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Home My WebLink AboutCouncil Study Session Agenda Packet 10/04/2004TOWN OF MARANA, ARIZONA STUDY SESSION AGENDA 13251 N. Lon Adams Road October 4, 2004 - 5:30 p.m. Mayor Vice Mayor Council Member Council Member Council Member Council Member Council Member Town Manager Bobby Sutton, Jr. Herb Kai Jim Blake Patti Comerford Tim Escobedo Ed Honea Carol McGorray Mike Reuwsaat Welcome to this Marana Study Session. This agenda may be revised up to twenty-four hours prior to the meeting. In such a case a new agenda will be posted in place of this agenda. If you are interested in speaking to the Council during the Study Session, you must fill out a speaker card (at the rear of the Council Chambers) and deliver it to the Clerk prior to the commencement of the meeting. It is up to the Mayor and Council whether individuals will be allowed to address the Council. All persons attending the Council Meeting, whether speaking to the Council or not, are expected to observe the Council Rules, as well as the rules of politeness, propriety, decorum and good conduct. Any person interfering with the meeting in any way, or acting rudely or loudly will be removed from the meeting and will not be allowed to return. To better serve the citizens of Marana and others attending our meetings, the Council Chamber is wheelchair and handicapped accessible. Any person who, by reason of any disability, is in need of special services as a result of their disability, such as assistive listening devices, agenda materials printed in Braille or large print, a signer for the hearing impaired, etc., will be accommodated. Such special services are available upon prior request, at least ten (10) working days prior to the Council Meeting. For a copy of this agenda or questions about the Study Session, special services, or procedures, please contact Jocelyn C. Bronson, Town Clerk, at 682-3401, Monday through Friday from 8:00 a.m. to 5:00 p.m. ACTION MAY BE TAKEN BY THE COUNCIL ON ANY ITEM LISTED ON THIS AGENDA. Amended agenda items appear in italics. Posted no later than September 30, 2004 by 5:30 o'clock p.m., at the Marana Town Hall, Marana Police Department, and the Marana Development Services Center. TOWN OF MARANA, ARIZONA STUDY SESSION AGENDA 13251 N. Lon Adams Road October 4, 2004 - 5:30 p.m. CALL TO ORDER GENERAL ORDER OF BUSINESS 1. Presentation: Institute for Global Pharmaceutical Development 2. Presentation: Council Handbook III. ADJOURNMENT Bobby Sutton, Jr., Mayor 2 TOWN COUNCIL MEETING INFORMATION TOWN OF MARANA MEETING DATE: October 4, 2004 AGENDA ITEM: Study Session 1. TO: FROM: SUBJECT: MAYOR AND COUNCIL Michael A. Reuwsaat, Town Manager Presentation: Institute for Global Pharmaceutical Development (IGPD) DISCUSSION Background information relative to this presentation is included for your review. RECOMMENDATION N/A N/A SUGGESTED MOTION IGPD Presentation 09/29/2004/10.'28 AM GTEC Greater Tucson Economic Council September 27, 2004 Mike Reuwsaat Town Manager Town of Marana 13251 N. Lon Adams Road Marana, AZ 85653-9723 Dear Mike: Thank you very much for taking the time today to meet with Colleen and me to discuss the Institute for Global Pharmaceutical Development (IGPD). As you saw, we've received a number of private sector commitments and anticipate quite a few more in the coming week. We've also met with a number of public sector officials in the region and look forward to their commitment to make this a reality for our region. We very much appreciate your offer to put this up for consideration in Marana. We're following up with Ray Woosley to see if he can attend the Study Session at 5:30PM on 10/4 and will advise as soon as we hear. In the meantime, and as always, feel free to contact me or Colleen if any questions arise. Steven W. Weathers President & CEO opportunity accelerated. 33 North Stone Avenue, Suite 800 Tucson, Arizona 85701 520.882.6079 FAX 520.622.6413 800.374. 4769 www. opportunitytucson, org Institute for Global Pharmaceutical Development Fact Sheet 8/23/04 Overview The Institute for Global Pharmaceutical Development (IGPD) will be an independent, free- standing, non-profit (501C3) organization whose mission is to conduct research and offer programs that will enable the pharmaceutical industry to accelerate the development of and access to new medications. The IGPD will be affiliated with three founding partners: the University of Arizona (UA), SRJ International (formerly known as the Stanford Research Institute), and the United States Food and Drug Administration (FDA). Each partner contributes unique strengths to the TGPD. The UA will provide the academic home and infrastructure for the IGPD's educational and research programs and an environment of innovation and inquiry. The participating FDA scientists will provide the first hand knowledge of the regulatory process and a wealth of experience in the evaluation of new pharmaceutical agents. SR~ will bring practical experience in pharmaceutical development, scientific expertise, and a track record of commercializing new drugs. Why form the ?GPD? The rising cost of medications is one of the greatest crises facing our nation. These costs impact consumers, employers, hospitals, insurance companies, and pharmaceutical companies. Funding of drug development has increased dramatically in the past 10 years. However, the number of new drugs being approved and taken into the marketplace has slowed, due in large part to the time and cost of development. A recent estimate by the Pharmaceutical Research and Manufacturers Association is that new drugs take on average 12-15 years and $1.7 billion to develop. This leaves only 2-5 years of patent protection for companies to recover their large initial investment, and accounts for the high cost of providing drugs to the consumer. In response to this crisis, the FDA is calling for ways to use technology and new approaches to streamline the approval process and expedite approvals. IGPD would play a critical role in helping the FDA to develop a new drug approval process. What are the benefits tO fQrminq the IGPD in Tucson? The potential economic development impact resulting from the establishment of the IGPD in Tucson is substantial. The IGPD represents a rare opportunity for Tucson to become a major international center of drug discovery and development. As the home of ]:GPD, Tucson will be recognized in the highly competitive biotechnology industry, and have a competitive advantage in establishing bio-tech start-ups and attracting major drug companies. IGPD would serve as a magnet for world-class scientists and researchers, investors and venture capitalist companies, contract research organizations and drug production operations. IGPD would serve as the platform for launching Tucson's biotechnology industry. What is needed to successfully establish IGPD in Tucson? The founding partners have agreed to develop a Memorandum of Understanding (MOU) by October i that will define the nature and extent of their shared commitment to the IGPD. Over the next four months, each partner will identify faculty and staff who will work together on the mission of IGPD. $20 million in commitments need to be secured by October 1 to successfully establish the IGPD. These funds will be used to operate the Institute for a period of five years (2004-2009). ~[t is expected that the Federal Government will provide substantial funding for the ]'nstitute beginning in FY 2007. Core funding in the amount of $12,500,000, or $2,500,000 annually, will be secured from a variety of sources including the founding partners, grants and contracts, and tuition and fees. This funding will include cash contributions and in-kind contributions for the use of facilities and equipment, loaned staff, and assistance from faculty and scientists. In addition, the Institute needs to secure additional annual funding of $7,500,000, or $1.5 million annually, from corporate, foundation, local government and individual donors. IGPD will seek funding from the State of Arizona to construct a high tech office and laboratory facility that will anchor a new UA biotechnology research park. The Institute will seek city and county government assistance in securing the land and improvements for the facility. Six potential sites are currently being evaluated. The UA Office of Economic Development is requesting a grant from the Arizona Commerce and Economic Development Commission (CEDC) in the amount of $400,000 to help defray the initial start-up costs of the ]:nstitute, including preparation of a business plan. The FDA may provide another source of funding for the TGPD. The FDA is expected to seek funding for centers like the IGPD in October 2006 for the fiscal year 2007. Tn addition, the TGPD will seek funding from government agencies, foundations and donors to support its educational and research programs. Specific research and educational projects will be funded by competitive awards or sub-contracts made by the IGPD to University faculty and programs. The FDA will contribute teaching faculty and research staff who will work on-site at the IGPD or in the FDA's facilities. If the necessary operational funds are committed in 2004, what are the next steps launching and operatinq a successful ZGPD? Year One - 2005 The IGPD will occupy interim offices in Tucson beginning in 3anuary 2005. The TGPD Board of Directors and Scientific Advisory Board will be appointed. Strategic and financial plans will be developed, and the TGPD's Research Director, Education Director and additional staff will be hired. Educational and research programs will begin. Year Two - 2006 A facilities plan will be designed and sent to bid, and a builder/general contractor retained. Year Three - 2007 The facilities will be constructed and occupied by end of year. Year Four - 2008 Expansion of educational and research programs. Year Five - 2009 Expansion of educational and research programs. How will the IGPD be orqanized? The IGPD will have an oversight board with members chosen jointly by Governor of Arizona, the President of the UA, the President of SRO, and Commissioner of the FDA. The board will include representatives of the private sector. There will also be a scientific advisory board of experts in drug development representing the UA, SRO, FDA and leading international institutions. For More ]:nformation about the IGPD, Contact: Dr. Raymond Woosley, University of Arizona, Vice President for Health Sciences, 520-235-9000 Bruce Wright, University of Arizona, Associate Vice President for Economic Development, Technology Park, (520) 626-4843 Dr. Curt Carlson, SRI ]:nternational, Inc., President, (650) 859-2000 Dr. 3anet Woodcock, US Food and Drug Administration, Acting Associate Commissioner, (301) 827-7861 Steve Weathers, President/CEO, Greater Tucson Economic Council, (:520) 882-6079 To Make or Inquire About Donations to the TGPD, Contact: Greater Tucson Economic Council, 882-6079 www. dailystar, com ~)www.azstar~t,~om' Richard Ducote: Here is a golden chance we must seize August 25, 2004 Watch this one closely. We may never see such an opportunity again. Tucson has a good shot at nailing down an important new drug development institute that could transform both pharmaceutical development and the economy of the whole state. Around 80 business leaders and investors gathered Monday at the University of Arizona to hear the pitch for startup funds for the project. Those people in the small room at the UA Foundation office hold our economic future in their hands. They and the people they contact in the next six weeks will determine if Tucson makes the leap to the future or continues to tread the same old economic path. The opportunity to snag the Institute for Global Pharmaceutical Development is, in the words of one observer, a rare alignment of stars. The UA, SR! !nternational and the U.S. Food and Drug Administration have an informal agreement to launch the new institute in Tucson if public or private contributions can be lined up to support operations for the first five years. SR!, formerly Stanford Research Institute, is a powerhouse in several fields of research, including biosciences. FDA backing will bring interest in the enterprise from pharmaceutical giants. A top focus of the proposed institute would be to streamline drug development to provide better, cheaper drugs faster. As the population ages and health costs continue to soar, there is no more important mission in biotech. You might guess that the price tag for this opportunity to play in the high stakes field of biotechnology would be very steep. !t's not. It amounts to a community contribution of $1.5 million a year for five years. That's $7.5 million total, or about $1.60 a year for each resident of the greater Tucson region. It would be hard to imagine an investment of private funds offering greater rewards. This institute would instantly put Tucson on the biotech map. It would likely draw private drug research and more to the area, offering high-tech jobs in research, development and other areas to young talent for decades. In collaboration with the startup of TGen - the Translational Genomics Research Institute - in Phoenix, to which the state of Arizona and other governments have committed $100 million long-term, Arizona could become a hot spot in biotech, the leading new industry of the new century. Tucson is getting this shot because the University of Arizona and its health sciences chief, Dr. Raymond Woosley, provide the talent, foresight and organization to make it work for SR! and the FDA. If Tucson doesn't come up with sufficient funds to seal the deal by Oct. :Z, the FDA will be forced to shop the institute around to various established biotech hot spots like San Francisco, Boston or Research Triangle Park, N.C. Tucson would stand little chance of winning that competition. This is a shot at playing in the big leagues. Every Tucson-area business, government, organization and individual must contribute something to this effort. It simply is not an option to go on to other things and let others worry about seizing this opportunity. If we win this prize, Southern Arizona's economy could be transformed by the end of the decade. More about the effort to land this important institute will come in future columns. For now, to contribute to this effort, contact the Greater Tucson Economic Council at 882-6079 or the UA Office of Economic Development at 62:L-4930. · Contact Richard Ducote at 573-4178 or rducote@azstarnet, com. 1 INNOVATION OR STAGNATION? Crisis and Opportunity on the Critical Path to New Medical Products U.S. Department of Health and Human Services Food and Drug Administration March 2004 �- INNOVATION OR STAGNATION? i TABLE OF CONTENTS EXECUTIVE SUMMARYI INTRODUCTION 1 INNOVATION OR STAGNATION? 2 NEGOTIATING THE CRITICAL PATH 4 SCIENTIFIC AND TECHNICAL DIMENSIONS ALONG THE CRITICAL PATH6 A BETTER PRODUCT DEVELOPMENT TOOLKIT IS URGENTLY NEEDED 7 TOOLS FOR ASSESSING SAFETY 9 Towards a Better Safety Toolkit 11 Getting to the Right Safety Standards 12 TOOLS FOR DEMONSTRATING MEDICAL UTILITY 12 Towards a Better Efficacy Toolkit 14 Getting to the Right Efficacy Standards 16 TOOLS FOR CHARACTERIZATION AND MANUFACTURING 16 Towards a Better Manufacturing Toolldt 17 Getting to the Right Manufacturing Standards 19 A PATH FORWARD 19 The Orphan Products Grant Program 20 The Next Steps 20 LIST OF TABLES AND FIGURES Figure 1: 10 -Year Trends in Biomedical Research Spending ...................... Figure 2: 10 -Year Trends in Major Drug and Biological Product Submissions to FDA.... Figure 3: The Escalating Cost of Development.... Figure 4: The Critical Path for Medical Product Development... Figure 5: Research Support for Product Development.... Figure 6: Working in Three Dimensions on the Critical Path.... Figure 7: Industry - FDA Interactions During Drug Development.... Figure 8: Problem Identification and Resolution During the FDA Review Process.... Table 1: Three Dimensions of the Critical Path..... Executive Summary This report provides the Food and Drug Administration's (FDA's) analysis of the pipeline problem — the recent slowdown, instead of the expected acceleration, in innovative medical therapies reaching patients. Today's revolution in biomedical science has raised new hope for the prevention, treatment, and cure of serious illnesses. However, there is growing concern that many of the new basic science discoveries that have been made in recent years may not quickly yield more effective, more affordable, and safe medical products for patients. This is because the current medical product' development path is becoming increasingly challenging, inefficient, and costly. During the last several years, the number of new drug and biologic applica- tions submitted to FDA has declined significantly; the number of innovative medical device applications has also decreased. The costs of product development have soared over the last decade. Because of rising costs, innovators concentrate their efforts on prod- ucts with potentially high market return. Developing products tar- geted for important public health needs (e.g., counterterrorism), less common diseases, prevalent third world diseases, prevention indications, or individualized therapy is becoming increasingly chal- lenging. In fact, with rising health care costs, there is now concern about how the nation can continue to pay even for existing thera- pies. If the costs and difficulties of medical product development continue to climb, innovation will continue to stagnate or decline, and the biomedical revolution may not deliver on its promise of bet - ter health. What is the problem? In FDA's view, the applied sciences needed for medical product development have not kept pace with the tremen- dous advances in the basic sciences. The