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U.S. Department of Health and Human Services

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Critical Path 2010 Update

Q's and A's
 

What is the Critical Path Initiative?

The Critical Path Initiative (CPI) is FDA's national strategy for transforming the way FDA-regulated products--human drugs, biological products, medical devices, and veterinary drugs--are developed, evaluated, and manufactured.  CPI's 2006 report outlined specific key areas of Critical Path focus identified by FDA experts and the public, including:

  • Developing better evaluation tools like biomarkers and new assays
  • Streamlining clinical trials by modernizing the clinical trial sciences to make trials safe and efficient
  • Harnessing bioinformatics (e.g.,  moving from a paper-based to electronic environment for exchanging information and overseeing the safety of FDA-regulated products)
  • Moving manufacturing into the 21st Century, using tools such as process analytic technology and nanotechnology
  • Developing products to address urgent public health needs, including, improved antimicrobial testing, new animal models to test bioterrorism countermeasures and vaccine testing
  • Focusing on at-risk populations, such as pediatrics  

The Initiative was launched in 2004.  For descriptions of the many projects under way in 2006, 2007, and 2008, see FDA's Critical Path Home page at www.fda.gov/CriticalPath

Has CPI expanded its scope to include more than human medical products?

FDA launched the Critical Path Initiative (CPI) in 2004 to tackle the steep decline in the number of innovative medical products being submitted for approval—and getting to patients—despite the enormous breakthroughs being made in biomedical science.  FDA established the Office of Critical Path Programs (OCPP) in the Office of the Commissioner to support the initiative. 

Because globalization, rapidly evolving technologies, and emerging areas of science are having an increasing impact on all FDA-regulated products, CPI has gradually expanded its scope, leveraging the knowledge gained from new scientific fields to enhance the tools used in human and animal medicine and food safety (e.g., new rapid tests to determine biological and chemical contamination of foods). 

CPI is also providing support to multiple projects related to streamlining information management systems for all Agency-related product information (e.g., encouraging electronic submissions, reporting of negative side effects, tracking human and animal food contaminations).  For detailed information on CPI, see our Web site.  

What has the Critical Path Initiative achieved?

Some CPI successes to date are listed below.

In the area of biomarker development and development of other tools:

  • As a result of collaborative research on the anti-coagulant drug warfarin, additional dosing information has now been added to warfarin labels.
  • The Predictive Safety Testing Consortium, a public–private partnership, led by the non-profit Critical Path Institute (C-Path), is facilitating the sharing of information by industry to develop new tools that can be qualified for use in drug development.  This effort is taking place under the advisement of FDA and the European Medicines Evaluation Agency (EMEA).  In May 2008, FDA and EMEA announced that they had reviewed and accepted seven new biomarkers—laboratory tests on urine that signal kidney injury.  These new tests can now be used in laboratory research to predict the safety of experimental drugs, enabling drugs to reach market faster and with greater confidence in their safety. 
  • The Predictive Safety Testing Consortium, a public–private partnership, led by the non-profit Critical Path Institute (C-Path), is facilitating the sharing of information by industry to develop new tools that can be qualified for use in drug development.  This effort is taking place under the advisement of FDA and the European Medicines Evaluation Agency (EMEA).  In May 2008, FDA and EMEA announced that they had reviewed and accepted seven new biomarkers—laboratory tests on urine that signal kidney injury.  These new tests can now be used in laboratory research to predict the safety of experimental drugs, enabling drugs to reach market faster and with greater confidence in their safety. 

In the area of clinical trials work: 

  • Together with Duke University, FDA launched a broad collaboration—the Clinical Trials Transformation Initiative, (CTTI to "modernize the U.S. clinical trials enterprise."  At last count, 48 representatives from academia, professional societies, patient and consumer groups, industry, and Federal agencies are exploring new methods and tools to make the current system more efficient.  
  • In November 2009, CTTI–FDA sponsored the first of its annual three-day training courses for clinical trial investigators, drawing 125 participants from around the world. 

