ISO/TC 150/SC 2 - Cardiovascular implants and extracorporeal systems

This document specifies important in vitro tests including functional and durability characteristics of transcatheter cardiac occluders, and their delivery systems and accessories. This document does not specify exact test methods for functional and durability testing, but it offers requirements and recommendations for performance tests of the cardiac occluder system. Surgical occluders have been omitted from the scope of this document given their significant differences in device geometry, materials, implantation methods, and test methods as compared to transcatheter cardiac occluders. This document is applicable to all intracardiac occluders intended for transcatheter implantation in humans (e.g. atrial septal occluder, ventricular septal occluder, patent foramen ovale occluder, left atrial appendage occluder, and paravalvular leak occluders). This document does not cover non-cardiac occluders, but elements of this document can be applicable to patent ductus arteriosus occluders. The following devices and components are outside the scope of this document: surgical devices, cardiac shunt devices, atrial flow regulators, active components (such as sensors), or degradable or animal tissue components. This document is applicable to both newly developed and modified cardiac occluders, their accessory devices, packaging, and labelling. This document defines operational conditions and performance requirements for cardiac occluders where either adequate scientific or clinical evidence, or both, exists for their justification. NOTE At the time of this document, it is impossible to take all future and emerging technologies into consideration. The cardiac occluder systems based on these new technologies can benefit from evaluation based on the basic requirements of this document. Testing beyond the scope of this document can also be necessary in order to verify and validate these cardiac occluder systems.

This document specifies the appropriate application of ISO 17327-1:2018 to coated endovascular prostheses, vascular stents, and vena cava filters. This document is intended to be used as a supplement to ISO 25539-1, ISO 25539-2, ISO 25539-3, ISO 12417-1 and ISO/TS 17137. The following coatings are within the scope of ISO 17327-1 and addressed in this document for endovascular devices: drug coatings (eluting and non-eluting), non-drug coatings (absorbable and non-absorbable), and chemistry-related surface modifications (oxide, such as TiO2, and non-oxide, such as amorphous silicon carbide and diamond-like carbon). This document is not applicable to coated delivery systems or coated ancillary devices (e.g. guidewires), as these coatings are not within the scope of ISO 17327-1, which is specifically directed to implant coatings. This document is not applicable to coverings of endovascular devices; however, if the covering of a device is coated, it is within the scope of this document. This document does not address the requirements for, and the evaluation of, viable tissues and non-viable biologic materials used as implant coatings.

This document establishes design evaluation requirements and recommendations for absorbable cardiovascular implants used to treat vessels and/or the vascular space within the circulatory system, including the heart and all vasculature. This document is intended to supplement device-specific standards by providing guidelines specific for either absorbable implants or components, or both. This document is applicable to implants in direct contact with the cardiovascular system, where the intended action is upon the circulatory system. This document does not address the specific evaluation of issues associated with viable tissues, viable cells, and/or implants with non-viable biological materials and their derivatives. Additionally, procedures and devices used prior to and following the introduction of the absorbable cardiovascular implant (e.g. balloon angioplasty devices) are excluded from the scope of this document if they do not affect the absorption aspects of the implant. A cardiovascular absorbable implant can incorporate substance(s) which, if used separately, can be considered to be a medicinal product (drug product) but the action of the medicinal substance is ancillary to that of the implant and supports the primary mode of action of the implant. NOTE 1 Some aspects of absorbable components of cardiovascular device-drug combination products (e.g. coatings) in their connection with drug-related aspects of the device are addressed in ISO 12417-1. NOTE 2 An explanation of the nomenclature of absorb, degrade and related terms can be found in Annex A.

This document specifies requirements for sterile, single-use cannulae for removal and delivery of patients’ blood during cardiopulmonary bypass (CPB) up to 6 h duration, extracorporeal lung assist (ECLA with VV, VAV, or AV cannulation strategies), left or right heart bypass (LHB, RHB), cardiopulmonary support (CPS), extracorporeal life support (ECLS with VA cannulation strategy), extracorporeal carbon dioxide removal (ECCO2R), and other extracorporeal circulation techniques. This standard does not apply to: — introducers (e.g., guidewires) as addressed in ISO 11070, — isolated organ perfusion cannulae, and — intravascular catheters as addressed in ISO 10555-3.

This document is applicable to all devices intended for implantation as a transcatheter heart valve substitute. This document is applicable to transcatheter heart valve substitutes and to the accessory devices, packaging and labelling required for their implantation and for determining the appropriate size of heart valve substitute to be implanted. This document establishes an approach for verifying/validating the design and manufacture of a transcatheter heart valve substitute through risk management. The selection of appropriate verification/validation tests and methods are to be derived from the risk assessment. The tests can include those to assess the physical, chemical, biological and mechanical properties of heart valve substitutes and of their materials and components. The tests can also include those for preclinical in vivo evaluation and clinical evaluation of the finished heart valve substitute. This document defines operational conditions and performance requirements for transcatheter heart valve substitutes where adequate scientific and/or clinical evidence exists for their justification. This document includes considerations for implantation of a transcatheter heart valve substitute inside a pre-existing prosthetic device (e.g. valve-in-valve and valve-in-ring configurations).

