FDABAA-15-00121.pdf

FDABAA-15-00121

Overview Information

Agency Name: Department of Health and Human Services, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993

Issuing Office: Department of Health and Human Services, Food and Drug Administration, Office of Acquisitions & Grants Service, 5630 Fishers Lane, Rockville, MD 20857

Research Opportunity Title: Food and Drug Administration Broad Agency Announcement for the Advanced Research and Development of Regulatory Science

Announcement Type: Broad Agency Announcement

Eligible Applicants: This BAA is open to ALL responsible sources. Offerors may include single entities or teams from private sector organizations, Federally Funded Research and Development Centers (FFRDCs) (see page 4 for FFRDC eligibility requirements) and academic institutions.

Research Opportunity Description: Food and Drug Administration solicits the advanced research and development for regulatory science. FDA anticipates that research and development activities awarded under this BAA will serve to advance scientific knowledge to accomplish its mission to protect and promote the health of our nation.

Types of instruments that may be awarded: Procurement Contracts

TABLE OF CONTENTS

INTRODUCTION

Part I: Research Areas of Interest

Part II: Reporting Requirements and Deliverables

Part III: Proposal Preparation and Submission

Section 1: The Application Process

Section 2: Stage 1 Quad Chart and White Paper

Section 3: Quad Chart and White Paper Submission

Section 4: Stage 2 Full Proposal Preparation

Section 5: Full Proposal Submission

Section 6: General Information

Part IV: Proposal Evaluation

Award Decision

Part V: Attachments

Attachment 1: Summary of Related Activities

Attachment 2: Government Notice for Handling Proposals

Attachment 3: Quad Chart and White Paper Format Template

Attachment 4: Research and Development Justification

FDA BAA-15-00121

INTRODUCTION

Advancing Regulatory Science and Innovation

This Broad Agency Announcement (BAA), which sets forth research areas of interest for Food and Drug Administration is issued under FAR 35.016(c) of the Federal Acquisition Regulation (FAR). The purpose of this BAA is to fulfill an FDA requirement to utilize industry capabilities to advance the state of the art and achieve improvements in technology, materials, processes, methods, devices, or techniques in specific topics as described in this document. Proposals selected for award are considered to be the result of full and open competition and in full compliance with the provision of Public Law 98-369, "The Competition in Contracting Act of 1984" and subsequent amendments.

The Food and Drug Administration (FDA) protects and promotes the health and safety of all Americans through enhancing the availability of safe medical products and foods and promoting innovation that addresses unmet medical and public health needs. FDA also protects and promotes the health and safety of animals through assuring the availability of safe animal drug products and food. FDA is a science-based regulatory agency and a critical component to the success of the nation’s public health, health care systems, and economy. FDA was created in 1906 as one of our nation’s principal consumer product protection agencies, and is now responsible for assuring the safety of biologics, such as blood products and vaccines, drugs, medical devices, foods, cosmetics, and many other consumer goods. Since 2009, it has also been responsible for regulating the manufacture, marketing, and distribution of tobacco products.

In the US, FDA-regulated products account for about 25 cents of every dollar spent by American consumers each year — products that touch the lives of every American every day. FDA is responsible for advancing the public health by helping to speed innovations that make foods safer and make medicines and devices safer and more effective. At the same time, FDA helps consumers and health care providers get the accurate and science-based information they need to make the best possible decisions about their use of medical products and foods for human and non-human animal use. FDA must make decisions based on the best available scientific data and using the best tools and methods available in order to ensure products meet the highest quality standards for consumers, while at the same time fostering and advancing innovation in the products it regulates.

The core responsibility of FDA is to protect consumers by applying the best possible science to its regulatory activities — from pre-market review of efficacy and safety to post-market product surveillance to review of product quality. In the last few years, rapid advances in innovative science have provided new technologies to discover, manufacture and assess novel medical products, and to improve food safety and quality; FDA must keep pace with and utilize these new scientific advances to accomplish its mission to protect and promote the health of our nation.

The BAA is open to all responsible sources. Offerors may include single entities or teams from private sector organizations, Federally Funded Research and Development Centers (FFRDCs), and academic institutions. Non-U.S. organizations and/or individuals may participate to the extent that such participants comply with any necessary nondisclosure agreements, security regulations, export control laws, and other governing statutes applicable under the circumstances.

Federally Funded Research and Development Centers (FFRDCs) and Government entities (e.g., Government/National laboratories, military educational institutions, etc.) are subject to applicable direct competition limitations and cannot propose to this BAA in any capacity unless they meet the following conditions:

1. Clearly demonstrate that the proposed work is not otherwise available from the private sector.

2. Provide a letter on official letterhead from their sponsoring organization citing the specific authority establishing their eligibility to propose to Government solicitations and compete with industry, and their compliance with the associated sponsoring agreement and terms and conditions.

Historically Black Colleges and Universities (HBCU), Minority Institutions (MI), Small Business concerns, Small Disadvantaged Business concerns, Women-Owned Small Business concerns, Veteran-Owned Small Business concerns, Service-Disabled Veteran-Owned Small Business concerns, and HUB Zone Small Business concerns are encouraged to submit proposals and to join other entities as team members in submitting proposals.