In the area of bioinformatics and safety:

  • FDA launched the Sentinel Initiative in 2008. In late fiscal year 2009, FDA competed and awarded a contract to Harvard Pilgrim Health (Mini-Sentinel pilot) to develop a miniature Sentinel System that could pilot a coordinating center and scientific operations and methodologies that will be needed for the ultimate Sentinel.
  • Cooperative projects with CMS and ASPE (Assistant Secretary for Planning and Evaluation) have been expanded to include other Federal partners (VA, DoD) (Federal Partners pilot) to develop active surveillance methodologies and conduct inquiries about negative side effects of drugs and other medical products, an effort that will contribute to the broader Sentinel Initiative.
  • SafeRx, a collaboration among CMS, FDA, and ASPE is up and running, enhancing FDA’s existing safety surveillance capacity and providing close to real-time vaccine safety monitoring of seasonal and H1N1 influenza vaccines.
  • In 2009, FDA spearheaded an unprecedented collaboration, the DAPT Collaboration, whose goal was to design and conduct a postmarket trial by regulated industry  fourdevice firms and four drug firms  and the clinical community to determine the ideal duration of dual antiplatelet therapy administration following stent implantation. This information will make the use of drug eluting stents safer for patients.  DAPT (dual antiplatelet therapy) is a combination of aspirin and a thienopyridine/antiplatelet medication to reduce thrombosis risk in patients treated with coronary stents.  This multicenter safety trial began enrolling the first of some 20,000 patients at 220 centers in North America and Europe in late September 2009.  
  • Human prescription drug labels are being made available electronically on the Internet free of charge at DailyMed, where more than 6,000 prescription drug labels can be viewed and printed; ultimately labels for all products will be available.

What is the goal of the FDA-NIH Collaboration announced in February 2010?

This new collaboration between FDA and the National Institutes of Health (NIH)―announced by HHS Secretary Sibelius on February 24, 2010―will help focus additional funding on developing and applying the new tools, standards, and approaches we need to properly assess the safety, effectiveness, and quality of products currently in development.  The collaboration will leverage NIH’s breadth of experience as a leader in biomedical sciences to help make the regulatory review process at FDA as seamless as possible.  Initially, $6.5 million is being made available to award eligible applicants with relevant project proposals in a variety of areas related to regulatory science. (The application deadline is April 27, 2010.) This collaboration is inviting the best minds and research institutions to help develop and apply the new, 21st-century tools, standards, and approaches we need to properly assess the safety, effectiveness, and quality of medical products currently in development.

What is the Advancing Regulatory Science Initiative?

The Advancing Regulatory Science Initiative is a broad, FDA scientific initiative, with many cross-agency components, that is building on existing efforts like the Critical Path Initiative and Food Safety.  FDA is requesting an additional $25 million (including more than $4 million to support CPI) for fiscal year 2011 to fund the Advancing Regulatory Science Initiative.  FDA believes that, with a focused agenda and a greater and more targeted investment of human and financial resources, it can expand its work with partners to transform the culture and science of product research, development, and evaluation.  FDA aims to focus initial efforts in FDA regulatory science on several broad areas:

  • Speeding therapies to patients
  • Setting standards for products with unmet public health needs 
  • Enhancing safety and health through informatics (information technology)
  • Protecting our food supply 
  • Modernizing toxicology and hazard assessment
  • Meeting the challenges for regulating tobacco

Advances in regulatory science will help modernize product development to provide better tools, standards, assays, disease models, and science-based pathways to improve the  efficiency, predictability, capacity, and quality of FDA-regulated products, as well as to support safety surveillance of FDA-regulated products once they reach the market. 

How does the CPI fit with the Advancing Regulatory Science Initiative?

The CPI is one of the many programs underway on which the Advancing Regulatory Sciences Initiative is building.  Since 2004, FDA has been working to bring together multiple partners to spur the transformation of processes through which FDA-regulated products are developed, evaluated, manufactured, and used.  CPI has helped support constructive partnerships, engaging academia, non-profits, and industry to address major regulatory science questions that cut across multiple interests.  Examples include validation of new biomarkers that better predict product safety or efficacy, new approaches to improve the quality and conduct of clinical studies, and new ways to monitoring the safety of approved products, the Sentinel Initiative and the DAPT Trial, mentioned in the question above being two examples.  For more information on specific projects, see the CPI reports from 2006, 2007, and 2008.

How does the FDA-NIH collaboration differ from the Critical Path Initiative? 

The FDA-NIH collaboration is aligned with CPI's goals and collaborative approach.  CPI has spawned numerous collaborations since its inception in 2004.  The FDA-NIH collaboration will help focus additional funding ($6.5 million in 2010) on many of the areas CPI has identified to support the development and evaluation of human medical products and ensure their safety and effectiveness.  The funding will go to applicants, awarded through an NIH competitive grant process.  (Link to RFA) A key goal of the FDA-NIH collaboration is to identify ways that FDA and NIH can work together to support common goals.