This document is applicable to heart valve substitutes intended for implantation and provides general requirements. Subsequent parts of the ISO 5840 series provide specific requirements. This document is applicable to newly developed and modified heart valve substitutes and to the accessory devices, packaging, and labelling required for their implantation and for determining the appropriate size of the heart valve substitute to be implanted. ISO 5840-1 outlines an approach for verifying/validating the design and manufacture of a heart valve substitute through risk management. The selection of appropriate qualification tests and methods are derived from the risk assessment. The tests can include those to assess the physical, chemical, biological, and mechanical properties of heart valve substitutes and of their materials and components. The tests can also include those for preclinical in vivo evaluation and clinical evaluation of the finished heart valve substitute. ISO 5840-1 defines operational conditions for heart valve substitutes. ISO 5840-1 furthermore defines terms that are also applicable to ISO 5840-2 and ISO 5840-3. ISO 5840-1 does not provide requirements specific to homografts, tissue engineered heart valves (e.g. valves intended to regenerate in vivo), and heart valve substitutes designed for implantation in circulatory support devices. Some of the provisions of ISO 5840-1 can be applied to valves made from human tissue that is rendered non-viable. NOTE A rationale for the provisions of ISO 5840-1 is given in Annex A.

This document is applicable to heart valve substitutes intended for implantation in human hearts, generally requiring cardiopulmonary bypass and generally with direct visualization. See Annex E for examples of surgical heart valve substitutes and their components. This document is applicable to both newly developed and modified surgical heart valve substitutes and to the accessory devices, packaging, and labelling required for their implantation and for determining the appropriate size of the surgical heart valve substitute to be implanted. This document establishes an approach for verifying/validating the design and manufacture of a surgical heart valve substitute through risk management. The selection of appropriate qualification tests and methods are derived from the risk assessment. The tests can include those to assess the physical, chemical, biological, and mechanical properties of surgical heart valve substitutes and of their materials and components. The tests can also include those for pre-clinical in vivo evaluation and clinical evaluation of the finished surgical heart valve substitute. This document defines operational conditions and performance requirements for surgical heart valve substitutes where adequate scientific and/or clinical evidence exists for their justification. For some heart valve substitutes (e.g. sutureless), the requirements of both this document and ISO 5840-3:2021 can be relevant and are considered as applicable to the specific device design and are based on the results of the risk analysis.

This document specifies requirements for the evaluation of stent systems (vascular stents and delivery systems) and requirements with respect to nomenclature, design attributes and information supplied by the manufacturer, based upon current medical knowledge. Guidance for the development of in vitro test methods is included in Annex D. This document is supplemental to ISO 14630, which specifies general requirements for the performance of non-active surgical implants. NOTE 1 Due to the variations in the design of implants covered by this document, and in some cases due to the emergence of novel types of such implants, acceptable standardized in vitro tests and clinical results are not always available. As further scientific and clinical data become available, appropriate revision of this document will be necessary. This document is applicable to vascular stents and vascular scaffolds (e.g. absorbable vascular scaffolds) used to treat vascular stenoses or other vascular abnormalities or pathologies. Some of the requirements are specific to endovascular treatment of arterial stenoses. Although uses of stent systems other than treatment of arterial stenoses (e.g. venous stenting) are within the scope of this document, comprehensive requirements and testing are not described for these uses. Similarly, specific stent configurations (e.g. bifurcation stents) are within the scope, but comprehensive requirements and testing are not described for these devices. Stents used in combination with an endovascular prosthesis to complete the treatment of a lesion, including bridging stents (e.g. stents placed in the renal arteries after deployment of a fenestrated endovascular prosthesis), are within the scope of this document, but test methods are not described for the combination. ISO 25539-1 also provides information relevant to the preclinical in vivo and clinical evaluations of such stents. Vascular stents that have surface modifications, such as drug and/or other coatings, are within the scope of this document. Stents covered with materials that significantly modify the permeability of the uncovered stent (e.g. by covering the stent-free-surface area) are within the scope of ISO 25539-1. The stent design or intended use might dictate the need to address functional requirements identified in both ISO 25539-1 and this document (e.g. stents used in combination with endovascular prostheses, stents used to treat aortic aneurysms). Balloons integral to the stent system are within the scope of this document. This document provides requirements beyond the requirements of ISO 10555-4, which are specific to the use of balloons with vascular stents. This document is not applicable to procedures and devices used prior to the introduction of the vascular stent, such as balloon angioplasty devices. Tacking devices intended to spot treat post-angioplasty dissections, coil supporting devices, and flow diverters are within the scope of this document, but comprehensive requirements and testing are not described for these devices. Although drug-eluting stents are within the scope of this document, this document is not comprehensive with respect to the drug-eluting properties of these devices. NOTE 2 Vascular device-drug combination products are within the scope of ISO 12417-1. Although absorbable stents and stents with absorbable coatings are within the scope of this document, this document is not comprehensive with respect to the absorbable properties of these devices. NOTE 3 Absorbable implants are within the scope of ISO/TS 17137. Although coated stents and coated stent systems are within the scope of this document, this document is not comprehensive with respect to coatings. NOTE 4 Some coating properties are within the scope of ISO 17327-1. This document does not address the requirements for, and the evaluation of, viable tissues and non-viable biologic materials used in the construction of vascular stents.

This document specifies minimum quality requirements for dialysis fluids used in haemodialysis and related therapies. This document includes dialysis fluids used for haemodialysis and haemodiafiltration, including substitution fluid for haemodiafiltration and haemofiltration. This document excludes the water and concentrates used to prepare dialysis fluid or the equipment used in its preparation. Those areas are covered by other International Standards. Sorbent-based dialysis fluid regeneration systems that regenerate and recirculate small volumes of dialysis fluid, systems for continuous renal replacement therapy that use pre-packaged solutions, and systems and solutions for peritoneal dialysis are excluded from this document.

