One measure of international efforts to reduce maternal and child mortality relate to the United Nations (UN) Millennium Development Goals (MDGs). First agreed at the UN Millennium Summit in September 2000, the eight MDGs set worldwide objectives for reducing extreme poverty and hunger, improving health and education, empowering women, and ensuring environmental sustainability by 2015. MDG four and five specifically relate to improving maternal and child health and reducing maternal and child mortality. At the UN MDG Summit in September 2010, world leaders reaffirmed their commitment to the goals and called for intensified collective action and the expansion of successful approaches. For example, a Global Strategy for Women’s and Children’s Health was launched and garnered over $40 billion in commitments. But despite this progress, more work is needed to meet the MDGs by 2015.

“Already the MDGs have helped lift millions of people out of poverty, save countless children’s lives and ensure
 that they attend school, said UN Secretary-General Ban Ki-moon said, in a July 7, 2011, press release. “They have reduced maternal deaths, expanded opportunities for women, increased access to clean water, and freed many people from deadly and debilitating disease. At the same time, the report shows that we still have a long way to go in empowering women and girls, promoting sustainable development, and protecting the most vulnerable from the devastating effects of multiple crises, be they conflicts, natural disasters or volatility in prices for food and energy.”

Some key points of progress is that the world as a whole is still on track to reach the poverty-reduction target, and by 2015, the global poverty rate should fall below 15%, well under the 23% target despite setbacks from recent economic, food, and energy crises. Some of the poorest countries have made the greatest strides in education. For example, Burundi, Rwanda, Samoa, Sao Tome and Principe, Togo, and Tanzania have achieved or are nearing the goal of universal primary education. The number of deaths of children under the age of five declined from 12.4 million in 1990 to 8.1 million in 2009, which means nearly 12,000 fewer children die each day. Increased funding and intensive control efforts have cut deaths from malaria by 20% worldwide from nearly 985,000 in 2000 to 781,000 in 2009. New HIV infections have declined steadily. In 2009, some 2.6 million people were newly infected with HIV, a 21% drop since 1997, when new infections peaked.  The number of people receiving antiretroviral therapy for HIV or AIDS increased 13-fold from 2004 to 2009, due to increased funding and expanded programs. An estimated 1.1 billion people in urban areas and 723 million people in rural areas gained access to an improved drinking water source during the period 1990–2008.

Despite these successes, more progress is needed. “Progress tends to bypass those who are lowest on the economic ladder or are otherwise disadvantaged because of their sex, age, disability or ethnicity,” said Ban in the UN statement.  “And disparities between urban and rural areas remain daunting.”

The report shows that the poorest children have made the slowest progress in terms of improved nutrition and survival. In 2009, nearly a quarter of children in the developing world were underweight, with the poorest children most affected. Children from the poorest households in the developing world have more than twice the risk of dying before their fifth birthday as children in the richest households.  Being poor, female, or living in a conflict zone increases the probability that a child will be out of school, the report says. Worldwide, among children of primary school age not enrolled in school, 42%, or 28 million, live in poor countries affected by conflict. While stressing that achieving the MDGs largely depends on ensuring women’s empowerment and equal opportunities for women and men, girls and boys, the report also shows that achieving this goal remains elusive. The report finds that opportunities for full and productive employment remain particularly slim for women. Following significant job losses in 2008–2009, the growth in employment that occurred during the economic recovery in 2010, especially in the developing world, was lower for women than for men.

In May 2011, the Global Strategy for Women and Children’s Health announced new commitments by 16 countries:  Burundi, Chad, the Central African Republic, Comoros, Guinea, Kyrgyzstan, the Lao People's Democratic Republic, Madagascar, Mongolia, Myanmar, Papua New Guinea, Sao Tome and Principe, Senegal, Tajikistan, Togo, and Vietnam. Nine of these 16 countries represent the African continent. These commitments come in addition to the 18 made in September 2010 by African states, bringing the total of African countries having committed to the health of women and children to 27. These commitments to the Global Strategy follow a declaration by heads of states at the 2010 July Summit of the African Union to strengthen efforts to improve maternal, newborn, and child health and a March 2011 Resolution by African ministers of finance and budget to improve health investment and strengthen their dialogue with health counterparts. 

'”The Global Strategy is an unprecedented opportunity to help the women and children who need it most. The commitments made by Members States, donors and other partners are an impressive signal that we collectively take responsibility to achieve the health-related Millennium Development Goals and save more women's and children's lives,'” said World Health Organization Director-General Dr. Margaret Chan, in a May 19, 2011, statement. 

Every year, 358,000 women in the developing world aged 15–49 die of pregnancy and childbirth-related complications. Every year, 2.6 million children are stillborn, and a further 8.1 million die before their fifth birthday, including 3.3 million babies in the first month of life. “Focusing on the women and children in greatest need is not only the right thing to do, it moves us faster and most cost-effectively towards meeting the health Millennium Development Goals,” said Anthony Lake, UNICEF executive director, in the May 19th statement. “By choosing to redouble their efforts on maternal and child health, these 16 nations are not only saving lives, they are making an investment in their future.” 

The commitments, made with the support of UNAIDS, UNFPA UNICEF, the World Bank and WHO (collectively known as the H4+ agencies), focus on measures proven effective in preventing deaths, such as increased contraceptive use, attended childbirth, improved access to emergency obstetric care, prevention of mother to child transmission of HIV, and childhood immunizations. 


 In September 2011, Merck & Co. announced the launch of "Merck for Mothers," a long-term effort with global health partners to prevent women from dying from complications of pregnancy and childbirth. The launch includes a 10-year, half-billion-dollar initiative that applies Merck's scientific and business expertise to make solutions more widely available, develop technologies, and improve public awareness, policy efforts, and private-sector engagement for maternal mortality.