The purpose of this BAA is to solicit proposals that focus on one or more of the following areas of interest as listed here and further described in Part I of this announcement.

1. Modernize Toxicology to Enhance Product Safety

2. Stimulate Innovation in Clinical Evaluations and Personalized Medicine to Improve Product

Development and Patient Outcomes

3. Support New Approaches to Improve Product Manufacturing and Quality

4. Ensure FDA Readiness to Evaluate Innovative Emerging Technologies

5. Harness Diverse Data through Information Sciences to Improve Health Outcomes

6. Implement a New Prevention-Focused Food Safety System to Protect Public Health

7. Facilitate Development of Medical Countermeasures to Protect Against Threats to U.S.

and Global Health and Security

8. Strengthening Social and Behavioral Science at FDA by Enhancing Audience

Understanding

9. Strengthening the Global Product Safety Net

Multiple awards are anticipated. The amount of resources made available under this BAA will depend on the quality of the proposals received and the availability of funds. Anticipated funding for the program (not per contract or award) may range from $200,000 to $50,000,000 dollars subject to congressional appropriations. This funding profile is an estimate only and will not be a contractual obligation for funding. All funding is subject to change due to government discretion and availability.

The Government reserves the right to select for negotiation all, some, one, or none of the proposals received in response to this solicitation, and to make awards without discussions with proposers. The Government also reserves the right to conduct discussions if it is later determined to be necessary. If warranted, portions of resulting awards may be segregated into pre-priced options. Additionally, FDA reserves the right to accept proposals in their entirety or to select only portions of proposals for award. In the event that FDA desires to award only portions of a proposal, negotiations may be opened with that proposer. The Government reserves the right to fund proposals in phases with options for continued work at the end of one or more of the phases.

To be eligible for award, a prospective recipient must meet certain minimum standards pertaining to financial resources, ability to comply with the performance schedule, prior record of performance, integrity, organization, experience, operational controls, technical controls, technical skills, facilities, and equipment.

This BAA is available on the following websites:

https://www.fbo.gov https://www.fda.gov

This BAA is a continuously open announcement valid throughout the period from the date of issuance through the closing date specified in fbo.gov. Amendments to this BAA will be posted to fbo.gov when they occur. Interested parties are encouraged to periodically check these websites for updates and amendments.

https://www.fbo.gov/ https://www.fda.gov/

Part I: Research Areas of Interest

Through this BAA, FDA seeks to support advanced research and development strategies in the following research areas of interest. This section presents the technical objectives that FDA seeks to achieve through this BAA. Offeror’s shall propose a Statement of Work (SOW) that is consistent with research and development work as defined in FAR 35.001. Proposal preparation and submission instructions are contained in Part III.

1. Modernize Toxicology to Enhance Product Safety

FDA seeks to improve the prediction of product safety and efficacy based on preclinical data by conducting internal and collaborative research and development. Areas of interest include:

1.1 Develop better models of human adverse response:

1.1.1 Evaluate and promote the use of cell and tissue based assays that more accurately represent human susceptibility than animal models to adverse reactions;

1.1.2 Modernize the development and use of animal models that consider the potential influence of disease progression and disease co-morbidities on the emergence of adverse events;

1.1.3 Promote a better understanding of toxicity mechanisms by evaluating safety assessment data at multiple levels of biological organization including genes, proteins, pathways, and cell/organ function;

1.1.4 Assess and characterize molecular targets and host genetic factors that may be associated with rare and unexpected adverse events (“off-target” drug effects);

1.1.5 Initiate in vitro and in vivo studies to identify potential markers of harm associated with exposure to tobacco constituents; and

1.1.6 Initiate in vitro studies to identify potential markers of harm associated with exposure to medical products.

1.2 Identify and evaluate biomarkers and endpoints that can be used in non-clinical and clinical evaluations:

1.2.1 Evaluate the accuracy (specificity and sensitivity) with which animal models and in vitro assays correctly predict potential human risk;

1.2.2 Assess concordance between animal and human markers of toxicity and determine how the performance of these markers and their interpretation may vary across different organ systems and human populations; and

1.2.3 Evaluate quantitative imaging (e.g. positron emission tomography, magnetic resonance imaging, computed tomography) and other advanced approaches (e.g. metabolomics) for identifying new biomarkers and predictors of efficacy and safety.

1.3 Use and develop computational methods and in silico modeling:

1.3.1 Improve the use of chemical Structure-Activity Relationship (SAR) models in the prediction of human risk and integrate this analysis into the review process;

1.3.2 Develop and implement approaches to link chemical structures and substructures to a wide range of information about product safety, disease targets, and toxicity mechanisms;

1.3.3 Develop clinical trial simulation models that can reveal interactions between drug or device effects, patient characteristics, and disease variables influencing outcomes;

1.3.4 Develop computer models of cells, organs, and systems to better predict product safety and efficacy;

1.3.5 Develop computer models that integrate pharmacokinetic, pharmacodynamic, materials science, or mechanistic safety data to predict clinical risk-benefit and confirm post-marketing safety in different patient populations; and

1.3.6 Develop and apply data mining, knowledge building, and data visualization tools to inform computer model development, clinical risk prediction, and regulatory decision-making.