This document specifies minimum requirements for concentrates used for haemodialysis and related therapies. This document is addressed to the manufacturer of such concentrates. In several instances in this document, the dialysis fluid is addressed, which is made by the end user, to help clarify the requirements for manufacturing concentrates. Because the manufacturer of the concentrate does not have control over the final dialysis fluid, any reference to dialysis fluid is for clarification and is not a requirement of the manufacturer. This document includes concentrates in both liquid and powder forms. It also includes additives, also called spikes, which are chemicals that can be added to the concentrate to supplement or increase the concentration of one or more of the existing ions in the concentrate and thus in the final dialysis fluid. This document also specifies requirements for equipment used to mix acid and bicarbonate powders into concentrate at the user's facility. Concentrates prepared from pre-packaged salts and water at a dialysis facility for use in that facility are excluded from the scope of this document. Although references to dialysis fluid appear herein, this document does not address dialysis fluid as made by the end user. This document also excludes requirements for the surveillance frequency of water purity used for the making of dialysis fluid by the dialysis facility. This document does not address bags of sterile dialysis fluid or sorbent dialysis fluid regeneration systems that regenerate and recirculate small volumes of the dialysis fluid. This document does not cover the dialysis fluid that is used to clinically dialyse patients. Dialysis fluid is covered in ISO 23500-5. The making of dialysis fluid involves the proportioning of concentrate and water at the bedside or in a central dialysis fluid delivery system. Although the label requirements for dialysis fluid are placed on the labelling of the concentrate, it is the user's responsibility to ensure proper use. This document does not cover haemodialysis equipment, which is addressed in IEC 60601-2-16:2012.

1.1 General This document is the base standard for a number of other standards dealing with water treatment equipment, water, dialysis water, concentrates, and dialysis fluid (ISO 23500 series) and provides dialysis practitioners with guidance on the preparation of dialysis fluid for haemodialysis and related therapies and substitution fluid for use in online therapies, such as haemodiafiltration and haemofiltration. As such, this document functions as a recommended practice. This document does not address clinical issues that might be associated with inappropriate usage of the water, dialysis water, concentrates, or dialysis fluid. Healthcare professionals involved in the provision of treatment for kidney failure should make the final decision regarding the applications with which these fluids are used, for example, haemodialysis, haemodiafiltration, high-flux haemodialysis, and the reprocessing of dialysers, and need to be aware of the issues that the use of inappropriate fluid quality raises in each of the therapies. The concepts incorporated in this document should not be considered inflexible or static. The recommendations presented here should be reviewed periodically in order to assimilate increased understanding of the role of dialysis fluid purity in patient outcomes and technological developments. 1.2 Inclusions This document addresses the user's responsibility for dialysis fluid once the equipment used in its preparation has been delivered and installed. For the purposes of this document, dialysis fluid includes: a) dialysis water (see 3.17 for definition) used for the preparation of dialysis fluid and substitution fluid, b) dialysis water used for the preparation of concentrates at the user's facility, c) concentrates, d) the final dialysis fluid and substitution fluid. The scope of this document includes a) the quality management of equipment used to treat and distribute water used for the preparation of dialysis fluid and substitution fluid, from the point at which municipal water enters the dialysis facility to the point at which the final dialysis fluid enters the dialyser or the point at which substitution fluid is infused, b) equipment used to prepare concentrate from powder or other highly concentrated media at a dialysis facility, and c) preparation of the final dialysis fluid or substitution fluid from dialysis water and concentrates. NOTE Because water used to prepare dialysis fluid can also be used to reprocess dialysers not marked intended for single use, this aspect of water use is also covered by this document. 1.3 Exclusions This document does not apply to sorbent-based dialysis fluid regeneration systems that regenerate and recirculate small volumes of dialysis fluid, systems for continuous renal replacement therapy that use pre-packaged solutions, and systems and solutions for peritoneal dialysis.

1.1 General This document is addressed to the manufacturer and/or supplier of water treatment systems and/or devices used for the express purpose of providing water for haemodialysis or related therapies. 1.2 Inclusions This document covers devices used to treat potable water intended for use in the delivery of haemodialysis and related therapies, including water used for: a) the preparation of concentrates from powder or other highly concentrated media at a dialysis facility; b) the preparation of dialysis fluid, including dialysis fluid that can be used for the preparation of substitution fluid; c) the reprocessing of dialysers intended for single use where permitted for multiple uses, d) the reprocessing of dialysers not specifically marked as intended for single use. This document includes all devices, piping and fittings between the point at which potable water is delivered to the water treatment system, and the point of use of the dialysis water. Examples of the devices are water purification devices, online water quality monitors (such as conductivity monitors), and piping systems for the distribution of dialysis water. 1.3 Exclusions This document excludes dialysis fluid supply systems that proportion water and concentrates to produce dialysis fluid, sorbent dialysis fluid regeneration systems that regenerate and recirculate small volumes of the dialysis fluid, dialysis concentrates, haemodiafiltration systems, haemofiltration systems, systems that process dialysers for multiple uses, and peritoneal dialysis systems. Some of these devices, such as dialysis fluid delivery systems and concentrates, are addressed in other documents such as ISO 23500-4 and ISO 23500‑5, This document also excludes the on-going surveillance of the purity of water used for dialysis fluid, concentrate preparation, or dialyser reprocessing which is addressed in ISO 23500‑1.