new science is not being used to guide the technology development process in the same way that it is accelerating the technology discovery process. For medical technology, performance is measured in terms of product safety and efficacy. Not enough applied scientific work has been done in creat- 'The term medical product includes drug and biological products as well as medical devices. i ing new tools to get fundamentally better answers about the safety and efficacy of new products, in faster time frames, with more cer- tainty, and at lower costs. As a result, the vast majority of investiga- tional products that enter clinical trials fail. Often, product develop - ment programs must be abandoned after extensive investment of time and resources. This high failure rate drives up costs, and devel- opers are forced to use the profits from a decreasing number of suc- cessful products to subsidize a growing number of expensive fail- ures. In addition, the path to market for successful candidates is Anew product long, costly, and inefficient, due in large part to the current reliance development on cumbersome assessment methods. In many cases, developers toolkit is have no choice but to use the tools and concepts of the last century urgently need - to assess this century's candidates. ed to improve y bilit A new product development toolkit — containing powerful new sci- and predictability entific and technical methods such as animal or computer -based predictive models, biomarkers for safety and effectiveness, and new along the criti- clinical evaluation techniques — is urgently needed to improve pre- Cal path dictability and efficiency along the critical path from laboratory con - cept to commercial product. We need superior development science to address these challenges — to ensure that basic discoveries turn into new and better medical treatments. We need to make the effort required to create better tools for developing medical technologies. And we need a knowledge base built not just on ideas from biomed- ical research, but on reliable insights into the pathway to patients. The medical product development process is no longer able to keep pace with basic scientific innovation. Only a concerted effort to apply the new biomedical science to medical product development will succeed in modernizing the critical path. FDA is uniquely positioned to see these problems and to identify the challenges to development. Directed by Congress to promote and protect the public health, FDA is responsible for ensuring that safe and effective medical innovations are available to patients .2 As part of its regulatory role, FDA must use available scientific knowledge to set product standards. During clinical testing, FDA scientists con- duct ongoing reviews of emerging data on safety, efficacy, and prod- uct quality. Agency reviewers see the complete spectrum of success- es and best practices, as well as the failures, slowdowns, barriers, and mi opportunities that occur during product development. 2 The FDA mission was set forth by Congress in section 406 of the Food and Drug Administration Modernization Act of 1997. li When serious problems emerge in the development process or com- mon problems continue to recur, FDA scientists attempt to address them by bringing them to the attention of the scientific community, or by conducting or collaborating on relevant research. As a result of such work, the Agency often makes guidance documents publicly available that summarize best practices in a development area and share FDA insights into specific issues or topics. The availability of guidance documents has been shown to foster development and innovation in areas of therapeutic need, to improve the chances of initial success of a marketing application, and to shorten the time it takes to get safe and effective treatments to patients. But more needs to be done. FDA is plan- The product development problems we are seeing today can be ning an initia- addressed, in part, through an aggressive, collaborative effort to cre- tive that Will ate a new generation of performance standards and predictive tools. The new tools will match and move forward new scientific innova identify and tions and will build on knowledge delivered by recent advances in prioritize the science, such as bioinformatics, genomics, imaging technologies, most pressing and materials science. development problems and. FDA is planning an initiative that will identify and prioritize (1) the .. the greatest most pressing development problems and (2) the areas that provide opportunities the greatest opportunities for rapid improvement and public health for rapid benefits. This will be done for all three dimensions along the critical path — safety assessment, evaluation of medical utility, and product improvement industrialization as described in our report. It is critical that we enlist all relevant stakeholders in this effort. We will work together to identify the most important challenges by creating a Critical Path Opportunity List. Concurrently, FDA will refocus its internal efforts to ensure that we are working on the most important problems, as well as intensifying our support of key projects. i Through scientific research focused on these challenges, it will be feasible to improve the process for getting new and better treat- ments to patients. Directing research not only to new medical break- throughs, but also to breakthrough tools for developing new treat- ments, is an essential step in providing patients with more timely, affordable, and predictable access to new therapies. We are confi- dent that, with effective collaboration among government, academia, and the private se ctor, these goals can be achieved. iii Innovation or Stagnation? Introduction The mission of the U.S. Food and Drug Administration (FDA) is, in part, to protect the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, and medical devices. The FDA is also responsible for advancing the pub- lic health by helping to speed innovations that make medicines more effective, safer, and more affordable; and helping the public get the accurate, science -based information they need to use medicines to improve their health. In keeping with its mission, FDA is issuing this report, drawing atten- tion to the growing crisis in moving basic discoveries to the market where they can be made available to patients. The report evaluates how the crisis came about and offers a way forward. It highlights examples of Agency efforts that have improved the critical path and discusses opportunities for future efforts. Finally, the report calls for a joint effort of industry, academia, and the FDA to identify key prob- lems and develop targeted solutions. I 1 Innovation or Stagnation? Figure 1: 10- YearTrends in Biomedical Research Spending 300 _ -a- US Pharmaceutical R &D Spending 250 -ems Total NIH Budget ° o •» 200 1511 C7 x 100 c so 0 1993 1994 1955 1996 1997 1958 1999 2000 2001 2002 2003 Year The figure shows 10 -year trends in biomedical research spending as reflected by the National Institutes of Health (NIN) budget and by Pharmaceutical companies' research and development (R &D) investment Figure 2: WYearTrends in Major Drug and Biological Product Submissions to FDA 150 140 130 120 110- 100- 100 LL 0 ° 80 -a^ Total NDA9 Rec'd by FDA 0 70 -{>- Original BLAs Go- so- 40- 30 20 10 0 1583 1994 1595 1996 1997 1598 1999 2000 2001 2002 2003 Year The figure shows the number of submissions of new molecular entities (NMEs) ---• drugs with a novel chemical structure --- and the number of biologics license - -- - - - - - -- application (BLPA submissions ve been observed at regulatory agencies worldwide. 2 Innovation or Stagnation? L Innovation or Stagnation? Challenge and Opportunity on the Critical Path to New Medical Products The sequencing of the human genome four years ago raised wide- spread hope for a new era in the prevention and treatment of disease created by the ongoing investment in biomedical research (Figure 1). But that new era has not yet arrived. Instead, 2000 marked the start of a slowdown in new' drug and biologic submission to regulatory agencies worldwide (Figure 2). The submissions of innovative med- ical device applications has also slowed recently.' At a time when basic biomedical knowledge is increasing exponentially, the gap between bench discovery and bedside application appears to be expanding. There is great concern about the ability to bring the hoped -for outcomes of basic research advances — much - awaited new treatments — to patients. There is concern that hoped -for advances in medicine and new treatments for diseases may never materialize. Current costs of bringing a new medicine to market, estimated by some to be as high as $0.8 to 1.7 billion, are a major barrier to invest- ment in innovative, higher risk drugs or in therapies for uncommon diseases or diseases that predominantly afflict the poor. Product development in areas crucial to public health goals, such as antibi- otics, has slowed significantly during the past decade. Inventors of candidate artificial organs, bioengineered tissues, and other novel devices face serious challenges and uncertainties. A viable path for developing many preventive therapies (e.g., some types of cancer chemoprevention) has not been elucidated. 3 For purposes of this document the terms novel or new application refer to applications for medical products of a type that have never before been sub- mitted to the Agency (i.e., new molecular entity - NME). °See http: / /www.fda.gov /cdrh /consumer /mda/index.htmi. STufts report Tufts Center for the Study of Drug Development, Backgrounder. How New Drugs Move Through the Development and Approval Process, _____ R gp;_lypy 9� 001_, and Gilhert J P Henske and A Sinnh "RPhuildinn _ —_— _ Big Pharma's Business Model," In Vivo, the Business & Medicine Report, Windhover Information, Vol. 21, No. 10, November 2003. 3 Innovation or Stagnation? Figure 3: Investment Escalation per Successful Compound EXHIBIT t 2.0 Investment required for one successful S1.7B drug launch (discovery through launch) 1.5 Phase III/Pile 51.1 S Critical 1.0 Path + ; EE RPrecllnical Critical Phase I Path Phase I 0.5 Discovery Discovery 0.0 1995 -2000 2000 -2002 SOURCE: Windhover's In Vivo: The Business Medicine Report, Basin drug econorrn ics model, 2003 Figure 4: The Critical Path for Medical Product Development Pro4otype FDA. Filing/ Banc Design or Clinical Development Approval & Research pment Launch Discovery )Preparation Market Approval Application Critical Path Figure 4 shores an idealized "critical path" that encompasses the drug, biological product, and medical device development processes. At the far left, ideas coming out of basic scientific research enter into an evaluation process (prototype design or discovery). In drug development the "discovery' process seeks to select or create a molecule with specific desired biological activities. Medical device development is actually :much more iterative, so that prototypes often build on existing technologies. The critical path begins when candidate products are selected for development. They then undergo a series of successively more rigorous evaluation steps as they move from left to right along the path. A low percentage of candidates entering preclinical development survive to the market application stage. 4 innovation or Stagnation? ti Recent basic science achievements promise significant payoffs in human health, but these potential benefits are threatened by low productivity — measured by the declining number of successful products reaching patients — and the high risks of failure in the cur- rent development processes. Often, developers must use the tools of the last century to evaluate this century's advances. And the situa- tion does not appear to be improving. Recent data suggest that the Often, develop- investment required to launch a new drug has risen 55 percent dur- ers must use ing the last five years (Figure 3). Pharmaceutical research productiv the tools of the ity appears to be declining at the same time that the costs to devel- last century to op a small number of treatments is rising. evaluate this century's If biomedical science is to deliver on its promise, scientific cre- ad vances ativity and effort must also be focused on improving the medical product development process itself, with the explicit goal of robust development pathways that are efficient and predictable and result in products that are safe, effective, and available to patients. We must modernize the critical development path that leads from scientific discovery to the patient (Figure 4). In response to the widening gap between basic biomedical knowl- edge and clinical application, governments and the academic com- munity have undertaken a range of initiatives. After decades of investment in basic biomedical research, the focus is widening to include translational research — multidisciplinary scientific efforts directed at "accelerating therapy development" (i.e., moving basic discoveries into the clinic more efficiently).' Notable are: • National Institutes of Health (NIH) Roadmap, announced in September 2003. This is a series of initiatives intended to "speed the movement of research discoveries from the bench to the bed side" ' • National Cancer Institute's (NCI) Specialized Programs of Research Excellence (SPOREs) 8 Finkelstein R, T Miller, and R Baughman, "The Challenge of Translational Research —A Perspective from the NINDS," nature neuroscience supple- ment, Vol. 5, November 2002. 7 See nihroadmap .nih.gov /overview.asp. $ See htto:/ /spores nci nih oov /applicants /guidelines /ouidelines full.html #1 b 5 Innovation or Stagnation? Figure 5; Research Support for Product Development V Prototype FICA Filings aas� Design or Prectirkal C linical Development Approval & Research Development Launch DiscoveryPreparation Translational Research D> Critical Path Research Figure 5 shop how different types of research support the product development process. Basic research is directed towards fundamental understanding of biology and disease processes. Basic research provides the foundation for product development as well as translational and critical path research. Translational research is concerned with moving basic discoveries from concept into clinical evaluation and is often focused on specific disease entities or therapeutic concepts. Crltical path research is directed toward improving the product development process itself by establishing new evaluation tools. The clinical phase of product development also depends on the clinical research infrastructure. One of the objectives of NIH's ORoadmap Initiative" is strengthening this infrastructure. 6 Innovation or Stagnation? • PharmaSTART, a collaboration of leading research organizations to "accelerate the translation of breakthrough new drugs from discovery into clinical use" 9 "Massive • In Europe, the European Organization for the Treatment of investments in Cancer ( EORTC) is committed to making translational research a one part of the part of all cancer clinical trials 10 network are • The British government announced the National Translational likely to be at Cancer Research Network, to facilitate and enhance translational least partly research in the United Kingdom " wasted unless the other links Although necessary for product development, these translational are strength- research efforts will not be sufficient. As one group has observed, ened as well "Massive investments in one part of the network are likely to be at least partly wasted unless the other links are strengthened as well. " A third type of scientific research is urgently needed, one that is complementary to basic and translational research, but that focuses on providing new tools and concepts for the medical product devel- opment process — the steps that must be taken to get from selection of a laboratory prototype to delivery of an effective treatment to patients. We call this highly targeted and pragmatic research criti- cal path research, because it directly supports the critical path for product development success (Figure 5). Negotiating the Critical Path To get medical advances to patients, product developers must suc- cessfully progress along a multidimensional critical path that leads from discovery or design concept to commercial marketing. 9 PharmaSTART Consortium, Five Leading California Research Institutions Collaborate to Bridge the Gap in Drug Development, SRI International News Release, August 1, 2003. '°Eggermont A and H Newell, "Translational Research in Clinical Trials: The Only Way Forward," European Journal of Cancer, Elsevier Science Ltd., 37 (2001). EORTC also set up in October 2002 the Translational Research Advisory Committee to support and provide expert advice on translational research projects conducted within EORTC. "Rowett, L, "U.K. Initiative to Boost Translational Research," Journal of the ____ Nation LCan_Cer Institi�t 94, No�0,11Aay_15, 2002 - - - -. -_ -- ' Baumann M, SM Bentzen, W Doerr, MC Joiner, M Saunders, et al., "The Translational Research Chain: Is It Delivering the Goods ?, Int. J. Radiation Oncology Biol. Phys., Vol 49, No. 2, 2001, Elsevier Science. 