Q&A for Developers of Intentional Genomic Alterations in Animals
- Q: What about all of the GE mice in my research laboratory?
- Q: I have a biopharm animal; do I have to communicate with CVM in addition to CDER or CBER? Whom should I contact first?
- Q. Why does CVM need to review GE animals that I’m developing as biopharm animals?
- Q: I haven’t made an animal with a heritable change, I am conducting gene therapy on animals; what should I do?
- Q. How should I dispose of my investigational animals?
- Q. Are surrogate dams without IGAs that gestate embryos/fetuses/offspring with IGAs subject to investigational food use authorization requirements?
- Q. If I’m not sure what to do, whom should I contact?
- Q: Must I notify FDA that I am working with IGAs in animals?
- Q: How early in my research should I contact FDA?
- Q. What do I do if I believe FDA should exercise enforcement discretion over my IGA in an animal?
- Q: What do I do if I need to establish an investigational file?
- Q: Can I participate in the Veterinary Innovation Program?
- Q: What is a sponsor?
- Q: Will I have to pay User Fees?
- Q: How often can I talk with CVM about my research?
- Q: Are there milestones on the way to approval that I can use to gauge my progress?
- Q: I’ve been working on my project for a while already, but haven’t contacted anyone at FDA; what should I do now?
Q: What about all of the GE mice in my research laboratory?
A. FDA is not recommending that researchers working with non-food laboratory animals for research purposes contact the agency. You are still responsible for determining whether your research falls under any NIH guidelines for recombinant DNA research, as well as any institutional animal care and use committees that you may have, and any rules that may be established, as the result of participation, to maintain AAALAC accreditation. If you have any questions about whether your IGA in laboratory animals should obtain agency approval, contact FDA and we will be happy to answer your questions and provide you with assistance. In addition, you are responsible for meeting all other applicable federal, state, local, tribal, and municipal requirements, for example with respect to the disposal of animals or their wastes.
Q: I have a biopharm animal; do I have to communicate with CVM in addition to CDER or CBER? Whom should I contact first?
A: You should contact CVM early in the process. The final product (e.g., the pharmaceutical), will be reviewed for approval by the product center at FDA responsible for that final product. CVM will be responsible for evaluating and approving the IGA in the animal. We encourage biopharm developers to contact CVM as early in their research and development as possible so that we can provide assistance with developing a regulatory submission, as well as coordinating with other FDA centers. We welcome frequent and regular conversation with developers, especially well before any pre-IND phase of development.
Q. Why does CVM need to review GE animals that I’m developing as biopharm animals?
A. An approval for the IGA in your GE animal is generally required prior to your approval for the human product as the animal is part of the “manufacturing process” for the human product. In addition, we want to be sure there are no risks from animals with IGAs to the food supply or to human and animal health. We recognize that biopharm animals will be highly valued and, from a business point of view, unlikely to be used for food; however, the agency would still need to determine that developers of IGAs in these animals not planned for use in food have sufficient safeguards in place to ensure that they will not inadvertently enter the food supply.
Q: I haven’t made an animal with a heritable change, I am conducting gene therapy on animals; what should I do?
A: You should still contact CVM. We regulate gene therapies in animals as well.
Q. How should I dispose of my investigational animals?
A. We recommend that investigational animals be disposed of by incineration, burial, or composting, and that appropriate records be kept of animal identification and disposition. Animals or edible products from them containing unapproved new animal drugs may not be put into the food or feed supply without prior FDA authorization during the investigational phase of development. Under an INAD, however, you may request an Investigational Food Use Authorization from the agency. In order to receive such an authorization, you must submit sufficient data to demonstrate that food from these investigational animals is safe to eat or use for animal feed, and the agency must explicitly issue such an authorization, which would allow you to send your animals to slaughter or rendering for feed.
Q. Are surrogate dams without IGAs that gestate embryos/fetuses/offspring with IGAs subject to investigational food use authorization requirements?
Surrogate dams (also referred to as embryo recipient animals) from certain species (cattle, swine, sheep, and goats) that gestate embryos/fetuses/offspring with IGAs resulting from a variety of assisted reproductive technologies (e.g., embryo transfer, cloning, artificial insemination, in vitro fertilization) and do not themselves contain an IGA are not “treated” within the meaning of our regulations (21 CFR 511.1) because they are extremely unlikely to contain the IGA, through placental transfer or otherwise. Therefore, edible products (e.g., meat or milk) from these animals may enter the food supply without prior FDA authorization. By contrast, fetuses and offspring from any species that do contain IGAs are considered “treated” and must not enter the food supply without prior FDA authorization. Please contact CVM if you have questions about such authorizations, or if you are seeking to introduce into the food supply surrogate dams from species other than cattle, swine, sheep, and goats.
