In vivo and in vitro testing for the biological safety evaluation of biomaterials and medical devices

Thrombogenicity testing continues to be a critical requirement for regulatory approval of blood-contacting medical devices and the ISO guidelines have recently been updates [1]. This new guideline ascribes value to both in vivo and in vitro testing including both the non-anticoagulated venous implant (NAVI) model, and the new methods for in vitro testing. One challenge with the animal-blood-based in vitro assays that have been validated and used for submissions is that they still may not accurately translate to clinical safety or predict the risk for thrombogenic potential in humans. We have previously described a model using minimally heparinized ovine blood and are continuing to improve the overall methodology [2,3]. In addition, we have transferred these methods to a human blood assay which therefore has enhanced potential for prediction of clinical risk. As with the ovine model, the key characteristics of a successful in vitro method include fresh blood, low levels of anticoagulation, flow conditions and minimization of air/blood interfaces. This human model integrates freshly harvested human blood containing minimal levels of heparin with variable flow from a unidirectional peristaltic pump and unlike many of the human blood assays, it can accommodate larger devices and higher flow rates than previously described [1,4]. Control materials which were optimized in the ovine model were also used to reproducibly elicit positive and negative thrombogenic responses. We feel that this model can be used for validation of the ovine model with cross comparisons of a number of legally marketed comparator devices. Alternatively, if the human blood methodology can be streamlined and performed cost effectively on a regular and basis, this assay could supplant the current ovine model and allow a highly predictive preclinical test for thrombogenicity of devices.

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In vivo and in vitro testing of gloves for protection against UV-curable acrylate resin systems

Contact Dermatitis ◽

10.1111/j.1600-0536.1984.tb01009.x ◽

1984 ◽

Vol 11 (5) ◽

pp. 279-282 ◽

Cited By ~ 32

Author(s):

Robert L. Rietschel ◽

Ronald Muggins ◽

Nicole Levy ◽

Pat M. Pruitt

Keyword(s):

In Vitro Testing ◽

Uv Curable ◽

Acrylate Resin

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Laboratory and in-vitro testing of skin antiseptics: a prediction for in-vivo activity?

Journal of Hospital Infection ◽

10.1016/0195-6701(91)90257-9 ◽

1991 ◽

Vol 18 ◽

pp. 5-11 ◽

Cited By ~ 13

Author(s):

F. Baquero ◽

C. Patrón ◽

R. Cantón ◽

M.Martínez Ferrer

Keyword(s):

In Vitro Testing

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Local Toxicity of Topically Administrated Thermoresponsive Systems: In Vitro Studies with In Vivo Correlation

Toxicologic Pathology ◽

10.1177/0192623318810199 ◽

2018 ◽

Vol 47 (3) ◽

pp. 426-432 ◽

Cited By ~ 3

Author(s):

Sivan Yogev ◽

Ayelet Shabtay-Orbach ◽

Abraham Nyska ◽

Boaz Mizrahi

Keyword(s):

Block Copolymer ◽

Ethylene Glycol ◽

Medical Devices ◽

Poly Lactic Acid ◽

Poly Ethylene Glycol ◽

Thermoresponsive Polymers ◽

Wide Range ◽

Poly Ethylene

Thermoresponsive materials have the ability to respond to a small change in temperature—a property that makes them useful in a wide range of applications and medical devices. Although very promising, there is only little conclusive data about the cytotoxicity and tissue toxicity of these materials. This work studied the biocompatibility of three Food and Drug Administration approved thermoresponsive polymers: poly( N-isopropyl acrylamide), poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) tri-block copolymer, and poly(lactic acid-co-glycolic acid) and poly(ethylene glycol) tri-block copolymer. Fibroblast NIH 3T3 and HaCaT keratinocyte cells were used for the cytotoxicity testing and a mouse model for the in vivo evaluation. In vivo results generally showed similar trends as the results seen in vitro, with all tested materials presenting a satisfactory biocompatibility in vivo. pNIPAM, however, showed the highest toxicity both in vitro and in vivo, which was explained by the release of harmful monomers and impurities. More data focusing on the biocompatibility of novel thermoresponsive biomaterials will facilitate the use of existing and future medical devices.

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Development of an in-vitro testing battery to assess biocompatibility of medical devices

Toxicology Letters ◽

10.1016/j.toxlet.2017.07.911 ◽

2017 ◽

Vol 280 ◽

pp. S256

Author(s):

Elisabeth Mertl ◽

Christian Kirchnawy

Keyword(s):

Medical Devices ◽

In Vitro Testing

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Biological Safety Evaluation of 99mTc-DTPA-Ketoconazole for Diagnosis of Fungal Infection

Indonesian Journal of Physics and Nuclear Applications ◽

10.24246/ijpna.v2i1.1-8 ◽

2017 ◽

Vol 2 (1) ◽

pp. 1

Author(s):

Maula Eka Sriyani ◽

Hendris Wongso ◽

Eva Maria Widyasari ◽

Rizky Juwita Sugiharti ◽

Iim Halimah ◽

...

Keyword(s):

Single Dose ◽

Fungal Infection ◽

Radiochemical Purity ◽

Safety Evaluation ◽

Fungal Growth ◽

In Vitro Assays ◽

Toxic Response ◽

Biological Safety ◽

Safety Parameters

Infectious diseases have become one of the leading cause of mortality around the world, including in the Southeast Asia. One of the microbial that cause infection is fungi. Occasionally, deep-seated fungal infection is difficult to detect using conventional diagnosis methods and therefore leads to inaccurate detection. Our previous research was conducted in order to obtain the labeled compound of 99mTc-DTPA-Ketoconazole with a high radiochemical purity (98.40 ± 0.86%). Moreover, the in-vitro assays showed that 99mTc-DTPA-Ketoconazole can potentially bind to Candida albicans. On the other hand, in clinical routine use, diagnostic kit should be safe for the patients. Consequently, this research was conducted to determine the biological safety parameters of 99mTc-DTPA-Ketoconazole on the animal study, including single dose and acute toxicity test, sterility, and apirogenicity test. The results showed that both the single dose at 34.6 μCi and dose until 149 times of the single dose did not stimulate the toxic response to the animals. In addition, the sterility data revealed that there was no microbial growth after 7 days of incubation at 37°C as well as fungal growth after 14 days of incubation at 25°C. Furthermore, the apirogenicity test using rabbits revealed that there was no increase in temperature more than 0.6°C for each animal and not more than 1.5°C of total increase of temperature for all the animals. It is concluded that the 99mTc-DTPA-Ketoconazole is satisfy the requirements of biological safety of a radiopharmaceutical and therefore was acceptable for fungal detection in nuclear medicine.

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