7 innovation or Stagnation? Currently, a striking feature of this path is the difficulty, at any point, of predicting ultimate success with a novel candidate. For example, a new medicinal compound entering Phase 1 testing, often represent- ing the culmination of upwards of a decade of preclinical screening and evaluation, is estimated to have only an 8 percent chance of reaching the market. This reflects a worsening outlook from the his - torical success rate of about 14 percent. In other words, a drug entering Phase 1 trials in 2000 was not more likely to reach the mar - The goal of ket than one entering Phase 1 trials in 1985. Recent biomedical critical path research breakthroughs have not improved the ability to identify research is to successful candidates. .develop new... The main causes of failure in the clinic include safety problems and sc ientific and lack of effectiveness: inability to predict these failures before human technical testing or early in clinical trials dramatically escalates costs. For tools... that example, for a pharmaceutical, a 10 percent improvement in predict make the ing failures before clinical trials could save $100 million in develop - development ment costs per drug. In the case of medical devices, current capac- process itself ity for technological innovation has outstripped the ability to assess more efficient performance in patients, resulting in prolonged delays between and effective design and use. For very innovative and unproven technologies, the probability of an individual product's success is highly uncertain, and risks are perceived as extremely high. Whole fields may stag- nate as a result of the failure of early products. The goal of critical path research is to develop new publicly available scientific and technical tools — including assays, standards, computer modeling techniques, biomarkers, and clinical trial endpoints— that make the development process itself more efficient and effective and more likely to result in safe products that benefit patients. Such tools will make it easier to identify earlier in the process those products that do not hold promise, thus reducing time and resource investments. 13 Gilbert J, P Henske, and A Singh, "Rebuilding Big Pharma's Business Model," In Vivo, the Business & Medicine Report, Windhover Information, Vol. 21, No. 10, November 2003. 14 Lloyd I, "New Technologies, Products in Development, and Attrition Rates: R &D Revolution Still Around the Corner," in PARAXEL'S Pharmaceutical R &D Statistical Sourcebook 200212003. '�6�5`t�rt - Cons . Genetics Will Affect Drug Development Costs and Times," in PAREXEL's Pharmaceutical R &D Statistical Sourcebook 200212003. 8 Innovation or Stagnation? Scientific and Technical Dimensions Along the Critical Path Whether working with devices, drugs, or biologicals — medical product developers must negotiate three crucial scientific /technical dimensions on the critical path from scientific innovation to com- mercial product (Table 1). These three dimensions are interdepend- ent, and in none is success assured. The vast majority of develop - ment costs are attributable to these three dimensions. Developers must manage the interplay between each dimension from the earliest phases of development. For example, the first dimension — ensuring product safety is crucial to consider when designing a drug molecule, choosing production cell lines or reference strains for biological production, or selecting biomaterials for an implanted medical device (Figure 6). The traditional tools used to assess product safety — animal toxicology and outcomes from human studies — have changed little over many decades and have largely not benefited from recent gains in scientific knowledge. The inability to better assess and predict product safety leads to fail- ures during clinical development and, occasionally, after marketing. The second dimension, demonstrating the medical utility of anew product — showing that it will actually benefit people — is the source of innumerable failures late in product development. Better tools are needed to identify successful products and eliminate impending failures more efficiently and earlier in the development process. This will protect subjects, improve return on R&D invest- ment, and bring needed treatments to patients sooner. A number of authors have raised concern that the current drug dis- covery process, based as it is on in vitro screening techniques and animal models of (often) poorly understood clinical relevance, is fun - damentally unable to identify candidates with a high probability of effectiveness. " The current scientific understanding of both phys- iology and pathophysiologic processes is of necessity reductionistic (e.g., is knowledge at the gene, gene expression or pathway level) 16 Duyk !, "Attrition and Translation," Science Vol. 302 October 24, 2003 _ 17 Horrobin DF, "Modern Biomedical Research: An Internally Self - Consistent Universe with Little Contact with Medical Reality ?," Nature Reviews Drug Discovery, Vol. 2, No. 2, February 2003. 9 Innovation or Stagnation? Table 1: Three Dimensions of the Critical Path Dimension Definition Activities (Examples) i Assessing Show that product is € • Preolinicat: product sate enough Safety adequately safe for each I do early human testing i stage of development Eliminate products with safety problems early 4 Clinical: show that product is safe enough for commercial distribution Demonstrating Show that the product • PrediniM. Select appropriate Medical benefits people design (devices) or candidate Utility (drutjsf with high probability of effectiveness • Clinical- Show effectiveness in fie 1 Industrialisation Go from lab cork or ' Design a high- qually product I prototype to a i Physical design manufacturanbfe product Characterization Specifications • Develop mass production capacity Manufacjurfng scale -up Quality control I This table refers to scientific and technical dimensions. Other business dimensions. (e.g., obtaining capital intellectual property considerations, marketing and distribution arrangements) are not within the scope of this table. Figure 6: Working in Three Dimensions on the Critical Path FDA Filing Basic fi Predinical Clinical Development A & Research Discovery Development Launc Material Selection In Vr:ro human Safety safety Stmoure and MOW and Animal Follow Activity Relationship Teaming Testing lap m C .2 Vitro and ab iomputer In Vero and Human Compute o mput , * Anwnai tai Efficacy E Futility models Evaluator �E vsi�atidm l Manufacturing $ Physical Gharactenzatran 5Ca19° Mass Industrial- Small -Scale Design Refined Proda�cGOn bation Produamn Specifications s 6 Figure 6 is a highly generalized description of activities that must be successfully completed at different points and in different dimensions ,along the critical path. Many af these a ctivities are highly complex — whole industries are devoted to supporting them. Not all the described activities are performed for every product, and many activities have been omitted for the sake of simpikity. 10 Innovation or Stagnation? and does not constitute knowledge at the level of the systems biolo- gy of the cell, organ, or whole organism, and certainly does not reach a systems understanding of the pathophysiology of particular dis- eases. Reaching a more systemic and dynamic understanding of human disease will require major additional scientific efforts as well as significant advances in bioinformatics. Nevertheless, progress in product development will continue, and as candidates emerge, the best tools available should be used for their evaluation. This will require strengthening and rebuilding the relevant disciplines (e.g., physiology, pharmacology, clinical pharmacology) and working to identify ways to bridge between the laboratory and the whole organ- ism. In addition, it is likely that more interest will develop in earlier "proof -of- concept" trials that seek to confirm pharmacologic activity in humans before a commitment to full -scale development is made. The FDA is working to facilitate such studies. The final dimension on the critical path can be described as the industrialization process — turning a laboratory concept into a consistent and well- characterized medical product that can be mass produced. The challenges involved in successful industrialization are complex, though highly underrated in the scientific community. Problems in physical design, characterization, manufacturing scale- up and quality control routinely derail or delay development pro- grams and keep needed treatments from patients. These problems are often rate - limiting for new technologies, which are frequently more complex than traditional products and lack standard assess- ment tools. A Better Product Development Toolkit Is Urgently Needed It is clear to FDA scientists, who have a unique vantage point and As part of its knowledge base, that a better product development toolkit is urgent - regulatory role, ly needed. The Agency oversees all U.S. human trials and develop - FDA sets the ment programs for investigational medical products. As part of its SC/ent/fIC and regulatory role, FDA sets the scientific and technical standards used in development and serves as a neutral, nonconflicted assessor of technical stan- dards used in drug develop- 1 'Glassman RH, and AY Sun, 'Biotechnology: Identifying Advances from the ment Hype," Nature Reviews Drug Discovery, Vol. 3, No. 2, February 2004. 11 Innovation or Stagnation? Figure 7. Industry - FDA interactions During Drug Developrm nt Prototype Cl"CW Development FDA Piling, Basic: C} Predirrcal Approval & Des Research Discovery Development Phase 1 Phase 2 Phase 3 Preparation Ak Industry - FDA PrOND Meeting End of Salety Update Interactions Phase During 2a Meeting Development Initial Market IND End of Phase Applicaaion S+�brrdssians 2 PAmeting SutMnission ongoing Pre -BLA or NDA Submission Mee&V IND FWew Phase Application Review Phase This figure depicts the extensive industry -FDA interactions that occur during product development, using the drug development process as a specific example. * Developers often meet with the agency before submitting an investigational new drug application (IND) to discuss early development plans. An IND must be filed and cleared by the FDA before human testing can commence in the United States. During the clinical phase. there are ongoing submissions of new protocols and results of testing. Developers often request additional meetings to get FDA agreement on the methods proposed for evaluation of safety or efficacy, and also on manufacturing issues. * Note: Clinical drug development is conventionally divided into 3 phases. This is not the case for medical device development. This is why preceding figures look slightly different. 12 Innovation or Stagnation? development. During clinical testing, Agency scientists conduct ongoing reviews of product safety, efficacy, and quality data. At the marketing application stage, data submitted by medical product sponsor are evaluated against the established scientific standards. FDA scientists are in frequent communication with industry and aca- demic scientists over development issues (Figure 7). Agency review- ers see the successes and best practices as well as the failures, slow- downs, barriers, and missed opportunities that occur during the course of drug development. In addition, data on product testing, safety evaluation, and clinical trials are stored in the millions of pages of FDA files. Because of their unique perspective, FDA review- ers frequently identify common themes and systematic weaknesses across similar products and can draw important lessons from what they see. Few other groups of physicians and scientists are positioned to see so much of the broad picture. Of course, industry scientists encounter these problems in terms of their own product portfolios, but often lack cross -cutting information about an entire product area, or complete information about techniques that may be used in areas other than theirs. Academic programs focused on the medical product development process are rare and cannot be informed by FDA's broad experience with, often, confidential information. In fact, since the details of most failed programs are not shared publicly, FDA holds the only broad, cross - cutting knowledge about how cer- tain investigational products fail, why certain therapeutic areas remain underdeveloped, and when certain development hurdles per- sist despite advances in technology that could mitigate them. Indeed, these failures may trigger regulatory actions such as putting clinical holds on human trials, or turning down applications. In the course of such an action, FDA identifies problems precisely and offers advice on how to overcome them. Advice given to product developers is based on FDA's experience with the totality of other applications and the latest science; it does not reflect specific propri- etary information from individual applications. Despite these efforts, the ability of product developers and FDA scientists to over - come development challenges is often confounded by the limitations of current tools to address development challenges. 13 Innovation or Stagnation? Figure 9: Problem Identification and Resolution During the FDA Review Process Problem C tn Reviet�+ ldentificaSon Sc Research gational and► (Academia, Government, Applications) Industry, F[lA) Use Wthin � Recornmended Review process t -*scientific Solution Development of Guidance Pubfec Standard Pu Ift Input (Advisory Committees, and Standards Scientit"ic Meetings and Workshops) Figure 8 shows hour FDA's review and oversight of clinical trials and marketing applications lead to a cycle of problem identification and attempted resolution. Recurring problems identified during review trigger efforts to develop scientific solutions. Multiple cycles of research and public input may be required TUNIC standards" include, for example, accepted laboratory test methods, animal efficacy models or safety test protocols, clinical trial designs or endpoints, and clinical monitoring methods. Once publicly accepted, these tools may be used by all developers. FDA often seeks international acceptance of such standard tools, thus reducing unnecessary animal or human testing worldwide. 14 Innovation or Stagnation? When the tools and concepts fall short, FDA works proactively with FDA Works product developers and the scientific community to identify and proactively with resolve critical development problems and stimulate research, product devel- encouraging the development of solutions. The Agency often makes opers and the this information available to the public through guidance documents that synthesize current knowledge on approaches to development munit y t0 de ide - n- problems, or, as appropriate, through workshops, or peer reviewed unit publications (Figure 8). tify and resolve critical devel- Experience has shown that the availability of FDA guidance docu- opment prob- ments often substantially decreases uncertainties associated with lems product development. For example, compared to devices lacking FDA guidance, medical devices developed in areas with extant FDA guidance documents are almost twice as likely to be approved after the initial review process and are approved in a third less time. However, despite ongoing efforts, FDA's current capacity to assist in the evolution of new scientific tools, concepts, and standards is con - strained by available resources, and the Agency can only focus on the most crucial public health issues. There is currently an urgent need for technologies such as genomics, proteomics, bioinformatics systems, and new imaging techniques to be applied to the science of medical product development. Properly applied, these new technologies could provide tools to detect safety problems early, identify patients likely to respond to therapy, and lead to new clinical endpoints. New medical technologies, including bioengineered tissues, cellular and gene therapies, nanotechnology applications, novel biomaterials, and individualized drug therapies, will all need new product development tools and standards, as dis- cussed below, to be able to move from the laboratory to the market quickly and safely. 79 The Agency publishes 50 to 75 draft and final guidances each year, includ- ing guidances resulting from involvement in the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). 20 FD A, Im provin g Innovation in Medical Tech B eyon d 2 002, Ja 2003. 2' For example, in January 2003, FDA announced its Initiative to Improve the Development and Availability of Innovative Medical Products. 15 Innovation or Stagnation? There is also an urgent need for improvement in the efficiency and effectiveness of the clinical trial process, including improved trial design, endpoints, and analyses. The NIH is addressing a number of clinical research infrastructure problems in its Roadmap initiative. However, much more attention and creativity need to be applied to disease- specific trial design and endpoints intended to evaluate the effects of medical products. Tools for Assessing Safety For effective development, safety issues should be detected as early as possible, and ways to distinguish potential from actual safety problems should be available. Unfortunately, in part because of lim- itations of current methods, safety problems are often uncovered only during clinical trials or, occasionally, after marketing. One phar- maceutical company estimates that clinical failures based on liver toxicity alone have cost them more than $2 billion in the last decade dollars that could otherwise be directed toward new product development.' Sometimes, early tests suggest the possibility of safety problems that never materialize, potentially eliminating candi- dates unnecessarily. Many of FDA's targeted efforts have involved defining more reliable methods for early prediction and detection of significant safety problems. The Agency seeks to prevent harm to patients during clinical development as well as potentially devastat- ing setbacks to a new technology's progress and to public confi- dence. Tools for safety assessments include product testing (e.g., for con - Most of the tamination), as well as in vitro and animal toxicology studies, and tools used for human exposure. Most of the tools used for toxicology and human toxicology and safety testing are decades old. Although traditional animal toxicolo- human safety gy has a good track record for ensuring the safety of clinical trial vol- unteers, it is laborious, time - consuming, requires large quantities of testing are product, and may fail to predict the specific safety problem that ulti- decades old mately halts development. Clinical testing, even if extensive, often fails to detect important safety problems, either because they are uncommon or because the tested population was not representative of eventual recipients. Conversely, some models create worrisome 22 Rotman, D, "Can Pfizer Deliver ?" Technology Review, February 2004. 