Department of Pharmacy (Pharmaceutics) | Sagar savale | Mr. Sagar Kishor Savale [Department of Pharmaceutics] | 2015-2016 SAGAR SAVALEWhat is biocompatibility? — Biocompatibility ability of material to elicit an appropriate biological response on a given application in the body. ~The ability of a material to perform with an appropriate host response in a_ specific application", Williams' definition. —"The quality of not having toxic or injurious effects on biological systems". sane SAGAR SAVALE 2NEED BIOCOMPATIBILITY TESTING Medical devices and their component materials may leach compounds or have surface characteristics that may produce undesirable effects when used clinically. The selection and evaluation of materials and devices intended for use in humans requires a structured program of assessment to establish biocompatibility and safety. Current regulations, whether in accordance with the U.S. Food and Drug Administration (FDA), the International Organization for Standardization (ISO), or the Japanese Ministry of Health, Labor and Welfare (JMHLW), require that manufacturers conduct adequate safety testing of their finished devices through prescliaical and clinical phases, as part of the regulatory clearance process.Guidelines ISO 10993-1 and FDA G95-1 Guidelines osaaH6 SAGAR SAVALEThree levels for biocompatibility testing “ Level 1 Series of preclinical test in animals and in vitro studies. These studies can be used as a screening phase but should be followed with more detailed investigation “ Level 2 In usage test in animals at the sites where the materials have to be used. © Level 3 Clinical trial in humans, after the data have been sufficiently screened in the first two Wels SAGAR SAVALE 3Classification of biological test 1, Cytotoxicity test 2, Sensitization 3. Intracutaneous Reactivity 4, Irritation 5. Systemic Toxicity (Acute Toxicity) 6. Sub chronic Toxicity (Sub acute Toxicity) 7. Chronic Toxicity. 8. Implantation 9. Haemocompatibility 10. Genotoxicity 11, Carcinogenicity 12. Reproductive & Developmental Toxicity 13. Biodegradation osaai6 SAGAR SAVALECytotoxicity “ Cytotoxicity test asses cell death caused by a material measuring cell number or growth before and after exposure to that material . osaaHe SAGAR SAVALESensitization © These tests estimate the potential for contact sensitization of medical devices, materials and / or their extracts using suitable animal models. These tests are appropriate because exposure or contact to even minute quantities of potential leachables can result in allergic or sensitization reactions Mandatory for all biomaterials osaaHie SAGAR SAVALE 8Irritation Test © These tests estimate the irritation potential of medical devices, materials or their extracts, using appropriate sites for implant tissue such as Skin Eye Mucous membrane in a suitable animal model. These tests are performed using appropriate route (skin, eye or mucosa) and duration of exposure or contact to determine irritant effects of materials or potential leachables. osaaHie SAGAR SAVALE 9Intracutaneous Reactivity " Intracutaneous Reactivity Assesses the localized reaction of tissue to medical device / material extracts. These tests are carried out in such devices, where determination of irritation by dermal or mucosal tests are not appropriate “ Eg : Devices having access to the blood path OR where material extractables are hydrophobic osaaHie SAGAR SAVALE 10Systemic Toxicity (Acute Toxicity) © Systemic Toxicity (Acute Toxicity) Estimates the potential harmful effects of either single or multiple exposures, during the period of less than 24 hours, to medical devices, materials or their extracts in suitable animal model osaaHe SAGAR SAVALE "Sub chronic Toxicity (Sub acute Toxicity) © Sub chronic Toxicity (Sub acute Toxicity) Estimates the potential harmful effects of either single or multiple exposures, during the period of NOT less than 24 hours to a period not greater than 10% of the life span of the animal model, to medical devices, materials or their extracts in suitable animal model " Note: These tests may be waived for materials which has chronic toxicity data osaaHie SAGAR SAVALE 2Pyrogenicity tests Pyrogenicity tests carried out to detect material mediated pyrogenic reactions of extracts of medical devices or materials Note :Pyrogenicity