INTRODUCTION

  • Preclinical evaluation of medical devices has multiple similarities with the drug approval process of pharmaceuticals.

  • Although Safety and Efficacy are the main objectifs, many manufacters are dealing with specific challenges related to the class of Medical device and the country in which they are looking to receive approval.

  • The preclinical programs consist of GLP/non-GLP necropsy procedures followed by specific histopathological evaluations.

  • Necropsy assessment should include at least the presence of absence of the device, with the associated host responses such as inflammation, adhesions, Haemorrhage, Exudation etc. The objective of the microscopic evaluations are semi-quantitatif, but also more in depth quantifications could be requested by regulatory authorities.

  • The histology department has a critical role in order to fixate, trimm the tissues/organs without damaging the host-device interface.  


SOCIETY OF TOXICOLOGY NEWSLETTER

PRECLINICAL EVALUATION OF MEDICAL DEVICE THE PATHOLOGIST’S PERSPECTIVE

 


PATHOLOGIST POINT OF VIEW

From a pathologist ‘(review) it is important to report all findings and interpret them consistently in order to classify them as adverse or not + related them to a short, medium OR long post-implantation period.

An experienced investigative team is critical.

This short review includes the key GLP challenges related to the surgically implanted mesh and haemostatic devices (Class III/IV), both used during peritoneal surgery.  

  1. Choosing the appropriate animal model remains an important challenge as various options are available, but only one animal model will include Your requested end points for Your program. Large animals (swine and sheep) versus small animals (rabbit, rat) will be considered.

  2. At necropsy: in situ and ex vivo documentations are vital as implanted-related adhesions should be separated from post-surgical-related adhesions. They may vary from fibrinous (loose) till fibrous (tight) and they may even migrate to abdominal organs (spleen, liver, kidneys,…). 

  3. Sampling of tissues, organs and/or adhesions, should be performed carefully and separate sets can be designed for different purposes such as: histology, mechanical properties, electronic microscopy, molecular analysis. Trimming notes are useful in documenting the study procedure. The goal is to obtain the representative sections in order to write the safety conclusion.

  4. Careful protocol and special procedures will support the GLP process as each study will vary depending on the material and its use in time.

  5. At microscopic evaluations, scoring systems support pathological evaluations. However, it is important to mention that each scoring system will be specific for each study and will vary for each different MD.

  6. Special histology procedures are available incl. special stains (trichrome Masson) but are recommended only for non-pathologists reviewers. In case of chronic implantation, fibrosis will provide different type of collagen fibers (Collagen type I, and type III). Remaining technics are IHC such as Ki67 and TUNEL.

From the pathologist view the following endpoints will include: fibrosis, inflammation, degree of tissue ingrowth, degenerative changes and implant-specific goals such as debris, migration of material. In addition to these local changes additional expertise is required for the local lymph nodes or surrounding lymphoid tissues.

Pathologists are asked to score the amount of ‘scar tissue ‘. Given the loose and colloquial definition of scar such evaluations should occur with caution and should include consideration of macroscopic and microscopic features discussed above.

 

With the clinical prevalence and increasing frequency, Medical Devices represent a common subject of

preclinical evaluation which is important for pathologists & toxicologists to understand.

The complexity of the Medical Device safety and efficacy studies are numerous, and range of evolving Medical Device designs calls for consistent and detailed pathologic evaluation (semi-quantitative and morphometry) to determine host responses and assess safety.

Overall, knowledge of anticipated responses at given time points will help to determine the appropriate tissue processing, staining, evaluation and interpretation of safety profile of mesh devices in the preclinical setting.

medical device expertise:

  • in depth knowledge of medical devices classifications

  • determine which medical device class

  • regulatory Guidelines

  • selection contract Research Organization

  • study monitoring

  • select histology procedures

  • peer review

  • scoring systems

  • literature review

  • keynote presenter

  • project management

  • gLP quality & compliance

  • medical writing & translations

  • clinical trial interpretator