16 Innovation or Stagnation? signals that may, in fact, not be predictive of a human safety prob- lem. Many of FDA's recent targeted efforts have involved defining more reliable methods to predict and detect significant safety problems. For example, in the past, failure to predict unfavorable human metabolism of candidate drugs has led to costly failures in the clinic as well as multiple drug market withdrawals. FDA recommendations on the use of human cell lines to characterize drug metabolic path- ways provide a straightforward in vitro method for prediction of human metabolism, allowing developers to eliminate early on com- pounds with unfavorable metabolic profiles (e.g., drug -drug interac- tion potential). Failures in the clinic due to drug interaction prob- lems are now far less likely. In another effort, FDA developed and standardized methods for doc- umenting clearance of retrovirus -like particles from tissue culture fluids. This effort successfully addressed potential safety concerns that surrounded the early use of monoclonal antibodies and paved the way for the development of many important medical treatments. Through its own laboratory efforts, FDA has continued to refine these methods, share them publicly, and reduce their cost. Additional examples of FDA efforts are listed under Highlights on the following page. Towards a Better Safety Toolkit There are currently significant needs, but also significant opportuni- ties, for developing tools that can more reliably and more efficiently determine the safety of a new medical product. Examples of tools that are urgently needed include better predictors of human immune responses to foreign antigens, methods to further enhance the safety of transplanted human tissues, new techniques for assessing drug liver toxicity, methods to identify gene therapy risks based on assessment of gene insertional and promotional events, and efficient protocols for qualifying biomaterials. 17 Innovation or Stagnation? Highlight: Tools for Assessing Safety 1. The need to ensure the safety of biological products by preventing contamination has resulted in numerous Agency research programs and resulting animal models, test methods, and technical standards. • A reference standard for evaluating gene therapy vector contamination by retroviruses has been developed with FDA input and is being distributed by the American Type Tissue Collection (ATTC). • In the wake of concern over the safety of gene therapies for genetic diseases, FDA developed an animal model for assessing the safety of adenovirus vectors. • FDA developed a several rodent toxicity models to assess the neurovirulence of live virus vaccines, an approach that has both reduced the use of primates for testing and sped the testing process. • With the potential resurgent need for smallpox vaccination, FDA scientists developed a new technique to detect the presence of contaminating virus in smallpox vaccine products. This technique can also be applied to characterization of other vaccine and cellular products. 2. FDA collaborated with industry and scientific groups to develop the data that allowed international adoption of a transgenic mouse model for drug carcinogenicity testing. This assay takes less time, saves two thirds of the cost, and uses half as many animals as a traditional study. 3. FDA has mined its databases to develop structure- activity relation- ship software to help identify molecular substructures with potentially negative toxicologic properties early in the development process. 18 Innovation or Stagnation? Opportunity: Proteomic and toxicogenomic approaches may ulti- mately provide sensitive and predictive safety assessment tech- niques; however, their application to safety assessment is in early stages and needs to be expanded ' Targeted research aimed at spe- cific toxicity problems should be undertaken. Opportunity: As biomedical knowledge increases and bioinformat- ics capability likewise grows, there is hope that greater predictive power may be obtained from in silico (computer modeling) analyses such as predictive toxicology. Some believe that extensive use of in silico technologies could reduce the overall cost of drug develop- ment by as much as 50 percent' • FDA's files constitute the world's largest repository of in vitro and animal results that are linked with actual human outcomes data. Further datamining efforts could form the basis for useful predictive safety models. • Use of extant clinical data may help construct models to screen candidates early in the development process (e.g., for liver toxicity). Opportunity: There is an urgent need to develop tools to accurate- ly assess the risk of new drugs causing heart rhythm abnormalities. For instance, there are ongoing international efforts to develop, test, and validate nonclinical models that may be useful in predicting human risk. In addition, the clinical risks associated with a small degree of QTc interval prolongation need to be fully defined. The above are only a few of the opportunities FDA reviewers have identified. Getting to the Right Safety Standards Because safety issues are a significant cause of delay and failure dur- ing development, some have advocated simply lowering safety stan- dards. This is not a desirable solution. For ethical human testing, 23 Petricoin EM, V Rajapaske, E H Herman, A M Arekani, S Ross, et al., "Toxicoproteomics: Serum Proteomic Pattern Diagnostics for Early Detection of Drug Induced Cardiac Toxicities and Cardioprotection," Toxicologic Pathology, 32(Suppl. 1): 1 -9, 2004. 24 PricewaterhouseCoopers, "Pharma 2005 Silicon Rally: The Race to e -R &D" Paraxel's Pharmaceutical R &D Statistical Sourcebook 2002/2003. 19 Innovation or Stagnation? there is wide agreement that reasonable assurance of safety must be achieved before clinical trials begin. Patients, prescribers, payers, and the public share the expectation that marketed medical prod- ucts will have a well- understood safety profile and a positive bene- fit /risk analysis. Today's problems arise from the inability to confi- dently predict safety performance in a timely and efficient manner. Current tools are not only cumbersome, they are also imprecise and thus leave considerable residual uncertainty. The degree of uncer- tainty inherent in current techniques results in conservative stan- dard setting. We need new tools that can eliminate problem prod- ucts early and can better predict ultimate safety performance. Applied critical path research provides the real opportunity for improving our ability to identify safety issues early and manage the remaining risks appropriately. Tools for Demonstrating Medical Utility Predicting and subsequently demonstrating medical utility (also Beter predic- called benefit or effectiveness) are some of the most difficult chal- tive nonclinical lenges in product development. Currently available animal models, screening used for evaluating potential therapies prior to human clinical trials, methods are have limited predictive value in many disease states. Better predic- tive nonclinical screening methods are urgently needed. In many urgently need- cases, developers must gamble on the results of the large- scale, ed expensive trials necessary to assess effectiveness in people. Such human trials are currently highly empirical, because most sources of variability in human responses are not understood and thus cannot be controlled for. It is clear to many in the field that new scientific advances have the potential to revolutionize clinical development. However, the path from scientific innovation to usable tool is not clear. FDA has identified a number of opportunities for targeted efforts in the area of effectiveness (see next section) and, as time and funding permitted, undertaken targeted action. For example, FDA scientists developed statistical methods to control reader variability in trials of imaging devices and made the analysis software publicly available. Use of this method allows the sample size of imaging device trials to 20 Innovation or Stagnation? be reduced by as much as 60 percent.' Similarly, FDA analysis of hypertension trials using automated blood pressure monitoring allowed for elimination of the placebo group in such trials. Adoption of a new biomarker or surrogate endpoint for effectiveness can drive rapid clinical development. FDA adoption of CD4 cell counts and, subsequently, measures of viral load as surrogate mark- ers for anti -HIV drug approvals allowed the rapid clinical workup and approval of life- saving antiviral drugs, with time from first human use to market as short as 3.5 years. FDA convened the data holders, con - ducted analyses in conjunction with industry and academia, and pro- vided guidance on trial design. Similarly, FDA adoption of the eradi- cation of H. pylori as a surrogate for duodenal ulcer healing greatly simplified the path of those therapies to the market. FDA often approves vaccines based on their meeting validated surrogate mark- ers for achieving protective levels of immunity. This greatly simpli- fies efficacy studies thus reducing time and costs. Highlights of other recent FDA efforts are provided on the following page. Although there are many examples of successful outcomes, similar efforts are needed in many areas of development to help improve the process for getting safe and effective new treatments to patients. Towards a Better Efficacy Toolkit We believe targeted efforts in a variety of areas could substantially improve the efficacy toolkit. These efforts, a few examples of which are listed here, can only be successful with the involvement of indus- try, academia, and the patient and health care communities. I Opportunity. There has been a significant increase in the number of pediatric studies of pharmaceuticals spurred by FDA actions and the subsequent passage of the "Best Pharmaceutical for Children Act." 25 See, for example, Wagner RF, SV Beiden, G Campbell, "An Approach to Multiple- Reader, Multiple -Case Receiver Operating Characteristic Analysis: Controversial — or Subtle ?," Acad Radiol. 2003, Oct; 10(10):1176 -7; Wagner RF, SV Beiden, 'Independent Versus Sequential Reading in ROC Studies of Computer- Assist Modalities: Analysis of Components of Variance," Acad Radiol., 2003 Feb; 10(2):211 -2. 26 Public Law 107 -109, Jan. 4, 2002. 21 Innovation or Stagnation? Highlight: Answering the Challenge of Bioterrorism — Evaluating Efficacy With the increasing challenges of bioterrorism, there is both a need and an opportunity for animal models that are relevant and predictive of countermeasure effectiveness in humans. In some cases, approval can be granted on the basis of animal model findings. FDA and its partners can play a major role in both developing such models and helping define appropriate and efficient pathways for their use in product development. Such efficiency is critical both for proper stew - ardship of what are often limited or ethically sensitive animal resources, as well as for ensuring reliable threat preparedness in a timely manner. • FDA developed an immunocompromised mouse model for studying the efficacy of treatments for smallpox vaccine side effects. • FDA defined appropriate animal studies to evaluate the efficacy of next generation anthrax vaccines. • Working with government and academic scientists, FDA developed protocols for the efficient use of animal models to evaluate antimicrobial efficacy against bioterrorist threat agents. Highlight: Trial Design for Digital Mammography — Overcoming Clinical Trial Hurdles • Although the initial approval of digital mammography did not include this claim, it was believed that digital techniques would prove more accurate than the conventional screen film. A 40,000 - patient study would be needed to evaluate this. No company was able to do a 40,000 - patient study. FDA proposed a trial in which four companies would each do a study of 10,000 patients, using a common protocol. The National Cancer Institute (NCI) was willing to conduct the study. The results from the four arms of the study could be pooled. The pooled trial will be able to test whether digital mammography is superior to conventional screen -film, and each firm will be able to use results from its own product. The trial costs have been shared among the companies and the NCI. The trial is completely enrolled and in the 1 -year follow -up phase. 22 Innovation or Stagnation? Although the results of each individual trial have been informative for the particular drug studied, a significant opportunity now exists for analysis of what has been collectively learned about the pharma cokinetics, pharmacodynamics, safety, and efficacy of drugs in chil- dren. Such an analysis could begin to build a knowledge base to bet - ter inform future pediatric studies. Opportunity: "The appearance of new quantitative measuring tech - "The appear- nologies absolutely galvanizes new drug research." 27 Additional bio- ance of new markers (quantitative measures of biological effect s) and additional quantitative surrogate markers (quantitative measures that can predict effective- measuring ness) are needed to guide product development. In some cases, dat- technologies amining and analysis, with possibly a single additional clinical trial, may be all that is necessary to confirm the surrogacy of a particular absolutely nne s new ew gal- marker. In other cases (e.g., the NIH's Osteoarthritis Initiative, epi- vaize demiologic studies on disease natural history must be undertaken to drug research provide data on markers of disease processes. For biomarkers that currently appear promising, specific projects need to be undertaken to: • Assemble existing data on the association of the marker with clinical outcomes • Assemble existing data on the performance of the marker during intervention trials compared to the performance of current outcome measure • Identify any data gaps or remaining uncertainties • Identify clinical trials under development in which the remaining questions could be addressed in a straightforward manner As previously stated, strengthening and rebuilding the disciplines of physiology, pharmacology, and clinical pharmacology will be neces- sary to provide the capacity to develop and evaluate new biomark ers and bridge across animal and human studies. 27 Nibiack J, "Biomarkers and Surrogate Endpoints," GJ Downing, ed. Exceptional Medical Int. Congress Series, 1205, Elsevier, 2000. 28 See http : / /www.niams.nih.gov /ne /oi /. 23 Innovation or Stagnation? Opportunity. Imaging technologies, such as molecular imaging tools in neurophychiatric diseases or as measures of drug absorp- tion and distribution, may provide powerful insights into the distri- bution, binding, and other biological effects of pharmaceuticals, but their predictive value needs further study and evaluation. New imag- ing techniques will ultimately contribute important biomarkers and surrogate endpoints, but how soon these new tools will be available for use will depend on the effort invested in developing them specif- ically for this purpose. Opportunity: For many therapeutics, effectiveness criteria are best defined by the practitioners and patients who use the products. Much work needs to be done on clinical trial design and patient-driv- en outcome measures to ensure that endpoints in new therapeutic areas accurately reflect patient needs and values. Community (health professional and patient) consensus on appropriate outcome measures and therapeutic claims can lay a clear development path for new therapeutics, especially when there is international regulato- ry harmonization. Opportunity: The concept of model -based drug development, in which pharmaco-statistical models of drug efficacy and safety are developed from preclinical and available clinical data, offers an important approach to improving drug development knowledge management and development decision making.' Model -based drug development involves building mathematical and statistical charac- terizations of the time course of the disease and drug using available clinical data to design and validate the model. The relationship between drug dose, plasma concentration (pharmacokinetics), bio- phase concentration, and drug effect or side - effects (pharmacody- namics) is characterized and relevant patient covariates are includ- ed. Systematic application of this concept to drug development has the potential to significantly improve it. FDA scientists use, and are collaborating with others in the refinement of, quantitative clinical trial modeling using simulation software to improve trial design and to predict outcomes. It is likely that more powerful approaches can be built by completing, and then building on, specific predictive modules. 29 Sheiner LB, "Learning VS Confirming in Clinical Drug Development," CPET, 1997, 61275 -291. 