This document specifies minimum requirements for water to be used in haemodialysis and related therapies. This document includes water to be used in the preparation of concentrates, dialysis fluids for haemodialysis, haemodiafiltration and haemofiltration, and for the reprocessing of haemodialysers. This document excludes the operation of water treatment equipment and the final mixing of treated water with concentrates to produce dialysis fluid. Those operations are the sole responsibility of dialysis professionals. This document does not apply to dialysis fluid regenerating systems.

This document specifies requirements for the blood circuit for devices used in extracorporeal blood filtration therapies such as, but not limited to, haemodialysis, haemodiafiltration, haemofiltration and transducer protectors (integral and non-integral) intended for use in such circuits. This document does not apply to: — haemodialysers, haemodiafilters or haemofilters; — plasmafilters; — haemoperfusion devices; — vascular access devices; — blood pumps; — pressure monitors for the extracorporeal blood circuit; — air detection devices; — systems to prepare, maintain or monitor dialysis fluid; — systems or equipment intended to perform haemodialysis, haemodiafiltration, haemofiltration or haemoconcentration. NOTE 1 Requirements for haemodialysers, haemodiafilters, haemofilters and haemoconcentrators are specified in ISO 8637‑1, and requirements for plasmafilters are specified in ISO 8637‑3. NOTE 2 Extracorporeal blood tubing sets can also be used for other extracorporeal therapies such as haemoperfusion, plasmafiltration and plasma adsorption.

This document covers the activities performed by perfusionists before, during, and after extracorporeal circulation. Clause 4 covers the perfusionists' actions during preoperative extracorporeal circulation (ECC) equipment setup prior to cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), cardiopulmonary support (CPS), left or right heart bypass (LHB/RHB) or venovenous (VV) extracorporeal support for liver transplantation. Its requirements can serve as a checklist for verifying that the equipment, devices or systems have been set up correctly. The sequence of use of checklist items listed below can vary depending on customary institutional use or individual user preference. There are also four additional checklists for different phases of ECC (see Clause 5, Termination; Clause 6, Post-extracorporeal circulation; Clause 7, Emergent reinstitution of extracorporeal circulation; and Clause 8, Peri-procedural).

This document specifies requirements and acceptance criteria (including test methods) for safety related parameters for plasmafilters. Only those requirements that are specific to plasmafilters have been included. It specifies requirements for sterile, single-use plasmafilters, intended for use on humans. This document does not cover matters related to toxicity. Such issues are covered in relevant parts of ISO 10993. It does not apply to the extracorporeal circuits that can be used for plasmapheresis vascular access devices, oxygenators or active medical devices. This document does not address the replacement fluid.

1.1 This document applies to all heart valve repair systems that have an intended use to repair and/or improve the function of native human heart valves by acting either on the valve apparatus or on the adjacent anatomy (e.g. ventricle, coronary sinus). 1.2 This document outlines an approach for verifying/validating the design and manufacture of a heart valve repair system through risk management. The selection of appropriate verification/validation tests and methods are derived from the risk assessment. The tests include assessments of the physical, chemical, biological, and mechanical properties of components and materials of heart valve repair systems. The tests also include preclinical in vivo evaluation and clinical investigation of the finished heart valve repair system to assess the safety and effectiveness of the heart valve repair system. NOTE For the purposes of this document, effectiveness endpoint includes clinical performance and benefits. 1.3 This document defines operational conditions and performance requirements for heart valve repair systems where adequate scientific and/or clinical evidence exists for their justification. 1.4 This document excludes Cardiac Resynchronization Therapy (CRT) devices, paravalvular leakage closure devices, systems that do not leave an implant in place (e.g. ablation, radio frequency annuloplasty), apical conduits and devices with components containing viable cells. This Standard also excludes materials not intended for repairing and/or improving the function of human heart valves according to its intended use (e.g. patch material and sutures used in general surgical practice). NOTE A rationale for the provisions of this document is given in Annex A.

ISO 8637-1:2017 specifies requirements for haemodialysers, haemodiafilters, haemofilters and haemoconcentrators, hereinafter collectively referred to as "the device", for use in humans. ISO 8637-1:2017 does not apply to: - extracorporeal blood circuits; - plasmafilters; - haemoperfusion devices; - vascular access devices; - blood pumps; - pressure monitors for the extracorporeal blood circuit; - air detection devices; - systems to prepare, maintain or monitor dialysis fluid; - systems or equipment intended to perform haemodialysis, haemodiafiltration, haemofiltration or haemoconcentration; - reprocessing procedures and equipment. NOTE Requirements for the extracorporeal blood circuit for haemodialysers, haemodiafilters and haemofilters are specified in ISO 8637‑2.

ISO/TR 12417-2:2017 provides region-specific information for - local submissions and approvals for vascular device-drug combination products (VDDCPs) in countries and regions around the world; - changes related to the drug containing part and how they are evaluated by the different local regions. For implanted products, this document is considered as a supplement to ISO 14630, which specifies general requirements for the performance of non-active surgical implants. ISO/TR 12417-2:2017 is considered also as a supplement to ISO 12417‑1, and any relevant device-specific standards, such as the ISO 25539 series specifying requirements for endovascular devices. Requirements listed in this document also address VDDCPs that are not necessarily permanent implants.

