Contact UsDiana Bartlett
Assistant Vice President,
Phone: (909) 607-9864
Email: diana_bartlett[at symbol]kgi.edu
Global Regulatory Landscape and U.S. Regulatory Strategy for Lung Cancer, Hypercalcemia of Malignancy and Graft Versus Host Disease
Amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes to dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be the world's largest independent biotechnology company. As Amgen continues to build a pipeline of therapeutic medicine with breakaway potential, its current products provide improved therapies to millions of patients around the world.
The Amgen Regulatory TMP developed regulatory landscapes for hypercalcemia of malignancy and lung cancer during the 1st semester. During the second semester, the team focused on a similar document for Graft Versus Host Disease (GVHD). Finally, the team developed a regulatory strategy for a hypothetical GVHD product seeking approval in the US marketplace. These landscapes and this strategy were presented to the senior staff of Amgen. The team will present the 2nd semester effort focused on GVHD.
To construct an FDA regulated landscape for therapies directed at GVHD, the team first characterized the disease demographics and pathologies. This work was then expanded to include an examination of the literature for previously approved therapies, clinical studies and investigational treatments for this disease. Ultimately, the team located essential public information and compiled a series of milestone reports with key observations and insights which might help guide Amgen as it navigates the regulatory barriers for GVDH disease. The Amgen TMP provided the student team with an excellent experience in the regulatory challenges associated hypercalcemia of malignancy, lung cancer and GVHD. Ultimately, the TMP team provided Amgen with detailed supporting information for these diseases as well as some discussion of the potential regulatory approaches to pursue investigational drugs in these therapeutic areas.
Benchmarking Study to Evaluate Best Practices in Supply Chain Management
Amgen, Inc., a world class biopharmaceutical company, discovers, develops, manufactures and delivers therapeutic products for the disease areas of oncology, hematology, inflammation, bone health, nephrology and cardiovascular diseases. Since its founding in 1980, Amgen has grown rapidly to attain a market capitalization of $91 billion with a world-wide presence in over 50 countries. Amgen currently produces 12 products for 20 different disease indications while pursuing numerous additional drugs through Amgen R&D. Amgen is headquartered in Thousand Oaks, California and employs 20,000 staff worldwide.
As Amgen's network evolves and grows to supply more countries with more products, their supply chain will face increasing challenges in planning, sourcing, and delivery. As a result of this growth, Amgen has sought to evaluate optimal supply chain models to ensure time to market, outstanding patient supply and efficient delivery of its products across world markets.
The Amgen Supply Chain TMP was asked to benchmark supply chain best practices across a number of selected industries. Model companies were chosen, by brainstorming with Amgen liaisons, from industries with high value products, stringent regulations, or highly efficient supply chain behaviors. The team gathered information about supply chain management and supply chain strategies for these prominent targeted companies in the pharmaceutical, biotechnology, diagnostic, consumer technology and e-commerce industries. From this research, the Amgen Supply Chain TMP identified best practices and common trends within and across these industries. After analyzing these industrial trends, the KGI team pursued two focus areas in the spring semester: global trade management and inventory management. Ultimately, the team performed an in-depth qualitative analysis of supply chain opportunities before making recommendations to Amgen regarding their use of new tools in global trade management and inventory management.
Optimization of the Capital Asset Procurement Process
BioMarin Pharmaceutical, Inc. began developing and commercializing therapies for rare genetic diseases in 1997. Their strategy to develop first-to-market therapies with an orphan disease status has been remarkably successful resulting in a product portfolio with five approved products and multiple pre-clinical and clinical candidates. Strategically, BioMarin intends to continue to focus on areas of high unmet medical need and to leverage their expertise to improve health outcomes for patients.
BioMarin's five-year trend reveals an average revenue growth of 14% each year. This level of growth has encouraged BioMarin to re-examine strategic aspects of the operations organization to more efficiently support the growing list of products. As BioMarin pursues major milestones in 2014 including the launch of a new drug, Vimizin, it is critical their processes withstand the influx of new projects as well as the increasing workload. BioMarin has undertaken the task of defining their 'Invest-to-Divest End to End Business Process' with an end goal of alignment, efficient decision-making, and communication. The BioMarin TMP team was tasked to analyze current business processes and assist in developing the 'Deliver Capital Assets' sub-processes.
Risks, resources, cost, and time-to-implement have been identified as key performance metrics to consider when devising recommendations for improved capital procurement efficiency. By analyzing primary and secondary literature and conducting interviews with key stakeholders at BioMarin and industry leaders, the team has exposed areas of inefficiencies in the process and identified factors that differentiate BioMarin from leaders in the industry. Upon completion of the project, the team delivered five specific recommendations outlining changes that might have the greatest potential to benefit BioMarin. The team provided detailed justification for implementing these recommendations and has assigned a process owner within BioMarin to facilitate the implementation of these solutions.
Evaluating and Optimizing the Perfusion Process for a CMO Universal Platform
Boehringer Ingelheim (BI), headquartered in Germany, is one of the world's leading contract manufacturing organizations (CMO) and one of the largest privately-held life science companies. BI has an established position in the biologics market having brought over 20 products successfully to the market for companies such as Amgen, Bayer, Genentech, and Pfizer. Overall, BI provides a comprehensive CMO platform with diverse capabilities from cell line development to product fill and finish, including the capacity to scale from clinical to commercial production. BI's mission is to add value through innovation includes investigating the potential benefits of the perfusion process.