24 Innovation or Stagnation? There are many important additional opportunities in the area of clinical trial design and analysis. More clinically relevant endpoints need to be developed for many diseases. Enrichment designs have the potential for providing much earlier assurance of drug activity. Bayesian approaches to analysis need to be further explored. Opportunity: The emerging techniques of pharmacogenomics and proteomics show great promise for contributing biomarkers to tar - get responders, monitor clinical response, and serve as biomarkers of drug effectiveness. However, much development work and stan- dardization of the biological, statistical, and bioinformatics methods must occur before these techniques can be easily and widely used. Specific, targeted efforts could yield early results. Getting to the Right Efficacy Standards In an era of concerns about health care affordability, we need to make sure that new medical products are effective and provide accu- rate up-to -date information about using them so patients and doc- tors can make smart decisions about health care. As health care costs rise, patients, medical professionals, and health care pur- chasers are all demanding more value from the medical treatments they use. With more treatments in development than ever before, finding better ways to demonstrate their effectiveness for particular kinds of patients is essential for making sure that all Americans get the most value from their health care dollars. Tools for Characterization and Manufacturing The industrialization challenges posed by the demands of physical product design, characterization, scale -up, and manufacturing are often little understood outside of FDA and the pharmaceutical and device manufacturing communities." Many product failures during development are ultimately attributable to problems relating to the transition from laboratory prototype to industrial product. It is crucial that technical standards (e.g., assays, procedures, or reference stan- dards) and improved methods for design, characterization, and prod- uct manufacture are available to improve predictability in this area. 30 See, for example, the Washington Fax interview with John La Montagne, Deputy Director of the National Institute of Allergy and Infections Diseases, National Institutes of Health, June 9, 2003. 25 Innovation or Stagnation? Highlight: Industrialization In the area of medical devices, blood glucose monitors represent a critical technology for many of the 16,000,000 diabetics in the United States. Numerous new devices are being developed for blood glu- cose monitoring. • FDA developed a uniform testing protocol to evaluate glucose meter performance and compared the measurements to the hexokinase (HK) laboratory method incorporating reference materials developed by the National Institute of Standards and Technology. • It was determined that separate accuracy and precision goals should be defined for extreme ranges to keep pace with changing clinical demands for tighter glucose measurement.' Highlight: Industrialization Standards • Together with CDC and industry, FDA was able to help make available difficult -to- obtain standards and samples needed for the successful rapid development and evaluation of West Nile Virus nucleic acid blood donor screening. ' Chen ET, Nichols JH, Duh SH, Hortin G, "Performance Evaluation of Blood Glucose Monitoring Devices," Diabetes Technology & Therapeutics, 5(5):749 -768, 2003 26 Innovation or Stagnation? Development of interim standards is especially important for novel tech- nologies and can help keep development on track as a new field matures. OtheMse, innovators are put in the position of having to invent stan- dards in addition to inventing new products. At the same time, such inter- im standards must allow for flexibility, innovation, and change as new fields develop. This takes expertise and effort and the right collaboration among industry, academia, and FDA. For example, recombinant proteins and monoclonal antibodies have pro- vided significant therapeutic advances over the last 15 years. During this time, FDA has issued multiple technical guidance documents on topics such as characterization of production cell lines, manufacturing and test ing techniques, specifications, stability evaluation, and changes to manu Rapid, S facturing processes. Recent guidances concern the use of transgenic ani- o pme l Beevv el- mals or bioengineered plants as production methods for such products. opment of new medical tech - As new industrialization challenges are identified during the review nologies process, Agency scientists routinely hold scientific workshops, conduct depends on research, collaborate with academic and industrial scientists and synthe- the ... avail- size the emerging data. Recently, when safety problems developed with ability of ade- gene therapy adenovirus vectors, the need for a better potency standard quate methods was recognized. FDA collaborated with industry and governmental part ners to develop the currently available reference standard for characteri- to characterize, zation of adenovirus vectors. To stimulate the needed vaccine develop- standardize, ment efforts, FDA scientists recently developed a breakthrough synthetic control, and technology for conjugate bacterial vaccines that increases yields three mass produce fold and also lowers costs. For additional examples, see Highlights on the them adjacent page. Towards a Better Manufacturing Toolkit Rapid, successful development of new medical technologies depends on the concomitant availability of adequate methods to characterize, stan- dardize, control, and mass produce them. Applied research in these areas is required to provide the infrastructure necessary for translating labora- t o ryprototypes into commercial products. There area number of urgent needs in the industrialization area FDA is actively working on guidance in many of these areas to the extent permitted by available resources. 91 See Agency guidances at http://www.fda.gov/opacom/morechoices/industry/guidedc.htm. 27 Innovation or Stagnation? Opportunity: Additional characterization procedures and stan- dards for expanded stem cell and other cellular products, bioengi- neered tissues, and implanted drug - device combinations (e.g., drug- eluting stents) are urgently needed. For example, developing test standards for coronary stent compressibility will decrease the likeli- hood of failed designs and allow smaller clinical trial programs. Opportunity: The pharmaceutical industry generally has been hes- itant to introduce state -of- the -art science and technology into its manufacturing processes, in part due to concern about regulatory impact. This led to high in- process inventories, low factory utiliza- tion rates, significant product wastage, and compliance problems, driving up costs and decreasing productivity. FDA has led an initia- tive to stimulate the use of process analytical technologies — auto- mated sensors that monitor and control processes — and other modern manufacturing technologies that can improve efficiency and increase flexibility while maintaining high quality standards. i Opportunity: Scientists involved in reviewing medical devices at FDA report an urgent. need for predictive software to model the human effects of design changes for rapidly evolving devices. We believe that such software may be attainable with a concentrated effort, by assembling currently available data and identifying exist- ing data gaps. Getting to the Right Manufacturing Standards Problems with scale -up and mass production can also slow develop- ment and escalate costs. Currently, FDA is involved in an extensive, multi -year effort to incorporate the most up-to -date science into its regulation of pharmaceutical manufacturing and to encourage the industry to adopt innovative manufacturing technologies' The availability of efficient, science -based standards for product characterization and manufacturing creates a win -win for con - sumers, patients, and the industry. 'ZSee "A Risk -Based Approach to Pharmaceutical Current Good Manufacturing Practices (cGMP) for the 21 st Century" at http:/Aovww.fda.gov/cder/gmp/. 28 Innovation or Stagnation? A Path Forward Greater success along the critical path demands investment in a spe- cific type of scientific research that is directed at modernizing the product development process. Such research — highly pragmatic and targeted in its focus on issues such as standards, methods, clin- ical trial designs and biomarkers — is complementary to, and draws extensively from, advances in the underlying basic sciences and new technologies. Without this investment, it is likely that many impor- tant opportunities will be missed and frustration with the slow pace Without this and poor yield of traditional development pathways will continue to investment ... escalate. frustration with the S10W pace Dealing with product development problems is the day-to -day work and poor yield of FDA review scientists. The Agency frequently attempts to resolve problems when they are identified during the review process. of traditional Extensive experience in evaluating and working to solve hundreds of development product development challenges and roadblocks has enabled FDA to pathways will intervene in a targeted manner, reducing or removing specific obsta- Continue to cles in areas critical to public health. However, Agency scientists escalate have identified a host of additional opportunities where more progress can be made. Due to the scope of the existing problems in product development and the expected surge in products resulting from investments in translational research, we believe that critical path research and standards programs should be significantly expanded to help ensure that scientific innovations can be translat- ed efficiently into public health benefits. These additional efforts should be targeted towards removing specific identified obstacles in development. Although there are numerous public and private groups with expertise to help develop solutions, we believe that FDA is ideally positioned to bring together the stakeholders to identify and address the most significant problems. We believe that efforts targeted at significant challenges and roadblocks have and can quickly yield important returns. i 29 Innovation or Stagnation The Orphan Products Grant Program FDA's Orphan Products grant program provides an instructive exam- ple of a successful targeted intervention. This program provides up to three years of very modest funding ($150- 300,000 per annum) for FDA's Orphan clinical development costs of qualified products. Between 1989 and Products grant 2003, 36 novel products (including 23 novel drugs) participating in program pro- this program were approved by the FDA. Thus orphan grant recipi- ents have been an appreciable part of the 20 to 40 new drugs VIdeS an approved yearly during the last 14 years, despite the fact that indus- instructive trial development of drugs for such limited uses is traditionally very example of a hard to stimulate.' Recipients of orphan grants also benefit from Successful tar- advice and direction from FDA scientific reviewers on surmounting geted interven- development obstacles. This program is widely viewed as a major tion success in assisting in development of treatments for rare diseases, at a very modest investment. The Next Steps Although we have seen recent and appropriate recognition of the importance of the basic biomedical research enterprise (as wit- nessed by the successful efforts to double the NIH budget), it is important to recognize that better biomedical ideas alone are not enough to ensure the successful movement of those ideas along the critical path of development, ultimately delivering reliable, safe, and effective treatments to patients at affordable prices. Directing research investment only into new biomedical break- throughs is not enough. We must also achieve breakthroughs in the way we get these treatments to patients and make them practical and efficient to develop and produce. This is an essential step in achieving more timely, affordable, and predictable access to thera- pies based on the latest biomedical insights — that so far are having little impact on patient care. If we do not work together to find fun- damentally faster, more predictable, and less costly ways to turn good biomedical ideas into safe and effective treatments, the hoped- for benefits of the biomedical century may not come to pass, or may not be affordable. 33 For comparison, FDA approved a total of 21 novel drugs in 2003. 30 Innovation or Stagnation? Ensuring that the development pathway keeps pace with biomedi- cine is crucial to advancing the health of Americans. This must be a joint effort involving the academic research community, industry, and scientists at the FDA, and it must be launched soon to have a timely impact. In the months ahead: FDA intends to • FDA intends to lead in the development a national Critical Path lead in the Opportunities List intended to bring concrete focus to the tasks development that lie ahead of a national • We will develop this list by extensive public consultation with all Critical Path the stakeholders. Opportunities • In addition, FDA will make internal changes to intensify its ability List ... to to surface crucial issues and to support relevant ongoing bring concrete research efforts. focus to the tasks that lie Since FDA is involved in setting standards for the development of new medical products, we must take proactive steps to use the ahead best science to guide the development process and ensure that development standards are rigorous, efficient, and achieve maxi - mum public health benefit. We look forward to working with the scientific and product develop - ment communities in improving the health of the public and its access to affordable, innovative treatments. 31 Innovations in The rising cost of medications is one of the greatest concerns Pharmaceutical Development across the nation. An opportunity in Arizona An opportunity in Arizona New Pharmaceuticals � F�A It s the translations 4 u It's not just the ideas::. Glinical:Trias" ;� Toxicology Pharmacokinetics fi ' f47anufairt� ring a � �x Formu9�tipt9 ;fir a ffledicinal � C�iemistry , . Res .. 10 year Trend in Biomedical R&D Spending INN OVATION •• p-t—ty I:R]&D US Pharmaceutic on the Ctitical Path to Bud a • •. New Medical Producu March 2004 R &D Spending Increased, but Product Approvals Have Not... v „ 6 q F O O 1994 1941 1992 t993 199-! 1495 1996 1991 1998 1999 20(10 2001 1002 Sw`es ✓r�f.Ym.irta4 ( .Y t. ^W 37.%i}'Vi, YY.Y' dKtc ,_ _ 10 year Trend in Now Applications to FDA New Drug Applications Now Biological Applications Investment Increased Per Successful Product Largest Delays are in Development Phases drug lauoch (discovery through launch, L@MCI t Figure 4: The Critical Path W Medical Product Dbualcl�t aunch Billi �� Visewoty Discovery :. ^; i. PtBdi" e2i!' Critical Path to Market I DO'S - 2001) 2000-2002 FDA encourages innovation...... Why is the FDA calling for innovation? "Often, developers must use the fools of •Average drug approved by FDA takes the last century to evaluate this century's 12 -15 years and $1.7 Billion to develop advances" he remaining z - � years cT patex�� iii "We must modernize the critical development path that leads from :. scientific discovery fo the patient" Delays in development also cost lives!! • Few bio & pharma companies can afford that much time or that many dollars Is it possible to speed drug " The goal of critical path research is to develop develo ment without takin dan eCOUS new... scientific and technical tools ... that make the p g g development process more efficient and effective" shortcuts? Yes !!!! HIV drugs were developed and approved in --3 years A proven concept........ Translational Research (TGen) Critical Resewch FDA Critical Pathways calls for...... ,,. Safety Aft and Technology T • Innovation in drug development, AND '� Moffett Center, U. Illinois, Chicago • FDA/industry /academia partnerships The NCFST is a unique research consortium composed of scientists from academia, the FDA •Coal: Develop all drugs in <_ 3 years with and food - related industries. The Center provides a neutral ground where industry, academia and ; greater evidence of effectiveness &safety the FDA scientists address food safety issues. Institute for Global Pharmaceutical IGPD's Drug Development Partner Development (IGPD) • Academic home for Innovations in Drug S .. , Development International • Learning Lab for students &interns • Affiliation with FDA: highest possible quality SRI International and standards YOUR BEST PARTNER FOR VALUE CREATION' The 'Cha perone ' - Who we are • • Founded by Stanford University in 1946 United Sta Patent Office t „t - A nonor alit corporation - Independent in 1970: changed name from u,�tt . ' s : Stanford Research Institute to SRI „,,;ate- ° ` ° •�„ µ" International in 1977 s m mo earn, ca' Acquired SarnoffCorporation in 1987 (formerly RCA Laboratories) • Combined power of 2,000 staff members I � •° , - 800 with advanced degrees - More than 15 offices worldwide • Consolidated annual revenues of 5300 million SanoR Corporatlow, SRI - Sta+c 't Coaege, PA w• .. + w Initiate SRI Both The Fi rst Wi red And sp Transmissi Wireless Internet new..ryan all 9b tnv� r ..we vwOw TecMwbaNa uro ero�ucm �—° .,p eot•O�o..y 7Ne �f.PP !+ *cw4w s ^rV wscwrcaa Q&c IPt+ R9a•VYbn nMMM+e cmnmumr.wu la•[% +IP 8ucu, tMky VNrn•seWaal Y» nw0,onYa. • • • 1 DRUG DISCOVERY PIPELINE • P Big s (Multinational) - B Eiris.I- tol -Myers Squibb - Proctor &Gamble - Bedex T•nwa•• - LIG•MD' - Phannacia & Upjohn - Roche - GSK - Abbott - Johnson & Johnson - Merck - ..._._ .- 4 / /o.rM Biotechnology -------------------- - Chiron - Amgen - TAP wrt - lconix - Hollis -Eden - Elan - Allos Therapeutics - AP Pharma - Guilford _ _ ------ - -------------------------- nr�n.o.wN,O - Angiotech - Vascular Therapeutics - Powderject - Large Scale Biology - Dura Pharmaceuticals - Gilead - Intermune - Sugen - Vertex International .++ r. F•- .