FY26 BAA Notice V1.pdf

FDABAA-26-00123

Overview Information

Agency Name: Department of Health and Human Services (HHS), Food and Drug Administration (FDA), 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, 4041 Powder Mill Rd. Beltsville, MD 20705

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

Announcement Type: Broad Agency Announcement (BAA)

Eligible Applicants: This BAA is open to ALL responsible sources and Small Businesses are strongly encouraged to respond. Offerors may include single entities or teams from private sector organizations, Federally Funded Research and Development Centers (FFRDCs) (see page 5 for FFRDC eligibility requirements) and academic institutions.

Research Opportunity Description: The FDA solicits advanced research and development proposals to support regulatory science and innovation. The 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 Only [Not Grants]

Notes: Regarding Funding

To ensure sufficient time to conduct the two-tiered evaluation described in Section I and still be considered for an award within the current fiscal year, prospective Offerors are strongly encouraged/required to submit Stage One Submittal Packages with:

1. Checklist following required template (See attachment 3)

2. Freestanding Concept Paper following required template (See attachment 4)

3. Freestanding Full Proposal following required template (see Part III for details)

Freestanding Concept Papers and Freestanding Full Proposal shall be submitted no later than 11:59 pm, Eastern Standard Time, February 24, 2026*, and earlier if possible.

Early applications are highly encouraged. A submission will be considered incomplete if any of these critical elements are missing. Stage One Submittal Packages (Checklist, Freestanding Concept Paper, Freestanding Full Proposal) received after that date will still be accepted, but due to a lack of lead time, will not be considered for award in FY27.

Notice and Disclosure Regarding Incomplete/Nonconforming Stage One Submittal Packages: All Stage One Submittal Packages received in response to this announcement must be complete and comply with all instructions provided herein (Note: Part III: Proposal Preparation and Submission must be considered; it lays out the details of what is included in Stage I and Stage II Package). The FDA reserves the right to reject (or otherwise give no further consideration to) any Packages that are found to be (1) missing any pertinent information, (2) submitted in a nonconforming format, or (3) otherwise require exchanges with offerors for the FDA to complete its evaluation due to patent or latent ambiguities contained within the submittal.

Contents

Overview Information

Introduction

Part I: Research Areas of Interest

Charge I: Modernize development and evaluation of FDA-regulated products

Charge II: Strengthen post-market surveillance and labeling of FDA-regulated products

Charge III: Invigorate public health preparedness and response of the FDA, patients, and consumers

I. Modernize the Development and Evaluation of FDA-Regulated Products A. New Approach Methodologies (NAMS) B. Advanced Manufacturing Approaches C. Analytical and Computational Methods including Artificial Intelligence Approaches D. Biomarkers E. Clinical Outcome Assessment (COA) F. Complex and Novel Clinical Trial Design G. Predictive Toxicology H. Methods for Assessing Behavioral, Economic, or Human Factors J. Methods to Assess Real-World Data (RWD) for Real-World Evidence (RWE) Generation K. Methods to Assess Data Source Interoperability

II. Strengthen Post-Market Surveillance and Labeling of Regulated Products A. Methods to Assess Real-World Data (RWD) to Support Regulatory Decision-Making B. Using and Validating Artificial Intelligence Approaches C. Novel Clinical Trial Design, Statistical and Epidemiologic Methods D. Automated Reporting Tools for Adverse Events and Active Surveillance 32 E. Methods to Improve Communication About Risk to Patients and Consumers

III. Invigorate Public Health Preparedness and Response of the FDA, Patients, and Consumers A. Medical Countermeasures B. Antimicrobial Resistance C. Substance Use and Misuse D. Global Product Safety Net E. Emerging Technologies

Part II: Reporting Requirements and Deliverables

Reports

Part III: Proposal Preparation and Submission Section 1: The Application Process Section 2: Stage 1 Concept Paper and Full Proposal

Preparation of Volume I – Technical Proposal

Preparation of Volume II – Cost Proposal

Preparation of Volume II – Cost Proposal Appendices

Submission of Full Proposal:

a. Any application submitted after 02/24/2026 without a freestanding Concept and a free standing Full Proposal will be considered incomplete and will not be considered for review process

b. Multiple submissions on the same topic or closely related topics are discouraged *Note: Each volume of the proposal must be submitted as a separate and searchable Portable Document File (PDF) compatible with Adobe Acrobat version 7.0 or earlier. 1. Send as single email with separate attachments Section 3: Stage 2 Revised Full Proposal Section 4: Withdrawal of Full Proposals Section 5: Representation and Certifications Section 6: Studies That Involve Human Subjects

352.270-4a Notice to Offerors, Protection of Human Subjects (DEC 2015)

