Patricia Van Arnum was executive editor of Pharmaceutical Technology.

Patricia Van Arnum

	Drug shortages, particularly those for sterile injectable drugs, took center stage last year. In response, industry and the federal government, including FDA, took steps to address the problem. Progress has been made, and Congress is further evaluating if additional steps need to be taken.

	Late last month, the Senate Health, Education, Labor and Pensions (HELP) Committee approved the 

Food and Drug Administration Safety and Innovation Act

. The bill, which now goes to the full Senate for approval, reauthorizes the FDA user-fee program and also contains measures to strengthen ways to deal with drug shortages. The bill proposes revising the timing of advance notifications of possible shortages, requiring a strategic plan on shortages, broadening the definition of what constitutes a meaningful disruption of drug supplies, and creating a process for physicians and others to report evidence of shortages, as outlined by the American Medical Association (AMA) in analyzing the bill. Industry groups, such as AMA and the American Society for Health-System Pharmacists, support these measures.

before the Subcommittee on Health of the House Committee on Energy and Commerce, which also is considering  measures to address drug shortages, FDA Commissoner Margaret Hamburg outlined the progress made in reducing drug shortages. Last October, President Barack Obama issued an Executive Order that directed FDA and the Department of Justice to take action to reduce and prevent drug shortages. Since the issuance of the Executive Order, FDA has successfully prevented 118 drug shortages and reduced the number of drug shortages. According to Hamburg’s blog, 42 new drugs in shortage have occurred in 2012 thus far compared to 90 new drugs in shortage in a comparable time period last year.

	In her testimony, Hamburg outlined FDA efforts. When it learns of a potential shortage situation, the agency works directly with the affected manufacturer in several ways: developing temporary workaround solutions to manufacturing or quality issues; consulting with the manufacturer to resolve the underlying problem; or helping the manufacturer find additional sources of raw materials. It also expedites the review of submissions by the manufacturer that may alleviate the drug shortage while continuing to meet safety standards, which may include requests to extend the expiration date of products, make manufacturing changes to increase capacity, use a new raw material source, or change product specifications. FDA can also use its regulatory discretion for a manufacturer to continue marketing a medically necessary drug if the manufacturer can develop a method to resolve a quality issue prior to the drug’s administration. In addition to working with the affected manufacturer, FDA also does the following: works with third parties to determine whether they can help avoid or minimize the shortage; expedite reviews of generic applications for products facing potential shortages; and in certain situations, when a shortage cannot be resolved immediately, FDA can use its regulatory discretion for the temporary import of non-FDA-approved versions of critical drugs after ensuring there are no significant safety or efficacy risks for US patients.

	These measures have had impact, but a question is whether more systematic means should be in play. Some commentary on this subject have suggested national stockpiles, such as those used for vaccines, be used to avert shortages. Whether this is an appropriate solution is unclear. What is clear, however, is that strengthening regulatory oversight to prevent or reduce drug shortages is an important goal for industry and consumers alike.

Articles

Drug shortages, particularly those for sterile injectable drugs, took center stage last year. In response, industry and the federal government, including FDA,

Drug Shortages Still in Focus

The Association of Clinical Research Organizations (ACRO) testified before Congress last month to provide FDA with a number of suggestions to improve the drug-development process, highlighted by a call to appoint a chief innovation officer within the agency. ACRO’s recommendations were included in testimony presented by Executive Director Doug Peddicord, PhD, at a public hearing titled “Modernizing the Regulation of Clinical Trials and Approaches to Good Clinical Practice.”

 “The current drug-development paradigm is unacceptable and unsustainable because too much time and too much money is spent producing too few new products,” said Peddicord, in a ACRO Apr. 20, 2012, press release. “CROs have a history of embracing innovative ideas, like electronic data capture and globalization, and stand willing and ready to work with sponsors and regulators to reduce the time and cost of drug development.” 

Peddicord expressed concern about the slow progress that has been made since the release of the FDA’s “Critical Path” whitepaper in 2004. He noted that while some FDA-supported efforts, such as the C-Path Institute and the Clinical Data Interchange Standards Consortium (CDISC), have had success developing tools to advance drug development, other efforts have fallen short. Notably, Peddicord singled-out the Clinical Trials Transformation Initiative (CTTI). The CTTI, which was launched by FDA, oversees specific projects to identify existing issues related to current practice, design models for improvement, and test new models and compare them to the existing system in an effort to modernize the clinical-trial process.