•�-------- •.'---- •--- - ->--- nc+nseo.wseo - Daiichi Pure Chemical - Mitsubishi Chemical - Taisho 2 marketed drugs; 2 in Phase III, 21n Phase II, 2 IND's within one year. - DSTL - CRUK - Sankyo 4 One of the Largest Institute for Global Pharmaceutical Contractors to NIH Development Mission: To conduct educational and Sole contractor „- MAID for thmpeutics for infectious research programs that enable the FDA and the Sol. contract- to NINM Sole contractor to NIDDK (re-cornpeting) pharmaceutical industry to accelerate the O ne of 2 contractors to MAID for vaccines #1 Provider of development of new medicines. O ne of 5 contractors to NO for can= therapeutics predinical One This Institute will have three founding the NIH rate was 71% partners: the UA, SRI International; and the FDA. 2 003 YTD is :0 Chunt —ds as lug. as ,60 To accomplish its mission, IGPD will affiliate Many are learning' grants, with University faculty dk ith other universities and institutes (TGen). �r IGPD Educational Programs IGPD Educational Programs • Careers in the pharmaceutical industry &FDA Training in GLP, GCP, GMP and cGMP Pharmaceutical Scientists •Symposia and lectures on global issues and MS, PharmD, PhD, MBA, Fellowships topics in pharmaceutical development. • Career Advancement (Certificate programs) A drug development planning program •Global pharmaceutical development (PharmaSTART) • FDA Regulatory Sciences Fellowships in pharmaceutical sciences •Basics of clinical investigation • Internships with SRI and pharmaceutical partners •FDA's basic training for medical \scientific reviewers. Potential IGPD Research Programs Biomarkers and surrogate endpoints (Neuroimaging for Parkinsons, Alzheimers, ALS) b • Predictive Toxicology for early Phase I �� Standardization " •Format for clinical data submission •Format for data storage /retrieval •Format for microarray /genomic data MEMORANDUM �$rzO� Date: September 30, 2004 To: The Honorable Chair and Members From: C.H. Huckelberry Pima County Board of Supervisors County Administ Re: Institute for Global Pharmaceutical Development - County Support assume you all received a hand delivered packet of material with a letter dated September 27, 2004 from Bruce Wright, Associate Vice President for Economic Development from the University of Arizona. The letter contained a formal request for assistance from Pima County for the establishment of a new non- profit that would conduct research and educational programs that will assist the U.S. Food and Drug Administration (FDA) in its role as an expediter and regulator of drug development. Apparently the three entities involved in the development of the Institute for Global Pharmaceutical Development will bethe University of Arizona (UA), SRI International (formerly known as the Stanford Research Institute), and the FDA. This affiliation shall be called the "Institute" for the balance of this memorandum. We understand that the Institute will be a non- profit entity created by three partners who will not profit from the creation of the Institute but will be able, through the actions of the Institute, to more effectively meet their societal missions for education and public service. We understand that the educational and research programs of the Institute will have a positive impact on the health of the citizens of the United States by enabling the more rapid development of medications for the treatment of patients with illness. In the proposal there is what has been called core funding of $2.5 million annually of "in kind" support (valued at $750,000 each) contributed by each of the partners in the form of personnel time contributed by employees of each of the partners who will contribute their activities and expertise to the shared mission of accelerating drug development. There is also an additional funding of $1.5 million in operating expenses annually. Obviously the funding between the partners and the core funding, whether it be in cash or in kind, will need to be disclosed. The $375,000 requested annually from the County for each of the next 5 fiscal years would support predominantly salaries for staff of the Institute. The Institute would not directly participate in the development of new drugs, but rather, would serve as a "think tank" for the processes and regulatory framework involved in drug development. It is hoped that housing the Institute in Pima County would lead to the attraction of related industry. PCPD -02 The Honorable Chair and Members, Pima County Board of Supervisors Institute for Global Pharmaceutical Development - County Support September 30, 2004 Page 2 � asV� am prepared to recommend to the Board that the Co years, su lec o annual appropnation giaai�ca in fiscal year 200_5/06 with the first paym made on o e anuary 1, 2006, subject to a funding agreement entered into with I nor ayment by the Count elieve t at 111: is essenfia that e agreement con gin certa con rtions and /or commitments that demonstrate local public benefit. Payments to the Institute may be delivered through supplemental funding provided to the recently proposed Economic Development Corporation for the purpose of maximizing future potential economic development options. Given the request for public funding, there will be a need for complete transparency and disclosure by the Institute. We will need to receive copies and review any agreements between the founding partners, memorandums of understanding, and letters between the partners that delineate the relationships forming the non - profit Institute. Staff has received copies of the contracts utilized in Maricopa County with public subsidy that was provided to the International Genomic Consortium and I have incorporated some of their structure in my O re ommendations. 1 recommend the following types of conditions be addressed in any agre ent we may consider with the Institute: A. Commitment to Stay y - The institute must agree to stay for a period of 15 ars. It is acknowledged that the investment in the Institute will not provide a direc return to Pima County in the form of tax revenues over the course of the 5 -year funding commitment. If the Institute dissolves or decides to relocate, the Institute must be held publicly accountable. B. Review and Approval of Institute Operating Budget and Business Plan - The County must thoroughly review and have the opportunity to comment on the operating budget and business plan prior to its adoption. The business plan shall include, at a minimum: a staffing plan and organizational chart, pro -forma statements of revenues and expenses and a detailed description of sources of anticipated revenues. C. Confirmation of Viability - The County must be secure in the belief that the aggregate D revenues anticipated to be received by the Institute will be sufficient to cover all operating expenses set forth in the Institute's budget and to implement the business Do plan adopted for that period. Disclosure of Pertinent Documents - The County must receive copies of all organizational documents, including but not limited to, certificate of good standing, determination letter from the Internal Revenue Service of 501 (c)(3) tax exempt status qualification, articles of incorporation and bylaws along with any amendments thereto and corporate resolutions authorizing execution of an agreement with the County. The Honorable Chair and Members, Pima County Board of Supervisors Institute for Global Pharmaceutical Development - County Support September 30, 2004 Page 3 E. Necessary Insurance - Delivery to the County of satisfactory insurance with appropriate indemnification. F. Documentation of Job Creation - Clear and verifiable documentation must be provided prior to each year's disbursement that the number of jobs reflected in the Economic Impact Analysis is actually being provided. The premise of the funding is based on the 160 jobs expected to be created within 5 years. � 0 cz, ,�6W Of- A4 clst CC G. Collaboration with Local Economic Development - Given the public infusion of dollars, it is appropriate that the Institute collaborate with the County and other groups in promoting the growth and development of the bio- industry sector in Pima County. Each year, the Institute should submit a report in acceptable format setting forth in detail its progress in meeting its goals and listing the benefit to the community. H. Local Reinvestment - Whenever possible, the Institute must strive to hire locally. Further, the Institute should partner with local providers in training and education programs. Effort must be given to provide opportunity to disadvantaged populations in employment and training programs. These conditions and commitments are important since they define the general terms of utilizing public funding to assist a private, non- profit enterprise that has potential and significant overall benefits to the community. When using public funds, it is important that community economic benefits accrue to every member of the community. CHH /jj w DRAFT 9/27/04 The Institute for Global Pharmaceutical Development This is a proposal for the creation of an institute in Tucson, Arizona to foster and conduct research and educational programs that will lead to accelerated pharmaceutical development. It will be a free - standing non - profit organization formed to facilitate collaboration between the University of Arizona, SRI International and the Food and Drug Administration (FDA). Background In the last decade U.S. pharmaceutical research and development expenditures have risen 250% and in the past five years the National Institutes of Health (NIH) budget for biomedical research has doubled. Although this has led to many advances in basic biomedical science, the number of new medical products submitted for FDA approval over this period has not increased and the number of applications to the FDA for new biological medications (BLAs) has declined. There is growing recognition that a major factor contributing to the bottleneck in drug development is the time - consuming and inefficient process for preclinical and clinical development. The science of drug development has not evolved to match the advances that are occurring in the basic sciences. As noted below, there has been little effort invested to improve the process of drug development that begins after drug discovery. The Pharmaceutical Research and Manufacturers of America, PhRMA, estimate that the industry must spend $1.7 billion and 12 -15 years of research and development on average to bring a product to market. This leaves only 2 -5 years of patent life and market exclusivity before generic competition determines the price of drugs. With such a limited time to recoup their investment, they are forced to charge increasingly higher prices. The rapidly escalating prices for branded prescription medications are resulting in the consideration of national drug policies and price controls that would seriously threaten the future of the research -based pharmaceutical industry in the United States. Higher development costs also limit accessibility of medications and discourage development of medications for orphan diseases, or diseases that affect primarily low income populations. The "Critical Path" The FDA has recently concluded an analysis of the causes for the delays in drug development. In March of 2004, the Food and Drug Administration released a white paper entitled "Innovation or Stagnation ?" This report included a challenge: "We must modernize the critical development path that leads from scientific discovery to the patient." The FDA calls for research to develop and validate new tools and methods for testing new medicines. The FDA is confident that this research and the resulting new tools can enable more rapid and informative drug development such as occurred for AIDS drugs in the 1980s and 90s. Under pressure from AIDS activists and Congress, the FDA worked closely with the pharmaceutical industry to develop new and innovative methods for the rapid developmen of new drugs for AIDS and HIV. This resulted in development times as short as two -three years for these drugs while, during t e same time peno the average development time for all drugs slowed to 12 years. This experience clearly demonstrates that e it is feasible to accelerate drug development without taking unnecessary and dangerous shortcuts. The pharmaceutical industry also has an acute need for employees with advanced training in drug development. Typical academic programs today do not adequately prepare scientists in applicable fields of expertise such as regulatory toxicology, regulations for Good Laboratory Practices (GLP) and Good Manufacturing Practice (GMP), clinical product GMP, clinical pharmacology and Good Clinical Practice (GCP) trial management. The Institute for Global Pharmaceutical Development We propose the formation of an Institute for Global Pharmaceutical Development (IGPD). The mission of IGPD is to conduct the educational and research programs that will enable the FDA and the pharmaceutical industry to accelerate the development of new pharmaceuticals. This Institute will be a separate non -profit corporate entity affiliated with three founding partners: the University of Arizona (UA), SRI International (formerly Stanford Research Institute); and the Food and Drug Administration (FDA). Each will contribute unique strengths to the Institute. The University of Arizona will serve as home for the Institute's educational and research programs and provide an environment of innovation and inquiry. The participating FDA scientists will provide the first hand knowledge of the regulatory process and a wealth of experience in the evaluation of new pharmaceutical agents. SRI will bring practical experience in modern pharmaceutical development, scientific expertise and a track record of commercializing innovations. Organization: It is proposed that the Institute will have an oversight board with members chosen jointly by the Governor of Arizona, the President of the UA, the President of SRI and the Commissioner of the FDA (or their designates). The Board will most likely include representatives of the City of Tucson, Pima County, the three founding partners and the community. The IGPD will also have a scientific advisory board of experts in drug development representing the University of Arizona, SRI, FDA and leading international institutions. Educational programs: These programs will be designed to provide the most advanced and innovative educational experiences for those seeking careers in the pharmaceutical industry or those already working in the industry and wishing to advance their skills. It is anticipated that programs will be available to study global drug development issues. It will also provide a curriculum for the global pharmaceutical community that includes FDA regulatory education, training and policy study. Real world experiences through internships with SRI and other pharmaceutical partners will be an integral part of the education. The current degree (PhD, PharmD, MS, MBA) and certificate programs of the University will be expanded to meet the educational needs of students and the industry as the programs grow. Research Programs: The University of Arizona will expand its already outstanding faculty to develop innovative methods for accelerated drug discovery and development. This will build upon the research already in place at the UA that includes a research contract from the FDA Office of Women's Health for the testing of drugs during pregnancy. Also, the University of - -- . rizona is�rre� on Therapeutics. This Center already works closely with the FDA conducting educational and 2 i research programs designed to reduce adverse events from drug interactions. SRI is also a major recipient of NIH funds for preclinical development of drugs and vaccines. The results of the research conducted in the Institute and in other institutions will be rapidly incorporated into the curriculum of the Institute. IGPD will not directly development new drugs. However, it will expedite drug development through its programs that bring together experts in drug discovery and development from academia, industry and the FDA. Timelines and Financial Plan: The University of Arizona, SRI and the FDA are prepared to enter into a 3 month planning phase in which a work plan and a financial plan will be created. During this phase, each partner will identify members of their current staff who have the scientific expertise required to execute the work plan and who are willing to participate in the IGPD programs. These scientists would be the initial participants in the IGPD. Once the work plan is completed, operating budgets for the first five years will be constructed. It is now estimated that a minimum of $1.5 million per year in operating capital will be needed to hire the required staff and to support the initial activities of the IGPD. Commitments for donations from the Southern Arizona community are now being sought to underwrite the first five years of startup costs for the IGPD. If sufficient funds can be identified, it is expected that the IGPD would be incorporated in early 2005 as a 5016 (or similar) non -profit organization with the mission of conducting research and education programs to accelerate the process of new drug development. The work plan and a financial plan will be presented to the founding partners and the community members who are committing the startup funds. Once approved, it is expected that the IGPD would become fully operational in early 2005. Once established, the Institute is expected to become self sustaining within the first 5 years and operate on funding from government agencies, unrestricted endowment from pharmaceutical foundations, grants and donors. The leadership of the FDA has indicated to us their intention to request a new appropriation from Congress in FYO6 to specifically support academic partnerships called for in the Critical Pathways document. If the IGPD can be successfully created, it should be very competitive for these funds. IGPD is expected to begin operations in rented offices near the UA or in space loaned by the UA. With continued success, it is expected that the State of Arizona would be asked to construct a new facility for the IGPD and an adjoining research facility for SRI. In return, SRI would be expected to place pharmaceutical contract research programs in the building and using it as a training and testing site for innovations in drug development. 