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Translational Science Resources

We offer a variety of resources that you can use to better understand translational science and the challenges it is addressing.

Our Translational Science Resources

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Amanda Vogel, Ph.D., M.P.H.
TDB Program Staff


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Translational science is the field that generates scientific and operational innovations that overcome the long-standing barriers along the translational research pipeline. By advancing translational science, we can improve the process of turning research observations into health solutions and ultimately bring more treatments to all people more quickly. Explore these resources to learn more about translational science.

Translational Science Infographic

Developing new treatments can take a very long time. This infographic highlights some of the challenges as well as translational science approaches we’re using to overcome them.


Drug Development Illustrated: Infusing Equity Into Preclinical Research

Historically, the focus on equity and reducing disparities in biomedical research was most often applied within the context of clinical research or health care delivery. The preclinical environment — situated in the center of the biomedical research ecosystem and bookended by clinical research and health care delivery — was generally excluded because of the presumed objectivity of bench science research in this phase. This presumed objectivity led to a lack of attention paid to the impact of broader infrastructural and global disparities on the understanding of rare diseases and the inclusion of the communities that have been historically underserved and underrepresented in biomedical research.

NCATS recognized the absence of equity considerations in the preclinical research phase and identified ways to begin understanding and addressing these gaps. The Division of Preclinical Innovation (DPI) Therapeutic Development Branch (TDB) embarked on an initiative to infuse equity into preclinical research and drug development, with rare diseases as the exemplar.

Patients, advocates, community knowledge interpreters and research partners reported unfamiliarity with the specifics of the drug development phase and requirements to proceed after initial drug discovery. They conveyed a need for educational resources that describe the preclinical journey and detail the drug development process.

To address this educational gap and respond to partner feedback, NCATS DPI TDB developed a Knowledge Guide. This resource was created to help partners become familiar with the preclinical phase of the drug development process. The Guide is expected to inform and engage a broad audience; reduce knowledge disparities; and advance equity, especially in rare disorders and for those underserved and historically underrepresented in biomedical research.

The Knowledge Guide illustrates the drug development journey, starting from when a drug candidate is chosen. A team of multidisciplinary scientists uses project management best practices to move through a two-stage preclinical process toward clinical development (Figure A). Paired with Figure A is a step-by-step description of how scientists develop a drug that will be safe to test in humans (Figure B). The Guide also includes key concepts and highlights an ecosystem that conveys the importance of equity throughout the span of preclinical biomedical research (Figure C).

Depiction of the drug development process as a metaphorical journey through a canyon with a central river. The process begins with selecting a drug candidate and assembling a multidisciplinary research team. The journey encompasses preclinical development through to investigational new drug (IND) application. The river emphasizes that equity, community engagement and patient advocacy run through all steps in the journey to New Drug Application (NDA). A kayak and canoe in the river indicate optional paths for repurposed or repositioned drugs. Key team members making the journey include Toxicology, (Tox) Chemistry, Manufacturing & Controls (CMC), Drug Metabolism and Pharmacokinetics (DMPK), Proof of Concept, (PoC) and Project Management (PM). After crossing the river, the team arrives at the pre-investigational new drug (pIND) milestone. Following directional signs for regulatory, IND-enabling activities, Good Laboratory Practice (GLP) Toxicology, and Good Manufacturing Practice (GMP) Drug Substance/Drug Product (DS/DP), team members climb up a cliff. When they arrive at the top, they are greeted by a helicopter representing the IND milestone. On distant canyon peaks, clinical trial Phases 1 through 3 are featured. A hot air balloon on the horizon symbolizes the ultimate NDA for approval for human use in clinical care.

Infusing Equity Into Preclinical Drug Development

Depiction of the drug development process as a metaphorical journey through a canyon with a central river.