 “Every Woman Every Child has shown what can be achieved through close cooperation among the UN, governments, and the private sector," said UN Secretary-General Ban, in a Sept. 20, 2011, Merck press release. "A great deal has been achieved in the last year, but progress must be accelerated if we are to achieve our goals of saving 16 million lives by 2015. I am delighted that despite difficult economic times, many governments, companies, and civil-society leaders are making significant commitments to Every Woman Every Child. These are smart decisions [that] visionary leaders recognize the value of investing in the health of women and children."

In September 2010, UN Secretary-General Ban launched the Global Strategy for Women's and Children's Health supported by Every Woman Every Child, a global effort to improve the health of women and children. Merck, in concert with the UN and its partners, has committed to help tackle the MDG that aims to reduce the maternal mortality ratio by 75% and create universal access to reproductive health.

Based on input from more than 100 experts in the field, Merck developed a strategic framework identifying where the company will focus its people and resources in the Merck for Mothers initiative. The initiative will focus on the two leading causes of maternal mortality (excessive and uncontrolled bleeding after childbirth, known as post-partum hemorrhage, and life-threatening high blood pressure during pregnancy, known as preeclampsia) as well as family planning, which is known to play an important role in reducing maternal mortality. The initiative will be guided by input from both an internal steering committee and an external advisory board. Merck will hold itself accountable for the initiative's programs and outcomes by ensuring that an independent organization will monitor and evaluate its efforts. There are three main approaches for the long-term initiative. 

The first approach is to accelerate access to proven solutions. Merck intends to improve the quality and supply of diagnostic, prevention, and treatment interventions for post-partum hemorrhage and preeclampsia. In addition, the company will strengthen medical education for skilled birth attendants, help develop sustainable models for health deliver, and expand access to family planning.

The company’s second strategy is product Innovation. Merck will collaborate with partners to develop maternal health technologies for widespread use in resource-poor settings. Merck will start with an assessment of more than 30 promising existing technologies in partnership with leading donors, nongovernmental organizations (NGOs), and researchers, with a goal of developing at least three innovations that address post-partum hemorrhage, preeclampsia, and family planning.

The company’s last effort focuses on global awareness and advocacy. Merck will join maternal-health experts to create greater public awareness of the need to reduce maternal deaths in an effort to improve global and national policy. Merck also will work with NGOs and multilateral organizations to advocate for broad private-sector engagement. As part of "Merck for Mothers", Merck is among the first companies to join the UN Global Compact/UN Foundation's Private Sector Task Force for Every Woman Every Child. 

Articles

CSR and Sustainability Forum

Pharmaceutical companies join international efforts to reduce maternal and child mortality in the developing world.

Pharma Companies Focus on Advancing Women

The pharmaceutical industry is undergoing a transition that is marked by evolving product demand, generic-drug incursion, a greater emphasis on specialty products, and an intensification in product development for biologic-based drugs. Industry growth patterns are shifting not only on a product basis, but on a geographic basis as well. Pharmaceutical companies are seeking to meet rising demand in emerging markets and face a more global and complex supply chain, both on an ingredient basis and on a finished-product level. John Kelly, vice-president of strategy and transitioning sites for Pfizer Global Supply (PGS), recently discussed these trends and Pfizer’s manufacturing and supply strategy to address the changing marketplace.

John Kelly, vice-president of strategy and transitioning sites for Pfizer Global Supply

“Our mission is to have an integrated internal and external supply network to provide a competitive advantage for Pfizer by offering fast, flexible, and innovative supply solutions,” says Kelly. That task involves aligning the company’s supply network, consisting of both external and internal partners, with changing product demand, as well as integrating the former Wyeth network with Pfizer’s supply network following Pfizer’s $68-billion acquisition of Wyeth in 2009. 

Pfizer has 87 manufacturing sites across all business sectors—pharmaceuticals, consumer healthcare, and animal-health care. This supply network includes 188 logistics centers, more than 500 supply partners, and more than 30,000 employees. On a geographic basis, the company has 30 sites in North America, 20 in Europe, seven in China, 17 in the rest of Asia, and seven in Latin America. On the pharmaceutical side, the company operates six small-molecule manufacturing sites, six biologic-based drug sites (five for drug substances and one for packaging), eight solid-dosage facilities, and four sterile-manufacturing sites. Additionally, the company operates six manufacturing sites for its consumer-healthcare business and 23 for its animal-health business.

 Kelly explains that the company’s supply network is focused on four main strategies: to optimize its supply network, optimize its network performance, increase commercial value, and enhance core process excellence. In building a cohesive strategy, Kelly points out that PGS has developed a co-manufacturing approach by combining and consolidating global operations, not only through its most recent acquisition of Wyeth in 2009, but through earlier large-scale acquisitions, namely Warner-Lambert in 2000 and Pharmacia in 2003, as well as through bolt-on acquisitions, with some recent examples being the animal-health care company Synbiotics in 2010, the specialty pharmaceutical company King Pharmaceuticals in 2011, and the consumer-healthcare business of Ferrosan, which the company announced earlier this year that it will acquire. 

With respect to its goal of optimizing its supply network, Kelly emphasizes that PGS’s strategy is to optimize internal and external partnerships in sourcing, capacity, capital allocation, costs, and asset utilization. Pfizer uses external partners for approximately 30% of its production on a cost-of-goods-sold basis, which includes API manufacturing and finished-product manufacturing. “External manufacturing is of increasing importance as we look at different ways to supply products,” says Kelly. 

In its goal of optimizing network performance and enhancing process excellence, the company measures and seeks continuous improvement in its manufacturing operations and supply-chain activities. The company recently adopted a balanced-scorecard approach for evaluating and improving the performance of its manufacturing network. The metrics from the balanced scorecard are applied on a site-specific basis and divisional level to assess PGS’s performance on processes, quality, and environmental, health, and safety compliance. PGS rolled out the balanced-scorecard approach in part in 2010, and this year is rolling it out fully across its network. 

