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

254 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITIONV. COMPLIANCE WITH APPROPRIATE GOVERNMENTALAND AAALAC INTERNATIONAL REGULATIONSThe performing laboratory must be operated in compliance with the appropriate governmental GLPs(see above). The animal research facility should be accredited by AAALAC International (Associationfor Assessment and Accreditation of Laboratory Animal Care International). Thus, the study should beconducted in compliance with appropriate GLPs and in compliance with the appropriate testing guidelines(e.g., FIFRA; 3,4,56 TSCA, 2,10 FDA, 55,129 ) and AAALAC International accreditation standards. Itmay be useful if the performing laboratory is also approved by the Ministry of Agriculture, Forestryand Fisheries (MAFF), Japan, for toxicology studies on agricultural chemicals, so that work performedunder EPA (FIFRA) GLPs and OPPTS or OECD testing guidelines will be acceptable to the Japaneseregulatory agencies. The quality assurance unit of the performing laboratory must review the protocoland any amendments; inspect all in-life phases, necropsy, and fetal evaluations; audit the raw andsummarized data and the final report; and provide a compliance statement to that effect for the finalreport. For further details regarding GLP compliance, refer to Chapter 18.With the increasing use of automated data collection systems, the possibility and usefulness ofsubmitting the final report in toto electronically to the appropriate federal or international agencyhas been recognized. To date, the FDA 130 has promulgated regulations for electronic records andelectronic signatures (known affectionately as CFR, Part II), and the EPA has published 131 aproposed rule on establishment of electronic reporting and electronic records (known asCROMERRR, Cross Media Electronic Reporting and Recordkeeping Rule).The objective of both the FDA and EPA initiatives is to “set forth the criteria under which theagency considers electronic records, electronic signatures, and handwritten signatures executed toelectronic records to be trustworthy, reliable, and generally equivalent to paper records as handwrittensignatures executed on paper.” 130 The EPA proposal rule 131 would “allow electronic reportingto EPA by permitting the use of electronic document recovery systems to receive electronicdocuments in satisfaction of certain document submission requirements in EPA’s regulations.” TheEPA acknowledges that “the electronic records criteria in [their] rule are not as detailed as thatcontained in FDA’s 21 CFR Part II.” 131 Laboratories providing studies for submission to the EPAor FDA should read the referenced documents in their entirety. One concern the authors of thischapter have is whether the electronic submissions would be limited to “read only” or would haveto be sent in a format that allowed manipulation by regulators (as is apparently one objective ofthe FDA code). The integrity of the text and data submitted by the performing laboratory must bemaintained. The study director will have no control over any alterations or manipulations to thedata (e.g., deletions of an animal’s data, a different interpretation of results, etc.) postsubmission.A. Status ReportsVI. REPORTSStatus reports should be provided to the sponsor at a frequency specified by the sponsor. The contentand format of these reports should remain flexible so as to accommodate unforeseen situations.B. Final ReportThe final report should include an abstract, objectives, materials and methods, results (narrativeand summary tables), discussion, conclusions, references, any deviations from the protocol, a GLPcompliance statement, a QA statement, and appendixes. The appendixes should include analyticalchemistry reports (if appropriate), data from individual mated females, individual embryo and fetaldata by litter and uterine location, histopathology and clinical chemistry reports (if appropriate),© 2006 by Taylor & Francis Group, LLC