ISO 25539-1:2017 specifies requirements for the evaluation of endovascular systems (prostheses and delivery systems) and requirements with respect to nomenclature, design attributes and information supplied by the manufacturer based upon current medical knowledge. Guidance for the development of in vitro test methods is included in an informative annex to this document. This document can be considered as a supplement to ISO 14630, which specifies general requirements for the performance of non-active surgical implants. ISO 25539-1:2017 is applicable to endovascular systems used to treat aneurysms, stenoses or other vascular anomalies or pathologies (e.g. dissections, transections) or to create shunts between vessels [e.g. creation of transjugular intrahepatic portosystemic shunting (TIPS)]. Some of the requirements are specific to endovascular treatment of arterial aneurysms or stenoses. Although uses of endovascular systems other than treatment of arterial aneurysms or stenoses (e.g. dissections, transections, shunts) are within the scope of this document, the specific requirements and testing are not described. Similarly, specific prosthesis configurations (e.g. fenestrated, branched) are within the scope, but specific requirements and testing are not described for these devices. ISO 25539-1:2017 is not applicable to vascular occluders, with the exception of contra-lateral iliac artery occluders when used as an integral part of aorto-uni-iliac endovascular prosthesis. Although contra-lateral iliac artery occluders when used as an integral part of aorto-uni-iliac endovascular prosthesis are within the scope of this document, specific requirements and testing are not described for these devices. Balloons used to achieve adequate apposition of the prosthesis with the vessel wall or overlapping components are within the scope of this document, even if they are not integral to the endovascular system. This document provides requirements beyond the requirements of ISO 10555‑4, specific to the use of balloons with endovascular prostheses. ISO 25539-1:2017 is not applicable to procedures and devices used prior to the introduction of the endovascular system, such as balloon angioplasty devices. The valve component of valved conduits constructed with an endovascular prosthesis component and the combination of the valved component and the endovascular prosthesis component are excluded from the scope of this document. This document can be helpful in identifying the appropriate evaluation of the endovascular prosthesis component of a valved conduit, but specific requirements and testing are not described for these devices. NOTE 1 Cardiac valved conduits are within the scope of ISO 5840‑1. Pharmacological aspects of drug eluting or drug coated endovascular prostheses are not addressed in this document. NOTE 2 Vascular device-drug combination products are within the scope of ISO 12417. ISO 25539-1:2017 does not address the requirements for, and the evaluation of, viable tissues and non-viable biologic materials used in the construction of endovascular prostheses. The requirements for, and the evaluation of, degradation and other time-dependant aspects of absorbable materials used in the construction of endovascular prostheses are not addressed in this document. NOTE 3 Absorbable materials are within the scope of ISO/TS 17137 and ISO/TR 37137.

ISO 7199:2016 specifies requirements for sterile, single-use, extracorporeal blood-gas exchangers (oxygenators) intended for supply of oxygen to, and removal of carbon dioxide from, the blood of humans. ISO 7199:2016 also applies to heat exchangers and arterial filters that are integral parts of the oxygenator. ISO 7199:2016 also applies to external equipment unique to the use of the oxygenator. ISO 7199:2016 does not apply to - implanted oxygenators, - liquid oxygenators, - extracorporeal circuits (blood tubing), - separate heat exchangers, - separate ancillary devices, and - separate arterial line filter.

ISO 18242:2016 specifies requirements for sterile, single-use, extracorporeal centrifugal blood pumps, whether coated, non-surface modified, or surface-modified, intended for producing blood flow during extracorporeal circulation. Such blood flow is most commonly used to provide systemic perfusion during cardiopulmonary bypass, but also has applications for veno-venous bypass, kinetic-assisted venous drainage, or extracorporeal membrane oxygenation. It does not apply to - centrifugal pumps used as ventricular assist devices, and - other components of extracorporeal circuits (e.g. blood tubing, pump console/driver).

ISO 18241:2016 specifies requirements for sterile, single-use, venous bubble traps intended to remove air entering the venous line during surgical procedures requiring extracorporeal circulatory support, which may include cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), or venovenous bypass for liver transplantation.

ISO 15675:2016 specifies requirements for sterile, single-use, arterial blood line filters intended to filter and remove emboli, debris, blood clots and other potentially hazardous solid and gaseous material from the blood of humans during cardiopulmonary bypass surgery.

ISO 15676:2016 specifies requirements for single-use tubing packs for cardiopulmonary bypass and extracorporeal membrane oxygenation (ECMO). This document is applicable to all medical tubing intended for cardiopulmonary bypass (CPB) and/or extracorporeal membrane oxygenation (ECMO), but specific requirements and tests are included for tubing intended for use with peristaltic pumps during (short-term, i.e. 24 h) ECMO procedures. The sterility and non-pyrogenicity provisions of this document are applicable to tubing packs labelled as "sterile". It is applicable only to the tubing aspects for multifunctional systems that may have integral components such as blood gas exchangers (oxygenators), reservoirs, blood filters, defoamers, blood pumps, etc.

ISO 15674:2016 specifies requirements for sterile, single-use, extracorporeal hard-shell cardiotomy/venous reservoir systems and soft venous reservoir bags intended for use as a blood reservoir during cardiopulmonary bypass (CPB) surgery. It applies only to the blood reservoir aspects for multifunctional systems which can have integral parts such as blood-gas exchangers (oxygenators), blood filters, defoamers, blood pumps, etc.

ISO/TR 19024:2016 recommends acceptable methodology for conducting gaseous microemboli (GME) testing and discusses limitations of current test methods. Tests described in ISO/TR 19024:2016 are limited to those conducted using an in vitro circulatory system. It is applicable to all devices intended for extracorporeal circulatory support during cardiopulmonary bypass (CPB). It outlines approaches currently used to assess the ability of CPB devices to handle GME.