The perfusion process offers an excellent solution for the manufacturing of unstable proteins. Perfusion allows proteins to be quickly removed from a cell culture bioreactor and stored under stable conditions for further processing rather than remaining in a potentially damaging cell culture environment. Furthermore, perfusion offers Boehringer Ingelheim the opportunity to reduce costs by using smaller scale bioreactors than the traditional setup for batch or fed batch cell cultivation. The goal of the BI TMP was: to grow and achieve a very high cell density on various cell lines; compare the retention analysis for the BI media versus commercial media; and, compare the density and product concentration of the fed-batch and perfusion process modes.
Successful perfusion experimental runs, for baseline data analysis, were conducted during the fall semester using commercialized media on various CHO (Chinese Hamster Ovary) cells. During the spring semester, the team ran various experiments utilizing adapted cell lines and collected valuable information which provided insights into the advantages of the BI proprietary media over the commercial media. By demonstrating, via the perfusion process, the ability of multiple cell lines to reach and maintain a high density in the BI media, the BI Perfusion Process TMP validated important aspects of the perfusion process. Ultimately, this information provided BI with critical data which supported the potential of a universal mammalian cell perfusion platform for the manufacturing of pharmaceutical products.
Streamlining the Quality Control Method Transfer Process
Boehringer Ingelheim (BI), headquartered in Ingelheim, Germany, is a family-owned global corporation founded in 1885 which is focused on Human Pharmaceuticals and Animal Health. The BI site in Fremont, CA is a division of the Global Biopharmaceutical Network. BI Fremont has state-of-the-art process development and manufacturing equipment with the capacity to annually produce over 200,000 liters (L) of cell culture product. BI Fremont currently supports both GMP clinical and commercial production, and has a global track record of over 140 biologic projects including 22 commercial products.
Due to the commercial and clinical production capability, capacity, and flexibility of the BI facility, many companies contract with BI as a Contract Manufacturing Organization (CMO). This contract business generates significant revenue to the company. Concomitant to transferring the manufacturing process to BI, these companies must also transfer analytical methods which ensure the product's efficacy, strength, purity, integrity, quality, and safety. These methods allow on-site/real-time testing for in-process sampling, as well as release and stability testing. Unfortunately, method transfers can be tedious and may take up to 60-90 days to complete. Additionally, because there are approximately 10 method transfers per project, project transfer timelines can take as long as 8-9 months. Lastly, because there may be as many as 3-5 concurrent projects, the organization may be transferring 30-50 methods at a time.
The BI Quality Control TMP was tasked with analyzing the current method transfer processes and implementing solutions to streamline the process and reduce method transfer times. The BI TMP team approached this project using the DMAIC (Define, Measure, Analyze, Improve, Control) methodology to construct a current-state process map, identify bottlenecks, eliminate waste in the system, and develop a future-state process map. Additionally, the team interviewed clients to gain input from the customer and conducted industry research to determine how many methods might be waived. This research and analysis enabled the team to create and implement solutions to streamline the method transfer process. In conclusion, the BI TMP Team made recommendations which should enable BI to expedite method transfers. It is hoped that these recommendations might allow Boehringer Ingelheim to reduce the cost and time required for method transfers - and, ultimately allow BI to tackle more projects and generate more revenue.
Evaluation and Recommendation of Investment Opportunities in Rare Diseases
Brace Pharmaceuticals, Inc., is an investment company created by EMS S/A, the largest pharmaceutical company in Brazil. Brace Pharmaceuticals is looking for partners interested in co-developing pharmaceutical products that complement its corporate and product development strategy. These opportunities include innovative, life-changing therapies for diseases with high unmet medical need, including orphan diseases.
Brace Pharmaceuticals intends to diversify its project portfolio by investing 80% of its funds in late-stage clinical phase projects and 20% in earlier phase projects. Brace's initial investments have been completed and evaluation of additional feasible projects is ongoing. The Brace TMP's main objective was to identify a short-list of projects that complement Brace's investment strategy in the area of rare diseases.
The team focused its initial efforts on evaluating potential candidates that have been granted orphan designations, orphan product approvals and/or awarded FDA grants to support clinical studies for rare diseases. These viable candidates were then analyzed based on scientific and medical rationale, regulatory considerations, intellectual property rights, and commercial potential. Future efforts will focus on identification and evaluation of candidates which have been approved in other markets.
City of Hope Beckman Research Institute
Development and Commercialization Strategy for Novel Epigenetic Cancer Therapy
City of Hope is a renowned non-profit organization focused on world-class research and treatment for cancers and other life-threatening diseases. The Beckman Research Institute (BRI) is one of six key strategic research programs at City of Hope, responsible for expanding the world's biological understanding of diseases such as cancer, HIV/AIDS and diabetes. The BRI encompasses over 60 years of expertise in scientific research, where investigators are committed to identifying opportunities at the cellular and molecular level to predict, prevent, diagnose, treat and cure such serious diseases.