tests are also conducted to ensure the safe level of endotoxins in the finished / sterlized product osaaHe SAGAR SAVALE 8Genotoxicity © Genotoxicity These tests apply mammalian or non-mammalian cell culture techniques to determine gene mutations changes in chromosomal structure and number other = DNA or gene toxicities caused by the device, material or their extracts. osaaHe SAGAR SAVALEImplantation = |mplantation Assesses the local pathological effects on the living tissue, at both the gross level and microscopic levels Sample of the material or the device is surgically implanted in an appropriate site (muscle, dentin or bone) based on the intended application "Note: For a material, these tests are equivalent to sub chronic toxicity tests, if systemic effects are also investigated. osaaHie SAGAR SAVALEHaemocompatibility “ Haemocompatibility Evaluates the effects on blood or blood components by blood contacting devices or materials. Haemolysis tests determine the degree of blood cell lysis and release of haemoglobin caused by device / material samples. osaaHe SAGAR SAVALEChronic Toxicity “Chronic Toxicity Estimates the effects of either single or multiple exposures, during the period of at least 10% of the life span of the animal model, to medical devices, materials or their extracts in suitable animal model. osaaHe SAGAR SAVALECarcinogenicity “These tests determine the tumorigenic potential of medical devices, materials or their extracts. The test duration shall cover a period over the major portion of the life span of the animal model Can be carried out along with chronic toxicity studies © Note: Required to be conducted only if there are suggestive data from other sources osaaHie SAGAR SAVALE 8Reproductive & Developmental Toxicity ' It studies the potential effects on reproductive function embryonic development (teratogenicity) prenatal and early post natal development © Note : Need to be conducted only if the device has potential impact on the reproductive potential of the subject osaaHe SAGAR SAVALE ®Biodegradation “Where the potential for resorption / degradation exists, these tests determine the process of degradation biotransformation elimination of degradation products “ Note : ISO 10993 is not very specific on the norms for selection of biodegradation studies; only the method is described. osaaHie SAGAR SAVALEsane BIOCOMPATIBILITY TESTING (meet snRD DED re TPAC secre) ORE TAS werceeneeenes a Contact 2 Shain 7 i animes [3]8 ee wovcona | “eset HUA jcseeena./3(3] FU} “eer” 3] | a2 Fim hiciness ‘enn 80 Inegulary Shaped (oem ito) pout pate, nn, me kc obent mld en: O5mmibick3x2ion? + Inepulay shaped 3x ty | Zink Herahsis ASTM Enact (21d 0S hick 3 ia? x Sar egal shaped 3 2p ma Hemobsis: NIH Die (ew dee matenab) 30.29 mM 3x15 a NA Na Pastal Throrbopastin Tne x Aart comparison samples) an (ampanson samgles) iro Hera x 2a (amaeson samples) Thrombust (nhc) 2009 (28cae) Oder me mates wae 2 test samples and 2 coparson spl [Length 18cm, MixirumD amet acer Mogesioy res) (84s) 2n2tont 2a ene 2x09 2x44 ant ese Mdsin = MEL (4 ap - 4p Rantacnr oan inte opm : 074 tr Tl mosome Aberration — IML [62 Ly BRE Gcey] Vivo Mouse Micronucles [55 dy 2u14g 5) Ranptarncta wore redcitann deypret|IRRITATION F STIMULATION enews AW 2 on? Du tn? 12g 24084 Sn. al Moca tal ‘Ok hes 2 Sn 2 é £ 2x08) Ns adsoles eae Noteal Medaled Rati ‘Ment 0y 4 ik Murine Loclyrgh Node 6x9 6x08 al i ‘Sn R Som i. Si cy Mee) 140 f Hache? ‘au tg q s CL cadens im toprodare 15 imple (0m WELW muscu nkarscals nga P J gi to produce 12 mpl, agg. {Omen Sh See ardtdent 23 SAGAR SAVALE EADEPARTMENT OF METALLURGICAL AND MATERIALS ENGINEERING NATIONAL INSTITUTE OF TECHNOLOGY WARANGALBiomaterials and Artificial Organs Dr. |. Manjubala' Presented By: Mr. M. B. Mulik Guided By: Di N, WAloorkarBIOMATERIALS AND ITS APPLICATIONS eect rete MR} Dey as Dula, Christine ce Lyye) ot a oe '® pes ‘4 a) lbw) BS att ma) eT perme SMe ONEIGHELS cnc a Urn MRA ea mgBIOMATERIALS a aT 8 AUR alaeCeramic Biomaterials (Bioceramics) The class of ceramics used for repair and replacement of diseased and damaged parts of the musculoskeletal system are referred to as bioceramics. OBJECTIVES * To examine chemical/physical properties of ceramics * To introduce the use of ceramics as biomaterials * To explore concepts and mechanisms of bioactivity