ISO 7198:2016 specifies requirements for the evaluation of vascular prostheses and requirements with respect to nomenclature, design attributes and information supplied by the manufacturer, based upon current medical knowledge. Guidance for the development of in vitro test methods is included in an informative annex to ISO 7198:2016. It can be considered as a supplement to ISO 14630:2012, which specifies general requirements for the performance of non-active surgical implants. NOTE Due to the variations in the design of implants covered by ISO 7198 :2016 and, in some cases, due to the relatively recent development of some of these implants (e.g. bioabsorbable vascular prostheses, cell based tissue engineered vascular prostheses), acceptable standardized in vitro tests and clinical results are not always available. As further scientific and clinical data become available, appropriate revision of ISO 7198 :2016 will be necessary. It is applicable to sterile tubular vascular grafts implanted by direct visualization surgical techniques as opposed to fluoroscopic or other non-direct imaging (e.g. computerized tomography or magnetic resonance imaging), intended to replace, bypass, or form shunts between segments of the vascular system in humans and vascular patches intended for repair and reconstruction of the vascular system. Vascular prostheses that are made of synthetic textile materials and synthetic non-textile materials are within the scope of ISO 7198:2016. While vascular prostheses that are made wholly or partly of materials of non-viable biological origin, including tissue engineered vascular prostheses are within the scope, ISO 7198:2016 does not address sourcing, harvesting, manufacturing and all testing requirements for biological materials. It is further noted that different regulatory requirements might exist for tissues from human and animal sources. Compound, coated, composite, and externally reinforced vascular prostheses are within the scope of ISO 7198:2016. Endovascular prostheses implanted using catheter delivery and non-direct visualization are excluded from the scope of ISO 7198:2016. It includes information on the development of appropriate test methods for graft materials, referenced in ISO 25539‑1 for materials used in the construction of endovascular prostheses (i.e. stent-grafts). NOTE Requirements for endovascular prostheses are specified in ISO 25539‑1. The valve component of valved conduits constructed with a tubular vascular graft component, and the combination of the valved component and the tubular vascular graft component, are excluded from the scope of ISO 7198:2016. It can be helpful in identifying the appropriate evaluation of the tubular vascular graft component of a valved conduit but specific requirements and testing are not described for these devices. Cardiac and pericardial patches, vascular stents, accessory devices such as anastomotic devices, staplers, tunnelers and sutures, and pledgets are excluded from the scope of ISO 7198:2016. NOTE Requirements for vascular stents are specified in ISO 25539‑2. Requirements regarding cell seeding are excluded from the scope of ISO 7198:2016. Tissue engineered vascular prostheses that contain or are manufactured using cells present many distinct manufacturing (e.g. aseptic processing, cell seeding, etc.) and testing issues than those produced with synthetic or non-viable biological materials. The in vitro testing requirements that are outlined in ISO 7198:2016 can be a useful guide for certain testing requirements for these cell-based products. Pharmacological aspects of drug-eluting or drug-coated vascular prostheses are not addressed in ISO 7198:2016. NOTE Requirements for vascular device-drug combination products are specified in ISO 12417-1. Degradation, tissue ingrowth and/or tissue replacement, and other time-dependent aspects of absorbable vascular prostheses are not addressed in ISO 7198:2016.

ISO 12417-1:2015 specifies requirements for vascular device-drug combination products (VDDCPs) based upon current technical and medical knowledge. VDDCPs are medical devices with various clinical indications for use in the human vascular blood system. A VDDCP incorporates, as an integral part, substance(s) which, if used separately, can be considered to be a medicinal substance or product (drug substance, drug product) but the action of the medicinal substance is ancillary to that of the device and supports the primary mode of action (PMOA) of the device. With regard to safety, this part of ISO 12417 outlines requirements for intended performance, design attributes, materials, design evaluation, manufacturing, sterilization, packaging, and information supplied by the manufacturer. For implanted products, this International Standard should be considered as a supplement to ISO 14630, which specifies general requirements for the performance of non-active surgical implants. This International Standard should also be considered as a supplement to relevant device-specific standards, such as the ISO 25539‑series specifying requirements for endovascular devices. Requirements listed in this part of ISO 12417 also address VDDCPs that are not permanent implants. NOTE Due to variations in the design of combination products covered by this part of ISO 12417 and due to the relatively recent development of some of these combination products, acceptable standardized in vitro test results and clinical study results are not always available. As further scientific and clinical data become available, appropriate revision of this part of ISO 12417 might be necessary. Delivery systems or parts of the delivery system are included in the scope of this part of ISO 12417, if they comprise an integral component of the vascular device and if they are drug-covered (e.g. drug-covered balloon catheters and drug-covered guidewires). Devices whose PMOA is to provide a conduit for delivery of a drug, are excluded from the scope of this part of ISO 12417 (e.g. infusion catheters), unless they contain a drug component that is intended to have an ancillary action to the device part (e.g. antimicrobial coated infusion catheter). Procedures and devices used prior to and following the introduction of the VDDCP (e.g. balloon angioplasty devices) are excluded from the scope of this part of ISO 12417 if they do not affect the drug-related aspects of the device. ISO 12417-1:2015 is not comprehensive with respect to the pharmacological evaluation of VDDCPs. Some information on the requirements of different national and regional authorities is given in Annex B. Absorbable components of VDDCPs (e.g. coatings) are addressed by this part of ISO 12417 in their connection with drug-related aspects of the device. Degradation and other time-dependent aspects of absorbable implants and coatings are not completely addressed by this part of ISO 12417. NOTE See also ISO/TS 17137 and ASTM F3036-13. ISO 12417-1:2015 does not address issues associated with viable or non-viable biological materials such as tissues, cells, or proteins. ISO 12417-1:2015 does not address issues associated with active surgical implants (i.e. implants that require power not generated by the human body or gravity).