“It helps us understand the progress we are making and how we are improving in several areas, such as how we serve our customers, how we meet our financial commitments, how we engage our colleagues, and how we improve our processes,” says Kelly. 

As part of its strategy to increase commercial value, the company focuses on developing and maintaining partnerships with the company’s business units to support innovation across the product life cycle, drive revenue creation and enhancement, and optimize supply-chain security. From an organizational perspective, PGS operates nine operating units, seven that support Pfizer business units and two that are responsible for managing external supply and transitioning sites. The PGS operating units support business units in specialty care, primary care, oncology, emerging markets, established products, animal health, consumer healthcare, and nutrition. The functions of these units and PGS operating units that focus on external supply and transitioning sites are supported by global logistics and supply activities, quality operations, global manufacturing services, and network-enabling functions, such as finance, human resources, legal, and procurement. 

 Kelly emphasizes that the company’s supply strategy is shaped by various factors affecting the industry. “The product mix is changing,” says Kelly. “We see shifts not only in small molecules versus large molecules, but see the need to address supply challenges caused by the changing blockbuster model and a move to smaller-volume products.” 

As part of those changes in product demand, as well as part of it integration with Wyeth, Pfizer announced plans to exit 13 sites during the next several years.The timing of specific exits will depend upon the complexity of operations, the amount of time needed for product transfers, and other business requirements.  Earlier this year, Pfizer sold its manufacturing plant at Dun Laoghaire, Ireland to Amgen. The 37,000-m

 aseptic operations facility has freeze-dried product and liquid vial-filling operations. Pfizer sold its bulk biologics facility in Shanbally, Ireland, to the biopharmaceutical company BioMarin. Pfizer also recently sold its consumer healthcare manufacturing facility in Richmond, Virginia, to Fareva, a pharmaceutical and consumer-products company, which will continue to supply Pfizer with product from the facility. 

 Pfizer's strategy includes plans to discontinue operations at three solid-dosage sites in Caguas, Puerto Rico; Loughbeg, Ireland; and Rouses Point, New York. Pfizer also announced plans to phase out pharmaceutical solid-dosage manufacturing in Guayama, Puerto Rico, but that site will expand its consumer-healthcare operations. Reductions are planned at two other solid-dosage facilities in Illertissen, Germany, and Newbridge, Ireland. Two aseptic facilities that make sterile injectable medicines were targeted for exit: Dublin, Ireland, (recently sold to Amgen), and Carolina, Puerto Rico. 

Pfizer also announced changes to its biopharmaceutical-manufacturing network. The company said it planned to exit operations in Shanbally, Ireland (recently sold to BioMarin), and Pearl River, New York. The Pearl River site, however, will remain Pfizer's center of excellence for vaccine R&D. Biotechnology plants in Sanford, North Carolina, Andover, Massachusetts, and Havant, United Kingdom, are expected to see reductions. Pfizer reported plans to cease production of consumer-healthcare products at its plant in Richmond, Virginia (sale of the facility to Fareva was recently completed), but consumer healthcare R&D operations will continue in the downtown Richmond site. 

Most recently, Pfizer announced plans to exit solid-dosage sites in St. Petersburg, Florida, and Bristol, Tennessee, as well as an animal-health diagnostic manufacturing site in Lyon, France.

In outlining the changes to its manufacturing network, Pfizer summarized how its transformed manufacturing network will look. Pfizer's solid-dosage network will include plants in Freiburg, Germany; Amboise, France; Vega Baja and Barceloneta, Puerto Rico; Ascoli, Italy; Newbridge, Ireland; and Illertissen, Germany. Its aseptic-manufacturing network will consist of plants in Puurs, Belgium; Perth, Australia; Catania, Italy; and Kalamazoo, Michigan. Its biotechnology-manufacturing network will consist of sites in Grange Castle, Ireland; Strangnas, Sweden; Algete, Spain; Havant, United Kingdom; Andover, Massachusetts; and Sanford, North Carolina. The consumer healthcare network will include plants in Guayama, Puerto Rico; Montreal, Canada; Albany, Georgia; Aprilia, Italy; Hsinchu, Taiwan; and Suzhou, Jiangsu, China.

Kelly explained that the changes underway at Pfizer reflect broader trends affecting the pharmaceutical industry. He points to the growing complexity of pharmaceutical companies’ product portfolios and the resulting need for increased flexibility, specialized capabilities, and technological complexity. He also points to a more dynamic market environment, which requires a need to develop and launch products quickly and to respond to pricing and supply changes as well as increased volatility in demand. These factors contribute to greater pressure on margins and a stronger need to reduce costs of goods sold and justify capital expenditures. As supply networks become more elaborate and costly to operate in light of these factors, Kelly says that “more value is placed on fungible assets for improved utilization and efficiency.  All this must be done while maintaining focus on quality and compliance, supply reliability, and delivering value to our customers,” he adds. 

“There is a critical need for the industry to focus on efficiency gains and value creation,” sums up Kelly. “Through the clarity of our vision and delivering on our strategies, Pfizer will achieve a competitive advantage by offering fast, flexible, and innovative supply solutions,” he concludes. 

http://pharmtech.findpharma.com/pharmtech/article/articleDetail.jsp?id=748002

 to listen to a podcast with John Kelly, vice-president of strategy and transitioning sites for Pfizer Global Supply, who discusses the company's manufacturing and supply strategy and network. 

Manufacturing

John Kelly, vice-president of strategy and transitioning sites for Pfizer Global Supply, discusses the company's manufacturing and supply strategy and network.

