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

QUALITY CONCERNS FOR DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGISTS 727A. OverviewV. QUALITY CONCERNS AND QUALITY CONTROL MEASURESDrawing from the experiences of scientists, technical support personnel, and quality assuranceprofessionals, critical quality issues encountered during the conduct of developmental and reproductivetoxicity studies have been identified. Based on “what makes sense” and “what has worked,”several alternatives for diminishing the potential of these issues to affect data integrity are presented.In no way should these approaches be considered the only means for correcting deficiencies. Whilemost scientists would agree that a well-designed study conducted by a well-trained staff has highpotential for success, experience shows that it requires much more.B. PrestudyConcernLack of understanding of studyprotocol and SOPs by studypersonnel and supportingscientists.Inaccurate database-drivencollection intervals for weights,food consumption, and clinicalobservations.ApproachHold a prestudy meeting with study personnel to review protocol and SOPs.Set clear expectations around communication.Have a QC process that requires data checks on a regular basis andincludes follow-through when consistent errors are observed.Establish adequate software validation procedures.Involve the study director, statistician, primary study technician, andapplication administrator in the prestudy meeting.Study director should issue and communicate amendments or changes tothe protocol in a timely fashion.C. In-LifeConcernDosing or dietpreparation errors.ApproachSD should review and sign documentation for calculations.Use dated version control measures to assure that the most current procedure is usedin diet or dosing preparation.Create a specialized, well-trained diet preparation or formulations group.Observe diet preparation to assure that all procedures are followed.Develop, follow, and document procedures for equipment cleaning that minimizepotential for cross-contamination, e.g., mixer, polytron, mortar and pestle.Develop and follow appropriate measuring and pipetting techniques. Use of disposableequipment (e.g., pipettes) is another option.Analyze each batch of test substance (GLP requirement) and recalculate diet or dosingformulas.Include a process for checking animal identification before and after dosing.Develop a process for comparing test substance identification in protocol, study records,documentation accompanying the test substance, and the final report.Verify that all test substance storage containers are labeled according to GLPrequirements — name, CAS number, batch number, expiration date, if any, and, whereappropriate, storage conditions necessary to maintain the identity, strength, purity, andcomposition. 2–4 This can prevent use of expired, incorrect, or improperly stored testsubstances.Follow well-documented test substance accountability practices.Assure that apparatus used in continuous i.v. dosing has been adequately calibratedso that the correct dose is injected over the correct timeframe.© 2006 by Taylor & Francis Group, LLC