GLP documentation

The use of electronic systems to generate, retain, distribute, review, and archive standard GLP documentation, such as SOPs, protocols and protocol changes, is increasingly common. There are many benefits, including elimination of paper, ease... 

Availability of the equipment with consideration given to the time taken for probe changes (including GMP/GLP documentation) and also any major disruption to tube NMR work required on the spectrometer. 

Box 5.3 Statements from the ISO and GLP documents that guide and regulate... 

It was an artefact. The proof for this interpretation of the results came from the neat reconstruction of the study procedures through the use of the correctly recorded GLP documentation. In the first instance, study personnel, when asked whether there had been any unusual occurrences during the study, the necropsy and the following sectioning and slide preparation steps, could not think of anything out of the normal. They maintained that everything had been done as usual, nothing special had happened, and all procedures had been performed in the standard way. Scrutiny of all the raw data of this... 

In accordance to GCP, the sponsor should appoint clinical trial monitors. These act as the main communication interface between the sponsor and the trial site, and should regularly visit the site to oversee that the trials are being conducted and correctly documented in accordance with the protocol and GCP. Reports should be supplied to the sponsor after each visit. It is also good practice for the sponsor to establish an auditing system for independently verifying that the activities in relation to the collection and processing of data at the trial site, and at related laboratories or sponsor s facilities, are conducted in accordance with applicable protocols, procedures, regulations, GCP and GLP. 

One of the characteristics of the pharmaceutical industry is large quantities of paperwork, particularly in areas where GMP/GLP are strictly enforced. The slogan documentation, documentation, and documentation. .. is always in the mind of laboratory scientists. 

In preclinical development, the GMP/GLP regulations are enforced not only for scientific data but also for text documents. This section discusses several types of controlled text documents used in preclinical development. Most of these documents are managed by the fully validated TIMS. 

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. 

In the author s experience, field residue trials can be conducted in Latin America under complete compliance with all ERA guidelines and recommendations. More time does need to be spent in planning and preparation to ensure that the personnel involved in the testing have been trained in GLP and that this training, as well as the compliance of equipment, storage and archival sites, standard operating procedures (SOPs), and quality assurance (QA) audits, are properly documented. 

The GLP training should consist of two parts first, a classroom presentation of the materials described in Section 4 above, and second, a field training session where the principals of documentation of mixing, calibration, and applications can be demonstrated. Disposal, cleaning, and maintenance procedures should also be discussed and demonstrated. The classroom presentation should stress that the four key areas to successful implementation of GLPs are (1) Good Science, (2) Documentation,... 

The Study Director is the pivotal person in any GLP study. The sponsor initiates the study and assigns a Study Director to act as the primary control point for all aspects of the study. The Processing Principle Investigator (PPI) acts as an agent of the Study Director and handles the processing phase of the study. The PPI reports directly to the Study Director, and quality assurance (QA) documents resulting from the processing phase are sent to the Study Director for approval. The Study Director has final say in all questions of compliance with GLP and interpretations of the protocol. The... 

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. 

Thereafter, the primary functions of the study QA specialist fell into two main headings. First, GLP compliance during the collection and documentation of commodity samples had to be assured. This was done via observation of several collections for different shops (collection incidents) at various geographic locations. In these audits, the study QA specialist examined specific items, such as (1) did the shopper follow the written instructions, (2) were the correct types and numbers of samples collected, (3) was the documentation maintained as required, (4) were the samples labeled and packaged correctly, and (5) were the samples delivered to the shipper as required Findings were communicated to study management and used as appropriate in subsequent shops. 

At this stage in planning, the essential study design information listed below should be determined and a written study plan (i.e., protocol) including these key study details prepared. A formal, pre-approved study plan is required for field soil dissipation studies conducted under Good Laboratory Practice (GLP). A written study plan for non-GLP studies is highly recommended since the document serves as valuable guidance for study personnel. 

Preparing a detailed protocol according to GLP standards may be useful for researchers planning a worker exposure or re-entry study, even though the study may never be submitted to the EPA to support the registration of a pesticide product. Having a detailed protocol helps to solidify one s plans for the study, and assists in the documentation phase of the study. This documentation phase will be addressed in some detail later. 

Field forms are necessary if GLP standards are to be followed. Field forms can be developed in such a manner as to document that each step of the protocol was followed during the course of the field execution of the study. 

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. 

GLP compliance for electronic records does not differ from GLP compliance for paper records. The increased access and distribution of records and documents enabled by electronic systems provide compliance challenges. There are many new questions to answer for example, what is the difference between electronic approvals and electronic signatures The solutions to these challenges lie in ensuring that system validation and management processes are in place, such as SOPs or procedures... 

This brings to mind another common problem. SOPs must be readily available in areas where GLP work is conducted. Protocols also must be accessible. Even when these documents exist only in electronic form, they must still be available, especially in the laboratory and study rooms. This means that computer systems that contain these documents must be available in the laboratory and study rooms and that all personnel who conduct work according to these SOPs must have access. The same is true for protocols and protocol changes. In cases where a merged system exists, i.e., both paper and electronic media are simultaneously in use, it is perfectly acceptable that only the electronic form is available in the laboratory areas while electronic or paper documents are available in offices. The only caveat is that a process must be in place to ensure the equivalency of the electronic and paper media. 

In a GLP-compliant electronic record keeping system, original raw electronic data will not be altered, but these data can be presented and interpreted for reporting. Any changes to the raw data are documented and maintained as audit trails. The audit trail becomes a part of the raw data for the study and is archived as such. 

To satisfy government agencies, instruments need to be adequately tested, calibrated, and/or standardized according to documented procedures. Current GLP standards state that equipment used in the generation, measurement, or assessment of data and equipment used for facility environmental control must be of appropriate design and capacity to function according to the protocol and shall be suitably located for operation, inspection, cleaning, and maintenance. 

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. 

FieldNotes user verification can be conducted by following the SOP written by Astrix, which can be downloaded from the Astrix Web site. The SOP contains a script that is typed into the computer system. If the printout matches the SOP script, then verification is complete. A record of this must be placed in the facility archive. This verification process takes 1 h or less. For FieldNotes, calculations are not verified at the field site since the manufacturer feels that the software developer and the sponsors have performed adequate validation of these calculations previously. This may, therefore, require a visit to the sponsor or to the manufacturer to confirm that this important step of the validation process has been completed and is adequately documented. By following the Astrix SOP, the user is simply ensuring that the program operates on their system(s). The SOP script must be typed in exactly as written in order to confirm the printout accuracy. QA must ensure that the verification documentation is properly archived. Just as with any other SOP, this SOP must be approved in writing by field site management to comply with GLP. 

The responsibility of the QA unit should not be limited to in-process inspections and data and report audits. To be in full compliance with GLP, the QA unit should review all procedures for storing and archiving electronic as well as paper raw data. This review should include ensuring that back up and archiving procedures were performed as specified in the SOPs, that archiving was documented properly, and that long-term storage procedures were followed. 

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