CPhI 2014 Highlights

CPhI Worldwide 2014, held in early October in Paris, France, presented an optimal opportunity for pharmaceutical manufacturers and their raw material suppliers and service providers to introduce new capabilities. According to UBM Live, host of the show, approximately 35,000 total attendees viewed the offerings of 2250 exhibitors that represented 140 countries. Companies both large and small highlighted a vast range of new products, technologies, services, and facilities designed to meet the needs of the pharmaceutical industry. A few of these new capabilities are described below.

Analytical equipment
Rigaku Raman Technologies, a manufacturer of portable Raman analyzers, highlighted its new Progeny handheld device for rapid material identification, including both raw and in-process materials, finished products, and products already on the market (as an anti-fraud measure). What sets Progeny apart from other handheld Raman analyzers, according to marketing director Jennifer Lynch, is the fact that it is the first fully sealed 1064-nm-powered handheld Raman analyzer that enables the analysis of fluorescent compounds, colored materials, and materials stored in colored containers, which hasn’t been possible in the past. “When a company adopts Progeny for their material analysis needs, the quality control laboratory can focus on more value-added work, such as methods development, instead of being bogged down by routine analyses,” Lynch says.

Analytical services
SGS Life Science Services, a pharmaceutical analytical and bioanalytical contract solutions provider, has grown rapidly since the business line was established 10 years ago. In 2014 alone, the company is expanding capacity in three regions of the world. Most recently, SGS completed the construction of a new 8000-sq.-ft. GMP/GLP facility in Carson, California, its fifth in North America and the first on the west coast. The location was chosen so the company can provide local support to the significant pharmaceutical and biotechnological community in California, according to Jeff McDonald, COO of SGS North America.

SGS is also investing in a new facility in Villeneuve la Garenne, France, which will replace an existing laboratory in Clichy and will include state-of-the art equipment designed to increase the quality control service throughput and support an ever-expanding research and development pipeline of new biopharmaceutical drugs within the country. Services will include analytical chemistry, microbiological analysis, stability studies and method development, as well as amino acid analysis and mycoplasma testing. “We see this investment as an strategically important for meeting the needs of both the small molecule and quality control markets,” notes Paul Beyou, director of life science services, Clichy. SGS is also increasing analytical capabilities at its facility in Poitiers, France, and the company opened a new laboratory in Italy in 2013.

In China, SGS is expanding its Shanghai facility, adding to its cGMP chemistry and microbiology laboratories; constructing a new biotechnology laboratory for cytotoxicity testing, cell-based assays, and endotoxin and ELISA testing; and introducing packaging testing capabilities, including extractables and leachables. “The investment in the Shanghai facility, and the increased and enhanced service offerings that will result, are essential to our continued expansion in China,” states Andy Yi, general manager, SGS Life Science Services, Shanghai.

Finally, SGS has also launched a new, searchable web-based database of biopharmaceutical, biosafety, and bioanalysis methods that are available throughout its global network of GMP, good laboratory practice, and good clinical-compliant laboratories. Selection criteria include service type, sample type (e.g., biologic, vaccine, biomarker), and technique.

Contract manufacturing
A notable trend in the contract manufacturing industry that was apparent at CPhI Worldwide 2014 is a growing emphasis on integrated services. In addition, several contract manufacturing organizations (CMOs) that are either a business unit of a larger pharmaceutical company and/or a manufacturer of generic APIs and sometimes formulated products see their positions as advantageous compared to CMOs that do not have such capabilities. Two companies in the former category include Pfizer CentreSource and CPS, the custom pharmaceutical services division of Dr. Reddy’s, while examples of the latter type include Hovione and Piramal Pharma Solutions.

Reorganization at Pfizer has Pfizer CentreSource (PCS) now reporting through Pfizer Global Supply, the external supply group that manages all the CMOs used by Pfizer. This alignment brings numerous synergies with respect to technology and market knowledge, according to Kenneth F. Ball, senior manager of marketing for PCS. The company is also adding capacity at its Ringaskiddy, Ireland facility, which is the product launch site for all of Pfizer, and thus has extensive experience working with R&D and third parties to introduce new processes and expertise in new product scale-up, process improvement, launch, and commercial manufacture, according to Jeffrey W. Frazier, vice-president of global marketing for fine chemicals at PCS. Additional investments in facilities located in important and stable emerging markets are also under consideration, such as Brazil, Morocco, and Indonesia.