46 does not directly regulate the use of autopsy materials; instead, applicable state and local laws govern their use

352.270-4b Protection of Human Subjects (DEC 2015)

352.270-10 Notice to Offerors – Protection of Human Subjects, Research Involving Human Subjects Committee (RIHSC) Approval of Research Protocols Required (DEC 2015)

352.211-3 Paperwork Reduction Act (DEC 2015) Section 7: Animal Welfare

352.270-5a Notice to Offerors of Requirement for Compliance with the Public Health Service Policy on Humane Care and Use of Laboratory Animals (DEC 2015) Section 9: Use of Select Agent Section 9.1: Experiments relevant to the United States Government Policy for Oversight of Dual Use Research of Concern and Pathogens with Enhanced Pandemic Potential Policy Section 10: Laboratory License Requirements Section 11: Data Rights Clause Section 12: Advanced Understandings Section 13: Conflict of Interest Section 14: General Information

Part IV: Proposal Evaluation A. Evaluation Criteria:

1. Scientific and Technical Merit:

2. Program Relevance

3. Capabilities and Experience:

B. Past Performance Information C. Cost Evaluation

Total Cost and Cost Realism

Award Decision

Part V: Attachments Attachment 1: Summary of Related Activities Attachment 2: Government Notice for Handling Proposals Attachment 3: FY26 BAA Application Checklist

Proposal Title:

FDA Regulated Areas:

Groups & Populations:

Attachment 4: FY26 BAA Application Concept Paper Template

c. Considerations: Brief description of the Offerors intellectual property ownership, data ownership, or licensure; statements on work experience for similar effort with FDA or another agency

3. Proposed Deliverables and Funding Attachment 5: FY26 BAA Volume I Technical Proposal Template

A. Volume I – Technical Proposal (Fifty [50] page limit for items 4 to 11)

B. Volume I – Technical Proposal Appendices Attachment 6: FY26 BAA Application Statement of Work Template

Introduction

Advancing Regulatory Science and Innovation

This Broad Agency Announcement (BAA), which sets forth research areas of interest for FDA, is issued under the Federal Acquisition Regulation (FAR) part 35.016(c). The purpose of this BAA is to provide a mechanism by which FDA can utilize industry and academia’s 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 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.

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. In the US, FDA-regulated products account for about 20 cents of every dollar spent by American consumers each year on products that touch the lives of every American daily. The 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. Since 2009, FDA has worked to reduce the harm from all regulated tobacco products. 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 FDA regulated products. FDA must make decisions based on the best available scientific data and using the best tools and methods available 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, ranging from pre-market review of efficacy and safety of many of its regulated products to post-market product surveillance, review of product quality, regulation of product manufacture, and distribution and marketing of products. In the last few years, rapid advances in innovative science have provided new technologies to discover, manufacture, and assess novel medical products. In order to improve regulated product 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. FDA also collaborates with other federal agencies to award research contracts.

Federally Funded Research and Development Centers (FFRDCs) and Government entities (e.g., Government/National laboratories, military educational institutions) 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.

The purpose of this BAA is to solicit proposals that focus on one or more of the following areas of interest as listed below in the regulatory science framework and further described in Part I of this announcement (Table 1). The goal of this regulatory science framework is to harness regulatory science research to accomplish the following three charges that directly align with FDA’s mission to:

I. Modernize development and evaluation of FDA-regulated products II. Strengthen post-market surveillance and labeling of FDA-regulated products III. Invigorate public health preparedness and response of the FDA, patients, and consumers

Multiple awards are anticipated. The amount of resources made available for individual contract awards under this BAA will depend on the quality of the proposals received and the availability of funds. All funding is subject to government discretion and availability.

This BAA is available on www..sam.gov using Keyword Search “FDABAA-26-00123.”

This BAA is a continuously open announcement valid throughout the period from the date of issuance through the closing date specified in the www.sam.gov announcement.

Amendments to this BAA, if necessary, will be posted on the same site when they occur.

Interested parties are encouraged to periodically check the website for updates and potential amendments. Any amendments posted to this announcement will be highlighted and indicated with #. Additional information for FDA BAA Program is available at Regulatory Science Extramural Research and Development Projects | FDA.

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/severable options. Additionally, FDA reserves the right to accept proposals in their entirety or to select only portions of proposals for award. In the event 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.

http://www..sam.gov/ http://www.sam.gov/ https://www.fda.gov/science-research/advancing-regulatory-science/regulatory-science-extramural-research-and-development-projects

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. The FDA will be giving preference to proposals that use a cost reimbursement model vice a firm fixed price model. Research, by definition, does not always produce a deliverable whether due to the nature of the research or the results of the research. By proposing a severable, cost reimbursable contract, risk is reduced to both the government and the awardee. In the future, the FDA may move to only utilizing a cost type model for this BAA award.