The BRI is interested in cancer related epigenetics, particularly in gene-regulatory proteins involved in cancer expression. Epigenetic regulators alter gene expression without changing actual DNA sequences. A class of proteins important for epigenetic regulation, histone methyltransferases (HMTs), plays multiple important roles in certain cancers. The BRI has recently developed a novel class of chemical entities that target a specific HMT for potential cancer treatment. This class of compounds targets a promising new therapeutic area that may have significant application in a number of cancer indications.
The City of Hope Epigenetics TMP team was tasked with creating a product development and commercialization plan for a potential epigenetic cancer therapy, based on a novel HMT inhibitor developed at the Beckman Research Institute. Throughout the project, the team investigated standards of care in a number of cancer indications, conducted detailed interviews with key opinion leaders in the field, and performed market and competitive analyses to evaluate the commercial potential of a new epigenetic cancer therapy. This effort resulted in the final deliverable which included a strategic recommendation outlining the critical steps needed to maximize the potential for commercial, clinical, and regulatory success of this new therapy.
City of Hope Beckman Research Institute
Developing a Business Plan for HIV Stem Cell Therapies
City of Hope is a leading research and treatment center for cancer and other life-threatening diseases. It includes the Comprehensive Cancer Center, the Beckman Research Institute, and the Irell and Manella Graduate School of Biological Sciences. The City of Hope celebrated its 100th anniversary in 2013 and is located in Duarte, California. Research at the City of Hope focuses on cancer biology, diabetes, immunology, and virology.
The Beckman Research Institute at City of Hope has developed a novel gene-modified stem cell therapy to treat HIV. To support this therapy, the City of Hope has just completed a human clinical trial which demonstrated the safety of the autologous stem cell product. To help the Beckman Research Institute commercialize its technologies, the City of Hope engaged KGI to assess the feasibility of commercialization through creation of a spin-off company.
The City of Hope HIV Therapies TMP team was charged with creating a business plan and commercialization strategy for this stem cell therapy. To accomplish this goal, the team: conducted a competitive analysis of current HIV therapies; performed primary and secondary market research regarding the RNA-based science of this therapeutic technology; and studied the unique challenges of commercializing a gene-therapy product. After reading key scientific articles and speaking to subject matter experts in venture capital, regenerative medicine, regulatory approval, technology transfer, and biotech operations, the team developed a comprehensive business plan. The plan highlights the market potential for HIV gene therapeutics; identifies critical marketing risk factors; and recommends an IP, marketing, operations and development strategy for the new firm. The business plan also includes detailed financial projections and identifies a series of funding milestones for equity investors to fund its operations.
Design, Implementation, and Testing of a New Biomedical Engineering Test Bench
Edwards Lifesciences is the global leader in the science of heart valves and hemodynamic monitoring. Founded in 1958, Edwards has grown into a global company with a presence in approximately 100 countries and more than 7,800 employees around the world. Edwards focuses on medical technologies that address large and growing patient populations in which there are significant unmet clinical needs, such as structural heart disease and critical care monitoring.
Edward's hemodynamic monitoring instruments measure cardiovascular parameters that are derived from sensor data. Typically, sensors are attached to, or integrated within catheters, which are inserted into blood vessels. Catheter associated sensors then generate signals that allow healthcare personal to make conclusions about patients' health. Sophisticated algorithms within Edward's patient monitoring software interpret these cardiovascular signals so that advanced health information can be displayed. Unfortunately, the only way Edwards can test these algorithms and their patient monitoring devices is through the use of animal studies and recorded patient data from a limited patient population. Further, many of Edward's available test benches are limited in function and cannot be used for complex R&D investigations. Yet test bench analysis is essential in understanding the various cardiovascular signals found in the field.
The core goal of the Edwards TMP was to facilitate software design, implementation, and testing of a new biomedical engineering test bench which would permit the testing and validation of Edward's products. The project focused on four interrelated subprojects: physiological modeling, embedded systems development, and physical experimentation. The key objective of the physiological modeling group is to further develop Edward's cardiovascular modeling tools making them more robust and easier to use. The key objective of the embedded systems development and the physical experimentation subgroup is to create a reliable and fully developed test bench which accurately simulates cardiovascular signals and expands Edward's cardiovascular research capabilities. In conclusion of the Edwards TMP, the team developed a signal test bench which is expected to enhance Edwards research capabilities. This test bench utilizes PythonTM tools for aortic pressure signal generation and modeling, and a physical test bench with protocols for performing frequency response experiments with Edwards products.
Eli Lilly & Company
Chorus Value Proposition Identification and Communication
Chorus is an autonomous group within Eli Lilly and Company that functions to determine the proof-of-concept of new clinical development molecules (assets) quickly, efficiently, and at low cost. Chorus was initially developed by Lilly as part of a fast-to-fail approach for secondary internal assets. It was hoped that this approach would reduce the cost of failed molecules yet accelerate the development of molecules with a successful proof-of-concept outcome by rapidly delivering them to the internal Lilly pipeline. Since its inception Chorus additionally developed assets from sources outside of Lilly-specifically assets funded directly or indirectly by Lilly's Capital Funds Strategy. These assets, selected for development by Chorus, were from therapeutic areas that matched those of Lilly's portfolio.
During the transition from developing "internal only" Lilly assets to developing assets from outside sources, some confusion has developed about the role of Chorus within Lilly. Simultaneously, the value of Chorus to external customers and Lilly's internal research engine has changed. Chorus has no desire to become a solely contract research organization which develops assets on a fee for service basis. Consequently, Chorus needed to identify their core capabilities and clarify their value to both their internal Lilly R&D as well as their external customers. Finally, Chorus wished to identify areas of research which were of particular value to their customers.
