Comment from Ryleigh Loper

As a veterinary student, I am writing to express concerns regarding potential restrictions on the ability of physicians, including veterinarians, to compound certain drug combinations within their facilities for patient care. Such restrictions would have significant unintended consequences for veterinary medicine, particularly for high-volume, high-quality (HVHQ) spay and neuter programs that serve a critical public health and animal welfare role. I currently work at a veterinary clinic that performs approximately 100 feline spay and neuter surgeries per day. In this setting, we rely on the in-house compounding of an anesthetic induction combination commonly referred to as KTX (ketamine, tiletamine-zolazepam, and xylazine). This protocol is widely used in HVHQ clinics and has been demonstrated in the peer-reviewed literature to be both safe and effective for short surgical procedures such as sterilization surgeries. A large retrospective study of free-roaming cats undergoing high-quality, high-volume spay and neuter procedures demonstrated that this anesthetic combination provides reliable anesthesia with low perioperative mortality and predictable recovery profiles (Shin et al., 2024). Concerns have been raised regarding the compounding of multiple active pharmaceutical ingredients and whether such preparations can achieve adequate homogeneity. From a pharmaceutical chemistry standpoint, the anesthetic agents ketamine, xylazine, and tiletamine-zolazepam are all formulated as water-soluble injectable preparations. When ketamine and xylazine solutions are used as the reconstitution medium for tiletamine-zolazepam, the resulting compounded preparation remains fully dissolved and homogeneous, with no precipitation or phase separation observed at clinically utilized concentrations. The similar solubility characteristics and compatible pH ranges of these agents support the physical and chemical stability of the compounded mixture, enabling consistent dosing and safe administration in high-volume clinical settings. This physical compatibility is further supported by published veterinary anesthesia protocols in which tiletamine-zolazepam, ketamine, and xylazine are premixed into a single injectable solution prior to intramuscular administration to achieve a balanced anesthetic combination, without reports of incompatibility or loss of efficacy (Ko et al., 1993). For example, controlled studies in veterinary species describe adding ketamine and xylazine directly to reconstituted tiletamine-zolazepam to create a single injectable anesthetic mixture that produced smooth induction and predictable anesthetic depth, implicitly demonstrating adequate homogeneity for safe clinical use (Ko, Williams, Smith, McGrath, and Jacobson, 1993). The ability to compound this anesthetic combination in-house is essential to maintaining efficiency, safety, and consistency of care in a high-volume environment. Requiring individual preparation of anesthetic drugs for each patient, or restricting access to compounded combinations altogether, would substantially increase preparation time, reduce the number of animals that can be treated each day, and limit access to care, particularly in rural and underserved communities. HVHQ spay and neuter clinics play a vital role in addressing companion animal overpopulation, reducing shelter intake and euthanasia rates, and relieving strain on local veterinary practices that may already be operating at or beyond capacity. These clinics also frequently provide care at reduced cost or with financial assistance, improving access for pet owners who might otherwise be unable to obtain necessary services. Restrictions on in-clinic compounding would disproportionately impact these programs and undermine their public health benefit. For these reasons, I respectfully request that the anesthetic agents ketamine, tiletamine-zolazepam, and xylazine, when compounded for in-house use by licensed veterinarians, be exempt from restrictive provisions under the proposed framework. Preserving veterinarians’ ability to compound necessary drug combinations within their facilities is critical to ensuring animal welfare, maintaining access to care, and supporting effective population control efforts which support overall public health concerns for humans and pets. Thank you for the opportunity to provide comment and for your consideration of the practical, clinical, and pharmaceutical implications of these regulations on veterinary medicine and community health.