Please note, the contract requirements differ between commercial and educational entities. It is HIGHLY recommended that all potential proposal submitters review Part 31

- Contract Cost Principles and Procedures:

31.103 Contracts with commercial organizations.

31.104 Contracts with educational institutions.

Part I: Research Areas of Interest

Through this BAA, FDA seeks to support advanced research and development strategies with potential for regulatory application in the following research areas of interest (See Table 1, which highlights the topic areas that are priorities for FDA for FY 26). This section presents the technical objectives that FDA seeks to achieve through this BAA. Offerors should 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. Because resources are limited, preference will be given to projects geared toward advancing regulatory science—the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products, which include medical devices, drugs, biologics, combination products, veterinary medicine, food, cosmetics, dietary supplements, and tobacco products—that will help advance FDA and HHS priorities1

1 See for example, Makary, MA, Prasad, V. Priorities for a new FDA, JAMA, Aug 19;334(7):565-566. doi:

10.1001/jama.2025.10116. Available at https://pubmed.ncbi.nlm.nih.gov/40493446/ and MAHA Commission (May 2025). The MAHA Report. The White House. Available at https://www.whitehouse.gov/maha/ https://www.acquisition.gov/far/part-31#FAR_31_103 https://www.acquisition.gov/far/part-31#FAR_31_104 https://pubmed.ncbi.nlm.nih.gov/40493446/

Table 1: Fiscal Year 2026 Priority Regulatory Science Research Areas of Interest

FDA-Regulated Areas

Groups & Populations

Charge

C ro ss cu tt in g

Bi ol og ic s

D ev ic es

Dr ug s

V et er in ar y

W om en

Pe rs on s w ith

R ar e

Di se as es

Pe rs on s w ith

Ca nc er s

I. Modernize Development and Evaluation of FDA-Regulated Products A. New Approach Methodologies X X X B. Advanced Manufacturing Approaches X X X X

C. Analytical and Computational Methods X X X X X X X X D. Biomarkers X X X X E. Clinical Outcome Assessment X X X X F. Complex and Novel Clinical Trial Design X X X X X G. Predictive Toxicology X X

H. Methods for Assessing Behavioral, Economic, or Human Factors

X X

I. Approaches to Incorporate Patient and Consumer Input

X X

J. Methods to Assess Real-World Data to serve as Real-World Evidence

X X X X X X X

K. Methods to Assess Data Source Interoperability

X

II. Strengthen Post-Market Surveillance and Labeling of FDA-Regulated Products A. Methods to Assess Real-World Data to Support Regulatory Decision-Making

X X X X

B. Using and Validating Artificial Intelligence Approaches

X X X X X

C. Novel Clinical Trial Design, Statistical and Epidemiologic Methods

X X

D. Automated Reporting Tools for Adverse Events and Active Surveillance

X X X X

E. Methods to Improve Communication About Risk to Patients and Consumers

X

III. Invigorate Public Health Preparedness and Response of the FDA, Patients, and Consumers

A Medical Countermeasures X X X B. Antimicrobial Resistance X

C. Substance Use and Misuse X X

D. Global Product Safety Net X X X X E. Emerging Technologies X

In addition to the product areas that FDA regulates, FDA aims to target innovation in regulatory science that advances the health of the following groups and populations, that are often underrepresented in clinical research resulting in a disproportionate burden of product risk and harm: women (including pregnant and lactating women), children, elderly, racial & ethnic minorities, persons with comorbidities (including chronic health diseases (e.g., cardiovascular disease, diabetes, chronic respiratory diseases, autoimmune diseases) and cancer (including rare cancers)), and persons with rare diseases.

FDA funded regulatory science researchers are encouraged to evaluate populations by including analyses according to sex, age, pregnancy, lactation status, and comorbidities, as appropriate. Investigators should consider sex as a biological variable regarding research aims, study designs, data collection and analyses, and reporting of research findings on cell lines, vertebrate animals, and humans.

FDA funded regulatory science researchers are strongly encouraged to reduce the reliance on animal testing through the development and/or use of new approach methodologies (NAMS). Proposals that include the use of animals should also include considerations on the use of NAMS.

The three charges are foundational to FDA’s mission and thus are not expected to change. We have designated areas to target regulatory science efforts that support the FDA’s mission for each charge. The areas of regulatory science are designed to change with the evolution of science, technologies, and public health needs. Moreover, each area has been designated under a specific charge, and where possible, specific product areas and/or demographics and populations have been labeled. When multiple product areas and/or demographics and populations have been identified for a given regulatory science area, we use the term crosscutting in place of the specific product area and/or groups or population. Through collaborative interactions with stakeholders, we aim to foster robust and innovative approaches to advance regulatory science through the following framework.