Pfizer Outlines Its Supply Strategy

 the Abbott Fund, and PATH have formed a partnership to address malnutrition by advancing the rice fortification market in India. Abbott is providing a three-year, $1.5 million grant for refining and scaling up the production and distribution of fortified rise using PATH’s UltraRice fortification technology. 

 has formed a collaboration with the World Health Organization’s Stop TB Department for a two-year pilot initiative to strengthen community-based prevent and control of tuberculosis, including co-infection with HIV in South Africa, Tanzania, Kenya, Ethiopia, and the Democratic Republic of Congo. 

contributed $12.3 million to the United Way, which represents contributions from Lilly’s US employees and retirees and a matching gift from the Lilly Foundation. 

In other news, Eli Lilly committed $30 million in funding to further support the Lilly MDR-TB Partnership, which seeks to fight multidrug-resistant (MDR) tuberculosis (TB). The funding will be used to support a third and final stage of the partnership through 2016 that will focus on providing training for healthcare providers and improving supply and access to safe, effective, and quality-assured second-line drugs. The partnership will operate globally with a specific focus in China, India, Russia, and South Africa, the four countries with the highest burden of MDR-TB. 

Eli Lilly also reported that it is improving its environmental footprint by achieving two of the company’s three environmental goals ahead of schedule. Through the end of 2010, the company reduced the amount of waster sent to landfills by about 50% and has reduced its water intake by more than 30%. The company is on track to meet its energy goals and has improved energy efficiency of its operations by almost 12% and reduced greenhouse-gas emissions by 9% through 2010. 

released results from a large-scale Phase II trial of RTS,S, a malaria vaccine candidate for children in Africa. The results showed that the vaccine reduced the risk of malaria by half in African children aged 5–17 months. The results were published in the 

 The vaccine is being developed in partnership with GSK, the PATH Malaria Vaccine Initiative, and African research centers. Further information about the longer-term protective effects of the vaccine, 30 months after the third dose, should be available by the end of 2014. 

 Neutrogena brand reports the successful conclusion of its second annual wave Wave for Change campaign, a charitable effort that makes it easy for teenagers to give back in the US and other parts of the world. This year’s program generated a total of $258,000 for use in assistance in educational and environmental efforts. 

committee awarded its 2011 Pro Bono Humanum Award to Dr. Paul Farmer for his lifetime contribution of humanitarian efforts in Haiti and throughout the world and his efforts in advancing the fight against infectious diseases, including AIDS and tuberculosis. 

World Intellectual Property Organization 

(WIPO) launched a new consortium with pharmaceutical companies and BIO Ventures for Global Health whereby public and private sector organizations share intellectual property and expertise with the global health research community to promote development of new drugs, vaccines, and diagnostics to treat neglected tropical diseases, malaria, and tuberculosis.  Membership in the collaboration, WIPO Re:Search, as a user, provider, or supporter is open to all organizations that endorse, adhere to, and support the project’s guiding principles. These principles include the commitment that the intellectual property licensed via WIPO Re:Search will be licensed on a royalty-free basis for R&D on neglected tropical diseases in any country and on royalty-free basis for sale of neglected tropical disease medicines in, or to, least-developed countries. Pharmaceutical companies participating in the initiative include, Alnylam Pharmaceuticals, AstraZeneca, Eisai, GlaxoSmithKline, Merck & Co., Novartis, Pfizer, and Sanofi. 

A roundup of developments in corporate social responsibility and sustainability from the bio/pharmaceutical industry, its suppliers, and other private and public organizations.

CSR and Sustainability in the News

 discusses strategies in optimizing API syntheses and manufacturing. Participants include Jan-Olav Henck, PhD, chief scientific officer at Aptuit, Fred Fleitz, senior manager of process R&D with Cambridge Major Laboratories, and Roger McDonald, director of business development with Cambridge Major Laboratories. Also, Annemieke Timmers, CPhI brand director with UBM, discusses CPhI Worldwide, which was held in Frankfurt in October 2011 and other CPhI events.

 to a podcast with Jan-Olav Henck, PhD, chief scientific officer at Aptuit, who discusses strategies and considerations in polymorph screening. 

 to a podcast with Fred Fleitz, senior manager, process R&D with Cambridge Major Laboratories, and Roger McDonald, director of business development with Cambridge Major Laboratories, discuss recent project work in optimizing several API syntheses. Fleitz discusses the approach taken in a condensation reaction between a naphthoquinone derivative and a substituted methyl vinyl ketone. McDonald discusses the optimization of a synthetic route for a complex natural product analogue. In another project, he discusses an approach taken to maintain the desired enantioselectivity of a molecule containing a chiral cyclopropane moiety during scale-up. 

 to a podcast with Annemieke Timmers, CPhI brand director with UBM, discusses CPhI Worldwide, which was held in Frankfurt in October 2011, and other CPhI events.

APIs

Pharmaceutical Technology's podcast series from CPhI.

Technical Perspectives from CPhI Worldwide

Below is a roundup of news from exhibitors at CPhI Worldwide, which was held in Frankfurt, Germany, in late October 2011. 

 has opened a new analytical chemistry laboratory and GMP suite to extend and enhance its formulation-development capability. The new facilities at Aesica’s site in Nottingham, United Kingdom, include a dedicated analytical chemistry laboratory to test inhalation devices and a new GMP manufacturing suite, which will almost double the production capacity of clinical-trial materials across all dosage forms. Following the expansion in the UK, Aesica also plans to extend its formulation-development capabilities by launching a second site from within its formulated-products plant in Zwickau, Germany. The site specializes in the production of tablets, capsules, and pellet/beads and has a development laboratory. The launch of the new site is set for January 2012.

a commercial unit of Ashland, plans to add a GMP hot-melt extruder in its Columbia, Maryland, R&D center. The 18-mm Leistritz extruder will allow companies to scale up GMP clinical and commercial quantities produced by hot-melt extrusion. Ashland will finish installing and testing the equipment in the fourth quarter of 2011 and begin offering a full-service offering early in 2012. Earlier this year, Ashland completed its acquisition of the fine and specialty chemical company, International Specialty Products. 