For biologics manufacturing, PCS is emphasizing its extensive network of manufacturing facilities and their broad range of capabilities, including mammalian cell expression, microbial fermentation, vaccines, and antibody-drug conjugates (ADCs). The company is also highlighting its high potency production capabilities. It has both development and commercial-scale facilities for the manufacture of high-containment, solid-dosage drugs. “In addition to the depth and breadth of our manufacturing capabilities, because PCS is part of Pfizer, we also have access to the technology and knowhow of a large, successful pharmaceutical company, that we can apply as needed to rapidly design effective solutions for our customers,” says Cristin B. Grove, PCS’s director of contract manufacturing.

CPS has made responsiveness to the market a key focus of the company, introducing a new “Power of Now” customer-centric initiative. “We differentiate ourselves in the marketplace by being aware of our customer needs, and today there is great demand for more rapid responses. The ‘Power of Now” reflects that need for immediacy, as well as empowerment of both our customers and employees, partnership, and trust,” says Christian Jones, head of Asia Pacific sales and business development for CPS. The initiative focuses on accelerating project delivery through dedicated response networks with shortened decision-making chains and reduced lead times, according to Jones. To support the initiative, CPS has appointed a new head of R&D and a new North American sales manager and created a new business development position in Asia that Jones has filled.

In addition to its increased responsiveness, Jones notes that CPS offers an integrated portfolio of services from discovery to formulation development through to commercialization and lifecycle extension that is backed by the extensive expertise in generic-drug manufacturing of its parent company. “The experience gained in the competitive generics industry is directly transferred to our CMO services at CPS in the form of efficient and robust process development that includes the use of green chemistry and continuous processing,” Jones notes. Other key technologies for CPS include chiral chemistry, highly potent drug substance and formulated product manufacturing at development and commercial scales, steroid manufacturing, and pegylation.

Hovione is a company that offers both customer-manufacturing services (e.g., intermediates, APIs, and finished products) and produces its own generic APIs and formulated products. CEO Guy Villax of Hovione does not see any conflict between the two operations, and in fact, believes that being in the generic-drug business has helped the company’s competitiveness as a CMO. “With generics, it is imperative to be as cost-effective as possible, and to do that requires advanced technologies and science. Those capabilities benefit our custom manufacturing efforts as well,” he says.

Hovione also has the largest installed capacity for commercial GMP spray drying, according to Villax. In 2014, the company is celebrating 10 years of spray drying services. “Through these 10 years, we have accumulated a large amount of knowledge, expertise, and data on spray drying that now enable us to control the physical processes involved in spray drying and predict product behavior on a commercial scale,” comments Villax.

In addition, to reflect the fact that it now has capabilities in both chemistry and biotechnology, Hovione changed its logo. The company will also be expanding its Hovione New Jersey manufacturing site, which has capabilities in cryogenic chemistry, hydrogenation, fluorination, and the production of highly potent APIs.
Piramal Enterprise is another company that offers contract research and manufacturing services across all phases of the drug lifecycle and the value chain, and has expertise in specialized services such as ADCs and highly potent compounds with a focus on green chemistry. To support its end-to-end manufacturing capabilities including discovery, Phase I-III clinical and commercial production, and off-patent formulation, the company is continuing to invest in its facilities and new technologies that provide value to customers, such as continuous flow chemistry and bio- and chemocatalysis. More than $70 million worth of investments are at various stages of execution, according to Vijay Shah, COO at Piramal Enterprises and pharma business lead. Specifically, the company invested approximately $10 million in a world-class, GMP clinical manufacturing facility in Ahmedabad, India, approximately $15 million in its Morpeth, UK site to triple production capacity for hormonal products, and approximately $5 million at its Grangemouth site to expand commercial ADC capacity. Piramal is also expanding capacity for generic drug production and has plans for the addition of a pilot plant and scale-up facility as it prepares for a tripling of this business over the next five years on a top-line basis.