Charge I: Modernize development and evaluation of FDA-regulated products A. New Approach Methodologies B. Advanced Manufacturing Approaches C. Analytical and Computational Methods D. Biomarkers E. Clinical Outcome Assessment F. Complex and Novel Clinical Trial Design G. Predictive Toxicology H. Methods for Assessing Behavioral, Economic, or Human Factors I. Approaches to Incorporate Patient and Consumer Input J. Methods to Assess Real-World Data (RWD) to serve as Real-World Evidence (RWE) K. Methods to Assess Data Source Interoperability

Charge II: Strengthen post-market surveillance and labeling of FDA-regulated products

A. Methods to Assess Real-World Data to Support Regulatory Decision- Making

B. Using and Validating Artificial Intelligence Approaches C. Novel Clinical Trial Design, Statistical and Epidemiologic Methods D. Automated Reporting Tools for Adverse Events and

Active Surveillance E. Methods to Improve Communication About Risk to

Patients and Consumers

Charge III: Invigorate public health preparedness and response of the FDA, patients, and consumers

A. Medical Countermeasures (MCMs) B. Antimicrobial Resistance C. Substance Use and Misuse D. Global Product Safety net E. Emerging Technologies

Additional information regarding specific FDA initiatives, and/or center and office priorities can be found in the Part I Appendix.

#Amendments (General, Executive Order Related)

I. Modernize the Development and Evaluation of FDA-Regulated Products

The following focus areas of regulatory science are identified to accomplish Charge I, modernize development and evaluation of FDA-regulated products:

A. New Approach Methodologies (NAMS)

Examples: Novel in vitro systems (e.g., complex in vitro models (CIVM) organoids, microphysiological systems (MPS), organ-on-chips, in silico tools and computational methods; refined in vivo models, use of alternative assays (e.g., high throughput cell-based screening)

1. Crosscutting

a. Integrate an understanding of product quality and safety based on novel genomic, proteomic, metabolomic, and other-OMIC technologies

b. Develop and use NAMS approaches such as MPS, CIVM, and computational modeling to improve the predictability of nonclinical testing and support the regulatory assessment of drug medical products, potentially address the 3Rs (replace, reduce, and refine) of animal use in product testing and scientific research, and support implementation of the Roadmap to Reduce Animal Testing in Preclinical Safety Studies

c. Develop and use novel bench testing methods to support evaluation of medical products

d. Develop and use novel bench testing methods to support evaluation of https://www.fda.gov/files/newsroom/published/roadmap_to_reducing_animal_testing_in_preclinical_safety_studies.pdf https://www.fda.gov/files/newsroom/published/roadmap_to_reducing_animal_testing_in_preclinical_safety_studies.pdf medical products

2. Rare Diseases

a. Develop NAMS such as MPS and CIVM to support regulatory assessments of medical product efficacy and safety for rare diseases2 (such as evaluating the relevance of a biomarker to disease pathology or effects of genetic variants on response to targeted therapies)

3. Women’s Health

a. Develop NAMS in support of the development of diagnostics and therapeutics targeting women including:

i. Methods to evaluate innovative new devices and diagnostics specifically designed for use in women.

ii. Methods to enhance the evaluation of devices used in both men and women to take into consideration sex differences like organ size/anatomy/ physiology/human factors differences that may affect device performance.

iii. Foster the development methods to evaluate sex-matched devices and companion diagnostics.

b. Develop NAMS to evaluate FDA regulated-product safety and effectiveness during pregnancy and lactation.

B. Advanced Manufacturing Approaches

Examples: New medical product manufacturing technologies and processes that can improve quality of FDA-regulated products, address shortages, and/or speed time-to-market; technologies may include but are not limited to continuous, additive and smart manufacturing, inline sensing technologies, or real time quality monitoring.

a. Facilitate the development and evaluation of:

i. Automated or semi-automated in-process monitoring and control systems and methods

ii. Test and validation metrics for advanced manufacturing processes including additive manufacturing, integration and intensification of process unit operations, adaptive processes, remote monitoring, and automation of operations

iii. New or improved ways to quickly measure protein, cell, and gene therapy product quality and manufacturing consistency

iv. Techniques and digital technologies that allow for feedback of process data (e.g., in situ monitoring) to dynamically improve product design, development, manufacturing, life cycle risk management, and responsiveness

b. Investigate the effect of advanced manufacturing on product quality including by:

2 The Orphan Drug Act defines a rare disease as a disease or condition that affects less than 200,000 people in the United States.