3 Institute for Global Pharmaceutical Development 8/23/04 Overview The Institute for Global Pharmaceutical Development (IGPD) will be an independent, free- standing, non - profit (5010) organization whose mission is to conduct research and offer programs that will enable the pharmaceutical industry to accelerate the development of and access to new medications. The IGPD will be affiliated with three founding partners: the University of Arizona (UA), SRI International (formerly known as the Stanford Research Institute), and the United States Food and Drug Administration (FDA). Each p q ch artner contributes unique strengths to the IGPD. The UA will provide the academic home and infrastructure for the IGPD's educational and research programs and an environment of innovation and inquiry. The participating FDA scientists will provide the first hand knowledge of the regulatory process and a wealth of experience in the evaluation of new pharmaceutical agents. SRI will bring practical experience in pharmaceutical development, scientific expertise, and a track record of commercializing new drugs. Why form the IGPD? The rising cost of medications is one of the greatest crises facing our nation. These costs impact consumers, employers, hospitals, insurance companies, and pharmaceutical companies. Funding of drug development has increased dramatically in the past 10 years. However, the number of new drugs being approved and taken into the marketplace has slowed, due in large part to the time and cost of development. A recent estimate by the Pharmaceutical Research and Manufacturers Association is that new drugs take on average 12 -15 years and $1.7 billion to develop. This leaves only 2 -5 years of patent protection for companies to recover their large initial investment, and accounts for the high cost of providing drugs to the consumer. In response to this crisis, the FDA is calling for ways to use technology and new approaches to streamline the approval process and expedite approvals. IGPD would play a critical role in helping the FDA to develop a new drug approval process. What are the benefits to forming the IGPD in Tucson? The potential economic development impact resulting from the establishment of the IGPD in Tucson is substantial. The IGPD represents a rare opportunity for Tucson to become a major international center of drug discovery and development. As the home of IGPD, Tucson will be recognized in the highly competitive biotechnology industry, and have a competitive advantage in establishing bio -tech start-ups and attracting major drug companies. IGPD would serve as a magnet for world -class scientists and researchers, investors and venture capitalist companies, contract research organizations and drug production operations. IGPD would serve as the platform for launching Tucson's biotechnology industry. What is needed to successfully establish IGPD in Tucson? The founding partners have agreed to develop a Memorandum of Understanding (MOU) by October 1 that will define the nature and extent of their shared commitment to the IGPD. Over the next four months, each partner will identify faculty and staff who will work together on the mission of IGPD. $20 million in commitments need to be secured by October 1 to successfully establish the IGPD. These funds will be used to operate the Institute for a period of five years (2004- 2009). It is expected that the Federal Government will provide substantial funding for the Institute beginning in FY 2007. Core funding in the amount of $12,500,000, or $2,500,000 a inua y, wi I be secure rom a variety of sources including the founding partners, grants and contracts, and tuition and fees. ti This funding will include cash contributions and in -kind contributions for the use of facilities and equipment, loaned staff, and assistance from faculty and scientists. In addition, the Institute needs to secure additional annual funding of $7,500,000, or $1.5 million annually, from corporate, foundation, local government and individual donors. IGPD will seek funding from the State of Arizona to construct a high tech office and laboratory facility that will anchor a new UA biotechnology research park. The Institute will seek city and county government assistance in securing the land and improvements for the facility. Six potential sites are currently being evaluated. The UA Office of Economic Development is requesting a grant from the Arizona Commerce and Economic Development Commission (CEDC) in the amount of $400,000 to help defray the initial start-up costs of the Institute, including preparation of a business plan. The FDA may provide another source of funding for the IGPD. The FDA is expected to seek funding for centers like the IGPD in October 2006 for the fiscal year 2007. In addition, the IGPD will seek funding from government agencies, foundations and donors to support its educational and research programs. Specific research and educational projects will be funded by competitive awards or sub - contracts made by the IGPD to University faculty and programs. The FDA will contribute teaching faculty and research staff who will work on -site at the IGPD or in the FDA's facilities. If the necessary operational funds are committed in 2004, what are the next steps to launching and operating a successful IGPD? Year One - 2005 The IGPD will occupy interim offices in Tucson beginning in January 2005. The IGPD Board of Directors and Scientific Advisory Board will be appointed. Strategic and financial plans will be developed, and the IGPD's Research Director, Education Director and additional staff will be hired. Educational and research programs will begin. Year Two - 2006 A facilities plan will be designed and sent to bid, and a builder /general contractor retained. Year Three - 2007 The facilities will be constructed and occupied by end of year. Year Four - 2008 Expansion of educational and research programs. Year Five - 2009 Expansion of educational and research programs. How will the IGPD be organized? The IGPD will have an oversight board with members chosen jointly by Governor of Arizona, the President of the UA, the President of SRI, and Commissioner of the FDA. The board will include representatives of the private sector. There will also be a scientific advisory board of experts in drug development representing the UA, SRI, FDA and leading international institutions. For More Information, Contact: Dr. Raymond Wooslev, University of Arizona, Vice President for Health Sciences, 520- 235 -9000 Bruce Wright University of Arizona, Associate Vice President for Economic Development, Technology Park, (520) 626 -4843 Dr. Curt Carlson, SRI International, Inc., President, (650) 859 -2000 Dr. Janet Woodcock, U Food and Drug Ad ministration, Acting Associate Commissioner, (301) 827 -7861 — -- Francie Merryman Chairman, Greater Tucson Economic Council, and VP, Northern Trust Bank, (520) 975 -6888 2 TOWN COUNCIL MEETING INFORMATION TOWN OF MARANA MEETING DATE: October 4, 2004 AGENDA ITEM: Study Session 2. TO: FROM: SUBJECT: MAYOR AND COUNCIL Jocelyn C. Bronson, Town Clerk Presentation: Council Handbook DISCUSSION A partial draft of a proposed Council Handbook is included for your review in conjunction with tonight's presentation. N/A N/A RECOMMENDATION SUGGESTED MOTION Town ClerkfJCB 09/29/2004/10.'26 AM DRAFT MARANA MUNICIPAI~ GOVERNMENT COUNCIL HANDBOOK Prepared by the Office of the Town Clerk September 2004 TABLE OF CONTENTS MARANA MUNICIPAL GOVERNMENT ....................................................................................... 1 ORGANIZATION ................................................................................................................................. 1 TOWN COUNCIL ................................................................................................................................. 1 Boards And Commissions ................................................................................................................ 3 Requirements .................................................................................................................................... 3 Qualifications ................................................................................................................................... 4 Residency ......................................................................................................................................... 4 Officers ............................................................................................................................................. 5 Council Representatives ................................................................................................................... 5 Other Representatives ....................................................................................................................... 6 Staff Liaison ..................................................................................................................................... 6 TOWN MANAGER ............................................................................................................................... 6 TOWN ATTORNEY ............................................................................................................................. 7 PRESIDING MAGISTRATE ................................................................................................................ 7 TOWN CLERK ...................................................................................................................................... 8 TOWN TREASURER ............................................................................................................................ 8 TOWN DEPARTMENTS ...................................................................................................................... 8 GENERAL INFORMATION ............................................................................................................. 9 AGENDAS ............................................................................................................................................ 9 Addendums ..................................................................................................................................... 10 Executive Sessions ......................................................................................................................... 10 Work Sessions ................................................................................................................................ 10 ALLIANCE FOR THE SECOND CENTURY .................................................................................... 11 APPROVAL AUTHORITY ................................................................................................................ 11 Document Signing .......................................................................................................................... 12 Check Signing ................................................................................................................................ 12 BUILDING MAINTENANCE ............................................................................................................ 13 CASH DONATIONS AND GIFTS ...................................................................................................... 13 TOWN CODE ...................................................................................................................................... 13 TOWN HALL - HOURS ...................................................................................................................... 13 Holidays ......................................................................................................................................... 14 TOWN OF MARANA ......................................................................................................................... 14 COMPUTERS ...................................................................................................................................... 14 General Computer Use ................................................................................................................... 15 Computer Viruses ........................................................................................................................... 15 E-Mail ............................................................................................................................................. 15 Illegal Software .............................................................................................................................. 16 Internet Usage ................................................................................................................................ 16 Websites ......................................................................................................................................... 16 CONFLICT OF INTEREST LAW (A.R.S. §38-503) .......................................................................... 16 Remote Interest ............................................................................................................................... 17 Substantial Interest ......................................................................................................................... 19 COPY POLICY .................................................................................................................................... 21 EMPLOYEE ADVISORY COMMITTEE ........................................................................................... 22 FACILITY USE PERMITS ................................................................................................................. 22 Contents Meeting Rooms .............................................................................................................................. 22 Parks and Recreation ...................................................................................................................... 22 Street Closures ................................................................................................................................ 22 GTEC ................................................................................................................................................... 23 INTERGOVERNMENTAL RELATIONS .......................................................................................... 23 Town/County Breakfast ................................................................................................................. 23 Lobbying ........................................................................................................................................ 24 KEYS ................................................................................................................................................... 24 LEAVE OF ABSENCE ........................................................................................................................ 25 Town Manager ............................................................................................................................... 25 Mayor ............................................................................................................................................. 25 LETTERS OF SUPPORT AND ENDORSEMENT SIGNED BY THE MAYOR ............................... 25 MAIL ................................................................................................................................................... 26 MAYOR'S AWARDS .......................................................................................................................... 26 MEETINGS ......................................................................................................................................... 26 Regular Council Meetings .............................................................................................................. 26 Special Council Meetings ............................................................................................................... 26 Executive Sessions ......................................................................................................................... 27 Work Sessions ................................................................................................................................ 27 OPEN MEETING LAW (A.R.S. §38-431 - 431.09) ............................................................................ 27 ORDINANCES AND RESOLUTIONS .............................................................................................. 31 Ordinances ...................................................................................................................................... 31 Resolutions ..................................................................................................................................... 32 PERFORMANCE EVALUATIONS ................................................................................................... 