What type of SOP's do I need to have in place in GLP ?

Whole Slide Imaging (WSI) is a technology that has the potential to transform the practice of pathology because it allows the digitalization of an entire glass, producing a digital image for review. Digital pathology offers a number of potential benefits as it enables electronic transfer of slides from the laboratory to the pathologist. This enable improved workflow in the laboratory, allow work to be shared across sites and between multiple pathologists. As with the adoption of all new technologies there is a need to balance the benefits of adoption against the associated risks, especially within a non-clinical environment compliant with the Code of Federal Regulations (CFR), Volume 21, Part 58 (Good Laboratory Practices) and Part 11 (Electronic Records). In order to achieve image data within an electronic form which are compliant with the regulatory GLP studies, it’s mandatory to have written standard operating procedures (SOP’s) in place and the Quality Assurance Unit may audit the individual workflow processes. Similar regulation rules apply within the European Union (OECD) and Japan.

A successful validation of the WSI will demonstrate that the system reliably produces expected performances and achieves the intended results. Each time a new intended use for WSI is contemplated, a separate validation for the new use should be considered. This validation project involves a collaborative team effort, which includes not only pathologists but also system owners, users, IT and QA personnel. The collection of appropriate SOP’s will assure that the WSI (a) is tested for its intended use, (b) provides pathologists the appropriate training and assurance that they evaluating true representation of the glass slide (c) proofs evidence of data integrity to QA management (d) provides regulatory agencies with documented evidence that the WSI respects CFR, Volume 21, Part 58 and Part 11.

This section describes the various SOP’s to have in place in order to support (a) validation of the Whole Slide Imaging Scanner (WSS), (b) validation of software required to view and manage the digital image (c) secure retention of electronic records and the ability to expediently retrieve these records from the archives.

The SOP-driven WSS (hardware) procedures should describe the intended use of the resultant WSIs (primary evaluation, peer-review, consultation, illustration, image analysis, etc.). US FDA GLP regulations (21 CFR Part 58) also state that the equipment used in the generation, measurement or assessment of data should be adequately tested, calibrated, and/or standardized. 

The SOP-driven WSI (software) procedures should state on the limited and authorized access and that roles have been established which define the level of access a particular individual may exert. The generation of raw data with a regulation environment (GLP) should be correctly identified and not be modifiable. Procedures should consider unique specimen tracking within the workflow management system and the digital image will support a change control, which purpose is to ensure that no unnecessary changes are made to the initial image. Any annotations or alterations such as image compression during its life cycle should not change the raw data but should be layered over the raw data. The SOP will confirm the tracking of potential changes through audit trails employing user-independent computer-generated time stamps. When digital images are transmitted to external users (peer-reviews), additional SOP’s need to describe the secure methods of exchanging raw data in detail. Importantly, both hardware and software SOP’s will describe how the digital image achieved a true representation of the stained histological tissue section, especially by defining color rendition, luminance, magnification, resolution, monitor specifications etc. It includes that additional scanning resolutions may be requested by the pathologist and that the glass slide remains the reference and can be used at any time during the process. 

The SOP-driven archive procedures are critical especially when the digital images are required for study reconstruction in a regulated environment. Digital images must be archived for the record retention period. The SOP should describe how secure retention should be maintained during this process and the ability to retrieve the images according to the US FDA CFR Title 21 Part 11. As mentioned earlier, European Union (OECD 1997) regulates the Medicinal Products according Annex 11 Computer Systems.

It’s remains evident of course that the preparation of the stained tissue sections on a glass slide from which the image is obtained, followed GLPs principles and is of sufficient quality for microscopic evaluation.