1.3.7 Develop computer models for assessing the risk of new tobacco products that will potentially enter the market by considering potential risks to users of the products based on demographic attributes of the users and usage patterns.

1.4 Develop Better Models to Investigate the Toxicology of Veterinary Drugs

1.4.1 Assesses whether zebrafish (Danio Rerio) serve as a good model to investigate the potential toxicity or health effects of approved and unapproved animal drugs.

2. Stimulate Innovation in Clinical Evaluations and Personalized Medicine to Improve Product Development and Patient Outcomes

FDA seeks to develop new tools and approaches needed to catalyze the development of personalized medicine and to modernize and advance the science and conduct of clinical trials.

Areas of interest include:

2.1 Develop and refine clinical trial designs, endpoints and analysis methods:

2.1.1. Refine clinical trial design and statistical methods of analysis to address issues such as missing data, multiple endpoints, patient enrichment, and adaptive designs;

2.1.2 Identify and evaluate improved clinical endpoints and related biomarkers for trials in areas where optimal endpoints are lacking (e.g., efficacy and safety endpoints for osteoarthritis in humans and animals, for gene therapy, for transplant- related studies (endpoints and duration), for ophthalmic indications, for tumor vaccines, and for stem cell-derived therapies);

2.1.3 Develop novel trial designs and endpoints for special needs (e.g., small trials for orphan indications, designs and endpoints for pediatric trials including neonatal trials);

2.1.4 Continue to refine the use of modeling and simulation in clinical trial design to enhance the effectiveness of clinical studies; and

2.1.5 Develop practical methods to assess the bioequivalence of locally acting drugs, including inhalants, topicals, and intraluminal GI drugs.

2.2 Leverage existing and future clinical trial data:

2.2.1 Develop quantitative models and measures of disease progression; and

2.2.2 Utilize large, pooled clinical trial datasets to identify potential trial endpoints, explore differences in specific populations and subpopulations (e.g., stage of disease, chronic disease states, sex, race and ethnicity, pediatrics and other age groups) and different subsets of diseases, improve understanding of relationships between clinical parameters and outcomes, and evaluate clinical utility of potential biomarkers.

2.3 Identify and qualify biomarkers and study endpoints:

2.3.1 Facilitate identification and qualification of new and improved biomarkers for safety and efficacy, pharmacodynamic response - dose selection, disease severity, progression and prognosis, and pharmacogenomics (to predict safety and efficacy or guide dosing); and

2.3.2 Develop and evaluate novel approaches for biomarker identification, including 'omics, systems biology, and high throughput methods.

3. Support New Approaches to Improve Product Manufacturing and Quality

FDA seeks to support the application of novel technologies to product development and innovative analytical approaches to improve product manufacturing and quality through active research.

Areas of interest include:

3.1 Enable development and evaluation of novel and improved materials and manufacturing methods:

3.1.1 Investigate the effects of continuous manufacturing (manufacturing using a continuous process, rather than a batch approach) on product quality;

3.1.2 Examine specific novel material and manufacturing technologies to determine how they impact product failure rates; and

3.1.3 Evaluate the role excipient ingredients and complex dosage forms on product safety, efficacy, and quality and further two state-of-the-art manufacturing strategies-Process Analytical Technology, and Quality-By-Design approaches-for impact on manufacturers’ ability to maintain consistent quality.

3.1.4 Explore novel approaches to incorporating medical device development concepts and methodologies, including quality and risk management.

3.2 Develop new analytical methods:

3.2.1 Investigate feasibility and value of using emerging and improved analytical technologies like NMR (Nuclear Magnetic Resonance), mass spectrometry, or near infrared or Raman spectroscopy for evaluating product quality of pharmaceutical agents, and evaluate whether these technologies should replace existing methods;

3.2.2 Evaluate applicability of various analytic technologies for determination of the “similarity” of biosimilars to their reference products;

3.2.3 Perform statistical research to support development and evaluation of new assays and tests needed to assure analytical methods give consistent reproducible results; and

3.2.4 Develop improved methods and tools to detect and measure the physical structure, chemical properties, and safety of engineered nanomaterials and complex dosage forms (e.g., transdermal patches, inhalation delivery systems, and targeted drug delivery systems etc.) in FDA-regulated products.

3.2.5 Develop Methods to Assess Quality of Glycerin

Develop methods to identify the quality (crude vs industrial vs usp) and potential contaminants in the various glycerin grades used in finished products (for example jerky pet treats for animals, drugs for humans and animals).

3.3 Reduce risk of microbial contamination of products:

3.3.1 Develop sensitive, rapid, high-throughput methods to detect, identify, and enumerate microbial and chemical contaminants and validate their utility in assessing product sterility; and

3.3.2 Develop and evaluate methods for microbial inactivation/removal from medical products that are not amenable to conventional methods of sterilization.