33 PROCLAMATIONS ............................................................................................................................ 33 PUBLICATIONS ................................................................................................................................. 34 Town to Citizen .............................................................................................................................. 34 TownScape ..................................................................................................................................... 34 PURCHASE ORDERS/REQUISITIONS ............................................................................................ 35 Petty Cash ....................................................................................................................................... 35 Vouchers ......................................................................................................................................... 35 Warehouse Orders .......................................................................................................................... 36 REQUESTS FOR INFORMATION .................................................................................................... 36 Council ........................................................................................................................................... 36 Media .............................................................................................................................................. 36 RULES OF ORDER ............................................................................................................................. 37 Guidelines For Conducting A Successful Meeting ........................................................................ 37 SALARIES AND BENEFITS .............................................................................................................. 39 Deferred Compensation .................................................................................................................. 39 Elected Officials' Retirement Plan (EORP) .................................................................................... 40 Insurance ........................................................................................................................................ 40 STATE AND LOCAL OFFICIALS ..................................................................................................... 40 Coconino County ............................................................................................................................ 40 TELEPHONES .................................................................................................................................... 41 Council Opinion Hotline ................................................................................................................ 41 Emergency Contact List ................................................................................................................. 41 Long Distance Calls ....................................................................................................................... 42 Telephone Lists .............................................................................................................................. 42 Voicemail ....................................................................................................................................... 42 TRAINING .......................................................................................................................................... 42 Aug-2004 Contents TRAVEL ....................................... 42 Vehicle Use Policy ......................................................................................................................... 43 WEEKLY REPORT ............................................................................................................................. 43 WORKPLACE ENVIRONMENT ....................................................................................................... 43 Harassment in the Workplace ......................................................................................................... 43 Sexual Harassment ......................................................................................................................... 44 Threat Management Plan ................................................................................................................ 44 LIST OF ATTACHMENTS .............................................................................................................. 45 ATTACHMENT 1, ORGANIZATION CHARTS ATTACHMENT 2, TOWN CHARTER ATTACHMENT 3, MAYOR AND COUNCILMEMBER LIST ATTACHMENT 4, RULES OF PROCEDURE FOR THE MARANA TOWN COUNCIL ATTACHMENT 5, BOARDS AND COMMISSIONS APPLICATION ATTACHMENT 6, BOARDS AND COMMISSIONS LIST ATTACHMENT 7, BOARDS AND COMMISSIONS HANDBOOK ATTACHMENT 8, DEPARTMENT AND DIVISION HEAD LIST ATTACHMENT 9, STAFF SUMMARY REPORT FORM ATTACHMENT 10, WORK SESSION SCHEDULE ATTACHMENT 11, ALLIANCE FOR THE SECOND CENTURY MEMBERSHIP ROSTER ATTACHMENT 12, MAYOR'S DECLARATION OF A STATE OF EMERGENCY ATTACHMENT 13, INTERIM CASH DONATION AND GIFT POLICY ATTACHMENT 14, GENERAL COMPUTER USE POLICY ATTACHMENT 15, COMPUTER VIRUS POLICY ATTACHMENT 16, ILLEGAL SOFTWARE POLICY ATTACHMENT 17, INTERNET USE POLICY ATTACHMENT 18, ORDINANCE NO. 1738 (EMPLOYEE ADVISORY COMMITTEE) ATTACHMENT 19, MEETING ROOMS POLICY ATTACHMENT 20, FACILITY USE PERMIT POLICY ATTACHMENT 21, SPECIAL EVENT PERMIT PROCESS ATTACHMENT 22, GFEC MASTER OPERATING AGREEMENT ATTACHMENT 23, GFEC BY-LAWS ATTACHMENT 24, LOBBYING POLICY ATTACHMENT 25, RESOLUTION NO. 1890: PERSONNEL EVALUATION PROCESS FOR TOWN COURT JUDGES ATTACHMENT 26, COUNCIL CONTACT POLICY ATTACHMENT 27, FEDERAL, STATE, AND LOCAL OFFICIALS LISTING ATTACHMENT 28, EMERGENCY CONTACT LIST ATTACHMENT 29, TOWN TELEPHONE DIRECTORY ATTACHMENT 30, TRAVEL POLICY ATTACHMENT 31, TRAVEL REQUEST FORM ATTACHMENT 32, TRAVEL REIMBURSEMENT FORM ATTACHMENT 33, VEHICLE USE POLICY ATTACHMENT 34, HARASSMENT IN THE WORKPLACE POLICY ATTACHMENT 35, SEXUAL HARASSMENT POLICY ATTACHMENT 36, THREAT MANAGEMENT PLAN Aug-2004 LIST OF ATTACHMENTS Attachment 1 Attachment 2 Attachment 3 Attachment 4 Attachment 5 Attachment 6 Attachment 7 Attachment 8 Attachment 9 Attachment 10 Attachment 11 Attachment 12 Attachment 13 Attachment 14 Attachment 15 Attachment 16 Attachment 17 Attachment 18 Attachment 19 Attachment 20 Attachment 21 Attachment 22 Attachment 23 Attachment 24 Attachment 25 Attachment 26 Attachment 27 Attachment 28 Attachment 29 Attachment 30 Attachment 31 Attachment 32 Attachment 33 Attachment 34 Attachment 35 Attachment 36 Organization Charts Town Charter Mayor and Council Member List Rules of Procedure for the Marana Town Council Boards and Commissions Application Boards and Commissions List Boards and Commissions Handbook Department and Division Head List Staff Summary Report Form Work Session Schedule Alliance for the Second Century Membership Roster Mayor's Declaration of a State of Emergency Interim Cash Donation and Gift Policy General Computer Use Policy Computer Virus Policy Illegal Software Policy Internet Use Policy Ordinance No. 1738 (Employee Advisory Committee) Meeting Rooms Policy Facility Use Permit Policy Special Event Permit Process GFEC Master Operating Agreement GFEC By-Laws Lobbying Policy Resolution No. 1890 - Personnel Evaluation Process for Town Court Judges Council Contact Policy Federal, State, and Local Officials Listing Emergency Contact List Town Telephone Directory Travel Policy Travel Request Form Travel Reimbursement Form Vehicle Use Policy Harassment in the Workplace Policy Sexual Harassment Policy Threat Management Plan Aug-2004 45 Marana Mzmicipal ~ MARANA MUNICIPAL GOVERNMENT ORGANIZATION The Town of Manna follows a Council-Manager form of government. (Attachment 1 is a copy of the Town's current organization chart.) Legislative policyis set by an elected Council and administered bythe Town Manager. The Marana Town Code is the basic governing authority of the Town and outlines the duties and responsibilities of each area of town government. TOWN COUNCIL The voters of Marana elect the Council to provide leadership and formulate the laws and general policies of the Town. Federal and State law and the Town Code guide the Council. Sep-2004 1 Marana Munidpal Gozerrvr~ The Town Council consists of a Mayor and six Council Members who are elected at large to serve as the legislative body of the Town. The Mayor is elected every two years. The Mayor acts as chairperson of the Council and presides over Council meetings. Council Members hold staggered, four-year terms, with three seats decided everytwo years. Shortly after every Town General Election, the Council chooses a Vice-Mayor to serve in the absence of the Mayor. As elected representatives of the citizens of Marana, the Council bears sole responsibility and exercises sole authority in establishing the policies governing the operation of the Town. The Town Council enacts local legislation, adopts budgets, and establishes public policy. The Council sets goals and objectives based on strategic planning; recommendations from the Town Manager, Town Attorney, and boards and commissions; public input; and through the budgeting process. Members of the Town Council are also called on to serve as Council representatives to most of the Town's 23 boards, commissions, and committees, and may represent the Council by serving on private, county, state, or intergovernmental associations as well. The Council appoints the Town Manager, the Town Attomey, the Town Magistrate, and members of the Town's boards and commissions. Sep-2004 2 Marana Muni~pal ~ Boards and Commissions The Town Council uses many different ways to establish community participation programs to allow for citizen involvement. The Town Code authorizes the creation of Town boards and commissions to assist the Council in developing appropriate hws and policies. Appointments to Town boards and commissions are made bythe Town Council. Applications (Attachment 5) are reviewed and discussed in Executive Session and appointments are made at the Council Meeting. Attachment 6 is a list of the Town's Boards and Commissions. Attachment 7 is a copy of the cover of the Boards and Commissions Handbook, which is provided to the Council under separate cover. Generally, the members of the Town's boards and commissions, and most committee members, are appointed bythe Town Council to three-year terms, unless a different term length is set by State law. Sometimes, however, an appointment is made for the balance of a member's term due to that member's resignation or disqualification from office. A board or commission member may be considered for reappointment to a second term by notifying the staff liaison or Town Clerk prior to the expiration of his/her ter~ Board and commission members seeking a second term are considered along with all other applicants for the vacant seat on the board or commission. The Town Clerk maintains the current membership roster for a]] of the Town's official boards and commissions and monitors the placement of appointments on the Town Council agenda. Sep-2004 3 Marana Mur~cipal C,-ou,,razre~ Although specific duties of each of the Town's advisory boards vary according to their purpose, there are certain responsibilities common to all of therm Board and commission members make recommendations on issues presented to them through staff reports, public input, and group discussion. When appropriate, these recommendations are presented to the Town Council. The Town Council reviews and considers the board and commission recommendations before making decisions. The final decision rests with the Town Council. Some boards and commissions have final authority for certain decisions specified by state or local laws. Board and commission members may not direct administrative staff to initiate programs, conduct major studies, establish official policy, or make expenditures without prior, formal approval of the Town Council and/or the Town Manager. Requirements By Council policy, an individual may serve on only one board or commission at any given time. A board or commission member may be removed from office for excessive absenteeism or by a vote of the Town Council for cause, including inefficiency, neglecting duty, or malfeasance in office. Qualifications Occasionally a board or commission's organizational structure will require a member to have a specific qualification or background. Sep-2004 4 Marana Municipal Gozorvrent Residency ~fhe Town Code requires all board and commission members to be residents of the Town of Marana at the time of their appointment and for the full duration of their term in office. A board or commission member who moves out of town during a term of office is no longer eligible to serve on the board or commission. Officers Most boards or commissions elect a Chairperson and Vice-Chair, usually on an annual basis. The Chairperson is responsible for conducting meetings and coordinating the preparation of meeting agendas. The Vice-Chair serves in the absence of the Chairperson. Council Representatives Most of the Town's boards and commissions have a Council Member, appointed by the Town Council, who serves as either a voting or non-voting member depending on the structure of the board or commission. These appointments are made during the annual Council organization meeting. Sep-2004 5 Marana Municipal Gozorvrem Staff Liaison The Town Manager assigns a Town staff member to work with each board or commission as an information resource and to provide technical assistance. Board and commission members may not assign projects or direct the work of staff. A board or commission may request staff's assistance on various projects; however, the Town Manager must approve all such requests in advance, typically delegated to department heads. TOWN MANAGER The Town Manager serves as the Town's administrative head and is directly responsible to the Town Council. The Town Manager oversees the day-to-day operation of the Town, including the hiring and management of all Town staff. The Town Manager ensures that all ordinances are enforced and that the provisions of franchises, leases, contracts, permits, and privileges granted by the Town are observed. The Town Manager implements Council policies and directives, including those involving Town boards and commissions, and makes recommendations to the Council on measures necessary for the efficient and effective operation of municipal services. Sep-2004 6 Marana Municipal Gozerrvrent The Town Manager signs travel vouchers and personnel action forms regarding hiring, termination, and pay raises for employees who are direcdy responsible to the Manager. The Town Manager keeps the Council advised of the affairs and needs of the Town, directs the preparation of the Town's annual budget, and submits the budget to the Council for approval. The Town Manager takes part in all Council discussions, except those direcdyinvolving the conduct or performance of the Town Manager. TOWN ATTORNEY The Town Attorney's Office serves as the legal branch of the Town, defending the Town's legal interests and fights and prosecuting criminal complaints. The Town Attorney drafts and/or reviews the Town's legal documents, including contracts, ordinances, and resolutions. PRE SIDING MAGISTRATE Appointed bythe Town Council, the Presiding Magistrate administers the Municipal Court system and determines cases arising within the jurisdiction of the Court. Activities of the Court include processing and recording criminal misdemeanors, traffic violations, and convictions; collecting fines; scheduling trials; preparing dockets; and juryprocessing. The Court provides all administrative and clerical support for case processing from filing to final disposition. The Court serges subpoenas and collects and disposes of outstanding warrants for traffic tickets and other charges. The Council approves the Town Court Magistrate. The Court Administrator and staff report to the Town Manager. Sep-2004 ? Marana Munictp' al Cwrorvre~ TOWN CLERK The Town Clerk is appointed by the Town Manager with the approval of the Council. The Clerk conducts Town elections, provides notice of all meetings of the Council in accordance with State law, prepares agendas and maintains and makes available to the public the official records of the Town. The Town Clerk also maintains current membership rosters for all of the Town's 22 official boards and commissions and monitors the placement of commission appointments on the Town Council agenda. TOWN FINANCE DIRECTOR The Town Finance Director is appointed by the Town Manager. The Finance Director has custody of the monies of the Town, and is charged with keeping and saving said money. The Finance Director dispenses monies as provided by ordinance and is bound bythe Constitution, State law, Town Code, and ordinances. Legal garnishments are served on the Finance Director. TOWN DEPARTMENTS The primary Town departments are: Accounting & Finance, Airport, Building Services, Community & Economic Development, Community Programs, Development Services, Geographic Information Systems, Human Resources, Information Technology, Municipal Court, Operations & Maintenance, Parks & Recreation, Planning, Police, Public Works, Legal, Clerk, Administration, and Water. Within these departments are approximately280 full-time and part-time employees. In addition, as many as XXX full-time and pm-time temporary employees are used throughout the year. Atzachment 1 contains the Town's organization charts. Attachment 8 is a list of the Department and Division heads. Sep-2004 8