https://www.fda.gov/industry/designating-orphan-product-drugs-and-biological-products/orphan-drug-act-relevant-excerpts

i. Examining specific, novel material and manufacturing technologies to determine how they impact product failure rates

ii. Researching technologies and materials that enhance control over critical quality attributes for medical products and their key inputs, including drug substances, drug products, polymers, medical devices, and accessories

iii. Improving automated or closed loop manufacturing capabilities for complex drugs and biologics

c. Investigate how advanced manufacturing can improve medical supply chain robustness to shortages, resilience to disruption, and capacity for demand fluctuations including:

i. Supply chain visibility, monitoring, and data sharing processes and platforms

ii. Decreased reliance on foreign supply chains, especially for medical products used for care and treatment of chronic diseases

d. Develop improved methods and tools to detect and measure the physical structure, chemical properties, and biological behavior of engineered nanomaterials, additively manufactured pharmaceuticals (pharmaco-printed products), biological products (e.g., therapeutic proteins or monoclonal antibodies) and complex dosage forms (e.g., transdermal patches, inhalation delivery systems, and targeted drug delivery systems) in FDA-regulated products

e. Investigate or develop methods to increase implementation and adoption of advanced manufacturing methods for essential medicines, devices, and vaccines, including demonstrations of their value proposition to patient access, economics, efficiency, and increased supply chair resilience including for rare and/or chronic conditions

2. Oncology

a. Create novel technologies and approaches to evaluate both efficacy and safety for neoantigen-based therapies that incorporate unique features of individual cancers, neoantigen and immune responses. Examples may include neoantigen-based vaccines, redirecting T-cell specificity by genetically modifying T cells with receptors specific against neoantigen-derived epitopes (Neo-antigen-based therapies for cancer)

3. Biologics

a. Explore novel applications of advanced (e.g., integrated and continuous) manufacturing processes for complex biologic products, such as vaccines, tissue-engineered products, and cell and gene therapies a n d describe the potential impact of the proposed enabling technology on process control strategy and its readiness for broad implementation in the biopharmaceutical industry including:

i. Closed and automated manufacturing processes

ii. Modular manufacturing platforms with integrated in-process testing capabilities

iii. Manufacturing process modeling and simulation

iv. Advanced or novel process analytical technologies for real time process control and release testing

v. Improved cell lines and improved upstream cell culture production processes for vaccine antigen or viral vector manufacturing

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

i. Identifying critical quality attributes (CQAs) and developing advanced assays for characterization of CQAs in products for gene and cell therapies

ii. Developing reference materials and standards for gene and cell therapies

4. Drugs

a. Develop improved methods for the manufacturing of sterile drug products including rapid monitoring for the detection of microbial contamination

C. Analytical and Computational Methods including Artificial Intelligence Approaches

Examples: Analytical method validation, bio-predictive dissolution method, in vitro-in vivo correlation development, development and use of computational methods and in-silico modeling; simulation-based approaches; advanced quantitative methods-based modeling; predictive analytics such as predictive modeling, model-informed drug development; artificial Intelligence (AI) and machine Learning (ML)

a. Develop and evaluate the use of model-based digitally integrated systems, artificial intelligence, machine learning and simulation in production or quality system activities including generative design, production simulation and simulated process validation, digital twins of manufacturing processes for product quality control, AI/ML application to quality system activities, Intelligent design control, closed loop risk-management

b. Develop computer models of cells, organs, and systems (including the impact of hormones) to predict product risk, safety, and efficacy of FDA regulated products including potential interactions with drugs and dietary supplements

c. Develop computer models that integrate pharmacokinetic, pharmacodynamic, materials science, or mechanistic safety data to predict clinical risk and corroborate post-market findings in different patient populations

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

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

f. Explore the role of digital health technologies in the evaluation of new medical products

g. Identify opportunities and develop computer simulation and modeling to streamline data analysis and model biological systems and their responses to agents of concern, such as toxins, toxic compounds, pathogens, and biomaterials

h. Develop clinical trial simulation models that can reveal interactions between drug effects, patient characteristics, and disease variables influencing outcomes

2. Oncology

a. Develop, optimize, and standardize bioinformatic algorithms for neoantigen identification and development of personalized therapies to help ensure the efficacy and safety of neoantigen-based products in the treatment of patients with cancer

b. Utilize text mining and/or artificial intelligence to analyze, assess and interpret the scientific literature and other public databases of genomic and transcriptomic analyses of pediatric cancers to (1) identify and prioritize drugs directed against molecular targets relevant to the growth and progression of pediatric cancers that have shown antitumor activity in adults, have not been previously studied in pediatric clinical trials, and may benefit pediatric patients with cancer (2) elucidate the relevance of specific molecular targets to the growth and/or progression of pediatric tumors to understand and assess target actionability

c. Develop novel selection/response biomarkers using algorithms combining different types of medical images including radiology images (e.g., CT, PET) and/or histopathology images combined with novel analysis approaches such as radiomics and artificial intelligence/machine learning

3. Rare diseases

a. Develop rare disease clinical trial simulation models that can reveal interactions between medical product effects and prognostic or predictive variables (e.g., patient characteristics and disease variables influencing outcomes). These models should address the challenges posed by small populations (e.g., pediatric population, patients with rare diseases) and heterogeneity of patients within the small populations.