Ashland Specialty Ingredients also launched Aquarius coatings based on a natural colors palette. The coatings systems use colorants based on natural ingredients that are color-stable under light and storage conditions. The company also announced the availability of three new commercial grades of Benecel hypromellose (HPMC) excipients for use in the formulation of matrix tablets: HPMC K250 PH PRM, HPMC K750 PH PRM, and HPMC K1500 PH PRM.

has developed a packaging system, PeroXeal, to protect its pharmaceutical excipient, Kollidon, which is based on polyvinylpyrrolidine, against contact with oxygen and subsequent oxidation. The system makes it possible to reduce the level of peroxide of Kollidon, thereby making the excipient suitable for use in oxygen-sensitive formulations as well. The PeroXeal packaging system consists of a multilayered and heat-sealed plastic film used as inner packaging material. The new packaging has been introduced for most Kollidon products at the company’s Luwigshafen and Minden, Germany, sites. BASF will offer all grades of the Kollidon line with the new technology starting by the end of 2013. 

 have formed a collaboration for the development of future film-coating systems using BASF’s Kollicoat SmartSeal 30D and a new Colorcon preformulated additives. Colorcon has developed a preformulated additive system for use with Kollicoat SmartSeal 30D to enable efficient preparation and application of this polymer in taste-masking applications. The preformulated additive lowers the number of materials to be dispensed by 50% and reduces the preparation time by almost 40%, according to the companies.

also has developed a portfolio of high-purity iron salts for API manufacturing. Solutions for iron-deficiency anemia, phosphate management, and magnetic resonance imaging are gaining in importance. The new iron salts have trace-metal impurities at the single-digit ppm level, therefore keeping them in compliance with EMA directives. The salts are available in quantities ranging from kilograms to commercial volumes. 

-methylpyrrolidone Life Science (NMP Life Science), which is a NMP grade with a very low level of free amines in the range of 1 part per million, equivalent to 0.0001%. The company notes that the product can be used in the solid-phase synthesis of therapeutic peptides and raise yields by more than 15%. BASF also featured its NanoSelect platform technology, which has been used to develop platinum-based catalysts for selective aromatic nitro group hydrogenation. The company says the new catalysts show high nitro group hydrogenation activity with lower platinum requirements. Additionally, the NanoSelect platform technology has enabled the production of modified platinum catalysts with good selectivity in halo nitro aromatic hydrogenation reactions, according to the company. 

, a French fine-chemicals company, has formed a strategic partnership agreement with 

, a US fine-chemicals company, to jointly market and distribute both companies’ organoboron compounds and synthetic intermediates. The partnership will help Boron Molecular better access European markets and facilities BoroChem’s access to the US market. 

 has expanded its cGMP facility in Charlottetown, Prince Edward Island, Canada, with the addition of a 1500-L fermentation unit for producing clinical and commercial products. The company will also be initiating production in a new wing dedicated to the manufacture of 50 metric tons of new drug substances and is in the design stage for the construction of new facility for manufacturing dedicated APIS. The initiatives are expected to completed in 2012. 

 were awarded to Glycotope (gold winner) for its development of the GlycoExpress platform technology to optimize the glycosylation of antibodies and other glycosylated biotherapeutics, Acuros (silver winner) for its disposable drug-delivery device that allows continuous delivery of small-volume parenteral drugs, and Johnson Matthey for its Catalyst Color-Tag Protein technology, which is used as marker for protein expression. 

, a biocatalysis company, reports that its Codex screening kits are in use or evaluation at 50 pharmaceutical companies worldwide. The company introduced the kits in October 2010. The company reported that through Sept. 30, 2011, more than 10,000 kg of various enzymes have been manufactured by the company’s enzyme production partners. Smaller 10–100 kg quantities have been manufactured at the company’s Redwood City, California, facility. 

has increased its capacity of propylene glycol by an additional 10 kilotons per year at its Stade, Germany, plant after completion of equipment optimization during scheduled routine maintenance. The capacity increase raises the plant’s propylene glycol nameplate capacity to approximately 280 kilotons per year.  Dow operates five global propylene glycol manufacturing facilities with a total global capacity of 700 kilotons per year. The company manufactures pharmaceutical-grade propylene glycol. 

, a business unit of Dow Chemical, is planning a capacity expansion project for the production of Carbowax Sentry solid-grade polyethylene glycols. The expansion project is expected to begin in 2012 and will support the global supply of Carbowax Sentry. 

, a CRO that provides custom synthesis and drug-discovery services  and 

, the testing and laboratory division of 

, have formed a strategic alliance. The new organization, GalchimiApplus, will perform R&D, scale-up and small production, as well as analytical development and validation. 

has started construction of a new, multipurpose, multiproduct API manufacturing facility, which is scheduled to be operational by June 2012. The plant will consist of two parallel streams and will accommodate 32 reactors with capacities ranging from 6 m

 for a total reactor volume of approximately 300 m

launched its Rapid Proof of Concept Study for the development of dry-powder inhalation products. The new service is intended to simplify the developing of formulations by producing a proof-of-concept formulation of a molecule in a few weeks.  Hovione also announced that it formed a nonexclusive, cooperative relationship with 

 a formulation-development company. The collaboration gives Bend Research clients access to Hovione’s commercial-scale pharmaceutical facilities on a global basis and provides Hovione’s clients access to Bend Research’s oral drug-delivery, formulation, and engineering expertise. 

 has been granted a global license to the full range of Buchwald dialkyl- biaryl- mono phosphine and related bis-phosphine ligands. The licensed patents include both the composition of matter of the family of ligands and the processes for use of catalysts containing these ligands in transition-metal catalyzed carbon–heteroatom and carbon–carbon bond-forming reactions. 