Infusing Equity Into Preclinical Drug Development

Depiction of the drug development process as a metaphorical journey through a canyon with a central river. The process begins with selecting a drug candidate and assembling a multidisciplinary research team. The journey encompasses preclinical development through to investigational new drug (IND) application. The river emphasizes that equity, community engagement and patient advocacy run through all steps in the journey to New Drug Application (NDA). A kayak and canoe in the river indicate optional paths for repurposed or repositioned drugs. Key team members making the journey include Toxicology, (Tox) Chemistry, Manufacturing & Controls (CMC), Drug Metabolism and Pharmacokinetics (DMPK), Proof of Concept, (PoC) and Project Management (PM). After crossing the river, the team arrives at the pre-investigational new drug (pIND) milestone. Following directional signs for regulatory, IND-enabling activities, Good Laboratory Practice (GLP) Toxicology, and Good Manufacturing Practice (GMP) Drug Substance/Drug Product (DS/DP), team members climb up a cliff. When they arrive at the top, they are greeted by a helicopter representing the IND milestone. On distant canyon peaks, clinical trial Phases 1 through 3 are featured. A hot air balloon on the horizon symbolizes the ultimate NDA for approval for human use in clinical care.
NCATS is making these materials available for use via a CC BY-ND 4.0 License.
https://creativecommons.org/licenses/by-nd/4.0/
Key Concepts and Ecosystem. 'Key Concepts Ecosystem' outlines essential functions and activities in preclinical research and development. The left side of the graphic is labeled “Key Concepts” and includes the following activities: Target Product Profile (TPP): A document describing the important features of a drug to effectively treat a disease in a specific population. The TPP helps guide preclinical development strategy. Regulatory Strategy: The steps and processes taken for a drug candidate to meet the requirements of regulatory agencies like the U.S. Food and Drug Administration during development and that safely allow for further testing in people. Good Laboratory Practice (GLP): The rules and guidelines that ensure the data collected during laboratory studies are high quality and trustworthy. Project Plan: A document that lists the key steps and research studies needed to develop a drug. It includes who is responsible for which steps, the overall timeline and important decision points along the way. Research Team: A group of researchers from multiple specialized fields (e.g., process chemistry, pharmacokinetics, toxicology) who work together to develop a drug. Clinical Plan: A document that outlines how a potential treatment will be tested in people. It proposes the type and number of participants, how the study will be conducted and what data will be collected. It informs the preclinical research project plan. Good Manufacturing Practice (GMP): The rules and guidelines that ensure a drug is produced safely and consistently and meets the highest quality-control standards. Reposition: Take a drug that has been developed to treat one condition — but has not yet been approved by a regulatory agency — and develop it to treat another. Repurpose: Take a drug that has already been approved by a regulatory agency to treat one condition and develop it to treat another. The right side of the graphic is labeled “Ecosystem” and includes a heading describing equity and the following elements and activities: Equity: Infusing equity in preclinical research and development creates an environment where all people can participate and can access and benefit from drug development and therapies. It also means the needs of historically underrepresented populations are considered and deliberate care is taken to avoid causing harm. Investing in equity-driven research enhances preclinical innovation by including diverse factors influencing health, such as genetics and environment. Resources: The funding, personnel, equipment and facilities required for drug development. Representation: The inclusion of the priorities and perspectives of diverse populations in drug development studies to ensure the medicinal product is not only safe but beneficially effective for all patients, particularly those who have been underserved by research. Genetic Diversity: The differences among people in genes and their expression that can cause various diseases and affect how they respond to the drug. Knowledge: Public access to clear and comprehensive information about processes, regulations and research. Providing this access includes publishing scientific findings and results, as well as creating educational materials and resources for all. Rare Disorders: Diseases or conditions affecting fewer than 200,000 individuals in the United States. Community Engagement: The involvement of patients, caregivers and other partners in drug development to ensure that their needs, perspectives and priorities are considered. Project Management: Planning, organizing and coordinating resources and communication to help a research project team realize specific goals in drug development. Patient Advocacy: The support and representation of patient interests, perspectives and priorities in drug development. Collaboration: The joint efforts of individuals or groups working together to achieve a common research goal or solve a scientific problem.

Key Concepts and Ecosystem

"Key Concepts Ecosystem" outlines essential functions and activities in preclinical research and development.