This International Standard specifies requirements for the physical, biological and performance testing of biocompatible modifications on extracorporeal devices. This International Standard is applicable to components of heart-lung bypass equipment and of extracorporeal life support equipment that carry blood and have modifications on the blood and tissue-contacting surfaces of the device. The assumption is that these devices will be used at conventional ranges of hypothermia and normothermia. If hyperthermia (>37 °C) applications are indicated, then testing is performed over the indicated range.

ISO 25539-3:2011 specifies requirements for vena cava filters, based upon current medical knowledge. With regard to safety, it gives requirements for intended performance, design attributes, materials, design evaluation, manufacturing, sterilization, packaging and information supplied by the manufacturer. ISO 25539-3:2011 supplements ISO 14630, which specifies general requirements for the performance of non-active surgical implants. The following are within the scope of ISO 25539-3:2011: vena cava filters used to prevent pulmonary embolism by mechanical filtration in the inferior vena cava: while ISO 25539-3:2011 might be useful with respect to filters implanted in other venous locations (e.g. superior vena cava, iliac veins), it does not specifically address use of filters in other implantation sites; sheath/dilator kits, providing that they comprise an integral component of the access, delivery or retrieval/conversion of the vena cava filter. delivery systems, providing that they comprise an integral component of the deployment of the vena cava filter. optional filters that can be retrieved or converted, and permanent filters together with their associated endovascular systems: while ISO 25539-3:2011 might be useful with respect to the evaluation of repositioning filters after chronic implantation, it does not specifically address filter repositioning. The following are outside the scope of ISO 25539-3:2011: temporary filters (e.g. tethered) that need to be removed after a defined period of time; coatings, surface modifications, and/or drugs; issues associated with viable tissues and non-viable biological materials; degradation and other time-dependent aspects of absorbable materials; procedures and devices (e.g. venous entry needle) used prior to the vena cava filter procedure.

This document outlines design evaluation guidelines for absorbable cardiovascular implants used to treat vessels and/or the vascular space within the circulatory system, including the heart and all vasculature. This document is meant to supplement device-specific standards by providing guidelines specific for absorbable implants and/or components This document is applicable to implants in direct contact with the cardiovascular system, where the intended action is upon the circulatory system. This document does not address the specific evaluation of issues associated with viable tissues, viable cells, and/or implants with non- viable biological materials and their derivatives. Additionally, procedures and devices used prior to and following the introduction of the absorbable cardiovascular implant (e.g. balloon angioplasty devices) are excluded from the scope of This document if they do not affect the absorption aspects of the implant. A cardiovascular absorbable implant may incorporate substance(s) which, if used separately, can be considered to be a medicinal product (drug product) but the action of the medicinal substance is ancillary to that of the implant and supports the primary mode of action of the implant.

ISO 5840-2:2015 is applicable to heart valve substitutes intended for implantation in human hearts, generally requiring cardiopulmonary bypass and generally with direct visualization. ISO 5840-2:2015 is applicable to both newly developed and modified surgical heart valve substitutes and to the accessories, packaging, and labelling required for their implantation and for determining the appropriate size of the surgical heart valve substitute to be implanted. ISO 5840-2:2015 outlines an approach for qualifying the design and manufacture of a surgical heart valve substitute through risk management. The selection of appropriate qualification tests and methods are derived from the risk assessment. The tests may include those to assess the physical, chemical, biological, and mechanical properties of surgical heart valve substitutes and of their materials and components. The tests may also include those for pre-clinical in vivo evaluation and clinical evaluation of the finished surgical heart valve substitute. ISO 5840-2:2015 defines performance requirements for surgical heart valve substitutes where adequate scientific and/or clinical evidence exists for their justification. For novel surgical heart valve substitutes, e.g. sutureless, the requirements of both this International Standard and ISO 5840‑3 might be relevant and shall be considered as applicable to the specific device design and shall be based on the results of the risk analysis. ISO 5840-2:2015 excludes heart valve substitutes designed for implantation in artificial hearts or heart assist devices. ISO 5840-2:2015 excludes homografts.

ISO 5840-1:2015 is applicable to heart valve substitutes intended for human implantation and provides general requirements. Subsequent parts of the ISO 5840?series provide specific requirements. ISO 5840-1:2015 is applicable to both newly developed and modified heart valve substitutes and to the accessories, packaging, and labelling required for their implantation and for determining the appropriate size of the heart valve substitute to be implanted. ISO 5840-1:2015 outlines an approach for qualifying the design and manufacture of a heart valve substitute through risk management. The selection of appropriate qualification tests and methods are derived from the risk assessment. The tests may include those to assess the physical, chemical, biological, and mechanical properties of heart valve substitutes and of their materials and components. The tests may also include those for preclinical in vivo evaluation and clinical evaluation of the finished heart valve substitute. ISO 5840-1:2015 defines operational conditions for heart valve substitutes. ISO 5840-1:2015 excludes homografts. NOTE A rationale for the provisions of this part of ISO 5840 is given in Annex A.