accepted an offer on Oct. 27, 2011, to divest Novozymes Biopharma Sweden to American-owned Repligen Corp. Earlier this year, Novozymes announced that the company has been looking for a potential spin off or divestment of its AMP (antimicrobial peptide) projects such as plectasin and arenicin.

also featured its ICH Q7 cGMP grade of hyaluronic acid (HA), a new 

-derived grade to improve processing and formulation of HA for medical-device and pharmaceutical applications. The HA is produced at a new Novozyme facility in Tianjin, China, and is produced using a water-based process that is free of animal-derived components and organic solvents. The HA will be commercially available in December. 

 reports that Boehringer Ingelheim has awarded the company two projects with combined revenues of more than $18 million during a three-year period. The projects are both fixed-dose combination drugs in development for treating Type II diabetes. 

reports that it is performing commercial-scale antibody–drug conjugate (ADC) manufacturing at its Grangemouth, Scotland, facility. The company is currently evaluating plans to build out additional manufacturing suites to accommodate kilogram batch sizes. Several ADC-based therapies are in late-phase clinical trials, approximately one dozen are in Phase I development, and more than 20 are in preclinical development. Earlier this year, Piramal opened a new $400,000-quality-control laboratory suite at its facilities in Grangemouth to support its ADC portfolio. 

 reports that its custom manufacturing and services business unit, 

, has completed an assessment by SafeBridge Consultants and has been granted SafeBridge certification for its commercial-scale high-potency API (HPAPI) facility in Verona, Wisconsin. Constructed at a cost of $30 million and officially opened in April 2010, the Verona site was built specifically to support manufacturing for Phase III and commercial scales up to Category IV compounds. The SafeBridge assessment also included a successful recertification of SAFC’s nearby Madison, Wisconsin, high-potency facility. 

 reports that it will build new production capacities for potent APIs at its facility in Redmond, Washington. The company will expand its production to produce and handle Category III substances. The capacity up to the kilogram range will become available at the beginning of 2012.

Global Feature

A roundup of news from fine-chemical suppliers, CDMOs, and CMOs from this year's installment of CPhI Worldwide.

Contract Manufacturers and Ingredient Suppliers Assemble at CPhI Worldwide

As pharmaceutical manufacturers face an increasingly competitive environment, they are looking for opportunities to reduce production costs without negatively affecting the yield or the quality of finished products. Energy-price volatility can negatively affect financial performance. The challenge of maintaining high product quality while reducing production costs can be met through investments in energy-efficient technologies and energy-efficiency practices. Energy-efficient technologies may offer additional benefits, such as quality improvement, increased production, and improved process efficiency, which can lead to further productivity gains. Energy efficiency also is an important component of a company’s environmental strategy because energy-efficiency improvements can lead to reductions in pollutant emissions. Because energy use varies across manufacturing segments given differences in unit operations, process principles, and equipment, it is difficult to address energy-saving measures in broad manufacturing terms. This articles examines opportunities to conserve energy in pharmaceutical manufacturing operations through currently available products and concepts.

Various opportunities exist within pharmaceutical laboratories, manufacturing facilities, and other buildings to reduce energy consumption while maintaining or enhancing productivity. While changes in equipment usually come to mind when considering energy-efficient investments, changes in staff behavior and attitude also can have a great impact. Training programs can help a company’s staff incorporate energy-saving practices into their day-to-day work routines. Personnel at all levels should be aware of their energy use and company objectives for energy-efficiency improvement. Placing posters near equipment detailing that machine’s running cost per hour can create awareness among operators. 

Management decisions regarding energy-saving measures should be passed on to the bottom layer of the organization. Programs that include regular feedback on staff behavior, including rewarding those incorporating rewards, have had the best results. Though changes in staff behavior (such as switching off lights or closing windows and doors) often save only small amounts of energy at one time, taken continuously over longer periods, they can have a much greater effect than other, more costly technological improvements. 


Energy-efficiency improvements should be approached from several directions. A strong, corporate-wide energy management program is essential. Ideally, such a program should take into account facilities, operations, environmental concerns, and employee health and safety. Energy-efficiency improvements to cross-cutting technologies, such as the use of energy-efficient motors and the optimization of compressed air systems, are well-documented opportunities for energy savings. Optimizing system design and operations, such as minimizing laboratory ventilation, can also lead to significant reductions in energy use. In addition, production processes can often be fine-tuned to produce similar savings. Figure 1 outlines key points in pharmaceutical production.

Energy-conservation measures can be implemented at any time, but it is better if optimizing energy use is considered from the early-concept stage. The benefits of considering energy-efficiency early include:  

 • The ability to design energy-efficient buildings and infrastructure that take into account such factors as natural light and wind flow to reduce electricity needs.

• The opportunity to implement an energy-efficient plant design that will ensure utility sources and supply points are optimally located to reduce head loss in transit and fittings.

 Changing how energy is managed by implementing an organization-wide energy-management program is one of the most successful and cost-effective ways to bring about energy-efficiency improvements. Energy efficiency does not happen on its own; a strong energy-management program is required to create a foundation for positive change and to provide guidance for managing conservation protocols throughout an organization. Energy-management programs also help to ensure that energy-efficiency improvements do not just happen on a one-time basis, but rather are continuously identified and implemented. Furthermore, without the backing of a sound management program, energy-efficiency improvements might not reach their full potential due to lack of a systems perspective and/or proper maintenance and follow-up. In companies without a clear program in place, opportunities for improvement may be known but may not be promoted or implemented because of organizational barriers, including a lack of communication among facilities, a poor understanding of how to create support for an energy-efficiency project, limited finances, or poor accountability.