3.4 Improve scientific approaches to evaluate generic drugs

In July 2012, Congress passed the Generic Drug User Fee Amendments (Title III of the Food and Drug Administration Safety and Innovation Act (Public Law 112-144)). The Generic Drug User Fee Amendments (GDUFA) is designed to enhance public access to safe, high-quality generic drugs, and to reduce costs to industry. To support this goal, FDA agreed in the GDUFA commitment letter to consult with industry and the public in order to create an annual list of regulatory science initiatives specific to research on generic drugs for each year covered by GDUFA. The research activities related to the FY 2014 topic areas are as follows:

3.4.1 Post-market Evaluation of Generic Drugs

3.4.1.1 Develop surveillance and monitoring methods for generic drugs.

3.4.1.2 Understand patient perceptions of generic drug quality and effectiveness.

3.4.1.3 Evaluate and verify therapeutic equivalence via brand to generic switching studies in patients for anti-epileptic drugs, immunosuppressant drugs, bupropion, ADHD drugs and cardiovascular drugs.

3.4.2 Equivalence of Complex Products

Develop research studies to establish bioequivalence methods for complex products such as liposomes, sustained release parenterals, and complex mixtures.

3.4.3 Equivalence of Locally Acting Products

Develop research studies into new bioequivalence (BE) methods and pathways for local acting drugs for inhalation, topical dermatological, nasal, GI acting, ophthalmic and otic products.

3.4.4 Therapeutic Equivalence Evaluation and Standards

3.4.4.1 Develop risk-based equivalence standards for narrow therapeutic index (NTI) drugs.

3.4.4.2 Investigate patient use factors such as tablet size for their impact on generic substitutability.

3.4.4.3 Evaluate IVIVC/predictive dissolution for solid oral dosage forms.

3.4.5 Computational and Analytical Tools

3.4.5.1 Develop modeling and simulation tools including PBPK/absorption models, PD models/clinical trial simulation, and quantitative risk modeling for generic drugs.

3.4.5.2 Develop analytical methods to characterize peptides and other complex mixtures and particle size and surface chemistry for potential generic products.

3.5 Identify and Qualify Pain-Associated Biomarkers that are Associated with Therapeutic

Control of Pain in Food Producing Animals

3.5.1 Identify molecular biomarkers (proteomic or genomic) that can be qualified against clinical signs to serve as surrogate endpoints in assessing the capacity of therapeutic agents to alleviate pain in food animals such as cattle, pigs, and goats.

3.6 Develop a Regulatory Database for Species Identification

3.6.1 Develop a DNA barcode sequence database for species identification

4. Ensure FDA Readiness to Evaluate Innovative Emerging Technologies

FDA seeks to evaluate new and emerging technologies through active research intramurally and collaboratively with external partners. Areas of interest include:

4.1 Develop assessment tools for novel therapies:

4.1.1 Develop new approaches such as in vitro and in vivo methods to identify measurable characteristics of product safety, quality, and potency when evaluating new therapeutics (e.g., engineered tissues or cell therapy products, including stem cell-derived products, for clinical application in regenerative medicine, additive manufacturing in medical products, nanotechnology in medical products);

4.1.2 Develop new ways to evaluate gene therapy and antisense therapy products developed in this period of fast-paced scientific progress;

4.1.3 Integrate an understanding of product quality and safety based on novel genomic, proteomic, metabolomic, and other -omic technologies; and

4.1.4 Explore the role of wireless and mobile application in new medical therapies and diagnostics.

5. Harness Diverse Data through Information Sciences to Improve Health Outcomes

FDA seeks to develop agency information sciences capability. Areas of interest include:

5.1 Develop and apply simulation models for product life cycles, risk assessment, and other regulatory science uses:

5.1.1 Identify opportunities and develop computer simulation and modeling to streamline data analysis and model biological systems and their responses to agents of concerns, such as toxins, pathogens, electromagnetic energy, and biomaterials; and

5.1.2 Promote novel clinical trial design using simulation, new statistical models, and novel animal models/animal model alternatives.

5.2 Analyze large scale clinical and preclinical data sets:

5.2.1 Refine methods for analysis of post-market data, including data mining of spontaneous reports and analysis of electronic health records from accessible large healthcare databases.

5.3 Computer Modeling and Simulation to Assess Product Risk

5.3.1 Develop new approaches to assess the risk of new tobacco products that will potentially enter the market by considering how such products are likely to harm, or potentially harm the users of this product based on demographic attributes of the users and usage patterns.

5.3.2 Develop novel methods to model the carcinogenicity, toxicity, and contribution to adverse health conditions of each component in a tobacco product based on available data – literature, EPA, legacy nonclinical studies, or submitted studies by industry.

5.3.3 Develop novel methods to model the demographics of a synthetic population in terms of probability distribution curves (normal distribution) based on:

a. Usage of tobacco product

b. Race

c. Gender

d. Age

e. Body Weight

f. Pregnancy state

g. Family structure and position within

h. Occupation and work premises (susceptibility to secondary ingestion)

5.3.4 Develop novel methods to display model output in both graphical and numeric formats.

5.3.5 Develop and disseminate computational models and simulations that can be used as evidence for the safety and effectiveness of medical devices; establish medical device modeling validation requirements.

