FDA-TRACK: Center for Veterinary Medicine - Emerging Technologies
FDA's Center for Veterinary Medicine (CVM) regulates animal drugs, animal devices and animal food under the Federal Food, Drug and Cosmetic Act. CVM protects and promotes the health of humans and animals by ensuring the safety of the American food supply, the safety of animal food and devices, and the safety and effectiveness of animal drugs.
Emerging technologies have the potential to influence multiple fields, including medicine, animal conservation, and agriculture. Modern molecular technologies, such as genetic engineering and genome editing, allow for the development of intentional genomic alterations (IGAs) in animals for purposes such as improving food production, research into human disease, production of substances for pharmaceutical use, and as sources of cells, tissues, or organs for transplantation into humans. Other products of emerging technologies such as animal cells, tissues, and cell- and tissue-based products (ACTPs) offer potential novel therapies for a variety of veterinary medical needs, including musculoskeletal diseases and inflammatory conditions.
CVM is committed to using a science- and risk-based approach to regulate products of emerging technologies. Our approach ensures consumer confidence and fosters development of emerging technology products with the potential to improve human and animal health. Based on our key initiatives, we established the following four goals to support this effort:
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Goal 1: Facilitate advancements in the development of emerging technology products to improve human and animal health through enhancements to the Veterinary Innovation Program
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Goal 2: Enhance the efficiency and predictability of our regulatory process
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Goal 3: Continue to refine and improve upon our science- and risk-based oversight approach for emerging technology products
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Goal 4: Increase transparency to stakeholders through public outreach and communication
Goal 1: Facilitate advancements in the development of emerging technology products to improve human and animal health through enhancements to the Veterinary Innovation Program
In October 2018, CVM launched the Veterinary Innovation Program (VIP). The VIP provides greater certainty in the regulatory process, encourages development and research, and supports an efficient and predictable regulatory approach for certain emerging technology products that provide a benefit to human or animal health, promote animal well-being, or improve food production.
Accomplishments: We initially launched the VIP as a pilot program; based on its success, it is now an established program. To date, we have enrolled over 50 products in the VIP and we continue to refine the benefits offered by this program. The following are VIP benefits that CVM has created:
- Intensive interactions to provide hands on assistance through the process
- Pre-investigational development meetings to discuss products early in the process
- Senior manager involvement to ensure appropriate resources and support to complete reviews in a timely fashion
- The VIP toolkit, which provides developers with information to assist them in preparing submissions
- Review benefits, including VIP review teams, stopping the review clock, pre-review feedback, and post-review feedback.
On September 15, 2023, the FDA announced expanded features of the Veterinary Innovation Program as part of the agency's Animal and Veterinary Innovation Agenda. VIP Plus includes new tools that will assist product development and continually improve the efficiency of the FDA's review process of VIP products by tailoring data requirements to answer risk questions specific to the product. The agency will also provide advanced computational tools that allow reviewers and developers to analyze complex genomic data. The agenda also includes plans to continue investment in data modernization, to re-imagine CVM's vision for its science program, and scan for emerging technologies and scientific developments that may eventually lead to new kinds of animal and veterinary products.
We also established a new type of veterinary master file (VMF), which developers may use to engage in early discussions and exchange information with CVM regarding research and pre-investigational development. Developers may also use this VMF when submitting information to support a CVM determination as to whether an ACTP or IGA in animals is sufficiently low risk that the agency does not intend to object to marketing of the product without prior FDA approval. The file allows for confidential exchange of information without triggering user fees.
Next Steps: We will continue to update the VIP toolkit with additional resources and helpful documents as available, refine our internal processes and procedures to facilitate efficient application of the VIP benefits based on lessons learned from their use, and work with developers to continue to develop alternative strategies for generating data.
Goal 2: Enhance the efficiency and predictability of our regulatory process
To ensure the efficiency of our regulatory process, we continue to develop helpful tools that will assist developers with submitting data and information in support of the development of IGAs in animals and ACTPs. We invite developers to establish a dialogue very early in the product development process and encourage frequent communications and meetings to expeditiously answer questions and address submission-related issues. Additionally, we have developed processes that support internal consistency and collaboration so that developers can better predict the regulatory approach for their specific product.
Accomplishments: We developed a suite of eSubmitter templates specific to submissions for IGAs in animals and ACTPs. These templates are designed to facilitate the submission of appropriate information, with the goals of reducing the need for amendments and increasing the likelihood of a one-cycle review.
To date, there are 51 eSubmitter templates designed specifically for emerging technology products. These templates are available through CVM’s eSubmitter application. For more information on eSubmitter and how to use it, please see the CVM eSubmitter Resource Center.
We encourage developers to interact with us early in the process through pre-investigational development meetings. These meetings facilitate early exchange of information, thereby ensuring efficient movement through the review process for the specific IGA(s) in animals or ACTP(s).