In a typical pharmaceutical plant, electric motors are a key component of almost all the equipment including reactors, centrifuges, air oven dryers, vacuum dryers, and blowers. Significant attention should be given to proper maintenance and operation of the motors. In the case of burnt-out motors, many operators prefer to do a rewinding or repair job and reinstall the motor without checking its efficiency/electricity consumption. Very often re-winded or repaired motors consume energy at a very high rate, and the running cost of the old motor becomes more than that of the cost of a new one.

Cooling water treatment is mandatory for any cooling tower, whether it be splash fill or film-type fill, to control suspended solids and algae growth. With increasing water costs, efforts to increase cycles of concentration (COC) can help reduce water requirements significantly. In large industries, such as power plants, COC improvement is often considered a front-line tool for water conservation. 

The purpose of a cooling tower fan is to move a specified quantity of air through a system, overcoming the system resistance, also described as pressure loss. The product of air flow and pressure loss is air power developed/work done by the fan; this may be also termed fan output. Fan input  (kW) depends on fan efficiency, which is in turn greatly dependent on the profile of the blade. An aerodynamic profile with optimal twist andtaper and a higher coefficient of lift to coefficient of drop ratio can provide the fan with a total efficiency as high as 85–92%. However, this efficiency is drastically affected by the factors, such as tip clearance, obstacles to airflow, and inlet shape. Because metallic fans are manufactured by either extrusion or casting processes,  it is difficult to generate the ideal aerodynamic profiles. Fiber reinforced plastic (FRP) blades are normally hand-molded, which generates the optimal aerodynamic profiles to meet specific duty conditions more efficiently. Cases have been reported where replacement of metallic or glass fiber reinforced plastic fan blades with hollow FRP blades yielded fan energy savings on the order of 20–30% with a payback period of six to seven months. Also because they are lightweight, FRP fans need less starting torque, thereby allowing lower horsepower motor to be used. The lightweight design also increases the life of the gear box, motor , and bearings and allows for easier handling and maintenance.

In process heating, more than 60% of the thermal energy used is in the form of steam. Process improvements to steam generation and more efficient use of steam can conserve large amounts of energy. One reason fuel and steam conservation opportunities can be so significant is because multiple system improvements can be made. Collectively, these changes can yield savings of 10-15% in many cases, with a general project payback period of less than two years. Steam traps should be inspected to determine whether they are functioning properly or allowing live steam to blow through. Programs for periodic inspection and maintenance of traps with correct reporting should yield savings. Typically, high-pressure traps should be inspected at least twice a month, medium-pressure traps once every two months, and low-pressure traps every six months. Plants in which traps have not been inspected or maintained for three years or more could have up to 30% of their traps blowing steam. This level could be brought down to less than 5% with a well-designed and executed maintenance program. 

Lighting is an essential part of operations. If energy conservation is considered at the design stage, lighting and ventilation costs can be reduced. The plant can be designed in such a way that proper lighting is maintained throughout the day. Windows or transparent glass can be positioned through walls and roof tops to maximize natural light. Employees also can be trained to be partners in energy-saving efforts, and individuals can be rewarded for exceptional conservation behavior. Adding technologies, such as light sensors that automatically switch lights on and off, will also help yield long-term energy savings. Because incandescent lamps convert just 5% of energy, with the remainder given off as heat, fluorescent lamps that turn 25% into light should be used wherever possible. These lamps also use less electricity and have a longer life span compared to incandescent lamps. Conventional fluorescent lighting systems operate from the mains using a simple series choke as the ballast, which creates sufficient voltage with the glow starter to both start the lamp and to limit the lamp’s current afterwards. Another energy-saving lighting solution is to replace the conventional magnetic ballast with electronic ballasts, which are more efficient and compact. This approach can save up to 20-25% of lighting cost wherever used. Similarly, old fan regulators should be replaced with electronic regulators to minimize the energy usage. Table I compares the performance of a conventional ballast with an electronic ballast. The drawback of the electronic ballast is the price, which is typically several times higher than its magnetic counterpart. 

Table I: Comparisons of the conventional and electronic ballasts for T8 36W fluorescent lamp.

Light-sensitive electronic ballast systems with the intelligence to sense outdoor light are now being used for many commercial buildings. The systems use a light sensing device to feedback ambient signals to a micro controller that adjusts the operation frequency of the inverter in the ballast. The light output is thus adjusted automatically according to the sunlight.

Agitators are an essential part of process equipment. Advances in technology have enabled new agitators that consume less energy without compromising product output and quality. 

 The benefits of using an Ekato Viscoprop agitator in place of a pitch-blade turbine include: 

High mixing efficiency for low and high-viscosity fluids. 

High fluid velocities at vessel bottom for the suspension of solids. 

High axial fluid velocities at vessel wall for  improved heat transfer. 

Impeller for small and large volume applications. 

Impeller can be applied in single or multiple-stage arrangement. 

Impeller pitch adapted for low and high viscosity fluids. 

Same mixing efficiency at reduced power input and torque. 

The Ekato agitator is more useful when the reaction mass or mixture consists of more than one phase, for example, heterogeneous mixtures where uniform mass distribution is needed. Uniform mass distribution is especially important in bioreactors where there is considerable biomass formation during the fermentation process and the availability of nutrients to the microorganisms is vital for productivity. The Ekato agitator ensures better mixing and uniformity of mass and power savings when compared to a standard turbine impellor. This agitator has been used successfully for the production of fermentation products such as lovastatin using 30 m

 bioreactors. Increased output and reduced energy quickly pays back the agitator cost. With varied impellor designs, it is also possible to reduce capital expenditures by optimizing the shaft diameter. Table II compares a pitch-blade turbine with Ekato Viscoprop.

 Table II: Comparison of a pitch-blade turbine with Ekato Viscoprop. 

 
 The benefits of using a Lightnin A-315 agitator in place of turbine include: 

Elimination of staging when compared with radial agitators. 

