Emerging technologies have the potential to influence multiple fields, including medicine, 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 research into human disease, production of substances for pharmaceutical use, and as sources of cells, tissues, or organs for transplantation into humans. Other technologies such as animal cells, tissues, and cell- and tissue-based products (ACTPs) offer potential novel drug 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 will ensure consumer confidence and foster 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:
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 pathway to approval 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 33 products in the VIP and we continue to refine the benefits offered by this program. To support the VIP, CVM has created internal processes and procedures to efficiently implement VIP benefits, such as:
- 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 sponsors with information to assist them in preparing required submissions
- Review benefits, including VIP review teams, stopping the review clock, pre-review feedback, and post-review feedback.
We also established a new type of veterinary master file (VMF), which sponsors may use to engage in early discussions and exchange information with CVM regarding research and pre-investigational development. Sponsors may also use this VMF when submitting information to support a CVM determination as to whether 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. The file allows for confidential exchange of information without triggering user fees.
Next Steps: We will update the VIP toolkit with additional resources and helpful documents as available, refine our internal processes and procedures for handling VIP benefits based on lessons learned from their use, and work with sponsors to continue to develop alternative strategies for generating data.
To ensure the efficiency of our regulatory process, we continue to develop helpful tools that will assist sponsors with submitting data and information in support of the development of IGAs in animals and ACTPs. We invite sponsors 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 develop processes that support internal consistency and collaboration so that sponsors can better predict the regulatory pathway 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 50 eSubmitter templates1 designed specifically for emerging technology products.
We encourage sponsors 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 approval 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, sponsors 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 sponsor. Additional working groups, such as the Emerging Technologies Focus Group, regularly meet to discuss and address unique challenges that sponsors face when pursuing the approval 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 the development of inter-agency working groups and through increased communication and data sharing to support regulatory alignment and efficiency.
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 approval of IGAs in animals and ACTPs and, when sponsors request it, a cooperative product review process. 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;
- a series of documents that will help facilitate the submission process and explain data expectations based on risk profile; and
- a series of case studies for emerging technology products, for which we will describe the regulatory process as well as data expectations for each technical section.
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 appropriate risk category for specific ACTPs or IGAs in animals and includes the flexibility to transfer products across these categories when we learn new information about the product.
Accomplishments: The flexibility of our risk-based approach allowed multiple emerging technology products to complete the FDA review process and be eligible to enter the market 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 Research (OR). 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.
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/OR 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 additional Guidance for Industry, covering topics including: donor eligibility and good manufacturing practices for ACTPs and the use of animals of food-producing species with IGAs as models of disease.
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 sponsors, as well as direct communication with sponsors, by presenting at external conferences and hosting stakeholder engagement meetings to increase a public dialogue.
Accomplishments: In April 2019, we held 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 IGA submissions. 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.
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 Alterations in Animals: Enforcement Discretion webpage, which lists all current products for which, based on low risk, CVM decided to exercise enforcement discretion and does not expect the sponsor to seek approval in order to market the product.
- CVM updated multiple webpages, including an Industry Q&A webpage that provides answers to frequently asked questions regarding regulatory pathways. 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.
Next Steps: We are planning to hold a series of animal biotechnology stakeholder outreach meetings. The goal of these meetings is to collect feedback on ways to enhance predictability, transparency, and efficiency of the review process for intentional genomic alterations in animals and to incorporate these ideas as enhancements to the Veterinary Innovation Program.
Due to restrictions related to COVID-19, we are unable to hold in-person animal biotechnology stakeholder outreach meetings as initially planned for Summer/Fall 2020. However, we plan to continue to offer additional resources and virtual meetings until in-person meetings can resume.
Following up on the case study webinar published in September 2020, we plan to publish additional outreach material and hold virtual meetings, as needed, to address the feedback received. We also intend to publish additional case studies and resources for stakeholders on our website.
We are also planning outreach webinars that will center on questions regarding ACTPs; these webinars will focus on issues such as donor eligibility and good manufacturing practices. CVM is also developing ACTP-specific webpages to provide answers to frequently asked questions.
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. In addition, FDA may change the type or amount of data provided on this website at any time.