A Practical Approach, Second Edition=Ronald D. Ho.pdf

714 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITIONI. INTRODUCTIONIn today’s business and regulatory climate the ability to generate quality products in the mostefficient manner is critical to maintaining competitiveness. Regulators must rely on the scientificcommunity to provide the best possible data for input into their decision-making process. Thoseresponsible for submitting applications to the regulatory agencies must continually strive for themost efficient way to develop a quality product. This chapter will• Review the Good Laboratory Practice Standards (GLPs), which describe minimal standards forconducting nonclinical laboratory studies that support or are intended to support applications forresearch or marketing permits for products regulated by the Food and Drug Administration (FDA)or the Environmental Protection Agency (EPA).• Provide guidance for developing and managing an effective GLP compliance program.• Discuss specific procedures for auditing developmental and reproductive studies.• Summarize quality concerns as solicited from a number of toxicologists, study personnel, andquality assurance unit (QAU) personnel from multiple organizations.• Discuss recommendations for addressing the quality concerns.We hope that the information presented herein will provide the developmental and reproductivetoxicologist with useful tools to consider during all aspects of a study, from protocol preparationto final report issue.A. BackgroundII. GOOD LABORATORY PRACTICE STANDARDSIn the mid-1970s, inconsistencies and unacceptable as well as fraudulent practices were uncoveredin several studies that had been submitted to the FDA. 1 The kinds of issues that surfaced had thepotential to have a detrimental, if not harmful, effect on the consumer.Because of the FDA’s commitment to and responsibility for protecting the consumer, the agencypromulgated the FDA Good Laboratory Practice for Nonclinical Laboratory Studies, finalized in1979 and revised in 1984 and again in 1987. 2 By 1983, the EPA had promulgated the EPA ToxicSubstance Control Act (TSCA) and Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) GLPs,both of which have since been revised. 3,4 The EPA’s TSCA and FIFRA GLPs were intended toconform as closely with the FDA GLPs as possible. 5Be aware that the issues prompting these responses by the federal regulatory agencies were notsimply minor judgmental oversights with little consequence. There were occurrences of underqualifiedpersonnel and supervision, selective reporting, poor animal care procedures, and inadequaterecordkeeping and missing data, sometimes a result of fraudulent activity. 3Over the years several international agencies have developed regulations or guidelines thatemulate the U.S. GLPs. For example, the Organization of Economic Cooperation and Development(OECD) Principles of GLP are based on the FDA GLPs and are similar though not identical tothem in content. 1B. RegulationsWhile the FDA and the EPA TSCA and FIFRA GLPs are not identical, there are enough similaritiesamong all three that if one adheres to the principles articulated by one GLP standard, very littleadjustment will be required to be compliant with another.© 2006 by Taylor & Francis Group, LLC