5.3.6 Develop novel methods to model inputs to allow one to compare at least two products and see a change reflected on the risk summary. Changes should be able to be qualitative (e.g. moderate smoker translated into 20 cigarettes per day) or quantitative (e.g. 40 cigarettes per day).

Changeable parameters should include:

a. Type of product (average US, brand A, and/or brand B – as well as others when present in the database)

b. Group of chemicals (e.g. vapor phase versus particulate phase)

c. Concentration in the smoke (mean, maximum, etc)

d. Cigarette intake rate – cigarettes per day (i.e. 5, 10, 20, 40, etc)

e. Exposure frequency - How frequently a user is exposed (i.e. daily, one time per week, five days per month etc)

f. Exposure duration – How long a person smokes (in years)

g. Body weight (i.e. Caucasian male, Asian female, etc.)

h. Averaging time – Lifespan for a given population (differing population dynamics)

6. Implement a New Prevention-Focused Food Safety System to Protect Public Health

Food Safety Modernization Act (FSMA) mandates a new approach to FDA’s current food safety system, emphasizing prevention and risk-based priority setting and resource allocation to address the challenges of the modern food safety environment. Although prevention is paramount, enhanced response and investigation efforts to foodborne outbreaks when they occur, is also critical. To effectively implement this new food safety mandate, it is imperative that FDA ensures a strong science infrastructure that clearly identifies its research needs and collaborates with other public health and research agencies in the Federal government, state government agencies, academia, and private industry. Areas of interest include:

6.1 Establish and implement centralized planning and performance measurement processes:

6.1.1 Harmonize microbiological and chemical analytical methods development and validation across the Foods Program to enhance detection and removal of unsafe contaminants from the Nation’s food and feed supply.

Note: Improved, validated rapid methods, with high levels of sensitivity and specificity, would enable FDA investigators and laboratories to quickly and accurately identify sources of contamination throughout the food supply chain, thereby protecting public and animal health. In addition, improved methods would also provide defensible data to show food products are free from microbial and chemical hazards and reduce the number of unnecessary recalls which currently result in significant repercussions for industry, consumers and FDA. Research that gives FDA validated, practical and usable regulatory tools would be of great benefit in making regulatory decisions or providing guidance to industry. By sharing and leveraging resources, FDA would like to keep pace with new food technologies, the expanding array of foods in the marketplace, and identifying emerging hazards such as new pathogens and chemical contaminants that would require strategic investments in regulatory science and review.

6.2 Maintain mission critical science capabilities:

6.2.1 Identify emerging disciplines, sciences, and technologies to mitigate future risks in food safety.

Note: The primary focus would be to advance research and development (R&D) into more rapid, sensitive and specific methods to detect, identify and quantify a variety of microbial and chemical hazards (e.g. Listeria, Salmonella, E. coli O157:H7, melamine, arsenic) in foods and animal feeds, as well as dietary supplements and cosmetics.

7. Facilitate Development of Medical Countermeasures (MCMs) to Protect Against Threats to U.S. and Global Health and Security

FDA seeks to facilitate development of safe and effective MCMs through both intramural research and collaboration with external partners (e.g., academia, U.S. government agencies, non- governmental organizations, and industry). FDA will conduct a review for the potential of Dual Use as defined and in accordance with USG policy. Areas of interest include:

7.1 Develop, characterize, and qualify animal models for MCM development:

7.1.1 Develop and evaluate animal models for the ability to demonstrate a response to the countermeasure that will be predictive for humans, including the ability to extrapolate pharmacokinetic/pharmacodynamic (PK/PD) data and/or immune correlates of protection to determine appropriate clinical dosing ; and

7.1.2 Refine existing animal models for Ebola virus disease to demonstrate a response to the countermeasure that will be predictive for humans, including the ability to extrapolate pharmacokinetic/pharmacodynamic (PK/PD) data and/or immune correlates to determine appropriate clinical dosing.

7.2 Modernize tools to evaluate MCM product safety, efficacy, and quality:

7.2.1 Identify and evaluate methods to improve availability and reuse of personal protective equipment;

7.2.2 Continue to develop electronic data standards and report forms to facilitate rapid assessment of the safety and efficacy of deployed MCMs;

7.2.3 Develop reference materials related to relevant threat agents to facilitate development of preventive vaccines, therapeutics, and detection and diagnostic methods;

7.2.4 Develop and evaluate high throughput, sensitive, specific, cost-effective methods to detect threat agents, diagnose the disease or condition, and perform broad-based pathogen detection.

7.2.5 Refine existing technologies to improve the sensitivity, specificity, and robustness of assays used to measure Ebola medical countermeasure potency and in-process and final drug substance characteristics; and

7.2.6 Improve the performance and quality of existing in vitro diagnostic tests for Ebola virus disease.

7.3 Identify and qualify biomarkers of diseases or conditions:

7.3.1 Improve knowledge of natural history of pathophysiology of human diseases or conditions caused by Chemical, Biological, Radiological and Nuclear (CBRN) agents to identify, qualify, and evaluate biomarkers; and

7.3.2 Identify and qualify biomarkers that enhance the understanding of the mechanism of action of MCMs, and may provide measures of MCM product efficacy.

