Substantial Evidence and SafetyVeterinary Drug Studies for Companion Animals
NOTE: information on this page concerns veterinary drugs (veterinary pharmaceuticals). Investigational veterinary products which are considered an immune modulator, vaccine, diagnostic kit, or immune stimulant may be considered a veterinary biologic (veterinary biological, veterinary biological product). Veterinary biologicals are regulated by the United States Department of Agriculture (USDA).
Prior to entering large multi-site field trials (studies), veterinary drug sponsors often conduct pilot studies. Often, these types of veterinary clinical studies are designed to obtain information about the safety, efficacy (not necessarily effectiveness), dose characterization, and pharmacokinetics. Pilot studies are not routinely used in support of target animal safety or substantial evidence of effectiveness since they are conducted in a small number of patients or subjects. However, veterinary pilot studies can serve as the basis for designing larger pivotal studies in preparation for filing an investigational new animal drug (INAD). Prior to initiating pilot studies, Sponsor’s can contact the Food and Drug Administration – Center for Veterinary Medicine (FDA-CVM) for guidance.
Dosage Characterization: These studies establish the intended dose to be used for substantial evidence of effectiveness studies. These studies may also incorporate pharmacokinetic analysis of the veterinary drug. Once the dose characterization has been completed, the sponsor often selects the optimal dose to be used for substantial evidence of effectiveness and certain safety studies.
Substantial Evidence: Substantial evidence of effectiveness is a required section of veterinary drug approval process. This is routinely conducted as a multi-site field study in client-owned dogs concerning the disease of interest. For major diseases in major species, these studies often require the enrollment of hundreds of veterinary patients.
Veterinary Safety Studies
The following describes common terms used in by veterinary pharmaceutical companies when declaring what types of studies are used in support of target animal safety. Some sponsors may incorporate different types of safety assessments into a single study, such as repeated dose and cardiovascular toxicity.
Safety: These are target animal studies and often designed to assess higher doses (3x and 5x) than the recommended dose (1x) for extended periods of time, and may also include a placebo or 0x group. The duration of these studies is often a multiple of the anticipated label claim’s duration of use. For instance, a single dose injection (1 time injection) may only require 3-7 days of testing. However, veterinary drugs intended for daily use, such as a non-steroidal anti-inflammatory drug, may require evaluation of the drug dosing over a 6-month period.
Pharmacokinetics (PK): Veterinary pharmacokinetic studies evaluate the quantity of drug in the body over time in the target species, as a basis for profiling drug exposure. Often, pharmacokinetic studies employ means of assessing the drug in serum, plasma, urine, or other bodily fluids or tissues. PK studies are laboratory based and utilize analytical chemistry which should be validated methods for assessing veterinary drug pharmacokinetics. The basic components of pharmacokinetics are absorption, distribution, metabolism, and excretion (ADME). Many times, PK studies are used to further assess toxicology and toxico-kinetics studies. These types of studies are also used for abbreviated new animal drug applications where the generic veterinary drug’s PK profile is compared to the pioneer drug (the one that received the NADA).
Field Safety: These target animal studies assess the adverse events and safety profile under field trial conditions. Assessment for safety and recording adverse events are often components to field pilot studies and are required elements of the substantial evidence of effectiveness study(s).
Acute Toxicity, Dose Escalation, Margin of Safety, Repeated Dose, and Tolerance Studies: These veterinary studies are used to determine the toxicological effects, often at multiple doses and/or increasing doses, over a set dosing period. These studies may evaluate toxicokinetic profiles and reversibility of pathological changes due a veterinary pharmaceutical.
Cardiovascular: Certain drugs, such as anti-neoplastics, may require a separate study to evaluate cardiac specific toxicity in the target species.
Human Safety and Labeling
Human Food Safety: Drugs labeled and approved for use in companion animals don’t typically require evidence of human food safety. Therefore, human food safety is often not a as a component to the veterinary drug registration process.
User Safety: Since humans are the ones typically dispensing the veterinary drug to their pet, labels require information to ensure appropriate handling and use, such as “NOT FOR USE IN HUMANS. KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN. ….” For certain drugs which represent safety concerns, such as anti-neoplastics, hormones, etc., additional warning statements may appear on the drug label. This may include warnings to avoid the pet’s urine, feces, vomit, etc. Also, labels may contain information on appropriately handle, contain, dispose of and clean areas contaminated with pet waste. For accidental exposure, labels may contain language on how to wash or clean the affected area, and how to appropriately seek medical attention.