Raw data notebook

The records required for field residue study authentication are the same records that would be required to reconstruct the study. Although this total volume of information is a necessary part of the GLP study record, the field summary report is a small fraction of that record. The field summary report is simply the information the EPA reviewers wish to see as they consider the data and determine how well they represent the crop situation for which the pesticide tolerance is being requested. At the current time, the field summary report should contain the information requested on pp. 48 and 49 of OPPTS 860.1500. The summary report for each test site in a study will typically form an appendix in the final study report. This information must be accurately extracted from the raw data notebook or field record and must be audited by... 

The GLP standards identify three types of deviations there are deviations from GLP standards, from the protocol, and from SOPs. Any deviation must be reported to the Study Director and documented in the raw data notebook. There are differences in the reporting process for the types of deviations. 

Protocol deviations in the processing phase of the study must be reported to the Study Director without delay. The Study Director will determine any potential impact upon the study that would result from the protocol deviation and will advise the PPI how to proceed with the study. Regardless of the form of communication by which the Study Director is notified of the protocol deviation, a formal description of the protocol deviation must be written by the PPI and submitted to the Smdy Director for an assessment of impact on the study. The assessment of impact by the Study Director should address any scientific and GLP compliance issues. A signed copy of the deviation report is included with the raw data notebook. 

GLP and SOP deviations are formally written up and signed by the PPI for inclusion with the raw data notebook. The PPI can assess the impact of the SOP deviation on the study. If there is no impact to the scientific or compliance aspects of the smdy, the signed original SOP deviation description is included in the raw data notebook. 

If the PPI determines that there may be an impact on the study, the Study Director must be consulted promptly to determine the proper course of action. Any impact on the scientific aspect of the study resulting from an SOP deviation may generate a protocol deviation. Any impact on the GLP compliance of the study resulting from an SOP or GLP deviation will at the very least need to be addressed in the GLP compliance statement from the processing facility which is included in the raw data notebook. 

The raw data notebook is normally submitted separately from the processing report. The information in the raw data is used to compile the processing report. All data... 

The raw data should be accessible in summary sheets the semi-graphical format is a big help because it exposes the problematic cases and provides a pointer to the notebook entries. 

Laboratory notebooks—It may be debatable to consider laboratory notebooks as text documents, but they should be mentioned here because of their importance in preclinical development. Laboratory notebooks are used to record experimental procedures, observations, raw data, and other important information. Although laboratory notebooks are rarely used for submission to regulatory agencies directly, they are available for inspection by the authorities in the Preapproval Inspection (PAI) and other GMP/GLP-related inspections. Currently, most of the major pharmaceutical companies still use paper-based laboratory notebooks. Electronic-based notebook systems are being developed and commercialized, which are discussed in Chapter 9. 

The form or format of the notebook is not as critical from a GLP compliance standpoint as the completion of the record in an accurate, timely, readable, and attributable manner. Company and PI conventions typically have evolved into cost-effective and very efficient data notebooks for field residue trials. These notebooks contain the actual raw data for the trial and once begun become extremely valuable legal parts of the study record. The notebooks should be audited by QA during the field phase of the study as well as at the end of the trial before the notebook is returned to the sponsor organization. The quality of the trial is easily refiected in the quality of the field notebook at the end of the season. 

The processing study raw data process notebook may include the following information ... 

Today, much more than just data are produced electronically. Many documents needed for studies that fall under the Good Laboratory Practice (GLP) standards regulations are being managed electronically. These records include not only data, such as chromatographic data from automated electronic capture systems and raw data collected in electronic field notebooks, but also other documents, such as methods, protocols, reports and standard operating procedures (SOPs). Frequently, these records are generated, distributed, reviewed, and archived electronically. 

With electronic notebook studies, there will also be paper data to audit. This will include facility data (e.g., weather data, equipment maintenance records, storage temperature logs, personnel records, etc.) and study specific documents, such as faxes, e-mails, paper notes, etc. When paper data have been transcribed into the electronic notebook, they should be checked by QA to ensure accuracy. Any data that have been transcribed for whatever reason must be identified as such with the original raw data attached to them. QA should ensure that all paper data have adequate identification (e.g., study and trial numbers), that they are recorded per GLP, including dated signatures, and that all of the pertinent paper data or exact copies are sent to the Study Director for archiving. 