7.4 Enhance emergency communication:

7.4.1 Evaluate past risk and emergency communications to identify and improve the effectiveness of communications in a public health emergency;

7.4.2 Improve quality and health literacy level of FDA communication about FDA-regulated products; and

7.4.3 Enhance FDA’s capabilities and develop new strategies to collect, monitor, and track during emergencies real time data on adverse events associated with the use of drug, biologic, and device MCMs.

8. Strengthening Social and Behavioral Science at FDA by Enhancing Audience Understanding

FDA seeks to identify and improve science-based approaches, including rapidly evolving communications technologies, to clear and effective communications on the appropriate uses of regulated products in order to promote health and reduce harms through informed decision making by consumers and health care professionals. There are four priority areas in which FDA seeks to improve comprehension among the recipients of FDA communications. Areas of interest include:

8.1 Assessment of how communications are understood, especially among diverse audiences and populations, and methods to improve the comprehension of content, including numerical information.

8.1.1 Identify effective ways to communicate so that patients and consumers, including those with low health literacy and limited English proficiency, are informed but not alarmed, assess knowledge and understanding of risk associated with use of FDA-approved products, assess the frequency and means of changing messages in order to promote continued attention to advice that is not new but remains important, evaluate methods to identify and accommodate cultural and language differences and assess the cost of these methods to the Government, and study the impact of different formats and amounts of numerical information in FDA communications for patients, health care providers, health educators and informal caregivers.

8.2 Exploration of how FDA communications can best complement those communicated by industry to enhance audience comprehension.

8.2.1 Assess awareness of direct-to-consumer advertising among patients and consumers, including those with low literacy and limited English proficiency, develop tools for measuring the effectiveness of messages that are being communicated to the public by industry advertisements and by FDA communications.

8.3 Research to assess public understanding of the regulatory terms in use.

8.3.1 Study the impact of FDA terms on the public’s ability to comprehend FDA communications, and identify explanatory strategies or alternatives. Examples of FDA terms include: “safe and effective,” Over-The-Counter (OTC) monograph drugs (GRAS, GRAE, “voluntary recall,” “product correction,” and disclaimers like “These statements have not been evaluated by the Food and Drug Administration.

This product is not intended to diagnose, treat, cure, or prevent any disease.”

8.4 Evaluation of timing of release of recall or warning messages, when the messages should be changed to enhance impact, and how to communicate the end of a recall or warning.

8.4.1 Characterize how consumers, patients, and caregivers understand and use emerging information including various types of uncertainty about newly identified potential risks of products; also, evaluate the ideal frequency and means of changing messages in order to promote continued attention to advice that is not new but remains important.

8.5 Studies to increase the safety of post approval drug use

8.5.1 Develop innovative methods to create, facilitate and encourage research in the area of safe medication use that seeks to reduce preventable harm from drugs. Approaches could include the use of clinical studies, education, innovative messaging strategies, electronic health records, or mobile technologies.

9. Strengthening the Global Product Safety Net

Globalization has made FDA’s responsibilities increasingly challenging, affecting every type of product FDA regulates. In 2002, 8 million import entry lines of FDA-regulated products arrived at our borders; in 2012, it grew to 28 million and in 2013, it’s expected to be 34 million.

Additionally, more and more products come from developing countries where manufacturing systems may be less sophisticated and regulatory and manufacturing oversight may be minimal. As FDA continues to transform into a public health agency fully prepared for a complex, global regulatory environment, there are 3 priority areas in which FDA seeks to improve its knowledge and capabilities to enhance its international operating model. Areas of interest include:

9.1. Advancing Global Public Health

9.1.1. Determine how to promote and assure implementation of the essential elements of a strong regulatory system in developing economies, including (a) determining core competencies for a regulatory workforce and components of a global regulatory workforce curriculum, (b) assessing other areas related to regulatory systems’ performance including conducting, costing, and financing analyses for regulatory systems, and

(c) identifying and assessing existing regulatory strengthening evaluation tools utilized by governments and international organizations.

Note: Research in this area could include advancing innovative regulatory science through the development of cutting-edge investigative, inspectional and analytical rapid-screening tools.

9.2. Leveraging and Collaborating

9.2.1. Determine how to best identify and leverage the efforts of public and private third parties to more effectively deploy resources against risk-based priorities. This could include researching, assessing and developing recommendations regarding the landscape of existing efforts, activities, and capabilities.

9.2.2. Work with other public and private stakeholders to ensure that standards are well understood and applied, foster best practices in industry, and promote innovation to drive safety and quality.

9.2.3. Foster global coalitions of regulators by, among other actions, developing strategic approaches to the harmonization and convergence of standards, contributing to the sharing of useful information, recognition determinations, mutual reliance, and an improved ability to make appropriate regulatory decisions in real time.

Note: Research in this area could include development and use of a tool to assess the governing authorities, regulations, and operating models of various regulatory agencies in order to inform comparability determinations; and the development and use of mechanisms to share information and best practices via existing or new electronic platforms. Research might also include an assessment of the current extent of standards implementation (intended use), gaps in implementation, and priorities for broadening and harmonizing the application of standards.