To support Chorus' goals, the KGI team was tasked with interviewing and surveying Chorus team members to identify the internal perceptions of their key capabilities as well as the areas they need to improve. Additionally, the team interviewed current and potential customers to crystallize their view of Chorus' strengths and weaknesses, the value of their capabilities, and to compare the internal and external customer perceptions of Chorus' capabilities. After generating a complete list of capabilities, current and potential customers were segmented based on their motivation and their needs in seeking development activities from Chorus. Lastly, the team analyzed the competitive landscape, and made recommendations for improving the communication of Chorus' value to current and potential customers.
Eli Lilly & Company
Social Media Data Mining for Patient Insight into Pharmaceutical Product Design
Eli Lilly and Company is a global, research-based pharmaceutical firm headquartered in Indianapolis, Indiana. Founded more than 135 years ago, Lilly is at the forefront of pharmaceutical research and development in both small molecules and biologics. Lilly's portfolio contains products that meet medical needs in the therapeutic areas of oncology, cardiovascular disease, diabetes, musculoskeletal disease, neuroscience, critical care and men's health. Eli Lilly's products are sold in more than 125 countries and include the blockbuster drugs Evista®, Cymbalta®, Humalog®, Gemzar® and Cialis®.
Eli Lilly believes that social media could represent a viable channel to understand patients' needs better. People regularly discuss their health and treatment options online. These conversations on social media websites may offer different points of view from traditional venues and may provide unique insight to drive pharmaceutical product design and innovation.
The Eli Lilly TMP team was asked to conduct a feasibility study to determine if valuable patient insight could be obtained from Twitter for the therapeutic areas of rheumatoid arthritis and Alzheimer's disease. To accomplish this goal, the TMP team worked with a third-party vendor to procure Twitter datasets. The team then analyzed these datasets utilizing Big Data analytic approaches to provide Lilly with recommendations on ways to apply these insights in product design. Additionally, the team provided Lilly with an algorithm which can be applied to other therapeutic areas of interest. In conclusion, the Lilly Data Mining TMP team provided an analysis of the potential options and limitations of leveraging the social media space. Furthermore, the TMP team clarified the constraints of leveraging social media in a highly regulated environment. As a follow-up to the Lilly Data Mining TMP research, the team expects to present its findings at a national conference in June.
Eli Lilly & Company
Regulatory Competitive Intelligence: Opportunities and Advantages Associated with Regulatory Interactions with the FDA
Eli Lilly & Co. is an Indianapolis- based company founded in 1876 with a vision to make medicines that help people live longer, healthier, and more active lives. The company continues to be committed to making a significant contribution to humanity by improving global health in the 21st century. Lilly has developed a diverse portfolio in several therapeutic areas, i.e. bone muscle joint, cardiovascular, diabetes, men's health, neuroscience and oncology. Lilly was the first company to mass-produce penicillin, the Salk polio vaccine and insulin. Lilly has locations in 18 countries and their products are sold in 125 countries.
The drug development process in the U.S. is highly regulated by the Food and Drug Administration (FDA), and it assesses safety and efficacy of the drug products to be used by the patients. Since it takes 9-12 years to bring a drug to the market, pharmaceutical companies diligently look for ways to improve the overall drug development paradigm, minimize the time to the product launch, provide timely valued medicines to patients and to decrease the duration of drug development and total cost. The conversations that take place between the Sponsor and the FDA during the development of a drug product appear to be instrumental in the drug's successful preclinical and clinical assessment and ultimate launch. Presently, it is unclear which types of interactions between the Sponsor and the FDA may be the most impactful to the successful development of a product. Therefore, it would be ideal to understand optimal interaction strategies between the Sponsor and the FDA and proactive approaches the Sponsor could undertake to improve the robustness of their internal portfolio development.
The Lilly Regulatory Affairs (Lilly-RA) Team Master's Project (TMP) team was asked to investigate the impact of formal and informal interactions, in the pharmaceutical industry, between the Sponsors and the FDA from 2009-2014 (last 5 years) by focusing on successful submissions of the New Drug Applications (NDAs) and new Biologics License Applications (nBLAs). To accomplish this objective, the Lilly-RA team: performed literature research on current FDA guidance's; devised and launched an industry-wide survey; interviewed experienced industry experts in the field of US-regulatory affairs; and, gathered publicly available documents. Upon consolidating the data from this research, the team assessed the industry's best practices. Ultimately, the team made recommendations to Lilly which describe the optimal interactions between the Sponsor and the FDA as well as the timing of these interactions to improve successful drug development.
Establishment of a Capital Project Management Process for the Engineering Team
Gilead Sciences, Inc. is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need. Gilead was founded in 1987 in Foster City, California. Over the past 25 years, it has grown to become one of the world's largest biopharmaceutical companies, with approximately 6,000 employees across five continents. Gilead has a portfolio of products and a pipeline of investigational drugs directed at therapies for HIV/AIDS, liver diseases, serious respiratory and cardiovascular conditions, cancer and inflammation. The Gilead site in San Dimas, one of the three manufacturing sites owned by Gilead, is a 200,000 square foot facility.