Improved mass transfer up to 30% and uniform distribution of mass across the reactor. 

Reduced energy consumption (up to 30–45%) 

The Lightnin agitator has been used successfully for various fermentation products where there is considerable biomass generation and the solids content may be up to 40-50%. This agitator also has the unique advantage of low shear stress, which helps in maintaining the integrity of the biomass and facilitating downstream processes. When used for the production of salinomycin in a 100 m

 bioreactor, the Lightnin A-315 agitator contributed to energy savings of up to 25% and increased productivity.

The pharmaceutical industry consume a considerable amount of energy during various unit operations. A strong and clear management policy for energy conservation is the first step toward energy savings. Unlike other process improvements  programs, energy saving is an ongoing effort with continuous opportunities for improvement. Managers must continually identify loopholes and plug them effectively to ensure the company remains profitable in an increasingly competitive environment. However, when considering replacing existing equipment with modern, energy efficient counterparts, the payback period should be taken into account in order to maximize return on investment. 

The authors discuss opportunities for energy efficiency in pharmaceutical manufacturing.

Energy Conservation in Pharmaceutical Manufacturing

The past six months have seen a spate of large acquisitions in the pharmaceutical services industry intended to create giant-scale service providers with global reach. Noteworthy deals are INC Research's acquisition of Kendle International, which boosted INC to $700 million in revenues; inVentiv's purchase of i3 and PharmaNet Development, which created a $900-million CRO; and Catalent Pharma Solutions' $400-million acquisition of Aptuit's clinical supplies business, which pushed Catalent into the number two slot in clinical packaging. 

The rationale cited for these megadeals is that global bio/pharmaceutical companies favor large CROs with broad capabilities in their selection of preferred service providers. These "strategic partnership" deals are the cornerstone of global bio/pharmaceutical companies' current sourcing strategies, which seek to leverage their massive buying power while reducing sourcing overhead expense and improving coordination with the CRO.  

The list of publicly announced preferred provider deals (see Table I) shows that global bio/pharmaceutical companies have clearly embraced the large multiservice provider, at least for now. However, there is a substantial probability that sourcing models will change significantly in coming years and threaten the business model upon which the recent megadeals are based. 

Table I: Publicly announced preferred-provider deals. 

We have already seen a major shift in sourcing strategies at one of the largest bio/pharmaceutical companies. Pfizer was an early proponent of the functional service provider (FSP) sourcing model but has now shifted to the integrated service provider (ISP) model. In the FSP model, Pfizer sought to engage the best-in-class service provider in each clinical research activity (e.g., site monitoring, data management, or central laboratory services) and to have those best-in-class providers support all of their trials. However, Pfizer executives found the FSP model too costly because too much internal overhead was required to coordinate the activities of the various FSPs.  

In its most recently announced strategic CRO deals with Icon and Parexel, Pfizer has moved to the ISP model in hopes of eliminating the high internal overhead costs. Now, Icon and Parexel will provide a broad range of services to each of the clinical trials they will manage on behalf of Pfizer. 

It should be remembered that both the global bio/pharmaceutical companies and their CRO partners are still very new to the strategic sourcing process. They have barely begun to progress down the learning curve of how to establish and manage these relationships; the bio/pharmaceutical industry is thought to be a decade or more behind other industries in its sourcing practices. As both sides gain experience and as some of these relationships blow up, as they inevitably will, the sourcing model will evolve in directions that have not yet been anticipated. 

At many of the global bio/pharmaceutical companies, the senior executives that negotiated these strategic sourcing deals had little previous direct experience in managing CRO relationships and often did not involve lower-level colleagues who did. It is likely that they underestimated the risks and challenges of those sourcing deals and the abilities of their partners to handle them.  

The consequences of adopting a radical new sourcing strategy with untested partners could be dire, if not catastrophic. Boeing demonstrated that with its Dreamliner supply-chain fiasco. The company outsourced major components of its new 787 Dreamliner passenger jet (including large sections such as the wings and fuselage) to partners around the globe. The company found out too late that many of its partners were not up to the task, which resulted in delaying delivery of the new plane by at least two years. In one case, Boeing had to acquire one of the partners providing critical components in order to regain control of the supply chain. 

Boeing ran into these major problems despite decades of experience in outsourcing major components for its civilian and military aircraft programs. It is not a big leap to imagine newcomers to strategic sourcing, which the global bio/pharmaceutical companies are, having significant problems themselves as they learn to master the new model. In circumstances similar to Boeing's, several bio/pharmaceutical companies have been forced to buy back manufacturing facilities that they had sold to startup contract manufacturers after those CMOs ran into financial problems and put the bio/pharmaceutical companies' product supply at risk. 

The point here is not to question the major acquisitions cited above or to question the business strategies of CROs and CMOs aimed at expanding their service offerings. They are a response to what the global bio/pharmaceutical companies are actually doing today and to ignore that would risk being shut out from the biggest opportunities. 

The further risk, however, is that in the two or more years it will take to fully integrate the parent and acquired companies into a genuinely single entity, the sourcing paradigm may have moved to a different place. The lessons of the first strategic partnering efforts will have been learned and applied to different sourcing arrangements.  

In the meantime, the CROs that are already big will be using their large scale to further their lead with new capabilities. For instance, Covance, the second largest clinical services provider by revenue, recently announced a new service to help bio/pharmaceutical companies select clinical sites more efficiently by using a database that incorporates information from the thousands of trials they have serviced in recent years. 

The CROs playing catch-up don't want to find themselves in the position of planning for the last war. Like the French military leaders who built the "impenetrable" Maginot line after World War I, they risk being circumvented by new technologies and the innovative strategies they make possible. 

 is president of PharmSource Information Services, Inc., and publisher of 

Outsourcing

CROs that have made big acquisitions could be outmaneuvered by evolving sourcing models.