Key Concepts and Ecosystem

Key Concepts and Ecosystem. 'Key Concepts Ecosystem' outlines essential functions and activities in preclinical research and development. The left side of the graphic is labeled “Key Concepts” and includes the following activities: Target Product Profile (TPP): A document describing the important features of a drug to effectively treat a disease in a specific population. The TPP helps guide preclinical development strategy. Regulatory Strategy: The steps and processes taken for a drug candidate to meet the requirements of regulatory agencies like the U.S. Food and Drug Administration during development and that safely allow for further testing in people. Good Laboratory Practice (GLP): The rules and guidelines that ensure the data collected during laboratory studies are high quality and trustworthy. Project Plan: A document that lists the key steps and research studies needed to develop a drug. It includes who is responsible for which steps, the overall timeline and important decision points along the way. Research Team: A group of researchers from multiple specialized fields (e.g., process chemistry, pharmacokinetics, toxicology) who work together to develop a drug. Clinical Plan: A document that outlines how a potential treatment will be tested in people. It proposes the type and number of participants, how the study will be conducted and what data will be collected. It informs the preclinical research project plan. Good Manufacturing Practice (GMP): The rules and guidelines that ensure a drug is produced safely and consistently and meets the highest quality-control standards. Reposition: Take a drug that has been developed to treat one condition — but has not yet been approved by a regulatory agency — and develop it to treat another. Repurpose: Take a drug that has already been approved by a regulatory agency to treat one condition and develop it to treat another. The right side of the graphic is labeled “Ecosystem” and includes a heading describing equity and the following elements and activities: Equity: Infusing equity in preclinical research and development creates an environment where all people can participate and can access and benefit from drug development and therapies. It also means the needs of historically underrepresented populations are considered and deliberate care is taken to avoid causing harm. Investing in equity-driven research enhances preclinical innovation by including diverse factors influencing health, such as genetics and environment. Resources: The funding, personnel, equipment and facilities required for drug development. Representation: The inclusion of the priorities and perspectives of diverse populations in drug development studies to ensure the medicinal product is not only safe but beneficially effective for all patients, particularly those who have been underserved by research. Genetic Diversity: The differences among people in genes and their expression that can cause various diseases and affect how they respond to the drug. Knowledge: Public access to clear and comprehensive information about processes, regulations and research. Providing this access includes publishing scientific findings and results, as well as creating educational materials and resources for all. Rare Disorders: Diseases or conditions affecting fewer than 200,000 individuals in the United States. Community Engagement: The involvement of patients, caregivers and other partners in drug development to ensure that their needs, perspectives and priorities are considered. Project Management: Planning, organizing and coordinating resources and communication to help a research project team realize specific goals in drug development. Patient Advocacy: The support and representation of patient interests, perspectives and priorities in drug development. Collaboration: The joint efforts of individuals or groups working together to achieve a common research goal or solve a scientific problem.
NCATS is making these materials available for use via a CC BY-ND 4.0 License.
https://creativecommons.org/licenses/by-nd/4.0/
Preclinical Drug Development: Stages and Milestones Infographic. The ecosystem of preclinical drug development, divided into early and late preclinical stages. Emphasis is on the iterative nature of drug development, ensuring regulatory compliance and safety before human clinical trials. Early Preclinical Stage: Scientists carry out more rigorous studies of the selected drug candidate in cells, tissues and animals to better understand its effectiveness, movement in the body, metabolism and general safety. In parallel, processes to manufacture and formulate the drug at scale are explored. Efficacy/Proof of Concept (PoC): The ability of a drug to produce the desired therapeutic effect. These robust studies in relevant disease models confirm preliminary discovery data. Process Development (CMC): The design and optimization of manufacturing steps to scale production of a drug. An environmentally friendly process, increased production efficiency and lowered cost are the objectives. Drug Metabolism & Pharmacokinetics (DMPK): Studies of the absorption, distribution, metabolism and elimination of a drug by the body. They show where the drug goes in the body and what the body does to the drug. Formulation Development (CMC): The selection and optimization of dosage form (e.g., tablet, liquid). This balances factors like route of administration, DMPK properties and shelf life of the clinical product. Dose Range Finding Toxicology: Exploratory study to establish the relationship among efficacy, clinical response and safety across a range of doses. It informs design of the later stage GLP toxicology assessments. Early Preclinical Milestone: Pre-Investigational New Drug (pIND): A formal interaction with regulatory agencies (e.g., U.S. Food and Drug Administration [FDA]) to discuss further development plans to enable filing an IND application. Guidance is provided to ensure compliance with regulatory standards. Late Preclinical Stage includes: GLP Toxicology & Safety Evaluation: Animal and cell-based studies conducted in compliance with Good Laboratory Practice (GLP) regulations to determine how different amounts of the drug may affect the body and identify any risks that could come with using the drug. These animal studies predict the overall safety of the drug. GMP Manufacture of a Formulated Drug Product: The production of the final dosage form including the use of any device for the drug product. This is done in compliance with current Good Manufacturing Practices (GMP) regulations to ensure that all registered specifications are met consistently. GMP Manufacture of a Drug Substance: The production of the active pharmaceutical ingredient in compliance with GMP regulations. This ensures the safe and reliable manufacturing of a well-characterized product. Late Preclinical Milestone: IND: A formal application submitted to regulatory agencies (e.g., FDA) for review of all the preclinical data. The agencies will communicate whether it is safe to proceed to human clinical trials. The stage of development in which the drug is manufactured at commercial scale and its safety and toxicology are assessed in accordance with stringent regulatory requirements. These activities are IND-enabling, in preparation for human clinical trials. This is a general representation of small molecule developments. Other modalities of drug development may differ in some details. Note: This content was generated with some assistance from ChatGPT-4o, an AI language model developed by OpenAI.