4. Women’s Health

a. Develop analytical and computational methods to evaluate sex differences in the safety and efficacy of FDA regulated products. Develop novel tools to evaluate regulated-product toxicity or the safety and efficacy during pregnancy and lactation

5. Biologics

a. Develop analytical and computational tools and models to predict immunogenicity for biologic products including modified protein sequences for mitigation of immunogenicity risk

6. Devices

a. Develop analytical and computational modeling and simulation methods to promote the use of in-silico assessment of devices for pediatrics and representative populations

b. Explore methods for patient input (e.g., through patient-generated data) into the development of analytical and computational methods related to medical devices.

7. Drugs

a. Advance analytical and computational methodologies to generate clinical evidence using AI/ML sufficient to support regulatory use including:

i. Demonstrating how clinical evidence generated from the use of AI could inform clinical studies for regulatory use

ii. Developing and validating tools and models that assess fitness of

AI/ML use to support regulatory decision making (e.g., using a placebo digital twin)

iii. Developing and validating methods to predict medical product performance using AI/ML

iv. Evaluating ML methods with a focus on identifying and/or addressing sources of methodological bias

v. Advancing causal AI inference

b. Generics (For more information, see the GDUFA science and research priority initiatives for FY 2026)

i. Develop methods for generics to address harmful impurities such as nitrosamines including:

1. Advancing the understanding how ingredients in generic drug products may either contribute to or mitigate the formation of harmful impurities such as nitrosamine adducts (including nitrosamine drug substance related impurities (NDSRIs)), evaluate the risk of human exposure to these impurities, and develop methods for abbreviated new drug application (ANDA) applicants to efficiently address the potential risks

ii. Enhance the efficiency of equivalence approaches for complex active ingredients including:

1. Improve advanced orthogonal methods for the characterization of chemical compositions, molecular structures, and distributions of complex active ingredients and associated impurity profiles so as to elucidate attributes of complex active ingredients and support immunogenicity risk assessments that may be critical to their performance and, thereby, support the development of efficient characterization-based bioequivalence (BE) and pharmaceutical equivalence (PE) approaches

iii. Enhance the efficiency of BE approaches for complex dosage forms and formulations including:

1. Improve efficient characterization- based (in vitro) BE approaches for complex dosage forms by identifying relevant critical quality attributes (CQAs) to characterize, and suitable test methods for doing so

iv. Enhance the efficiency of BE approaches for complex routes of delivery including:

https://www.fda.gov/drugs/generic-drugs/generic-drug-research-priorities-projects https://www.fda.gov/drugs/generic-drugs/generic-drug-research-priorities-projects https://www.fda.gov/drugs/generic-drugs/generic-drug-research-priorities-projects

1. Advancing the understanding of how ingredients and other aspects of a formulation influence drug absorption via complex routes of delivery, building in vivo predictive models and identifying corresponding failure modes for BE, to support the development of efficient BE approaches for these

v. Enhance the efficiency of equivalence approaches for complex drug-device combination products including:

1. Evaluate the impact of identified design differences in the user-interfaces, hardware, software or propellants between a prospective generic and the reference listed drug to elucidate how such design differences may cause medication errors if the product was dispensed to a patient, or impact the BE, therapeutic equivalence or post- marketing safety of generic drug-device combination products

vi. Improve the efficiency of BE approaches for oral and parenteral generic products including:

1. Advancing the understanding of how ingredients in non-complex drug products may modulate bioavailability, and improve bio-predictive dissolution methods, in vitro-in vivo correlations (IVIVCs), as well as in silico models to support the expansion of biowaivers and to support global harmonization(including expanding the eligibility for biopharmaceutics classification system (BCS)- based biowaivers and efficient methods for the evaluation of additional strengths of oral drug products and establishing approaches to manage potential risks related to subject safety more consistently when developing in vivo BE study recommendations and elucidating potential failure modes for BE with special populations (e.g., pediatric, or geriatric patients))

vii. Facilitate the utility of model-integrated evidence (MIE) to support demonstrations of BE including:

1. Develop tools and advance approaches to integrate complementary in silico (modeling), in vivo, and in vitro evidence in ways that collectively mitigate the risk of failure modes for BE and support a framework for virtual BE studies including research on the use of MIE to evaluate failure modes for BE and to optimize the design of BE studies3

viii. Expand the use of artificial intelligence (AI) and machine learning (ML) tools including:

1. Build systems and infrastructure that support the functionality of AI/ML tools which FDA can use to improve the efficiency and consistency of scientific assessments and advice including using

3 For example, while it may not be feasible to adequately characterize the long-term bioavailability of drugs from for long-acting injectable, insertable or implantable (collectively, LAI) products using in vivo or in vitro methods alone, it may be feasible to integrate limited in vivo and in vitro data with PBPK models that generate the remaining evidence needed to support a demonstration of BE.