 “While CTTI is well-intentioned, it has not taken on projects that have the potential to be ‘transformative’,” said Peddicord, in the release. “Every effort at innovation that the FDA supports, directly or through the funding of public-private collaborations, should be measured against three objectives: does it make the drug development process faster, cheaper or more productive.” 

 ACRO made several specific recommendations for the FDA to consider, including the appointment of a chief innovation officer at the agency with broad authority to approve novel approaches to clinical trials. Several other organizations, led by the Biotechnology Industry Organization, have expressed support for this concept and it is expected to be included in the Prescription Drug User Fee Act reauthorization later this year, according to the ACRO release. 

• Incorporating more modern regulatory science into clinical trial design so that a sponsor can potentially generate the data necessary for product approval with fewer subjects 

• Simplifying the informed consent process so that the information provided to potential participants is more intelligible and meaningful • Testing, across therapeutic areas, the use of a single, central institutional review board on a country level to improve the quality of independent review 

• Approaches to risk-based oversight of sites/investigators by sponsors, including statistical and other sampling, remote and other technology-enabled monitoring 

• Expanding regulatory cooperation and information sharing for multiregional clinical trials to limit or eliminate duplicative audits, examinations and reviews. 

 “ACRO’s recommendations are by no means exhaustive but rather represent a starting point for the FDA to address widely-acknowledged areas of inefficiency,” said Peddicord. “But the agency must encourage and reward innovation because without proper assurances no organization will be willing to undertake the serious financial or operational risks associated with an unpredictable regulatory environment.” 

Clinical research organizations see reform in clinical-trial process, including the establishment of chief innovation officer at FDA.

CROs Urge for Modernization of Clinical Trials

Universal sustainability is an economic and social discipline that seeks to marry economic growth, competitiveness, and innovation with larger societal goals for economic, social, and environmental progress (1). By its nature, sustainability is interdisciplinary and requires the participation of industry, government, educational institutions, and nongovernmental organizations (NGOs). For the pharmaceutical industry and its stakeholders, sustainability plays a role not only in individual company activity, but also in collective efforts, such as in global health, where public, private, and public–private partnerships play a crucial role in advancing sustainable healthcare. 

 conducted a roundtable with Jane Griffiths, PhD and company group chair of Johnson & Johnson’s Janssen for Europe, the Middle East and Africa (EMEA), and Emma Waters, MD and specialty registrar at the Sustainable Development Unit (SDU) at the UK government’s National Health Service (NHS). Griffiths is responsible for the EMEA region of Janssen, the pharmaceutical division of Johnson & Johnson, and is also chair of the Johnson & Johnson Global Pharmaceuticals Sustainability Council.  In her position with the UK NHS, Waters is helping the SDU establish metrics for measuring sustainable development and to coordinate the SDU’s work with pharmaceutical companies to develop guidance for uniform carbon foot-printing of pharmaceuticals and medical devices.  Both Griffiths and Waters will be speakers at

 a conference addressing the goals and ways to achieve universal sustainability, which will be held June 21–22, 2012, in Dublin, Ireland. Griffiths and Waters are part of a specialized track on global health and sustainability. Other sessions at SustaiNext EU will address the interrelationships between sustainability and transportation, education, agriculture and food, and global society. 

SustaiNext EU is supported by the Sustainability Collaborative, a cross-functional coalition of representatives from industry, academia, government, and NGOs. The Sustainability Collaborative was created in 2009 to stimulate partnerships and connections between academia, business, government, nonprofits, and communities in pursuit of universal sustainability. It now has more than 800 participants, which include representatives from organizations, such as Dublin City University, Rutgers University, Drexel University, Advancing Sustainability in Higher Education, Johnson & Johnson, BD, SIMS, Sustainable Brands, Best Foot Forward, and Source 44. 

What role does sustainability play in addressing the goals of global health initiatives overall and with respect to specific objectives, such as increasing access to medicines? Can you offer examples from an industry perspective and/or from your own organization? 