Preclinical Drug Development: Stages and Milestones Infographic

The ecosystem of preclinical drug development, divided into early and late preclinical stages. Emphasis is on the iterative nature of drug development, ensuring regulatory compliance and safety before human clinical trials.

Preclinical Drug Development: Stages and Milestones Infographic

Preclinical Drug Development: Stages and Milestones Infographic. The ecosystem of preclinical drug development, divided into early and late preclinical stages. Emphasis is on the iterative nature of drug development, ensuring regulatory compliance and safety before human clinical trials. Early Preclinical Stage: Scientists carry out more rigorous studies of the selected drug candidate in cells, tissues and animals to better understand its effectiveness, movement in the body, metabolism and general safety. In parallel, processes to manufacture and formulate the drug at scale are explored. Efficacy/Proof of Concept (PoC): The ability of a drug to produce the desired therapeutic effect. These robust studies in relevant disease models confirm preliminary discovery data. Process Development (CMC): The design and optimization of manufacturing steps to scale production of a drug. An environmentally friendly process, increased production efficiency and lowered cost are the objectives. Drug Metabolism & Pharmacokinetics (DMPK): Studies of the absorption, distribution, metabolism and elimination of a drug by the body. They show where the drug goes in the body and what the body does to the drug. Formulation Development (CMC): The selection and optimization of dosage form (e.g., tablet, liquid). This balances factors like route of administration, DMPK properties and shelf life of the clinical product. Dose Range Finding Toxicology: Exploratory study to establish the relationship among efficacy, clinical response and safety across a range of doses. It informs design of the later stage GLP toxicology assessments. Early Preclinical Milestone: Pre-Investigational New Drug (pIND): A formal interaction with regulatory agencies (e.g., U.S. Food and Drug Administration [FDA]) to discuss further development plans to enable filing an IND application. Guidance is provided to ensure compliance with regulatory standards. Late Preclinical Stage includes: GLP Toxicology & Safety Evaluation: Animal and cell-based studies conducted in compliance with Good Laboratory Practice (GLP) regulations to determine how different amounts of the drug may affect the body and identify any risks that could come with using the drug. These animal studies predict the overall safety of the drug. GMP Manufacture of a Formulated Drug Product: The production of the final dosage form including the use of any device for the drug product. This is done in compliance with current Good Manufacturing Practices (GMP) regulations to ensure that all registered specifications are met consistently. GMP Manufacture of a Drug Substance: The production of the active pharmaceutical ingredient in compliance with GMP regulations. This ensures the safe and reliable manufacturing of a well-characterized product. Late Preclinical Milestone: IND: A formal application submitted to regulatory agencies (e.g., FDA) for review of all the preclinical data. The agencies will communicate whether it is safe to proceed to human clinical trials. The stage of development in which the drug is manufactured at commercial scale and its safety and toxicology are assessed in accordance with stringent regulatory requirements. These activities are IND-enabling, in preparation for human clinical trials. This is a general representation of small molecule developments. Other modalities of drug development may differ in some details. Note: This content was generated with some assistance from ChatGPT-4o, an AI language model developed by OpenAI.
NCATS is making these materials available for use via a CC BY-ND 4.0 License.
https://creativecommons.org/licenses/by-nd/4.0/

Drug Discovery, Development and Deployment Maps

The Drug Discovery, Development and Deployment Maps (4DM) represent the modern therapeutic development process to more easily identify opportunities to expedite it. The maps provide a common framework for discussing the therapeutic development process and serve as an education tool for those who are new to it. They also can facilitate discussions on innovative solutions to existing bottlenecks.

Two versions of the 4DM are available: one for small molecules (Figure A), and another for biologics, using monoclonal antibodies as the representative therapeutic (Figure B). They illustrate some of the unique differences between the development of these products. Both files are licensed to the public under the Creative Commons Attribution-Share Alike International 4.0 (CC BY-SA 4.0) license, which allows use and adaption as long as the user provides attribution and shares any adaptations back to the public under the same license. Read more about the 4DM.

Small 4D Molecule Map

Figure A: Small molecules

Biologics 4D Molecule Map

Figure B: Biologics


Translational Scientists

The Role of Translational Scientists

There is tremendous need for people to discover, develop and disseminate the next generation of science and technology to improve human health. Watch the video above to learn more about translational scientists.

Translational Science Characteristics

Translational scientists are innovative and collaborative, searching for ways to break down barriers in the translation process.

Learn more about being a translational scientist.

Last updated on October 4, 2024