Piramal is also focused on becoming more customer-centric, and has established an internal customer advocacy team that represents the customer throughout all stages of a project. Its PULSE program, launched early in October 2014, is a values-based initiative designed to take the pulse of the customer and create a culture of ‘customer centricity’ across the organization. “It is critical that we maintain our focus on the customer at all times, both internally and externally,” says Shah.

Patheon, a pharmaceutical services business owned by DPx Holdings, a holding company focused on the CDMO business, is not part of a larger pharmaceutical company, but has been expanding its capabilities through numerous acquisitions to create a true integrated offering. Recent activities have included a merger with DSM Fine Chemicals in March 2014 and most recently the acquisition of Gallus Biopharmaceuticals in August 2014. At CPhI Worldwide 2014, Patheon introduced OneSource, its new integrated development offering for Phase I through Phase II projects. “When assembled correctly and executed with great discipline, an integrated service offering such as OneSource will deliver innovative solutions with regard to critical timing, including contracting, liability coverage, and tax advantages in the design of the supply chain,” states DPx Fine Chemicals president Lukas Utiger. Patheon also has future plans to provide similar simplicity to Phase III through commercial-scale capabilities as well. “We feel strongly that it is important to bring fast and simple solutions to our customers that really address their needs,” Utiger observes.

Excipients
Excipients are crucial for effective drug formulation, and excipient manufacturers continue to make advances in technology designed to address the formulation challenges presented by new drug substances.

Dow Pharma & Food Solutions, meanwhile, has expanded its AFFINISOL portfolio of excipients for the solubility enhancement of spray-dried dispersion (SDD) and hot-melt extrusion (HME) formulations. Dow began production of AFFINISOL hydroxypropyl methylcellulose acetate succinate (HPMCAS) products in October 2013 in a new facility located at the Cambrex Karlskoga site. The polymers are the result of a research collaboration between Dow Pharma & Food Solutions and Bend Research that are designed to maintain stable solid dispersions and inhibit API crystallization when formulated as spray-dried dispersions. The original products, however, require the use of plasticizers for processing over a wide temperature range. At CPhI Worldwide 2014, Dow also introduced versatile AFFINISOL HPMC HME with a low glass transition temperature requiring no plasticizers, thus allowing formulation of stable amorphous solid dispersions and controlled-release profiles via extrusion processes. The effectiveness of the new excipient has been demonstrated with the Biopharmaceutics Classification System (BCS) Class II API itraconazole and the BSC Class II API griseofulvin, according to Christophe Massip, global marketing director, Dow Pharma & Food Solutions.

Separately, as part of its Dow-Colorcon alliance (the Controlled Release Alliance), Dow announced at CPhI Worldwide 2014 that its next-generation METHOCEL DC2 hydroxypropyl methyl cellulose (HPMC) polymer, an excipient that facilitates roller compaction and direct compression of tablets as alternatives to wet granulation, will be commercially available on a global basis by the end of 2014. Installation of its new manufacturing line in Midland, MI is being finalized, according to Massip. “The designed morphology of METHOCEL DC2 notably improves the flow and processability of powder blends for compression into matrix tablets, which helps the drug product manufacturer produce higher quality tablets using streamlined manufacturing processes,” notes True Rogers, technologies leader for Dow Pharma & Food Solutions.

Lubrizol is another company that has, for many years, provided a wide range of polymer-based excipients for use in solid, semisolid, and liquid dosage forms. At CPhI Worldwide 2014, the company highlighted is new Pathway excipient-grade thermoplastic polyurethanes (TPUs) for controlled, sustained drug release in implantable drug delivery and combination products. "As pharmaceutical companies face the challenges of the patent cliff, the development of new routes of administration for existing drug products is an important strategy they can use to help maintain the success of their product franchises. Our new Pathway excipient portfolio is designed to help drug manufacturers achieve their goals of developing these novel, controlled-release drug products," observes Jean Claude Deneuville, global business director for Lubrizol’s LifeSciences business.