As perhaps the highest profile social issue facing the pharmaceutical industry, it’s only natural that access to medicines is one of the most important elements in our sustainability strategy. A large percentage of the world’s population lives without access to basic medicines that can significantly reduce the impact of disease, improve the quality of life, and in some cases, save lives. A number of factors can affect access to medicines. In many areas, such as sub-Saharan Africa, the medical infrastructures are not well developed.  As a result, many other challenges still stand in the way even when we provide low-cost medicines, such as the ability to get the medicines registered for sale, the lack of a medical education infrastructure to help ensure proper use of medicines, efficient distribution of medicines, and even questionable business ethics. 

 We have a responsibility as a healthcare company to work with nongovernmental and governmental organizations to create better access to medicines. Licensing to local manufacturers is one pathway that has helped increase access, which we have done with some of our HIV/AIDS medicines.  In other cases, it may be through working with organizations, such as the TB Alliance, to help accelerate the development of our tuberculosis (TB) treatments to address the increase in drug-resistant strains of TB. 

 Another issue that crosses social and business lines is the cost of our current healthcare systems and the role we play as producers of healthcare products. Obviously, the cost of a product is only part of the total healthcare cost, but there is a lot of pressure on us to reduce cost. It’s inevitable that for a sustained healthcare system, the whole system needs to become more cost-effective, but on the other hand, there needs to be enough budget to continue to research and develop better and more effective products. In some cases, there might be other options than the use of healthcare products but that means a paradigm shift in society. We’ve been working with the NHS on assessing opportunities in the pathways of diseases, for example, Type 2 diabetes. We all know that obesity is a major cause of Type 2 diabetes, and that in many cases, lifestyle choices relate to obesity. Therefore, it’s interesting to see whether the healthcare industry can offer prevention rather than a cure, which obviously has a significant impact on the cost of healthcare. Such options, however, need a holistic approach, much in line with universal sustainability, including the food and transport industry. 

 It is known that climate change will have a significant negative impact on health (2).  However, it is also known that many strategies to reduce climate change also will have significant benefit to health (i.e., health co-benefits). For instance, enabling active transport, such as walking or cycling, will obviously have health benefits in addition to reducing greenhouse-gas (GHG) production. Low-carbon patient healthcare pathways and, when appropriate, community healthcare or telehealthcare also can improve health outcomes. Schemes, such as smoking cessation, which improve public health and reduce the need for patients to access healthcare, also will reduce carbon emissions. Finally, the World Health Organization and member states are committed to reducing health inequalities (3). However, it is recognized that climate change has the potential to increase health inequalities, both within countries and internationally (4). Therefore, climate- change mitigation is essential to help prevent increases in health inequalities. 

 How does sustainability factor into the pharmaceutical supply chain?  Where do you see areas of greatest impact, such as in green-manufacturing processes for pharmaceutical products, green procurement practices for pharmaceutical ingredients or products, or distribution activity? Can you offer examples from an industry perspective and/or from your own organization? 

With healthcare spend accounting for anywhere from 6 to 16% of GDP [gross domestic product] in developed countries, it follows that healthcare has a very large associated environmental footprint. Our largest customers, (e.g., government accounts and large hospital networks), where the environmental impact can be seen at a macro level, are starting to take notice of that environmental footprint and are reaching out to their suppliers to help them minimize waste, save energy, eliminate toxics, and reduce water consumption. The benefits spread beyond the environment as they can save them money as well. We need to continue to develop greener products that are more environmentally friendly, not only for our customers but all along their value chain. 

 For J&J, we have a product stewardship program known as Earthwards that guides and assists development teams in each of the sectors to deliver greener products.  For pharmaceuticals, developing greener products begins with having a full understanding of what happens to our pharmaceuticals once they enter the environment; incorporating green-chemistry principles into our chemical synthesis and processing; leaning our packaging and incorporating more sustainable packaging materials; and ensuring that our suppliers also take great care to minimize their impacts to the environment and the communities in which they are located. 

While we expect that we will have chemical-based pharmaceuticals with us for some time, in the longer term, we believe the move to biologic-based treatments will address many of the concerns around chemicals in the environment.  However, biologics have their own set of environmental effects, such as significant water use and cold-chain distribution, which we need to address over time. We are confident, however, that overall we are moving into a period where healthcare products will have less of an impact on the environment. 