We established working groups comprised of subject matter experts that collaboratively work on improving both pre- and post-market regulatory efficiency and predictability. For example, the Emerging Technologies Regulatory Status (ETRS) working group developed a process for responding to new product inquiries. First, developers provide specific information in response to a set of questions. Then, the ETRS working group uses this preliminary information to determine the appropriate oversight and regulatory approach for the proposed product. For example, the ETRS working group may evaluate the risk for a possible determination that we intend to exercise enforcement discretion (i.e., a determination that an ACTP or IGA is sufficiently low risk that the agency does not intend to object to marketing of the product without prior FDA approval) for a specific IGA in an animal or ACTP. The ETRS working group would then communicate these decisions to the developer. Additional working groups, such as the Emerging Technologies Focus Group, regularly meet to discuss and address unique challenges that developers face when seeking FDA review of products utilizing these technologies. Finally, we furthered our collaboration with other centers across FDA and other regulatory agencies (e.g., EPA and USDA) through inter-agency working groups such as the Biotechnology Working Group and through inter-agency work in response to executive orders such as the one on Advancing the Bioeconomy.
For developers participating in the VIP, we offer pre-review feedback to provide CVM’s input on the organization and general contents of a submission prior to formal submission and review. During pre-review, we provide high-level feedback sufficient to identify data gaps and address specific questions regarding overall submission content. We also offer post-review feedback to provide clarity on any comments that CVM has provided in response to an incomplete submission. We have engaged in pre- and post-review feedback for an increasing number of submissions for products enrolled in the VIP.
Next Steps: We continue to refine our current eSubmitter templates and are developing new eSubmitter templates for other submission types. We also continually develop and refine our internal process documents and working groups, including those related to the VIP. We are working with international regulatory agencies to support better communication and regulatory cooperation regarding emerging technologies. This involves, when possible, engaging in scientific discussions, sharing experiences, and discussing other topics impacting FDA review of IGAs in animals and ACTPs. Other resources in development include:
- a process that will allow for electronic submission of large datasets and streamline the submission and review of next generation sequencing data typically generated in support of molecular characterization of IGAs in animals;
- case studies and other resources that will help facilitate the submission process for emerging technology products and provide examples of the information expectations outlined in GFIs #218 and 187.
Goal 3: Continue to refine and improve upon our science- and risk-based oversight approach for emerging technology products
We developed risk-based regulatory processes to evaluate the safety and effectiveness of emerging technology products. This framework focuses on sound science to support innovation and ensure consumer confidence. It entails determining the risk profile for specific ACTPs or IGAs in animals in order to determine data expectations and includes the flexibility to adjust those expectations when we learn new information about the product.
Accomplishments: The flexibility of our risk-based approach has allowed multiple emerging technology products to complete the FDA review process since 2005.
Our risk-based approach continues to be informed by ongoing research projects that are coordinated by the Office of New Animal Drug Evaluation (ONADE), Division of Animal Bioengineering and Cellular Therapies (DABCT) and conducted by the Office of Applied Science (OAS), Division of Applied Veterinary Research (DAVR). These research projects provide knowledge that is essential to our approach and led to the publication of multiple articles on ACTPs and IGAs in animals.
In October 2022, we issued two guidance documents that will help manufacturers of ACTPs understand current good manufacturing practice (CGMP) requirements for ACTPs. The first guidance, #253, “Good Manufacturing Practices for Animal Cells, Tissues, and Cell- and Tissue-Based Products” provides manufacturers of ACTPs with recommendations for meeting requirements for CGMP. It addresses the methods, facilities and controls used for manufacturing ACTPs, including steps in recovery, processing, storage, labeling, packaging and distribution. The guidance also addresses methods for preventing contamination and ensuring quality of the ACTP during manufacturing. The second guidance #254, “Donor Eligibility for Animal Cells, Tissues, and Cell- and Tissue-Based Products” assists developers, firms, or establishments that participate in the manufacturing of ACTPs or perform any aspect of the ACTP donor eligibility determination.
Next Steps: We are committed to the continued development and expansion of our risk-based approach to emerging technologies. We continue to target new research questions through the DABCT/DAVR Research Program to inform our regulatory framework and further the state of the science for emerging technologies. We are working on updates to draft Guidance for Industry #187 “Regulation of Intentionally Altered Genomic DNA in Animals.” We also plan to publish draft Guidance for Industry #251 that covers the use of animals of food producing species with IGAs as models of disease and draft Guidance for Industry #260 that covers Type VII veterinary master files for research and development and low risk determinations.
Goal 4: Increase transparency to stakeholders through public outreach and communication
CVM is committed to engaging with industry, academia, animal owners/producers, and other stakeholders to increase the transparency of our regulatory process. Our outreach goals include the development of informational web resources for developers, as well as direct communication with developers, by presenting at external conferences and hosting stakeholder engagement meetings to increase a public dialogue.
Accomplishments: We have held various public webinars and meetings as part of our outreach and transparency efforts.