The San Dimas operation supports manufacturing, filling, packaging and labeling for a variety of products representing over 70% of Gilead's products destined for the "Americas". To support these operations, the engineering department at San Dimas, manages capital projects ranging from $3,000 to over $40 million using different management tools. Unfortunately, Gilead's current capital management approaches, adapted from the chemical industry, do not address pharmaceutical industry specific requirements such as aseptic manufacturing. In addition, the lack of a uniform predefined business process may introduce capital management errors which can lead to extended project timing and increased costs.
The Gilead TMP team was responsible for designing a 'Business Process' to enable the planning, prioritization, management, monitoring and evaluation of all capital projects at San Dimas. Additionally, the team was responsible for creating documentation including SOPs, guidelines and templates to support the capital process. To achieve these objectives, the team identified industry best practises for the capital project management process through literature review and input from key stakeholders. The team was able to establish a standard 'Business Process' tailored specifically for projects at San Dimas. 32 key documents for engineering and project management aspects were identified and developed to support the implementation of these processes. After launch of the process, Gilead, San Dimas should be able to adopt a streamlined approach to all its capital projects, leading to significant savings in terms of time and money. In the future this process may potentially be expanded to other sites at Gilead.
Commercial Solutions to Improve Operations Efficiency
Gilead Sciences is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need. Its focus is to transform and simplify care for people with life-threatening illnesses around the world. Gilead's portfolio of products and investigational drugs includes treatments for HIV/AIDS, liver diseases, serious respiratory and cardiovascular conditions, cancer and inflammation. Gilead has several manufacturing facilities. Gilead's San Dimas facility is a sterile-fill facility which is responsible for the manufacturing of an antifungal agent, AmBisome®; the packaging and labeling of Gilead's antiviral products; and, the distribution of products to the America's and the Pacific Rim.
Pharmaceutical manufacturing processes are strictly regulated and accurate documentation is of paramount importance. Every step in the manufacturing process must follow established protocols. Documentation, during the manufacturing process, provides a summary of real-time events and confirms all validated processes were carried out according to specifications. Currently, Gilead's San Dimas facility has highly manual methods of documenting manufacturing processes. Key documented processes include data entry by shift leaders to account for labor allocation and the compilation of FDA-mandated batch records. Each of these processes is manually carried out by employees. While the San Dimas' manual documentation methods are sufficient to ensure that their products meet FDA standards, their manual documentation methods do not provide management the level of visibility needed to track and assess performance and overall equipment efficiency (OEE).
The Gilead Operational Excellence TMP team was tasked with understanding data gathering systems currently in place in the manufacturing department at the San Dimas facility. Further, the team was asked to recommend improvements or to recommend new systems for Operational Equipment Effectiveness (OEE) studies which would include the analysis of labor and process tracking. After analyzing the current data gathering systems, they identified equipment, process and people tracking needs and prioritized them in the form of a user requirement specification list (URS). A comprehensive search for commercial OEE solutions was performed which identified the top options. Eventually, the team identified solutions for high, mid, and low tier automated options as well as an improved manual option. These recommendations were followed by a SWOT analyses of the solutions to evaluate how well they meet San Dimas's needs. Finally, the team provided an implementation plan for the improvement/new system in the facility.
Analysis of the Pharmaceutical Industry's Approach to Measuring and Controlling Subvisible Particulates in Parenteral Drug Products
Since 1987, Gilead Sciences has worked to discover, develop, and commercialize medications in order to advance the care of patients suffering from life-threatening diseases in areas of unmet medical need. In just over 25 years, Gilead has become a leading biopharmaceutical company with a portfolio of 16 marketed products, a growing pipeline of investigational drugs and approximately 5,800 employees in offices across five continents. Gilead Science's primary areas of focus include HIV/AIDS, liver disease, and serious cardiovascular, metabolic, and respiratory conditions. Gilead's office in Oceanside, California is responsible for the clinical manufacture and process development of biologics candidates in preclinical, Phase 1 and Phase 2 testing.
The Gilead Particulates TMP was asked to perform an in depth analysis of the biopharmaceutical industry's efforts to use the characterization and quantitation of subvisible particulates as a tool to control the quality of biological drugs. The size and count of protein particle aggregates within biopharmaceutical formulations is a major quality concern which can negatively impact safety and/or efficacy of drug products. It is thus important to carefully monitor and characterize these particles. The current regulatory size limit for particles in formulation is 10 microns, as defined by FDA and ICH guidance. However, recent research has shown that this standard is not sufficient because of the prevalence of subvisible particles below 10 microns in size.
The aim of this project was to assess the advancement in regulatory and industrial standards, as well as in technologies used to monitor these subvisible particles (SVPs) in parenteral drug products - within the size range of 0.1 to 10 microns. Through in-depth literature research and interviews with key opinion leaders (KOL) within academia, industry, the FDA, and commercial vendors, the team gained insight into the progress of regulatory standards and identified the latest technologies that are most suitable for use in the surveillance of SVPs. The results of this study were compiled into a final report, which was submitted to the team's corporate liaison at the conclusion of the project.