 It is known that globally, pharmaceuticals contribute a large proportion of healthcare GHG emissions. For instance, research carried out by the NHS Sustainable Development Unit (SDU) found that in 2010, an estimated 22% of the National Health Service (NHS) for England’s GHG emissions were attributable to pharmaceuticals (5). It is essential that healthcare providers take action to reduce their carbon emissions, and the UK’s NHS has committed to an ambition of reducing its carbon dioxide (CO

) equivalent emissions by 80% by 2050. Due to the significant proportion of GHG emissions that are attributable to pharmaceuticals, it is obviously essential that the all parts of the pharmaceutical supply-chain and end-of-use factors are considered when reducing GHG emissions. However, for many pharmaceutical products, there is only limited data available regarding their complete life-cycle CO

 equivalent footprint. For this reason, the NHS SDU is currently working with industry partners, international health providers, and an environmental consultancy firm to develop uniform international guidance to aid in the development of CO

 equivalent foot-printing for the complete life cycle of pharmaceuticals. It is hoped that the resulting guidance will highlight to the pharmaceutical industry and healthcare providers areas of high GHG emissions and allow them to work together to reduce carbon emissions. 

From your perspective, where do you see the greatest progress to date in achieving sustainability with respects to the pharmaceutical industry and/or global and national health policy? Looking ahead five to 10 years, what might be some future goals or aspirations in this area?

The greatest progress to date is the ongoing discussion around this topic. This might seem strange, but the fact that all the stakeholders in our industry are now actively engaged with identifying and discussing opportunities to make healthcare more sustainable has moved it away from being a ‘flavor of the day’ to a embedded part of our strategies. Obviously, there were immediate steps that we were able to take, such as making our processes more lean and reducing waste and energy use, in some cases quite dramatically. 

 In the longer term, say 10 years from now, I think technological advances, such as the continued development of early diagnostic technologies and chronic disease intervention, personalized medicine, telemedicine, and preventive therapies, such as next-generation vaccines, all stand to help reduce the footprint of care while increasing the quality of care.  However, healthcare companies, systems, and governments that can commercialize prevention, that is, getting patients to really place a value on their health and preserve it, will be the most successful going forward.  Elimination of preventable diseases, especially chronic and disabling diseases, really should be our goal, and we really can’t afford not to achieve that goal. 

Currently, multisectorial collaborations, such as the international collaboration to create uniform carbon foot-printing guidance already described, and collaborations between industry and healthcare providers to create low-carbon patient-care pathways are making important contributions toward the ambition to reduce pharmaceutical related GHG emissions. Ultimately, the SDU envisages that sustainable healthcare will involve a move toward a service-based model of healthcare where providers support the system through providing services around fewer products rather than the current more product-based system. 

1. R.L. Lattimer, “Universal Sustainability: The Economy and Competitiveness 2012,” 

Rio Political Declaration on Social Determinants of Health 

(Rio de Janeiro, Brazil, Oct. 21, 2011). 

(NHS Sustainable Development Unit, 2012). 

Industry leaders share their perspectives on how the pharmaceutical industry is and can further advance sustainability.

The Marriage of Global Health and Sustainability

Last month, GlaxoSmithKline (GSK) released its 2011 corporate social responsibility report, which included the company’s progress and goals for environmental improvement. The company estimates its carbon footprint across its value chain to be 14 million metric tons of carbon dioxide. It is implementing an environmental sustainability strategy across the value chain from raw materials to product disposal. The strategy focuses on carbon dioxide and other emissions that contribute to climate change, water use, waste reduction, and environmental stewardship. By 2050, the company is aiming to have a carbon-neutral value chain. 

• Reduced greenhouse gas emissions from its facilities by 5.3%; its overall carbon dioxide impact rose slightly due to increased production volumes 

• Reduced water use by 6.9% and waste sent to landfill by 25% with 30 sites now sending zero waste

• Developing a product carbon-footprint approach that will be used with individual products to identify carbon hotspots and measures to reduce them 

• Continued to pilot a take-back scheme for used inhalers in the United States and United Kingdom to reduce waste and greenhouse-gas emissions 

• Recycled its own waste polyethylene terephthalate (PET) plastic to make new Ribena bottles (Ribena is an uncarbonated soft drink by GSK)

• Received an “‘A” rating for performance and scored 93% on disclosure in the Carbon Disclosure Project assessment 

• Had its first office building certified as gold under the Leadership in Energy and Environmental Design (LEED) environmental-rating system 

• Published a report, with partners, exploring the impact of climate change on health. 

