title: Quality management of pharmacology and safety pharmacology studies.
abstract: Pharmacology has traditionally been excluded from the mandatory application of good laboratory practice (GLP) principles. Consensus has been reached through the process of the International Conference on Harmonisation (ICH, Topic S7A) with regard to the definitions of the different types of pharmacology studies (ICH S7A): primary pharmacodynamic, secondary pharmacodynamic and safety pharmacology studies, and guidance on the quality standards (expectations for GLP conformity) for these study types have been provided. Primary pharmacodynamic studies are the only study types that are fully exempt from GLP requirements. Secondary pharmacodynamic and safety pharmacology studies are expected to be conducted to GLP quality standards -- preferably to full, formal GLP compliance, when results are used for human safety assessment. At the present time, regulatory authorities will most likely be prepared to exercise flexibility in their requirement for GLP compliance, however, if non-clinical studies used in human safety assessment are not formally in compliance with the principles of GLP, regulatory acceptance may not be guaranteed. Historically, the application of formal GLP standards in safety pharmacology studies appears to vary between test facilities, and a number of study components in safety pharmacology studies, e.g. ECG monitoring, may not always conform to formal GLP standards. Apparently, however, formal GLP standards for these study components can be implemented for a relatively low additional cost. Based on the guidance given in the ICH S7A guideline, it thus appears logical to recommend that test facilities and sponsors consider their organisation of safety pharmacology studies in view of sound study management and formal implementation of GLP, where needed. Organisation of study management should facilitate collaboration across scientific disciplines because a plethora of data, originating from basic pharmacodynamics, toxicology, kinetics, and metabolism, as well as from clinical investigations, are involved in a safety pharmacology assessment. Applying formal GLP standards to safety pharmacology studies, and, when indicated, to secondary pharmacodynamic studies, does not influence the scientific standards of studies. However, applying formal GLP standards will ensure the quality, reliability and integrity of studies, which reflect sound study management. It is important to encourage a positive attitude among researchers and academics towards these lines, whenever possible. GLP principles applied to the management of non-clinical safety studies are appropriate quality standards when studies are used in the context of protecting public health, and these quality standards are therefore obviously pivotal for regulatory acceptance of non-clinical safety studies in general, and of safety pharmacology studies in particular.
authors.affiliation: H. Lundbeck A/S, Ottiliavej 9, DK-500 Valby, Denmark. psp@lundbeck.com
authors.forename: Per
authors.initials: P
authors.lastname: Spindler
authors.forename: Jürg P
authors.initials: JP
authors.lastname: Seiler
mesh_terms: D004353:Drug Evaluation, Preclinical / Q000592:standards*; D015507:Drugs, Investigational / Q000009:adverse effects*; D017408:Guidelines as Topic; D007391:International Cooperation; D007753:Laboratories / Q000592:standards*; D010601:Pharmacology, Clinical / Q000592:standards*; D011786:Quality Control; D013678:Technology, Pharmaceutical / Q000592:standards*; D009626:Terminology as Topic
chemical_list: D015507:Drugs, Investigational