- In April 2019, we held a public webinar on “Genome Editing in Animals.” The topics included a review of the science behind genome editing in animals and the promising uses of this technology in animals; an outline of the potential risks; and a description of our legal authority and our flexible, risk-based oversight of products developed using genome editing. The live webinar was attended by 320 participants from a range of sectors, including industry, trade associations, government (e.g., state government agencies, international government agencies, etc.), and other public entities. Following the meeting, we posted all materials (e.g., webinar recording, transcript) to CVM’s website.
- In September 2020, we posted the FDA CVM Animal Biotechnology Webinar for Developers, where we presented hypothetical case studies with information about CVM’s risk assessment process, as well as data expectations for these IGA case study examples. This information will help developers understand CVM’s data expectations for the marketing of specific product types prior to investing in the development of a new product. We strongly encourage stakeholders to provide us with feedback on this webinar.
- In July 2021, we held a public Animal Biotechnology Stakeholder Outreach session, presented during the Genome Writer’s Guild 2021 Conference. The session was designed to collect feedback from stakeholders on CVM’s regulatory process for intentional genomic alterations (IGAs) in animals. The feedback will help CVM to enhance the predictability, transparency, and efficiency of the IGA review process under the VIP.
- In October 2021, we posted a webinar entitled “CVM Draft Guidance for Industry Documents #253 and 254: Good Manufacturing Practices and Donor Eligibility for Animal Cells, Tissues, and Cell- and Tissue-Based Products (ACTPs)”. The webinar provides information and examples on current good manufacturing practice related to preserving cellular function and integrity, ensuring consistency of the process and product, preventing contamination and preventing transmission of disease.
- In June 2022, we posted a webinar entitled “FDA Animal Biotechnology Webinar Case Study: Low-Risk Intentional Genomic Alteration in Animals for Food Use”. This webinar focused on the agency’s recent determination of low risk for the marketing of products, including food, from two genome-edited beef cattle and their offspring after determining that the IGA does not raise any safety concerns (low-risk determination). The IGA results in the equivalent genotype (genetic make-up) and short-hair coat trait seen in some conventionally bred cattle, known as a “slick” coat. During the webinar, the FDA discussed risk questions the agency posed during its recent review of genome-edited beef cattle and focused on its low-risk determination as a case study.
- In May 2023, we posted a webinar entitled "FDA Animal Biotechnology Case Study Webinar for Investigational Food Use Authorizations of Animals with Investigational Intentional Genomic Alterations" to provide information about the process of requesting an investigational food use authorization (IFUA) for animals with IGAs. The webinar covers what an IFUA is; when it is appropriate to make an IFUA request; the types of data and information the FDA reviews in support of an IFUA request; three case study examples that cover different types of scenarios where developers of IGAs in animals might request IFUAs; and administrative procedures that developers of IGAs in animals follow when submitting an IFUA request.
Since 2017, we increased both attendance and presentations at external conferences and meetings to improve the exchange of information between CVM and its stakeholders.
We make our regulatory and policy decisions public, when possible, in order to inform industry and the public. We increased the available resources on our website and updated existing resources to provide insight into our current regulatory thinking on multiple areas. For example:
- CVM created the Intentional Genomic Alterations in Animals: Low Risk IGAs webpage which lists all current products for which, based on low risk, CVM decided to exercise enforcement discretion and does not expect the developer to seek approval in order to market the product.
- CVM created the Animal Cells, Tissues, and Cell- and Tissue-Based Products (ACTPs): Lower Risk ACTPs webpage, which is a publicly-available list of those ACTPs that the agency has determined are lower risk following a review of product-specific information.
- CVM created the Animal Biotechnology Products Resource Center to assist developers of animal biotechnology products with navigating the approval process. Each document provides information on a different topic to assist developers in administrative procedures and interactions with DABCT.
- CVM updated multiple webpages, including an Industry Q&A webpage that provides answers to frequently asked questions regarding regulatory approaches. For example, as surrogate dams from certain species carrying embryos with IGAs do not themselves contain an IGA, CVM clarified that these animals are able to enter the food supply with no prior FDA authorization.
- CVM created the Clinical Field Studies for ACTPs webpage, which is a resource that provides animal owners, veterinarians, researchers, and the public with access to information on clinical field studies investigating the use of ACTPs in veterinary patients.
- CVM created two webpages to provide answers to frequently asked questions. The Q&A for Pet Owners on ACTPs webpage answers questions regarding the use of ACTPs in veterinary medicine and the way these products are regulated by FDA. The Q&A for Developers of ACTPs webpage answers questions regarding the development process for ACTPs.
Next Steps: We are planning to hold additional animal biotechnology stakeholder outreach meetings. We also intend to publish additional case studies, resources, and webinars for stakeholders on our website.
Note: The data provided on this website is produced on an ongoing basis for performance management purposes and is subject to change due to updates of preliminary estimates, corrections, or other reasons.