In reducing its carbon-dioxide-equivalents from its facilities by 5.3% in 2011, GSK’s main focus has been on energy-efficiency activities, where it saw a 7.2% decrease in carbon-dioxode-equivalent emissions. This reduction has been offset by increases in its manufacturing and production volume. Production-related carbon-dioxide-equivalent emissions increased 5.4%, and transport emissions increased 8.4%. The combined total reduction in facilities and transport emissions was 2.6%. 

Combined heat and power (CHP) generation also is playing a growing role in decreasing the company’s carbon emissions. In 2011, GSK installed five CHP units, bringing the total to 16 operating units across 10 sites. For example, its manufacturing site in Irvine, Scotland, has reduced greenhouse-gas emissions by 12% during the past three years.  The site makes the active ingredient for for the antibiotic Augmentin in an energy-intensive process, and the company aims to secure its energy supplies from renewable sources by installing wind power. The first turbine should be operating early in 2013, with two to follow subject to planning approvals. Together, they will deliver annual savings of 8000 metric tons of carbon-dioxide equivalents. 

 The company also approved a £15 million ($24 million) project to convert waste to heat at its plant in Singapore, with estimated annual savings of  7700 metric tons of carbon-dioxide-equivalents from 2014. In 2011, the vaccine site at Sainte-Foy in Quebec supported renewable energy and energy reduction projects. Over the past four years, it has supported over 800 projects that have saved approximately 170,000 metric tons of carbon-dioxide equivalents. 

 Also, its factories in India for Horlicks (a malted milk drink made by GSK) uses coal to generate energy, which creates approximately 72,000 metric tons of carbon-dioxide-equivalent emissions per year, or approximately 5% of the total for GSK’s operations. In 2011, sites began trials to switch from burning coal exclusively to blending it with waste biomass. The company tested several options, such as rice husk, pellets made from waste wood, sawdust, grain straw, cotton straw, and ground nut shells. If further trials in 2012 prove successful, GSK plans to blend up to 30% waste biomass at all three sites, thereby avoiding 19,800 metric tons of emissions per year. In the longer term, the company aims for 100% waste biomass for steam generation and investment in combined heat and power technology to generate its  own electricity. 

 Other measures involved eliminating chlorofluorocarbon gases from its products (completed in 2010), which has substantially reduced inhaler emissions from 24 million metric tons of carbon dioxide-equivalents in 1998 to less than five million metric tons. Although progressing in this field, the company notes that its replacement propellant is still a greenhouse gas and seeks to reduce this further by such means as supplying dry-powder inhalers where appropriate. 

Unlike carbon emissions whose impacts are global, water use has local and global impacts and needs to take into account all users of a watershed as well as seasonality and water quality. GSK is active in the UN CEO Water Mandate, under which it cosponsors work to develop disclosure guidelines. These guidelines will help companies to measure andcommunicate performance more effectively. A eventual goal is to develop a water-footprint approach similar to the greenhouse-gas protocol. 

 On a company basis, GSK also continues site-level action to improve water use with a 6.9% reduction in 2011. The company has developed a “water kaizen” rapid improvement process to identify more efficient ways to use water. It piloted this approach at its Worthing and Maidenhead sites in England and identified potential savings of more than 25%. Examples of projects implemented include fitting aerators to taps, decommissioning redundant equipment, optimizing service water flows, and fitting trigger guns to water hoses. Both sites are investigating other opportunities identified in the kaizen process, such as whether high-grade wastewater from one part of the plant could be used elsewhere instead of using additional potable water in its supply chain.