Developers continue to be responsible for keeping out of the food supply edible products from surrogate dams that contain violative drug residues by following meat withdrawal/milk discard provisions on approved drug labels. Alternatively, for extralabel drug use, they should apply veterinarian-established withdrawal/milk discard times under a valid veterinarian-client-patient relationship (21 CFR 530).
Q. If I’m not sure what to do, whom should I contact?
A: If you have any questions we invite you to contact us at AskCVM@fda.hhs.gov. We are happy to help.
Q: Must I notify FDA that I am working with IGAs in animals?
A. In general, yes, particularly if you are working with a species traditionally consumed as food. Based on risk, there are some IGAs in animals for which the agency may exercise enforcement discretion and not take action against the unapproved IGA. For example, FDA is already exercising, and intends to continue to exercise, enforcement discretion for non-food species laboratory animals used for research. On a case-by-case basis, the agency may consider exercising enforcement discretion over other low-risk IGAs in animals.
Q: How early in my research should I contact FDA?
A: You are always welcome to contact us if you have any questions regarding whether the IGA in animals you are developing will need premarket approval or whether FDA may exercise enforcement discretion over them. Regardless, we encourage you to talk with CVM as soon in your development process as possible. We can then work closely with you during the investigational phase of development to ensure that animals do not inadvertently enter the food supply, and that data to support approval are developed efficiently and appropriately.
Q: What do I do if I believe FDA should exercise enforcement discretion over my IGA in an animal?
A: You should contact CVM at AskCVM@fda.hhs.gov, and ask what kinds of data you should submit to enable the agency to determine whether it may be willing to exercise enforcement discretion. The primary questions that the agency recommends you be prepared to address include whether there is anything about the IGA that poses a human, animal, or environmental risk. The agency will review the data on these issues, and then determine whether there are any safety questions that have not been adequately addressed. If we intend to exercise enforcement discretion over specific IGAs in animals, we post a statement describing that intent on our website here.
Q: What do I do if I need to establish an investigational file?
A. First, contact CVM at AskCVM@fda.hhs.gov to determine what type of file you should open, either an investigational file or a veterinary master file. To establish an investigational file (INAD), you will need to submit a letter to CVM containing such a request. In, or attached to that letter, please provide us with some background information regarding the species of animal used, a description of the IGA, and the intention of the IGA. We recommend that this information be at approximately the level of detail that would normally be required for an NIH grant application.
All applications and submissions, addressed to the Office of New Animal Drug Evaluation (ONADE), need to be submitted to CVM electronically using the eSubmitter tool. Paper submissions are no longer accepted by CVM/ONADE. For information about submitting electronically to CVM, please see our Electronic Submissions webpage.
If you have any questions regarding electronic submissions, email CVM’s Electronic Submissions Support Team at cvmesubmitter@fda.hhs.gov.
Q: Can I participate in the Veterinary Innovation Program?
The Veterinary Innovation Program or VIP is for certain products, including intentional genomic alterations (IGA) in animals. The goal of the VIP is to facilitate advancements in development of innovative animal products by providing greater certainty in the regulatory process, encouraging development and research, and supporting an efficient and predictable pathway to approval for ACTPs and IGAs in animals.
The VIP offers benefits including extensive interactions between CVM and the developer (you). These interactions can increase the predictability of the regulatory pathway, facilitate a lower number of review cycles, and reduce the overall time to approval. Developers of IGAs in animals that provide a benefit to human health, animal health, animal well-being (e.g. husbandry improvements), or enhanced food production may participate in the VIP. You can find more information about the VIP here.
Q: What is a sponsor?
A: A sponsor is either an applicant named in an application for approval or a person who has submitted a request to open an investigational file (INAD). All developers, producers, manufacturers, researchers, etc. who establish an INAD with CVM are considered, and referred to as sponsors.
Q: Will I have to pay User Fees?
A: Generally, sponsors pay certain fees that support the review of products and applications. The fees include sponsor fees, establishment fees, and application fees. Some sponsors of IGAs in animals will qualify for waivers or reductions from fees, for example if they qualify for a barrier to innovation waiver or the IGA they are developing is in a minor species animal. You will find more information here regarding user fees generally and here regarding user fee waivers and reductions.
Q: How often can I talk with CVM about my research?
A: There are no limits to how often you can talk to or meet with CVM regarding your product development. In fact, we encourage developers to meet with us frequently so that we can make the process of data gathering and preparation of your submission more efficient for both you and the agency.
Q: Are there milestones on the way to approval that I can use to gauge my progress?
A. As we complete our evaluation of the individual components of your application, we issue letters saying that you have satisfactorily completed that portion of the process.
Q: I’ve been working on my project for a while already, but haven’t contacted anyone at FDA; what should I do now?
A. Please contact us using the information provided in the answers preceding this one. Once we determine whether FDA might be willing to exercise enforcement discretion over your research or if you should establish an INAD file or a veterinary master file, we can help you organize your data for submission and review.