AI/ML tools such as natural language processing (NLP) that automate the assembly of key information routinely assessed during the development of recommendations in Product-Specific Guidelines (PSGs), or during the assessment of ANDAs, as well as AI/ML tools that facilitate planning and resource allocation to support GDUFA commitments

8. Veterinary

a. Develop a rigorous bioinformatics pipeline for evaluating intended genomic alterations in animals including

i. Confirming intended genetic modifications.

ii. Detecting unintended alterations from embryo-edited and cloned pigs

iii. Accepting data from multiple sequencing platforms

b. Develop novel in vitro dissolution methods to identify optimal equipment and methodologies for dissolution testing, determine formulation and manufacturing factors that influence between-strength comparability (Critical Quality Attributes (CAQs), and evaluate the impact of chewing mechanics on drug release profiles and how identified CQAs influence this relationship to enable the efficient evaluation of formulation or manufacturing differences between strengths, and supporting post-approval changes

c. Evaluate the critical material attributes (CMAs) of flavor components in animal drug products, including both hard compressed tablets and soft chewable formulations focusing on characterizing flavor components using advanced analytical techniques, assessing flavor component effects on product quality, stability, drug release, and bioavailability, and developing alternative testing methods to replace traditional animal testing through biorelevant dissolution methods and in vitro permeation studies to develop rapid quality assessment methods for immediate-release flavored dosage forms, quality-by-design frameworks for flavor component selection and control, and create risk assessment tools for evaluating flavor component changes

D. Biomarkers

Examples: Molecular biomarkers such as specific gene mutations, protein levels, or metabolic signatures; imaging biomarkers: radiological or other imaging features that indicate biological processes, examples include tumor size measurements or specific imaging patterns; digital biomarkers: data collected from digital health technologies like wearable devices, examples include heart rate variability or activity patterns; biomarker development and regulatory acceptance encompasses biomarker identification; qualification;

evaluation, and validation.

a. Advance methodologies for qualification of biomarkers and to support analytical and clinical validation of biomarkers that can provide objective measures to replace or complement subjective classifications of disease diagnosis or progression

b. Advance biomarker and clinical tool validation to reduce disease heterogeneity in clinical trials by refining clinical disease classification or inform reproducible patient stratification based on risk factors in therapeutic areas with unmet need

c. Assess concordance between animal and human biomarkers of toxicity and determine how the performance of these biomarkers and their interpretation may vary across different organ systems and human populations

d. Evaluate the biomarkers and the role of the microbiome in contributing to adverse responses through alterations in metabolism or other mechanisms, especially in pediatrics, and the associated long-term health impact

e. Evaluate strategies for validation of innovative biomarkers or clinical tools, including those that are derived from digital health technologies, that offer a sensitive and specific reflection of the pathophysiologic state for progressive diseases with unmet need

f. Demonstrate how terminology for encoding biomarkers in real-world data can integrate with patient care data encoding standards recommended by the Office of the National Coordinator (SNOMED, LOINC, and RxNorm)

g. 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 tumor vaccines, and for stem cell-derived therapies)

2. Oncology

a. Advance the understanding of tumor biomarkers (e.g., spatialomics, transcriptomic, proteomic analyses) that would predict subsequent radiologic and clinical outcomes (e.g., prolonged stability/ subsequent response vs. continued progression) in patients who have radiologic progression without signs of clinical progression that allows for discretionary continuation of current immune-checkpoint inhibitor therapy

b. Further the characterization of molecular mechanisms of immunologically cold tumors that could potentially translate into therapeutic interventions (

c. Identify and explore approaches to validate biomarkers (including liquid biopsy and multiomic biomarkers) that capture the dynamic nature of cancer and treatment resistance, including for treatment escalation/de-escalation in the neoadjuvant, adjuvant, advanced and recurrent disease settings)

d. Conduct studies to compare the analytical and clinical performance of local and centralized molecular tests used for patient enrollment on cancer clinical trials

e. Conduct studies to understand why tumors originating from different organ sites with molecular alterations in the same target respond differently to therapies to inform future potential tumor agnostic drug development

f. Develop preclinical models to evaluate the antitumor activity of immunotherapy agents in pediatric solid tumors (including CNS malignancies) to facilitate decision-making regarding their potential evaluation in pediatric oncology clinical trials

g. Develop innovative approaches to identify new biologically driven opportunities for clinical development of previously approved drugs (or drugs for which development has been discontinued) in rare cancers

