Opinion on Maintaining In-House GLP Status for Toxicologic Pathology in Pharmaceutical and (Agro)Chemical Development.

Many pharmaceutical companies have recently elected to stop maintaining good laboratory practices (GLP) status of their R&D sites. Similar discussions have also been engaged in the (agro)chemical industry. This opinion paper examines the pros and cons of maintaining facility GLP status for the purposes of performing the pathology interpretation or peer reviews of GLP studies internally. The toxicologic pathologist provides gross and histomorphologic evaluation and interpretation of nonclinical exploratory and regulatory studies during drug and (agro)chemical development. This assessment significantly contributes to human risk assessment by characterizing the toxicological profile and discussing the human relevance of the findings. The toxicologic pathologist is a key contributor to compound development decisions (advancement or termination) and in the development of de-risking strategies for backup compounds, thus playing a critical role in helping to reduce the late attrition of drugs and chemicals. Maintaining GLP compliance is often perceived as a costly and cumbersome process; a common and short-term strategy to reduce the costs is to outsource regulatory toxicity studies. However, there are significant advantages in maintaining the GLP status for toxicologic pathology activities in-house including the sustainable retention of internal pathology expertise that has maintained the necessary training needed to manage GLP studies. [Box: see text].

Toxicologic Pathology Forum*: Opinion on Integrating Innovative Digital Pathology Tools in the Regulatory Framework.

Digital pathology is defined as the ability to examine digitized microscopic slides and to generate qualitative and quantitative data. The field of digital pathology is rapidly evolving and has the potential to revolutionize toxicologic pathology. Techniques such as automated 2-D image analysis, whole slide imaging, and telepathology are already considered "mature" technologies and have been used for decades in exploratory studies; however, many organizations are reluctant to use digital pathology in regulatory toxicology studies. Innovative technologies using digitized slides including high-content imaging modalities and artificial intelligence are still under development but are increasingly used in toxicologic pathology. While software validation requirements are already described, clear guidance for application of these rules to the digital pathology field are few and the acceptance of these technologies by regulatory authorities remains necessary for successful adoption of digital pathology into the mainstream of toxicologic pathology. This topic was discussed during a roundtable at the 2018 Annual Congress of the French Society of Toxicologic Pathology. This opinion article summarizes the discussion regarding the current questions and challenges on the integration of innovative digital pathology tools within a good laboratory practice framework and is meant to stimulate further discussion among the toxicologic pathology community. *This is an opinion article submitted to the Toxicologic Pathology Forum and does not constitute an official position of the Society of Toxicologic Pathology or the journal Toxicologic Pathology. The views expressed in this article are those of the authors and do not necessarily represent the policies, positions, or opinions of their respective agencies and organizations. The Toxicologic Forum is designed to stimulate broad discussion of topics relevant to regulatory issues in Toxicologic pathology. Readers of Toxicologic Pathology are encouraged to send their thoughts on these articles or ideas for new topics to toxicologicpathologyforum@toxpath.org .

Specificities of the Skin Morphology in Juvenile Minipigs.

The Göttingen minipig is recognized by the scientific community and by health authorities as the animal model of choice to evaluate dermally applied drugs under development. Young adults of approximately 4 months of age are most generally chosen to participate in dermal pharmacology and toxicology studies, and recently, minipigs have been proved to be also suitable for juvenile studies. A complete anatomical cartography of the skin morphology of juvenile male and female minipigs from postnatal day 1 (PND1) to twelve weeks of age was performed measuring the thickness of skin layers for each anatomical location and time point. Overall, the neonatal skin of minipigs (PND1 and PND8) shows prominent cellularity, similar to that seen in human neonates, and the morphology of the skin of older animals is considered similar to that of young adult minipigs. Epidermal thickness varies only minimally over the period; whereas, the dermal and more markedly, the subcutaneous thicknesses increase over time.