Understanding Molecular Diagnostic Testing Laboratories' Needs and Decision-making Process
Life Technologies Corporation (Life Tech), now the Life Science Solutions Group of ThermoFisher Scientific, is a global biotechnology business dedicated to improving the human condition. Life Tech provides a wide variety of tools designed to assist the life science community and is a global leader in genetic analysis through its real-time PCR (qPCR), capillary electrophoresis (CE) and next generation sequencing (NGS) platforms.
Molecular diagnostic labs face difficult decisions regarding which platforms to choose for testing of different diseases (e.g. cancer, inherited diseases, etc.) and clinical indications (e.g. screening, diagnosis, staging, therapeutic choice, etc.). These decisions are further complicated by an industry that is undergoing drastic changes including the introduction of new technology and a complete overhaul of the reimbursement system. This Team Master's Project aimed to better understand the needs and the decision-making process of diagnostic testing laboratories regarding qPCR, CE, and NGS platforms.
In order to understand how these laboratories make decisions, the KGI team conducted extensive research. The team began by consulting secondary sources such as scientific literature and market research reports to gain an understanding of the industry. This knowledge was used to structure interviews with key opinion leaders, which provided the team with a qualitative understanding of their thought processes. Based on these results, the team constructed and administered a survey to labs across the country to obtain actionable, quantitative data. These results helped the team develop a strategy to guide Life Tech in their efforts to effectively market these platforms to the most applicable sectors of the molecular diagnostics industry.
Design of a Portable Device for the Detection of Soil Pathogen
Monsanto is a sustainable agricultural company. Founded in 1901, Monsanto has been at the forefront of many scientific advancements in the agricultural industry. Monsanto is devoted to delivering agricultural products that support farmers all around the world. Current work at Monsanto is focused on increasing yields in core crops with a combination of advanced plant breeding, biotechnology, and improved farm management practices.
As plant diseases lead to significant annual crop losses, disease management strategies are an important element of Monsanto's goal to increase crop yields. This requires the accurate detection and monitoring of the presence of pathogens in the field. Current methods require samples to be transported to a centralized lab. Monsanto would like to develop a method for pathogen detection that can be used in a field setting. This would reduce the time and cost of detection and allow a more immediate response to a crop disease.
The Monsanto TMP team developed a method that can be used to detect a fungal pathogen in a field setting. To achieve this objective, the team identified various gold standard protocols designed for a lab setting, modified the procedures so that they can be performed on site with minimal training and equipment, and tested their performance. Ultimately, the Monsanto TMP team used a pre-existing instrument to develop a device which permits sample extraction and DNA purification that is coupled to target sequence amplification and quantitative detection on.
National Science Foundation Partnerships for Innovation grant
Diagnosing Ventilator Associated Pneumonia through Analysis of Volatile Organic Compound Biomarkers
The National Science Foundation (NSF), under its "Partnerships for Innovation" (PFI) program, provides funding for collaborations between academic institutions and small companies, to facilitate the translation of academic discoveries into novel products. This TMP team is working on an NSF-PFI funded project involving Keck Graduate Institute (KGI), Pomona College, and four small business partners: Tanner Research, Claremont Biosolutions, Lambda Solutions Inc, and Synedgen. The goal of this project is to develop and market a device that will allow for the early non-invasive diagnosis of Ventilator-Associated Pneumonia (VAP) through analysis of Volatile Organic Compound (VOC) Biomarkers.
Patients on ventilator support are frequently colonized with pathogenic bacteria that grow as biofilms inside the endotracheal tube. However, the presence of such biofilms does not necessarily lead to active pneumonia. The gold standard for VAP diagnosis therefore involves quantitative culture of a bronchoalveolar lavage sample, which is highly invasive and involves long turnaround times, thus leading to high costs, presumptive treatment prior to confirmed VAP diagnosis, and over-use of antibiotics. The overall goal of the NSF-PFI project is to enable early, noninvasive, differential diagnosis of VAP by measuring changes in VOCs exhaled by patients on mechanical ventilator support.
To identify unique VOC signatures that can differentiate bacteria present as biofilm versus infectious, planktonic form, the team developed a setup to grow bacterial biofilms and collect emitted VOCs, followed by analysis via GC-MS. Through literature searching and bioinformatics tools, the team investigated the scientific background and identified differentially regulated metabolic pathways that may be involved in production of unique VOC signatures.
The partnering organizations of this NSF PFI project are developing a device, consisting of a disposable sample collector, and a compact instrument, that can be used to identify VOC signatures from the exhaled breath of mechanically ventilated patients. To better understand how this device could be integrated into current clinical practice, the team is conducting primary user research to identify unmet needs and clarify product requirements. Furthermore, the team is analyzing the competitive landscape and market potential, and is identifying potential strategic partnerships. By developing a preliminary commercialization plan, the team aims clarify alternative paths for market entry.
NuSil Technology LLC
Investigating Novel Market Opportunities for Silicone Drug Delivery Devices in Women's Health
NuSil is the leading global manufacturer of medical grade silicone. Founded in 1979, NuSil is a privately held company headquartered in Carpentaria, California. Notably, with approximately 400 global employees, NuSil has additional facilities located in California, Texas, and France. The company focuses on the manufacturing of silicone compounds for the healthcare, aerospace, electronics, and photonics industries. The healthcare division is further divided into long-term and short-term implantable silicones, skin care, and drug delivery.