9.3. Analyzing and Utilizing Global Data to Manage Risks

9.3.1. Define analytical methods and tools to foster improved utilization of risk analytics to inform strategies, priority-setting, and timely decision-making in the areas of inspections, training, regulatory cooperation and surveillance.

9.3.2. Develop predictive risk models that treat like risks in like ways across the supply chain regardless of the origin of the product.

9.3.3. Adopt new approaches to better aggregate and analyze multiple sources of information to fully identify risks and emerging trends based on comprehensive assessments of existing information platforms. The developed approach should include data mining of intelligence related sources (event reporting, testing results, alerts, customer complaints, news reports) to enable statistical analysis of correlations and threats. As an extension, integrate intelligence-based threat analysis into the risk-based allocation of inspection and testing resources.

9.3.4. Filter and analyze external indicators/signals/environmental vulnerabilities in the supply chain from various open-source intelligence and other sources to proactively identify the need for appropriate FDA interventions.

Note: Research in this area could include the development of informatics tools to connect multiple sources of information such as regulatory, economic, environmental, political and industrial factors to detectable risk signals and emerging risk trends. It could also include the development of data collection and analysis systems for external indicators/signals/environmental vulnerabilities in the supply chain from various sources intelligence and other media to alert FDA at early onset of the need for appropriate FDA actions or interventions.

9.4. Manage Risks Related to Intentional Disruptions to Food Supply

9.4.1. Conduct empirically-based, quantitative analyses to evaluate the risk of intentional disruptions to the food supply system. Scenario-based risk analysis shall include evaluation of the magnitude of specific threats to each supply chain component, identification of supply chain vulnerabilities, and determination of expected consequences for each scenario.

9.4.2. Utilize results of the risk assessment of intentional disruptions to food supply to conduct cost-benefit analysis of proposed prevention and/or response mechanisms.

Generate return-on-investment data to support decision-making and investment options.

Part II: Reporting Requirements and Deliverables

As part of the work to be performed under this BAA, the Contractor shall prepare and deliver the following reports throughout the period of performance. For all reports the Contractor shall submit electronic copies to the Contracting and Project Officer.

Reports:

1. Monthly Technical Progress Reports

On the fifteenth (15) day of each month for the previous calendar month, the contractor shall submit to the Project Officer and the Contracting Officer a Technical Progress Report.

Instructions for formulating Technical Progress Reports are detailed below. The technical Progress Reports shall include project timelines and milestones summaries of product manufacturing, testing, and clinical evaluation. A Technical Progress Report will not be required for the period in which the Final Report is due. The Contractor shall submit two copies of the Technical Progress Report electronically via e-mail to the Contracting Officer and Project Officer. Any attachments to the e-mail report shall be submitted in Microsoft Word, Microsoft Excel, and/or Adobe Acrobat PDF files. Such reports shall include the following specific information:

a. Title page containing: Technical Progress Report, the contract number and title, the period of performance or milestone being reported, the contractor’s name, address, and other contact information, the author(s), and the date of submission;

b. Introduction/Background: An introduction covering the purpose and scope of the contract effort;

c. Progress: The report shall detail, document and summarize the results of work performed, test results, milestones achieved during the period covered and cumulative milestones achieved. Also to be included is a summary of work planned for the next two (2) reporting periods on a rolling basis;

d. Issues: Issues resolved, new issues and outstanding issues are enumerated with options and recommendation for resolution. An explanation of any difference between planned progress and actual progress, why the differences have occurred, and, if progress activity is delinquent, and what corrective steps are planned. Revised timelines are to be included.

e. Invoices: Summary of any invoices submitted during the reporting period.

f. Action Items: Summary table of activities or tasks to be accomplished by certain date and by whom.

g. Distribution list: A list of persons receiving the Technical Report

h. Attachments: Results on the project are provided as attachments

2. Final Report: By the expiration date of the contract, the Contractor shall submit a comprehensive Final Report that shall detail, document, and summarize the results of the entire contract work. The report shall explain comprehensively the results achieved.

A draft Final Report will be submitted to the Project and Contracting Officers for review and comments, then the Final Report original, copies, and an electronic file shall be submitted to the Project and Contracting Officers for distribution to the Program office.

*Note: Some reports and other deliverables are relevant to specific activities that may or may not be performed during the contract period of performance. The Contractor, Contracting Officers Representative and Contracting Officer shall agree in the final contract negotiations on which reports and other deliverables are relevant and shall be required as deliverables as determined in the negotiated Statement of Work.

These reports are in addition to other reports and deliverables that may be required in the final negotiated SOW as referenced above.