The non-biodegradable excipients are ideal for drug delivery over an extended period of time and work with both hydrophobic and hydrophilic APIs. Drug loading can be achieved through blending, or for thermally stable APIs, melt-processing followed by injection molding or extruding. The API and TPU can also be dissolved in a suitable solvent and then cast into shapes such as rods, tubes, films, or a variety of matrix-type designs, according to Deb Langer, vice-president and general manager of Lubrizol Life Sciences. Implantable devices can provide sustained drug delivery for short and longer time periods with, for example, 30-day contraceptive and/or HIV vaginal rings and other subcutaneous implants that last up to 18 months.

“TPUs have a long history of use in medical devices because they are robust and readily customizable. Polyether, polyester, or polycarbonate-based soft segments can be combined with aromatic or aliphatic hard segments to obtain a vast range of release properties while retaining durability chemical resistance, clarity, and abrasion resistance,” says Deneuville. He adds that TPU excipients are being investigated in formulations for hormone regulations and the treatment of mental health, in addition to HIV and pain. They can be used in controlled-release products, as drug reservoirs and matrices, in rate-controlling membranes and drug-eluting medical implants, and other applications. Possible routes of administration include subcutaneous, transdermal, oral, interorganal, intraperitoneal, and intravaginal, among others, according to Langer.

Specialty chemicals
Vertellus has long been recognized as an expert in pyridine chemistry, offering both standard catalog products and custom manufacturing important pharmaceutical building blocks. At CPhI Worldwide 2014, the company was looking to increase awareness of its full and much broader capability for meeting the needs of the pharmaceutical industry. “The Vertellus Specialty Materials (VSM) business unit comprises a broad basket of complex technologies, manufacturing biomaterials, CPC (cetylpyridinium chloride) biocides, pyridine derivatives, DEET (N,N-diethyl-meta-toluamide), sulfones, EMA (ethylene maleic anhydride) copolymers, alkenyl succinic anhydrides, reducing agents, and a host of natural and renewable chemistries based on castor and citrates, and we specialize in developing and producing fine chemicals and intermediates for sophisticated chemistry applications,” explains global sales director Mark Lewis. He adds that for the pharmaceutical industry in particular, the company has a broad range of products and synthesis technologies that provide pharmaceutical companies with a unique combination of intermediates and customer manufacturing capabilities.

Vertellus was established in 2006 when Rutherford and Reilly merged, and was then acquired by Wind Point Partners in 2007. President and CEO Rich Preziotti was previously vice-president and general manager of Honeywell’s $1.2 billion chemicals business and is focused on improving productivity, reducing costs, and enhancing customer relationships, according to Lewis.

Tablet coating
BASF announced at CPhI Worldwide 2014 that Colorcon will be using its Kollicoat IR immediate-release coating polymer in Colorcon’s fully formulated ready-to-use coatings. Kollicoat IR is an ethylene glycol and vinyl alcohol graft copolymer that enables processing at low temperatures and high solids contents while delivering targeted coating results, according to Daniele Piergentili, vice president of global marketing for pharma ingredients at BASF. With the addition of Kollicoat IR to its portfolio, Colorcon will be able to expand its polyvinyl alcohol-based offerings, providing more choice to its customers, according to Cornelis van den Muyzenberg, vice-president of sales and business development at Colorcon.

Vaccine manufacturing
IDT Biologica, a manufacturer of human vaccines for infectious diseases, announced at CPhI Worldwide 2014 that it has completed and certified a new large-scale production facility in Dessau, Germany for the filling and lyophilization of biologics and vaccines. The facility includes a sterile liquid filling line for up to 24,0000 vials per hour and has been certified to biosafety levels 1 and 2 for live vaccines. Notably, in addition to capacity for live recombinant and non-recombinant vaccines, the plant includes capacity for the fill-finish of other biologics and small-molecule drugs, including cytotoxics, in separate units. “Completion of this project allows us to accommodate production of an ever more diverse range of biomedical technologies with the precision and efficiency that comes with a highly integrated and automated facility,” says Dr. Ralf Pfirmann, IDT Biologica CEO.