During phase I of the NuSil TMP project, the team was assigned the task of identifying novel commercial opportunities for silicone drug delivery devices. To complete this task, the team evaluated areas of women's health, wound healing, and antimicrobials. For each of these market opportunities, the team investigated market size, current research, competing biomaterials in addition to the intellectual property surrounding the use of silicone in each of these defined markets.
Upon the identification of women's health as the most promising commercial opportunity through secondary research and KOL interviews, the team was tasked with identifying strong opportunities in women's health. We successfully characterized over 30 disease indications in women's health, and ranked them according to market opportunity. The top four disease indications were the selected for further market research analysis. The team's analysis included areas ranging from unmet clinical need, disease prevalence and demographics, adoption rates, socio-economic analysis, technical feasibility, regulatory pathways, IP considerations and risk management. Ultimately, the NuSil TMP team produced an abbreviated business plan, which NuSil can use as a tool for the identification of new investment opportunities.
30 Years Since the Orphan Drug Act: A Comprehensive Database and Current Trends
The orphan drug act (ODA) was passed in 1983 to encourage the development of drugs aimed to treat rare diseases that affect fewer than 200,000 Americans. Some of the incentives under this act include market exclusivity for the drug maker, tax/financial incentives and expedited review by the FDA. Given the increasing cost of developing large market 'blockbuster' drugs and breakthroughs in the understanding of the molecular basis of disease progression, there is a rapidly growing interest in the development of drugs designed to treat rare diseases.
Pfizer, the world's largest pharmaceutical company in revenues, is currently exploring the rare disease space which is currently dominated by biotech companies. Pfizer's current diversified global health care portfolio includes medicines, vaccines, nutritional products, and many of the world's best-known consumer products. To help guide Pfizer in making informed decisions in pursuing orphan drug development, a comprehensive centralized resource of all orphan designations since the passing of the ODA was developed. The database will additionally serve as a guiding resource for patients and caregivers.
The goal for this team was to create a database which- includes all orphan drug designations (current as of May 2014), with associated disease area classification, stage of development, incidence/prevalence numbers, support group and sponsor information. Within the database there are 3000 plus orphan disease designations. Each designation was classified into major disease focus groups and further sub classified into specific disease therapeutic areas. The staging of development information for therapeutics in this area was derived from clinicaltrials.org. Support group information and incidence/prevalence data were obtained from reliable federal and state websites and peer-reviewed journals. A user-friendly front-end application to analyze and filter the database on the disease area, designated drugs, phase of development, etc. was also developed. By using the developed database, the team analyzed historical and current trends within the data to determine opportunities and areas of need for various rare disease classifications.
Raptor Pharmaceutical Corp.
Mapping the Clinical Landscape of Huntington's Disease
Raptor Pharmaceuticals Inc. is a publicly traded biopharmaceutical company that develops and commercializes therapeutic drugs for rare inherited diseases. The company was founded in 2005 by former executives from Biomarin Pharmaceuticals Inc., and they have been actively pursuing the development of multiple drugs in several disease indications. Their current lead product is a small molecule therapeutic known as Procysbi® (delayed release cysteamine bitartrate), which was approved for the treatment of nephropathic cystinosis in April 2013. Raptor is currently seeking to expand the utility of this active ingredient, RP103, into other potential indications such as for Huntington 's disease (HD).
In February of 2014, Raptor reported the completion of an 18-month Phase 2/3 clinical trial conducted by the Centre Hospitalier Universitaire d'Angers (CHU) in France, which indicated that the therapeutic administration of RP103 attenuated the total motor decline of HD patients. The current Standard Of Care (SOC) for HD management aims to treat chorea, one aspect of the motor decline experienced by HD patients. Given that there are currently no drugs that slow the disease progression, the CHU trial results indicate a promising potential for this first-in-class drug. In order to streamline the development and potential commercialization of RP103 for treatment of HD, the team focused on identifying signatures of HD diagnosis, disease progression and treatment outcomes.
The project was divided into three phases. In Phase I, the team conducted an extensive literature review in order to establish the landscape of HD. This was accomplished by curating published data on HD pathogenesis, patient Quality Of Life (QOL), clinical trials, current SOC and alternative therapies. Additionally, this data was used as a basis of information for the next project phase. Phase II focused on designing questions for patient and Health Care Provider (HCP) surveys, which were conducted by a contracted market research firm. These surveys helped identify patient referral pathways, HD diagnosis protocols and unmet clinical needs through consistencies and discordances among primary and secondary research. In the final phase, the team identified key opinion leaders (KOLs) using quantitative weighting measures, and began to address the clinical need for HD patient outcomes research by utilizing a proprietary insurance claims dataset. It is expected the output from this TMP will give Raptor insights into signature issues associated with HD treatment and economics, and support the marketing strategies for RP103.
Evaluation of continuous bioprocessing: industry best practices; available equipment; cost of goods; and, plant capacity for production of monoclonal antibodies and Fc fusion proteins
Regeneron is a leading science-based biopharmaceutical company based in Tarrytown, New York that discovers, invents, develops, manufactures, and commercializes medicines for the treatment of serious medical conditions. Regeneron markets medicines for eye diseases, colorectal cancer, and rare inflammatory conditions. Additionally, Regeneron has product candidates in development for other areas of high unmet medical need, including hypercholesterolemia, oncology, rheumatoid arthritis, allergic asthma, and atopic dermatitis.