3. Invoices: Cost and Personnel Reporting, and Variances from the Negotiated Budget:

i. The contractor agrees to provide a detailed breakdown on invoices of the following cost categories:

a. Direct Labor - List individuals by name, title/position, hourly/annual rate, level of effort, and amount claimed.

b. Fringe Benefits - Cite rate and amount

c. Overhead - Cite rate and amount

d. Materials & Supplies - Include detailed breakdown when total amount is over $1,000.

e. Travel - Identify travelers, dates, destination, purpose of trip, and amount. Cite COA, if appropriate. List separately, domestic travel, general scientific meeting travel, and foreign travel.

f. Consultant Fees - Identify individuals and amounts.

g. Subcontracts - Attach subcontractor invoice(s).

h. Equipment - Cite authorization and amount.

i. G&A - Cite rate and amount.

j. Total Cost

k. Fixed Fee (if applicable)

l. Total

Monthly invoices must include the cumulative total expenses to date, adjusted (as applicable) to show any amounts suspended by the Government. The contractor shall be held accountable for being in compliance with the stipulations stated in FAR 52.232-20 Limitation of Cost. Furthermore, invoices submitted under BAA awarded contracts must comply with the requirements set forth in FAR Clauses 52.232-25 (Prompt Payment) and 52.232-33 (Payment by Electronic Funds Transfer-System for Award Management) and/or applicable Far Clauses specified in the actual contract document.

Part III: Proposal Preparation and Submission

Section 1: The Application Process The application process is in two stages as follows:

Stage 1: Complete a cover page, Quad Chart, and White Paper in accordance with the preparation guidance below. Quad Charts and White Papers shall describe the effort in sufficient detail to allow evaluation of the concept's technical merit and its potential contribution to the FDA mission. Offeror’s whose Quad Chart and White Paper receive a favorable evaluation may be invited to submit a Full Proposal. Offeror’s whose Quad Chart and White Paper did not receive a favorable evaluation will be notified by email and will be informed of what technical issues the product needs for further FDA consideration.

Stage 2: Submit Full Proposals in accordance with the instructions provided in Section 5 below.

Full Proposals will be evaluated against criteria as described in Part IV. Full Proposals that do not conform to the requirements outlined in the BAA or in the invitation will not be reviewed or considered for further action.

Proposal Stage Deadline for Submission Stage 1: Quad Chart and White Paper Anytime during open period

Stage 2: Full Proposal Within 30 calendar days of Invitation

(unless designated otherwise by the CO)

Section 2: Stage 1 Quad Chart and White Paper

Interested Offeror’s shall submit a White Paper which expands on the information provided in the Quad Chart. The initial submission is limited to a cover page, one-page Quad Chart (see attachment 3), White Paper not to exceed ten (10) pages, an addendum not to exceed two (2) pages and a Research and Development Justification not to exceed one (1) page, as discussed below. If submissions exceed these limitations, only those pages previously defined will be reviewed.

Combine all files and forms into a single searchable PDF file before submitting.

Quad Chart Format (One Page Limit): All quad charts shall include the information indicated on the sample template located in Attachment 3.

1. Heading: Title, Research Area Addressed, Offeror point of contact, Company’s Name

2. Upper left: Objective, description of effort

3. Lower left: Benefits of proposed technology, challenges

4. Upper right: Picture or graphic

5. Lower Right: Milestones, cost, period of performance.

White Paper Technical Information (Ten Page Limit):

1. In general, the White Paper should provide a brief technical discussion of the Offeror’s objective, approach, level of effort, and the nature and extent of the anticipated results. Specifically, the White Paper shall include, at a minimum, the following core elements:

a. brief discussion on how the proposed project aligns with the objectives of the FDA Advancing Regulatory Science Plan.

b. a high-level Gantt chart showing an overview of the proposed activities and timelines.

c. a brief description of the Offeror’s intellectual property ownership of the proposed project.

d. an overview of the Offeror’s capabilities and experience (past and current) as they relate to the proposed program.

2. The cost portion of the White Paper shall contain a brief cost estimate revealing the component parts of the proposal and a breakdown of the total cost per year.

Addendum (Two Page Limit):

As an addendum to the White Paper, include overviews (two pages total) of the key personnel who will perform the research, highlighting some of their qualifications and experience.

Justification for Research and Development (One Page Limit):

Offeror’s shall submit, with the white paper package, a one (1) page justification describing how the Offeror’s project falls under the FAR definition of Research and Development (See attachment 4 for details).

Restrictive markings on White Papers: Proposal submissions will be protected from unauthorized disclosure in accordance with FAR Subpart 15.207, applicable law and HHS regulations. Offeror’s that include in their proposal, data that they do not want disclosed, shall mark their proposal in accordance with the instructions contained FAR 52.215-1(e) ‘Restrictions on disclosure and use of data.’

Mark the title page with the following legend:

This proposal includes data that shall not be disclosed outside the Government and shall not be duplicated, used, or disclosed—in whole or in part—for any purpose other than to evaluate this proposal.

If, however, a contract is awarded to this offeror as a result of—or in connection with—the submission of this data, the Government shall have the right to duplicate, use, or disclose the data to the extent provided in the resulting contract. This restriction does not limit the Government's right to use information contained in this data if it is obtained from another source without restriction. The data subject to this restriction are contained in sheets [insert numbers or other identification of sheets]; and

Section 3: Quad Chart and White Paper Submission

White Papers shall be emailed directly to the following email address:

FDABAA@fda.hhs.gov.

Include “Research Area #_ FDABAA-15-00121 WHITE PAPER” in the email subject line.

Offerors must select a primary research area to submit the…