What kind of funding support does the CPI receive?

FDA’s CPI has received appropriated funding from Congress each of the last three years ($8 million, $16 million, and $18 million in 2008, 2009, and 2010, respectively) to support project activity areas across all FDA centers (including veterinary medicine and foods).  These activities contribute to transforming the processes through which FDA-regulated products are developed, evaluated, manufactured, and used.   Some of this funding has been awarded to collaborative organizations through grants and contracts; some has gone to support projects in the centers, often encompassing extensive collaborations.  FDA is also fostering many CPI projects that are part of an overall, decades-long effort to enable FDA to manage electronically the massive amounts of information submitted to the agency.  Information technologies are making FDA’s mission more efficient and effective as we leave behind the paper-based systems we have used for the past century.  FDA is asking for an increase in funding for CPI in its 2011 budget.

How are FDA's Center for Veterinary Medicine and Center for Food Safety and Applied Nutrition related to CPI activities?  What are some examples?

It quickly became evident that many projects in one FDA product area were directly or indirectly related to projects in other product areas.  Therefore, CPI began expanding its scope to include research in all FDA centers. 

CPI was launched in 2004 with the goal of driving innovation to tackle bottlenecks in human drug development (i.e., a steep decline in innovative new treatments coming on the market, despite huge investments and discoveries in basic research).  To leverage all of the innovative work in progress within the agency—not to mention in collaboration with stakeholders—it became essential for CPI to expand to support agency-wide research into tools and methodologies because they would improve the way all FDA-regulated products are developed, evaluated, manufactured, and used.  As the examples listed above show, CVM and CFSAN are collaborating on an antimicrobial project that will ultimately lead to improved tools for surveillance of enteric pathogens.  And similar research in antimicrobial resistance is providing insights into antibiotic use in animals and in humans.  NCTR works closely with other FDA centers on a variety of cutting-edge projects that will lead in the future to increased ability to individualize, or personalize, treatment in humans. 

FDA centers are working together, often with outside collaborators to create new tools to help with the development, evaluation, manufacture, and use of FDA-regulated products.  Here are three examples of ongoing CPI projects:

  • CVM and CFSAN are working to design a cutting-edge, high-density tool that can detect and describe 38 different Salmonella genomes that have been implicated in human and animal infections.  The project's goals are to identify new biomarkers, virulence factors, and antimicrobial resistance determinants that can be used to increase the timeliness and specificity of public-health monitoring of FDA-regulated food and animal feed products.  
  • CVM and CDRH have launched a project to develop an alternative test method to improve the drug development process involving clinical safety and effectiveness studies.  The project is studying the genomics of the multi-drug resistant MDR-1 protein.  For example, heartworm drugs such as ivermectin are especially toxic to dogs that have a mutated MDR-1 protein.
  • FDA’s National Center for Toxicological Research (NCTR) has projects in progress with all the centers. NCTR is working with CFSAN on test methodologies for detecting pathogens that have demonstrated extremely high accuracy in detecting E.coli 0157 in nine food types as part of a Food Emergency Response Network Level-2 validation study. 

What are the next steps for the Critical Path Initiative? 

Creating safer, more effective treatments and ensuring that our nation remains safe and globally competitive are all part of FDA’s responsibility to fulfill its mission.  CPI is a key driver of FDA’s Advancing Regulatory Science Initiative (ARS), launched in early 2010.  FDA is seeking increased funding for the ARS initiative in the 2011 budget, including additional funding for CPI. Plans are underway to enhance outreach and issue new solicitations for interest in partnerships and applied research. Key CPI areas of focus include:

  • Supporting partnerships to accelerate the development of personalized medicine
  • New approaches to toxicology
  • New efforts to help meet unmet U.S. and global public health needs
  • Increased support of informatics activities to facilitate FDA's ability to carry out its mission as efficiently as possible
  • Training
  • Research within FDA and with external partners
  • Policy development
  • Outreach

Beginning in 2010, CPI is launching a new project aimed at enhancing the development and availability of diagnostics and therapies for tropical diseases, especially tuberculosis (TB)--an effort strongly supported by Congress. TB continues to be a major global killer, and, because of multi-drug resistance, remains a threat to U.S. health and security.

FDA is escalating its Critical Path work because a strong FDA is imperative to moving discoveries "from microscope to market," as Commissioner Hamburg explained, when announcing the FDA-NIH Collaboration in February 2010.

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