The Regeneron TMP team was asked to evaluate aspects of continuous bioprocessing including: 1) available types of equipment; 2) the impact of this technique on cost of goods; and 3) a continuous bioprocessing plant's capacity for the production of monoclonal antibodies and Fc fusion proteins. As part of the TMP team's effort, an initial survey was conducted to determine industry trends and best practices regarding the use of upstream and downstream continuous bioprocessing. Additionally, a second survey was conducted to evaluate the equipment used in continuous bioprocessing. The project culminated in the production of a final report detailing the global cost of goods and associated plant capacity analysis related to the implementation of continuous bioprocessing technologies.
In order to complete the initial survey related to industry trends and best practices centered on continuous bioprocessing, the Regeneron TMP team constructed and deployed a digital survey to key opinion leaders in the pharmaceutical industry. The second survey focused on making direct contact with equipment manufactures and vendors with knowledge of state-of-the-art bioprocessing technologies, in order to document the available equipment for continuous processing applications. Using a Greenfield facility as a basis, the team's final project task was to perform a cost of goods and plant capacity assessment of continuous processing versus fed‐batch processing at a commercial scale. The results and the analysis of the first survey were conveyed to Regeneron in early January of 2014, and results of the second survey and the Greenfield analysis were presented to Regeneron in early May 2014.
Evaluation of the Market Potential and Development Feasibility of Seven Rare Disease States
Sarepta Therapeutics is focused on developing first-in-class RNA-based therapeutics to improve and save the lives of people affected by life-threatening rare and infectious diseases. The company's long-term vision is to become a leading, independent biotech company capable of sustainably developing a pipeline of breakthrough therapeutics and bringing them to the patients who need them. To accomplish this vision, Sarepta has a unique phosphorodiamidate morpholino oligomer (PMO) technology at its disposal that is uniquely versatile, allowing for the development of a range of therapeutic candidates that target different types of RNA.
Sarepta's pipeline currently includes its lead clinical candidate, eteplirsen, for the treatment of Duchenne muscular dystrophy as well as potential treatments for influenza and Marburg hemorrhagic fever virus. Sarepta is interested in adding candidates to its pipeline that are based on its platform PMO technology. However, Sarepta has devoted its resources to gaining approval for its current pipeline and hasn't formally evaluated which disease state the company should pursue next.
The Sarepta TMP team was tasked with evaluating the risk/benefit profiles of 7 disease states to determine which indications would provide the highest return on investment (ROI) while limiting risk. To accomplish this task, an IP landscape and competitor analysis was conducted to look for areas with freedom to operate. Next, the feasibility of conducting and designing successful clinical trials that would support a regulatory pathway with limited clinical endpoints was analyzed. Finally, a financial analysis that compared the potential market opportunity to the costs of development of a therapeutic for each disease was completed to ascertain ROI. In support of the original objective, a report which included a high level comparative analysis of the risks and benefits of developing a therapeutic was performed for each of the variables being examined to form the prioritization strategy for Sarepta.
Sigma-Tau Pharmaceuticals Inc.
Epidemiological Landscape of cerebrotendinous xanthomatosis (CTX) and Recommendations for the Implementation of a Newborn Screening Test
Sigma-Tau Pharmaceuticals is dedicated to helping patients affected by rare diseases. The FDA defines a rare disease as a disease that affects fewer than 200,000 individuals in the United States. Sigma-Tau's core belief and dedication is that the study of rare diseases should be an integral part of its research activity. Consequently, Sigma-Tau has chosen to specialize in these diseases by discovering novel therapeutics to help patients suffering from these rare conditions.
Sigma-Tau Pharmaceuticals is in the process of exploring and expanding their rare disease product profile for cerebrotendinous xanthomatosis (CTX). Unfortunately, there is no current standardized screening method in the United States for CTX. Consequently, without proper disease detection, CTX patients can remain undiagnosed or misdiagnosed until their disease state has progressed. Sigma-Tau is interested in generating a road map for the inclusion of CTX in newborn screening. The establishment of a standard for the CTX screening of newborns will help patients by providing a more timely diagnosis of disease, provide patients with earlier therapeutic intervention and increase the market opportunity for Sigma-Tau Pharmaceutical's CTX-related products.
The Sigma-Tau TMP team was given two main goals: 1) gain an in-depth understanding of the epidemiology of CTX; and, 2) generate a road map for the possible adoption and implementation of a test for CTX in the existing newborn screening panel. To accomplish these objectives, the team performed a comprehensive literature search and interviewed Key Opinion Leaders of CTX to understand unmet clinical needs associated with CTX diagnosis and treatment. The team then synthesized collected information to produce an overview of CTX diagnosis within the United States and to develop a strategy for the newborn screening of CTX. In addition, the team identified diseases mechanistically related to CTX and compiled an Orphan Drug Application (ODA) involving a promising new indication for one of Sigma-Tau's CTX-related products. This ODA was provided to Sigma-Tau for possible submission to the FDA. Upon project completion the TMP team provided Sigma-Tau a CTX status report which included: all available CTX epidemiologic and diagnostic data; identified current unmet clinical needs associated with CTX; explored and identified the role of patient advocacy groups within the CTX community; provided recommendations to increase CTX awareness; and, recommendations regarding the implementation of a newborn screening test for CTX.