GSK’s total waste (hazardous and nonhazardous) fell by 1.2% and volumes to landfill were down by 25.5% in 2011. A total of 30 sites now send zero waste to landfill.  Some examples of waste-reduction and reuse projects included using panelling from its refrigerated vaccines shipping packaging as insulation material for the construction industry. Reusing these materials reduces waste by 64 metric tons per year that previously went to landfill. Another innovation in 2011 led to its own waste PET plastic being used to make bottles for Ribena. Previously, waste contractors disposed of approximately 700 metric tons of PET packaging trays used to deliver components to GSK’s  sites at Ware, UK, and Evreux, France. The material is being recycled to create new Ribena bottles saving approximately more than 3000 metric tons of carbon-dioxide-equivalent emissions per year. Other examples of reducing packaging waste in 2011 include converting from glass to plastic bottles for Horlicks, reducing packaging material on consumer healthcare products, and converting from blister packs to film wrapping for its nasal spray Flixotide. GSK estimates these measures will avoid more than 10,000 metric tons of carbon-dioxide equivalents per  year.

In its sustainability report, GSK also noted certain practices to help meet its environmental profile. For example, a green packaging guide helps designers to avoid waste and choose the most sustainable option and includes sustainability-assessment tools covering energy and water use as well as the carbon footprint of packaging materials and transport. A carbon tracker collects data to monitor progress in the use of materials for its new pharmaceutical products. The average mass efficiency of the new primary processes transferred to manufacturing in 2011 was 2.2%, compared to its 2015 target of 2.5%. The company aims to increase the mass efficiency of products transferred to manufacturing to 3% by 2015 through measures such as solvent recovery. 

 In 2011, the company created a new R&D group working on second-generation product development to improve the sustainability profile of the R&D and manufacturingportfolio of projects through the product life cycle. GSK also continued its collaboration with the GSK-Singapore Partnership for Green and Sustainable Manufacturing. Its R&D groups have also worked with other industry partners to create a €20 million ($32 million) Sustainable Chemistry partnership with academia through the European Innovative Medicines Initiative, which begins work in 2012. GSK is also part of the American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable, where it collaborates with other pharmaceutical companies on green chemistry and engineering in the pharmaceutical industry. 

The company provides progress made in 2011 and future environmental objectives.

GlaxoSmithKline Outlines Its Sustainability Goals

Late last month, the Obama Administration released the National Bioeconomy Blueprint. The report outlines steps that federal agencies will take to drive the bioeconomy—economic activity driven by research and innovation in the biosciences—and details ongoing efforts across the federal government to realize this goal. A key part of these efforts are ways to improve innovation, development, and regulation of pharmaceuticals. 

In 2010, the Obama Administration included in its science and technology priorities as part of federal agency budget submissions a priority for federal agencies to “support research to establish the foundations for a 21st century bioeconomy.” In September 2011, President Obama announced that his Administration would release a National Bioeconomy. Modeled after the Administration’s 2011 Blueprint for a Secure Energy Future, the 2012 National Bioeconomy Blueprint has two purposes: to lay out strategic objectives that will help realize the full potential of the US bioeconomy and to highlight early achievements toward those objectives. 

 The report recognizes the importance of biotechnology not only in healthcare but in other sectors. “The bioeconomy emerged as an Administration priority because of its tremendous potential for growth and job creation as well as the many other societal benefits it offers,” says the report.” A more robust bioeconomy can enable Americans to live longer and healthier lives, develop new sources of bioenergy, address key environmental challenges, transform manufacturing processes, and increase the productivity and scope of the agricultural sector while generating new industries and occupational opportunities.” 

 The Bioeconomy Blueprint outlines five strategic imperatives: support R&D investments; facilitate the transition of bioinventions from research laboratories to market, including an increased focus on translational and regulatory sciences; reduce barriers to increase the speed of regulatory processes; update training programs and align academic institution incentives with student training for national workforce needs; and identify and support opportunities for the development of public–private partnerships and precompetitive collaborations. 

In laying out a plan to increase R&D investment, the report emphasizes the need to increase coordination of federal bioeconomy-related research activities to improve the efficiency and effectiveness of R&D investments. The report also emphasizes the importance of multiagency collaborations for emerging foundational technologies, such as synthetic biology, biology-related information technologies, and proteomics and the integration of disciplines. The report says that the Administration will prioritize additional multidisciplinary efforts in physics, chemistry, engineering, computer sciences, and mathematics, to support the bioeconomy. The report also calls for federal agencies to further explore the use of new or modified funding mechanisms in and across agencies to stimulate the discovery of new bioinventions with potential to grow the bioeconomy. 