ISO/TS 17137:2014 outlines design verification and validation considerations for absorbable cardiovascular implants. ISO/TS 17137:2014 is applicable to implants in direct contact with the cardiovascular system, where the intended action is upon the circulatory system. ISO/TS 17137:2014 does not address the specific evaluation of issues associated with viable tissues, viable cells, and/or implants with non-viable biological materials and their derivatives. Additionally, procedures and devices used prior to and following the introduction of the absorbable cardiovascular implant (e.g. balloon angioplasty devices) are excluded from the scope of ISO/TS 17137:2014 if they do not affect the absorption aspects of the implant. A cardiovascular absorbable implant may incorporate substance(s) which, if used separately, can be considered to be a medicinal product (drug product) but the action of the medicinal substance is ancillary to that of the implant and supports the primary mode of action of the implant.

ISO 23500:2014 provides dialysis practitioners with guidance on the preparation of dialysis fluid for haemodialysis and related therapies and substitution fluid for use in online therapies, such as haemodiafiltration and haemofiltration. As such, ISO 23500:2014 functions as a recommended practice. ISO 23500:2014 addresses the user's responsibility for the dialysis fluid once the equipment used in its preparation has been delivered and installed. For the purposes of ISO 23500:2014, the dialysis fluid includes dialysis water used for the preparation of dialysis fluid and substitution fluid, dialysis water used for the preparation of concentrates at the user's facility, as well as concentrates and the final dialysis fluid and substitution fluid.

ISO 13958:2014 specifies minimum requirements for concentrates used for haemodialysis and related therapies. For the purpose of ISO 13958:2014, "concentrates" are a mixture of chemicals and water, or chemicals in the form of dry powder or other highly concentrated media, that are delivered to the end user to make dialysis fluid used to perform haemodialysis and related therapies. ISO 13958:2014 is addressed to the manufacturer of such concentrates. ISO 13958:2014 includes concentrates in both liquid and powder forms. Also included are additives, also called spikes, which are chemicals that may be added to the concentrate to increase the concentration of one or more of the existing ions in the concentrate and thus in the final dialysis fluid. ISO 13958:2014 also gives requirements for equipment used to mix acid and bicarbonate powders into concentrate at the user's facility.

ISO 11663:2014 specifies minimum quality requirements for dialysis fluids used in haemodialysis and related therapies. ISO 11663:2014 includes dialysis fluids used for haemodialysis and haemodiafiltration, including substitution fluid for haemodiafiltration and haemofiltration.

ISO 26722:2014 is addressed to the manufacturer and/or supplier of water treatment systems and/or devices used for the express purpose of providing water for haemodialysis or related therapies. ISO 26722:2014 covers devices used to treat water intended for use in the delivery of haemodialysis and related therapies, including water used for: (1) the preparation of concentrates from powder or other highly concentrated media at a dialysis facility; (2) the preparation of dialysis fluid, including dialysis fluid that can be used for the preparation of substitution fluid; (3) the reprocessing of dialysers for multiple uses. Included within the scope of ISO 26722:2014 are all devices, piping and fittings between the point at which potable water is delivered to the water treatment system, and the point of use of the dialysis water. Examples of devices included within the scope of ISO 26722:2014 are water purification devices, online water quality monitors (such as conductivity monitors), and piping systems for the distribution of dialysis water.

ISO 13959:2014 specifies minimum requirements for water to be used in haemodialysis and related therapies. ISO 13959:2014 includes water to be used in the preparation of concentrates, dialysis fluids for haemodialysis, haemodiafiltration and haemofiltration, and for the reprocessing of haemodialysers.

IEC/TR 62653:2012(E) which is a technical report, describes the technical requirements for use of equipment in haemodialysis, haemofiltration and haemodiafiltration. These principles should be complied with to ensure safe, permissible and proper application. The physician is responsible for the haemodialysis treatment prescription. However, the organization administering the treatment is responsible for all resources, structures and processes used in connection with the treatment. These responsibilities will not be described here. If applicable, the scope may be applicable to the use of the equipment in paediatrics, home haemodialysis, acute and sorbent dialysis systems. This technical report is not intended to be used as the basis of regulatory inspection or certification assessment activities.

ISO 5840-3:2013 outlines an approach for verifying/validating the design and manufacture of a transcatheter heart valve substitute through risk management. The selection of appropriate verification/validation tests and methods are to be derived from the risk assessment. The tests may include those to assess the physical, chemical, biological and mechanical properties of heart valve substitutes and of their materials and components. The tests can also include those for preclinical in vivo evaluation and clinical evaluation of the finished heart valve substitute. ISO 5840-3:2013 defines operational conditions and performance requirements for transcatheter heart valve substitutes where adequate scientific and/or clinical evidence exists for their justification. ISO 5840-3:2013 is applicable to all devices intended for implantation in human hearts as a transcatheter heart valve substitute. ISO 5840-3:2013 is applicable to both newly developed and modified transcatheter heart valve substitutes and to the accessory devices, packaging and labelling required for their implantation and for determining the appropriate size of heart valve substitute to be implanted.

ISO/TS 23810:2012 covers the activities performed by perfusionists during preoperative extracorporeal circulation (ECC) equipment setup prior to cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), cardiopulmonary support (CPS), left or right heart bypass (LHB/RHB) or venovenous (VV) extracorporeal support for liver transplantation. Its requirements can serve as a checklist for verifying that the equipment, devices or systems have been set up correctly.