity and recently added a new non-GMP drug formulation-development facility in Craigavon for a total investment of £13.7million ($21 million). The commercial expansion adds blending equipment and an automated packing and integrated cartoning line for high-volume bulk commercial manufacturing scheduled to begin in November 2013. Almac also launched US commercial packaging services following a successful FDA inspection and new client partnership for its facility in Audubon, Pennsylvania. The facility offers flexible packaging from primary packaging of solid oral dosage forms to customized secondary labeling and packaging of sterile biopharmaceutical products.

Metrics launched a new proprietary technology (SUBA) that enhances the bioavailability of poorly water-soluble drugs. The technology was successfully used by the parent company of Metrics, Mayne Pharma, which acquired Metrics in 2012. Mayne Pharma has applied SUBA technology to improve the bioavailability of the antifungal drug itraconazole. Metrics also introduced proprietary taste-masking technology, Cleantaste. The company also launched capabilities to produce nonsterile liquids, creams, and gels. The company’s cream suite can manufacture two- and three-phase suspensions and emulsions, including pastes, creams, lotions, and gels. Its two filling lines, which are modular and can be assembled according to product format, and its liquid-processing equipment can produce batch sizes ranging from 250 kg to 2000 kg. Metrics also introduced proprietary pellet technologies for controlled-release applications. Mayne Pharma has successfully applied the pellet technology to a number of proprietary pharmaceuticals with modified-release profiles, including Eryc (delayed-release erythromycin), Doryx (delayed-release doxycycline), Kadian (extended-release morphine), Astrix (delayed-release low-dose aspirin), and pulsed-release diltiazem.

The CDMO UPM Pharmaceuticals acquired a former Pfizer 500,000-ft² commercial-manufacturing facility in Bristol, Tennessee. The acquisition provides UPM with large-scale commercial capabilities for manufacturing and packaging of solid oral dosage tablets and capsules as well as for semisolid manufacturing of creams and ointments. The facility further provides for technology-transfer support, pilot-plant scale-up capabilities, analytical and microbial testing, and dedicated suites for potent compounds. As part of the purchase, UPM will continue to manufacture Pfizer’s current portfolio of products within the facility for two years. Pfizer gained the facility with its acquisition of King Pharmaceuticals in 2012. King Pharmaceuticals was founded by UPM’s current Chairman and CEO John Gregory. In addition, in May 2013, UPM increased its capabilities for API-in-capsule dosage forms with the addition of a powder-microdosing system (Xcelodose, Capsugel). The company also added to its analytical capabilities with the addition of a differential scanning calorimeter and a thermogravimetric analyzer.

Parenteral drug manufacturing and analytical support

Several companies recently expanded their parenteral-drug manufacturing capabilities. In late 2012, AAIPharma Services announced the expansion of its parenteral-drug manufacturing facility in Charleston, South Carolina. The expansion includes the installation of compounding and aseptic processing suites to contain a newly acquired Monoblock vial-filling machine, expansion of a microbiology laboratory, onsite formulation-development capabilities, and enhanced analytical instrumentation. Following the company’s opening of its technology center in May 2012, AAIPharma acquired additional instrumentation to support its analytical and biopharmaceutical development laboratories. It added systems for new inductively coupled plasma-mass spectrometry, gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, ultra-high-performance liquid chromatography, and high-performance liquid chromatography. The company also expanded its biopharmaceutical development services by adding a micro-flow imaging system, a multi-angle laser light-scattering detector, and a dynamic light-scattering detector to support aggregate and particulate-testing services. A capillary isoelectric focusing system was added to support protein analysis. AAIPharma also expanded its extractable and leachable) testing services.

In 2013, Vetter’s new filling line at the company’s Ravensburg Vetter South facility in Ravensburg, Germany was fully validated for cGMP filling. The line’s capacity ranges from mid- to large-volume batch sizes, with a maximum filling speed of 800 presterilized syringes per minute. The line currently fills 1-mL-standard-format syringes, with additional formats to be added in the near and long terms. Also, its 18,000-ft2 facility, known as Ravensburg Vetter West, which began operations in April 2012, successfully completed an FDA inspection. The site provides high-bay warehousing for cold storage and room-temperature products as well as visual inspection. Additionally, Vetter broadened its portfolio for lyophilized substances by offering its filling service for high-quality sterile water for injection syringes with five years of stability data.

In January 2013, Dalton Pharma Services began the first stage of its aseptic-filling expansion plan. The investment adds high-speed sterile vial-processing and washing capability, an upgraded high-purity water system, vial-depyrogenation capabilities, lyophilization capacity, and automated vial-inspection capabilities. The upgraded GMP sterile-manufacturing capabilities will allow the company to handle larger-volume commercial aseptic filling of sterile liquids and sterile powders. Later stages of the sterile-processing expansion will include additional GMP manufacturing facilities, equipment, and automation to provide integrated sterile manufacturing services from preclinical to commercial production for sterile API and finished doses.

High-potency additions

Companies also have made investments to increase capacity for high-potency forms. In February 2013, Baxter International’s BioPharma Solutions business began an approximately 1750-m2 capacity expansion at the company’s fill-finish cytotoxic contract-manufacturing facility in Halle (Westfalen), Germany. This expansion follows previous expansions in Halle in 2007 and 2011. In April 2013, Goodwin Technology and Coldstream Laboratories agreed to develop and manufacture high-potency, highly cytotoxic materials, such as small molecules, protein toxins, cytotoxic ADCs, and other bioconjugates. Goodwin will use Coldstream’s cGMP platform of services, including analytical testing, formulation, liquid or lyophilized fill-finish, storage, and shipment of manufactured highly potent bioconjugates. In May 2013, Penn Pharma successfully completed the first batch of coated tablets at its new contained manufacturing facility in South Wales, UK. The facility is designed for the clinical and commercial manufacture of tablets and capsules. Penn invested £14 million ($21 million) for the new 15,000-ft2 facility, which includes the capability to handle potent compounds. In July 2013, the company announced an additional £3-million investment ($4.6 million).

Other moves

Other companies are making moves as well. Bend Research expanded its GMP analytical capabilities with the addition of onsite stability storage and additional GMP testing capabilities for clinical-trial material supply. The company recently added instrumentation to its existing suite of GMP-qualified analytical equipment, including a differential scanning calorimeter and particle-size analyzer. In May 2013, Halo Pharma took a minority ownership position in and established a formal collaboration with the drug-formulation and development company Altus Formulation. Capsugel launched its new LIPIDEX technology platform that integrates its lipid, liquid, and semisolid fill technologies, product-development capabilites, and commercial-manufacturing infrastructure. The platform is part of Capsugel’s Dosage Form Solutions business unit.

Earlier this year, Azaya Therapeutics, an oncology company developing cancer treatments through its nanotechnology platform, launched Parexo Labs, a CDMO providing contract chemical testing and liposomal manufacturing services. In April 2013, the fine-chemicals company Ajinomoto acquired the CDMO Althea Technologies, which offers protein formulation and fill-finish services as well as contract biologics manufacturing. Aptuit launched a translational strategy (i.e., Complementary Vision) for chemistry, manufacturing and control (CMC) services. It is an approach that encompasses all the services that precede and follow CMC in the target product profile: API development and manufacture; qualitative/quantitative chemical, physical and biopharmaceutical characterization of actives and dosage forms; dosage-form design; development and manufacturing for preclinical and clinical dosing; and the development, manufacturing and testing of inhaled products such as dry powder inhalers.