 In facilitating the transition of bioinventions from research laboratory to market, the report emphasized an increased focus on entrepreneurship, translational sciences, regulatory science, and technology transfer, including strategic, coordinated investments in translational and regulatory sciences to accelerate progress. To capitalize on the promise of the newly reauthorized Small Business Innovation Research (SBIR) program, the report said that federal agencies should evaluate and update SBIR programs. Some relevant objectives include reducing application response times, hiring/training program staff to enhance relevant in-house experience, and increasing the use of industry experts as peer reviewers to evaluate industry proposals. The report also stressed the importance of enhancing entrepreneurship at universities and using federal procurement to encourage the development of biobased products. 

The blueprint calls for regulatory reform by reducing barriers, increasing the speed and predictability of regulatory processes, and reducing costs while protecting human and environmental health. When an emerging technology enters the regulatory process, federal agencies are asked to have a robust framework that identifies lead agency responsibilities, clarifies supporting agency roles, and delivers timely, specific guidance for applicants. The report also calls for stakeholder collaborations to identify needs and reduce impediments. 

The report also calls for updating training programs and aligning academic institution incentives with student training for national workforce needs. At the K-12 and undergraduate levels, the report cites progress in developing approaches to improve science, technology, engineering, and mathematics (STEM) education and increasing the number and diversity of STEM students. The report points to the Educate to Innovate campaign, launched in 2009, to move American students from the middle to the top of international rankings in STEM achievements over the next decade. The report says that by building upon and expanding these efforts, particularly with regard to graduate-level training enhancements, would help to align academic institution incentives with training for future workforce needs. 

The blueprint also calls for increased partnerships between employers and educational institutions, including incentives for academic institutions to enhance entrepreneurship and restructure training programs. Following reengineering of training programs, the report says that agencies should consider convening industry stakeholders from various sectors to assess the success of training programs to meet the needs of employers.

The report also calls for identify and supporting opportunities for the development of public–private partnerships and precompetitive collaborations—where competitors pool resources, knowledge, and expertise to learn from successes and failures. “Many companies do not invest in early ideas because they are unlikely to pay off immediately. This is one place where the government can play a crucial role,” says the report. Moving forward, the report emphasizes that federal agencies provide incentives for public–private partnerships and precompetitive collaborations. 


In laying out a blueprint, the report also identifies areas of progress, including those relating to pharmaceuticals and biomedical innovation. One area cited by the report is the need to improve the information technology infrastructure of FDA and the access to this information to “transform FDA archives into a driver of discovery and development,” says the report. It notes that FDA currently houses one of the largest known repositories of clinical data, including safety, efficacy, and performance information, and an increasing amount of postmarket safety surveillance data. Integrating and analyzing these data, with appropriate patient privacy protections, is one way to advance biomedical research, notes the report. The report points to FDA efforts to rebuild its information technology and data analytic capabilities and establishing “science enclaves”— virtually networked IT environments where multidisciplinary teams can work together to analyze large sets of data extracted from the FDA data resources while complying with applicable law concerning proprietary information and patient privacy. The enclaves can also be used to design new software that should enhance the quality, efficiency, and accuracy of FDA regulatory reviews. 

 Other projects cited by the report are the recent launch of Intramural Center for Regenerative Medicine (CRM) at the National Institutes of Health (NIH) to support induced pluripotent cell technology. NIH CRM and its partners are exploring the development of iPS cell therapies to treat blood-related diseases, such as leukemia and metabolic diseases, including lysosomal storage diseases that affect children. In addition, researchers will investigate whether iPS cells can be used to develop blood products that could help meet the demand for blood transfusions during medical emergencies and surgeries. NIH also recently embarked on a major effort to use iPS technology to advance research into neurodegenerative diseases. That effort already has developed and made widely available neural cell lines for Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. 

Also, the NIH’s newest center, the National Center for Advancing Translational Sciences (NCATS), recently teamed up with Eli Lilly to create a step-by-step playbook to help researchers from all sectors translate their basic findings into potential treatments for patients. The Assay Guidance Manual will be available as a free e-book in early May. 

