Re: Guidance for Industry 218 Cell-Based Products for Animal Use
Dear College of Veterinary Medicine:
FDA’s Center for Veterinary Medicine (CVM) is aware that regenerative medicine is an active area of research for many universities. We are writing to inform you of the finalization of CVM’s Guidance for Industry 218: Cell-Based Products for Animal Use.1 Cell-based products meeting the definition of a new animal drug are subject to the same statutory and regulatory requirements as other new animal drugs.2 This guidance describes FDA’s jurisdiction over cell based products for animal use and FDA’s current thinking on how existing regulations apply to these products.
FDA, like the scientific community at large, believes that research in regenerative medicine holds great promise for future safe and effective treatments for many veterinary conditions. However, the ultimate proof rests in obtaining interpretable data from well-conducted, well-designed scientific studies. The results of this research will help all of us more fully understand the potential benefits and risks associated with cell-based products.
This letter and Guidance for Industry 218 serve to remind those involved in researching, manufacturing, and marketing cell-based products for animal use that such activities may require an investigational new animal drug exemption (INAD) or an approved new animal drug application (NADA).
Universities that may be involved in the manufacture, marketing, and/or investigational use of cell-based products should be aware of the regulatory requirements and their responsibilities, which differ for each activity.
- Marketing and manufacturing cell-based products that meet the definition of a new animal drug:
Cell-based products for animal use require an approved NADA or another type of regulatory approval from CVM in order to be legally marketed. At this time, there are no FDA approved cell-based products for animal use. Guidance for Industry 218 establishes risk-based categories and describes the regulatory considerations for each category of cell-based products.
Persons performing operations required to produce a marketed cell-based product for animal use are considered manufacturers and are subject to the same statutory and regulatory requirements as manufacturers of other new animal drugs, including current good manufacturing practices.
If your university is marketing xenogeneic, allogeneic, or autologous type I cell-based products that meet the definition of a new animal drug, you should stop marketing these products and contact FDA to determine the appropriate pathway to obtain an approved NADA. If your university is manufacturing xenogeneic, allogeneic, or autologous type I cell-based products that are being marketed, you should stop manufacturing this product.
If your university is manufacturing and/or marketing an autologous type II cell-based product, you should ensure that the product is being manufactured and marketed in compliance with FDA regulations and expectations as stated in Guidance for Industry 218, including ensuring your facilities are manufacturing in accordance with current good manufacturing practices.
- Investigational use of cell-based products:
Investigational use of cell-based products in animals used solely for research purposes is allowed, provided the requirements set forth in 21 CFR Part 511 are met. There are two categories of investigational exemptions for cell-based products that meet the definition of a new animal drug; one for clinical investigations (studies in client-owned animals) and one for tests in vitro and in laboratory research animals.
a. Clinical investigations: Cell-based products used in clinical investigations in animals (research involving client-owned animals) may be eligible for an investigational exemption under 21 CFR 511.1(b). This exemption allows a sponsor to legally deliver the product for investigational use in clinical studies if the sponsor meets certain conditions.
These conditions include using the product only for bona fide scientific investigations, submission of notices of claimed investigational exemption (drug delivery notices) to FDA, retaining all reports received from investigators, providing for current monitoring of investigations, and use of the labeling statements provided in the regulation. Sponsors must also report any findings that may suggest significant safety hazards to FDA and all investigators. These conditions also prohibit commercial distribution and test marketing, unduly prolonging distribution, or representing that the product is safe and effective. For a complete list of requirements refer to 21 CFR 511.1(b) and 511.1(d)(2)).
If your university is conducting, or intends to conduct, clinical investigations (studies in client-owned animals), you should contact CVM to discuss the requirements for the clinical investigational exemption and determine the appropriate path forward. Before initiating clinical investigations you should establish an Investigational New Animal Drug (INAD) file with CVM. During the study, you must submit delivery notices and serious adverse events to CVM. Additionally, you may not charge for the investigational product in your studies. You should review the regulations in 21 CFR 511.1(b) to ensure your university is in compliance with the regulations.
b. Tests in vitro and in laboratory research animals: Cell-based products intended solely for in vitro studies or tests in laboratory research animals used solely for research purposes may be eligible for an investigational exemption under 21 CFR 511.1(a). This exemption allows a sponsor to legally deliver the product for investigational use in vitro and in laboratory research animals, provided that recordkeeping and product labeling are consistent with the requirements of 21 CFR 511.1(a). You should note that laboratory research animals do not include food producing animals or client-owned animals.
If your university is solely conducting tests in vitro and in laboratory research animals, you do not need to contact CVM or open an INAD. However, you should review the regulations in 21 CFR 511.1(a) to ensure your university is in compliance with the regulations.
We encourage you to review Guidance for Industry 218 and share it and this letter with those in your institution that are responsible for the research, manufacture, and clinical application of veterinary cell-based products. If they have any questions regarding their responsibilities, please have them contact Dr. Lynne Boxer at firstname.lastname@example.org, for further information.
FDA’s Center for Veterinary Medicine
2 In general, cell-based products meet the definition of a new animal drug, if among other things, those products are intended to diagnose, cure, mitigate, or prevent disease in animals, or are intended to affect the structure or function of the animal.