Tests to establish the identity, strength, and purity of the test and control articles need not comply strictly with GLP requirements (e.g., protocol, QAU inspection requirements), but good documentation of anal5dical test results (usually in a laboratory notebook) and retention of raw data for such tests is a good practice. As the development process proceeds and the same material is used in both nonclinical and clinical studies, CGMP principles wiU apply to the production and characterization processes. 

All raw data from the experiment are to be recorded directly in your notebook, not on separate sheets of paper or paper towels. Calculations involving the data must be included for at least one series of measurements. Proper statistical analysis must be included in this section. 

In a modern laboratory, automated computer software for data acquisition and processing performs most of data reduction. Raw data for organic compound and trace element analyses comprise standardized calibration and quantitation reports from various instruments, mass spectra, and chromatograms. Laboratory data reduction for these instrumental analytical methods is computerized. Contrary to instrumental analyses, most general chemistry analyses and sample preparation methods are not sufficiently automated, and their data are recorded and reduced manually in laboratory notebooks and bench sheets. The SOP for every analytical method performed by the laboratory should contain a section that details calculations used in the method s data reduction. 

The current good manufacturing practices (GMP) state that Laboratory records shall include complete data derived from all tests necessary to assure compliance with established specifications and standards [5]. This includes all electronic and hard copies of raw data, laboratory notebooks, and/or worksheets and reports. Additionally, the regulations require that records shall be readily available for authorized inspection [6]. Consequently, the organization must have a well-defined audit trail for the generation, storage, and retrieval of reports and raw data. It must also be shown that there is adequate document management and security of all raw data and reports in terms of both disaster recovery and prevention of falsification of results. 

The organization must have a well-documented audit trail to raw data that will facilitate the retrieval of any supporting data that may be required during a regulatory inspection. In case of any off-site inspection, it may be prudent to include a copy of all notebook pages and all raw data. 

Never record your data on separate sheets of paper. Rather, record all your data directly in your notebook. You may consider using one side of the notebook for raw data and calculations and the other side for results and interpretation. 

A sample calculation should also be presented as an appendix to an undergraduate laboratory report. This appendix should show how one obtains tlie final results starting from the raw data. In general, the numbers used in the computations should have more significant fignres than are justified by the precision of the final result, in order to avoid mathematical errors due to roundoff. Units should be included with each step of the calculation. Also specify the source of raw data used (e.g., mn 5 on page 14 of notebook). 

Test results and the corresponding raw data must be maintained in an organized and legally defensible form. The use of notebooks or other doc-... 

Process validation for a bulk pharmaceutical chemical (BPC) may include development data that describe the limitations and efficiency of the process. .. Their laboratory notebooks and their processing records also may be reviewed because these records may constitute the raw data for process validation (5). 

In the same way are those instances to be regarded where all original observations are entered in a bound laboratory notebook which ultimately will then contain raw data from several studies. The original raw data will certainly be contained in this notebook, which consequently will have to be archived in a proper way as soon as it is full. At the time of completion of any such study the ultimate location of the notebook will not be known, and therefore, verified copies thereof will have to be made and archived with the study raw data. These records should, by the way, also bear the identification of the notebook itself, so that later on a comparison between the various types of raw data may be possible. 

The GLP Principles recognise this need for copying certain raw data in that they allow verified copies thereof to be treated as raw data. For the purpose of facilitating Quality Assurance control or the work of compliance monitoring inspectors, it would be advisable also to mention the location of the true original on all copies made and filed with other studies, or the designation of the notebook, in order to allow an easier comparison between copy and original. 

More recently, storage of information in computers has tended to superseded use of notebooks. The computerized LIM system can include all such information and relate it to sample ID and QC data presentation. Use of notebooks often continues on a limited basis. This dual data record may be a lag in technology development or reasoned record duplication in recognition of computer imperfections. In either case, storage of all analytical records, including raw data printouts, whether hard copy, disk, or tape, is mandatory, and the information must be retrievable, as dictated by the QAP. 

If the anomalous result can be unequivocally assigned to laboratory error, the result may be invalidated. Marking the notebook entry as invalid and retaining all related instrument outputs will be invaluable during future audits, to account for the raw data and results which are retained in the instrument electronic database. 

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