The Obama administration details five strategic imperatives to drive bioscience research as a means of economic growth.

White House Releases National Bioeconomy Blueprint

Researchers recently reported positive clinical results for a targeted therapeutic nanoparticle as an anticancer therapy. The targeted nanotechnology-based drug-delivery method is considered an important breakthrough in targeting and better controlling dosing of a chemotherapeutic agent.  

The targeted polymeric nanoparticle (TNP) contained the chemotherapeutic docetaxel and was developed from a combinatorial library of more than 100 TNP formulations varying with respect to particle size, targeting ligand density, surface hydrophilicity, drug loading, and drug-release properties (1). The targeted nanoparticle, BIND-014, is a nanomedicine that combines a targeting ligand and a therapeutic nanoparticle containing docetaxel encapsulated in biocompatible and biodegradable polymers. BIND-014 is targeted to the prostate-specific membrane antigen (PSMA), a cell-surface antigen abundantly expressed on the surface of cancer cells and on new blood vessels that feed a wide array of solid tumors. In preclinical cancer models, BIND-014 was shown to deliver tenfold more docetaxel to tumors than an equivalent dose of conventional docetaxel. The increased accumulation of docetaxel at the site of disease translated to marked improvements in antitumor activity and tolerability, according to an Apr. 4, 2012, press release by the Prostate Cancer Foundation.   

BIND-014 entered clinical trials in January 2011. The Phase I clinical trial was performed by researchers at the biopharmaceutical company BIND Biosciences, a company cofounded by Robert Langer, the David H. Koch Institute Professor in the Department of Chemical Engineering at the Massachusetts Institute of Technology (MIT), and Omid Farokhzad, director of the Laboratory of Nanomedicine and Biomaterials at Brigham and Women's Hospital and associate professor of anesthesia at Harvard Medical School. 

"The initial clinical results of tumor regression even at low doses of the drug validates our preclinical findings that actively targeted nanoparticles preferentially accumulate in tumors," said Langer, in an Apr. 4, 2012, MIT press release. "Previous attempts to develop targeted nanoparticles have not successfully translated into human clinical studies because of the inherent difficulty of designing and scaling up a particle capable of targeting tumors, evading the immune system, and releasing drugs in a controlled way." 

The BIND-014 nanoparticles have three components: one that carries the drug, one that targets PSMA, and one that helps evade macrophages and other immune-system cells. "This study demonstrates for the first time that it is possible to generate medicines with both targeted and programmable properties that can concentrate the therapeutic effect directly at the site of disease, potentially revolutionizing how complex diseases such as cancer are treated," said Farokhzad in the MIT release. One of the challenges in developing effective drug-delivery nanoparticles is designing them so they can evade the body's normal immune response and reach their intended targets. "You need exactly the right combination of these properties because if they don't have the right concentration of targeting molecules, they won't get to the cells you want, and if they don't have the right stealth properties, they'll get taken up by macrophages," said Langer in the MIT press release.  

The Phase I clinical trial involved 17 patients with advanced or metastatic tumors who had already gone through traditional chemotherapy. To determine safe dosages, patients were given escalating doses of the nanoparticles. In the 48 hours after treatment, the researchers found that docetaxel concentration in the patients' blood was 100 times higher with the nanoparticles as compared to docetaxel administered in its conventional form. Higher blood concentration of BIND-014 facilitated tumor targeting resulting in tumor shrinkage in patients, in some cases with doses of BIND-014 that correspond to as low as 20% of the amount of docetaxel normally given. The nanoparticles were also effective in cancers in which docetaxel usually has little activity, including cervical cancer and cancer of the bile ducts. The researchers also found that in animals treated with the nanoparticles, the concentration of docetaxel in the tumors was up to tenfold higher than in animals treated with conventional docetaxel injection for the first 24 hours, and that nanoparticle treatment resulted in enhanced tumor reduction, according to the MIT release.  

The Phase I clinical trial is still ongoing and continued dose escalation is underway. BIND Biosciences is now planning Phase II trials, which will further investigate the treatment's effectiveness in a larger number of patients.  

Targeted polymeric nanoparticles are an important vehicle for controlling and targeting dosing of chemotherapeutic agents.