Medical Device Assessment: Updates for Thrombogenicity and Skin Irritation скачать в хорошем качестве

Medical Device Assessment: Updates for Thrombogenicity and Skin Irritation

Presentation 1: In vitro methodology for medical device material thrombogenicity assessments: a use condition and bioanalytical proof-of-concept approach Presenter: Michael F. Wolf, Medtronic Device manufacturers and regulatory agencies currently utilize expensive and often inconclusive in vivo vascular implant models to assess implant material thrombogenicity. We report an in vitro thrombogenicity assessment methodology where test materials (polyethylene, Elasthane™ 80 polyurethane, Pebax®), alongside positive (borosilicate glass) and negative (no material) controls, were exposed to fresh human blood, with attention to common blood-contact use conditions and the variables: material (M), material surface modification (SM) with heparin, model (Mo), time (T), blood donor (D), exposure ratio (ER; cm2 material/mL blood), heparin anticoagulation (H), and blood draw/fill technique (DT). Two models were used: (1) a gentle-agitation test tube model and (2) a pulsatile-flow closed-loop model. Thrombogenicity measurements included thrombin generation (thrombin-antithrombin complex (TAT) and human prothrombin fragment F1.2), platelet activation (β-thromboglobulin), and platelet counts. We report that: (a) thrombogenicity was strongly dependent (P less than 0.0001) on M, H, and T, and variably dependent (P between 0.0001 to 0.05) on Mo, SM, and D (b) differences between positive control, test, and negative control materials became less pronounced as H increased from 0.6 U/mL to 2.0 U/mL, and (c) in vitro to in vivo case comparisons showed consistency in thrombogenicity rankings on materials classified to be of low, moderate, and high concern. In vitro methods using fresh human blood are therefore scientifically sound and cost effective compared to in vivo methods for screening intravascular materials and devices for thrombogenicity. Presentation 2: In Vitro Irritation Testing for Medical Devices: A Progress Update Presenter: By Kelly P. Coleman, PhD, DABT, ERT, Medtronic Assessment of skin irritation is an essential step in the biocompatibility evaluation of medical devices. During 2016–2017 an international round robin validation study was conducted to evaluate reconstructed human epidermis (RhE) tissue models as potential alternatives to the rabbit skin irritation test, which is currently used for medical devices. Four irritant polymers and three non-irritant controls were used as positive and negative test samples. Two types of RhE tissues were dosed with 100 μL aliquots of either saline or sesame oil extracts. Incubation times were 18–24 hours. Cell viability reduction greater then 50% was indicative of skin irritation. Both RhE tissue types correctly identified virtually all of the irritant polymer samples either in the saline, sesame oil or both solvent extracts. These results indicate that RhE tissue models can detect the presence of strong skin irritants at low levels in dilute medical device polymer extracts. Therefore, it was concluded that RhE models are suitable replacements for the rabbit skin irritation test to support the biocompatibility evaluation of medical devices. In 2018, the results of this work were published in a special issue of Toxicology In Vitro. In 2019–2020 a follow-up study was completed with two other types of RhE tissues that produced results similar to the round robin. In addition, a simultaneous intradermal rabbit skin irritation study was conducted using the same extracts. This study confirmed that the in vivo rabbit results were essentially the same as the in vitro RhE tissue results. In 2020 a new ISO 10993-23 standard on irritation testing of medical devices was finalized which states that the use of RhE tissues is preferable to rabbits.