Chapter 2 Veterinary Drug Development and Control Copyright © 2011 Delmar, Cengage Learning
Stages of Veterinary Drug Development In the United States, new veterinary drugs must go through a series of tests mandated by the FDA There are four major steps in drug development: Synthesis/discovery of a new drug compound Safety/effectiveness evaluation Submission and review of the New Animal Drug Application (NADA) Postmarketing surveillance stage Copyright © 2011 Delmar, Cengage Learning
Copyright © 2011 Delmar, Cengage Learning Stage One Preliminary studies: determine the intended effect and possible toxic side effects May include computer modeling, testing in lab media, or testing on bacteria or fungi Copyright © 2011 Delmar, Cengage Learning
Copyright © 2011 Delmar, Cengage Learning Stage Two Preclinical studies: determine a drug’s safety and effectiveness Short-term and long-term tests Check for immediate drug reactions, organ damage, reproductive effects, carcinogenicity, and teratogenicity Submit Investigational New Animal Drug (INAD) application for the drug to the FDA Clinical trials begin once application is approved Copyright © 2011 Delmar, Cengage Learning
Copyright © 2011 Delmar, Cengage Learning Stage Three Satisfactory clinical trial results allow scientists to file a New Animal Drug Application (NADA) with the FDA, EPA, or USDA Approval and license are granted for successful drugs Copyright © 2011 Delmar, Cengage Learning
Copyright © 2011 Delmar, Cengage Learning Stage Four Postmarketing surveillance stage The drug company and the government monitor the product as long as the drug is manufactured This monitoring ensures product safety and efficacy Copyright © 2011 Delmar, Cengage Learning
Safety and Effectiveness Evaluation Short-term tests hours following a test dose check the animal for obvious adverse reactions Long-term tests typically run for 3 to 24 months of repeated dosing check the animal’s various organ systems for toxicity damage Copyright © 2011 Delmar, Cengage Learning
Safety and Effectiveness Evaluation Special tests Reproductive affects Conception, fertilization, pregnancy Carcinogenicity Cancer causing Teratogenicity Fetal defects in pregnant animals Copyright © 2011 Delmar, Cengage Learning
Copyright © 2011 Delmar, Cengage Learning Toxicity Evaluation Conducted on mice Highest dose that results in tissue and organ damage Highest dose that results in permanent injury or death Copyright © 2011 Delmar, Cengage Learning
Effective and Lethal Dose Effective dose: the amount of the test drug that causes a defined effect in 50% of the animals that receive it ED50 Lethal dose: the amount of the test drug that kills 50% of the animals that receive it LD50 Copyright © 2011 Delmar, Cengage Learning
Copyright © 2011 Delmar, Cengage Learning Therapeutic Index Therapeutic index is the drug dosage or dose that produces the desired effect with minimal or no signs of toxicity Also called the margin of safety Determined by comparing the lethal dose and effective dose of the drug LD50 ÷ ED50 A wide therapeutic index means that the drug can produce its desired effect without approaching toxicity Copyright © 2011 Delmar, Cengage Learning
Copyright © 2011 Delmar, Cengage Learning Additional Testing Systems-oriented screening Evaluation of long-term effects Evaluation of reproductive effects, carcinogenicity, and teratogenicity Copyright © 2011 Delmar, Cengage Learning