3. Women’s health

a. Identify, develop, evaluate, and qualify biomarkers that can better measure and predict the safety and efficacy of medical products in women in preclinical and clinical studies and identify sex differences in the performance of medical products

4. Rare Diseases

a. Develop, validate, and qualify novel biomarkers for use in rare disease patient diagnosis, early phase dose-finding studies, and the evaluation of efficacy and safety (e.g., surrogate endpoints for accelerated approval, confirmatory evidence of effectiveness)

E. Clinical Outcome Assessment (COA)

COA is a key tool for patient focused drug development (PFDD) and medical device development. Examples: Patient-reported outcomes; clinician-reported outcomes; performance outcomes, observer-reported outcomes.

1. Oncology

a. Investigate the sensitivity and measurement characteristics of existing patient-reported or digitally derived physical function measures in patients with rare and ultra-rare cancers

b. Investigate open label bias including the evaluation of the impact of patient knowledge of their treatment on patient-reported outcomes in cancer clinical trials)

c. Study existing methods and develop novel methods to measure patient-reported symptomatic ocular toxicity in patients receiving anti-cancer therapy

2. Women’s Health

a. Assess the impact of lifestyle factors, including but not limited to diet, exercise, and stress on health conditions that uniquely or disproportionately impact women

b. Develop and validate new patient-reported outcome measures that capture the unique experiences and challenges faced by women in relation to their health

3. Rare Diseases

a. Develop and characterize novel functional assessments (COA-based, digital health technology-based) to be utilized for rare disease drug and device development, particularly for indications with small, heterogenous patient populations, to measure outcomes for clinical benefit and/or safety

4. Devices

a. Develop COAs and methods for predicting, evaluating, and monitoring clinical performance of devices, including the use of data from digital health technologies (DHTs)

b. Modify or adapt existing COA instruments for a representative population, regulatory use, intended use, (e.g. pediatric population for myopia control devices) or context of use, including at home, and collect evidence to support the modification or adaptation

c. Explore combined use and respective performance of COAs and patient-generated health data in as study endpoints, components of clinical or post-market datasets and/or artificial intelligence studies

d. Identify and if possible, quantify, known biases (e.g., open-label bias, placebo effect, sex bias) for patient-reported outcomes

e. Investigate patient preferences in benefit-risk assessments and clinical trial design (including endpoints) for representative populations

f. Explore methods for reducing the burden of conducting patient preference information studies early in the total product life cycle (e.g., use of case examples)

g. Conduct studies among representative populations that investigate patient preferences in benefit-risk assessments, proposed endpoints, or potential device features to advance understanding and aid regulatory decisions

F. Complex and Novel Clinical Trial Design

Examples: Advancing the use of complex adaptive, Bayesian, and other novel clinical trial designs(methods may include design elements and/or analysis approaches that generally require computer simulations to determine the statistical properties of a clinical trial (e.g., power optimization, Type I error control)) and methods for considering different endpoints, approaches for utilizing and validating artificial intelligence, machine learning, and natural language processing.

1. Oncology

a. Develop innovative trial designs (e.g., master protocols) for a group of cell or neoantigen-based therapies that were developed using a common platform (but target distinct antigens) to compare safety and clinical activity among products to identify the most promising candidates for further development

b. Develop innovative clinical trial designs to establish safety and efficacy in cell and gene therapies in randomized clinical studies where feasible

c. Define and consider methods for validation of novel clinical trial endpoints and how these endpoints perform relative to traditional endpoints used in clinical trials to support regulatory approval oncology products, such as overall response rate, progression-free survival (PFS), and overall survival

d. Evaluate statistical methods for intercurrent events in oncology clinical trials, including but not limited to cross-over, treatment switch, treatment discontinuation, subsequent progressions (e.g., for PFS2), or other events that could induce informative censoring

e. Develop clinical and statistical input for novel methods to isolate the contribution of treatment effect of combination therapies and the combination contribution of phase for oncology therapeutics which are used in more than one phase of care (ex. neoadjuvant, adjuvant and/or maintenance)

f. Develop innovative clinical trial designs to find the optimal dose for oncology therapeutics

g. Advance the design and analysis of pragmatic trials, for example using cluster randomization techniques (

h. Develop statistical methods for quantitative bias assessment when RWD is used in…