1.PURPOSEThe purpose of this work instruction is to define the process to determine and document whether a post-market clinical follow-up study is required forTDI Foot/Ankle Array 8ch medical devices bearing the CE mark. The process will lead to a determination of whether a post-market clinical follow-up study is required and provide guidance for post-market clinical monitoring requirements if a study is not required.2.SCOPEThe work instruction applies to all medical device businesses and sites operating under the TDI Foot/Ankle Array 8ch Healthcare QualityManagement System.Only medical devices bearing the CE Mark will be required to follow this work instruction.3.REFERENCES3.1.External Referencesws▪Council Directive 93/42/EEC of 14 June 1993 concerning medical devices including amendments through 05 September 20073.1.2.Guidance Documents▪European Commission Enterprise-Directorate-General MEDDEV 2.12-2 Guidelines on Post Market Clinical Follow-Up dated May 2004▪MEDDEV 2.7.1 Rev.3 guidelines on medical device-clinical evaluation-a guide for manufacturers and notified bodies dated April 2009▪GHTF Post-Market Clinical Follow-Up Studies; SG5(PD)N4R7 (Proposed document 23 July 2008)▪GHTF Clinical Investigations; SG5(PD)N3R7 (20 January 2008)4.ROLES AND RESPONSIBILITIESImportant:When a title of a position is listed in this work instruction, it relates to that position or its equivalent.Below are the roles and responsibilities discussed within this document.Table 4-1: Roles and ResponsibilitiesTable 4-1: Roles and Responsibilities5.WORK INSTRUCTIONPost-market clinical monitoring is an essential element in establishing long term safety follow-up data and possible emergent risks for medical devices. These risks and data cannot adequately be detected andcharacterized by relying solely on pre-market clinical investigations.Post market clinical monitoring may include a combination of several strategies:▪Product complaint review▪Post-market event reporting review of users and patients▪Literature review▪Post-market clinical follow-up studies (PMCFS)This work instruction was created to determine when a PMCFS is necessary to maintain an adequate post-market surveillance system, as required bythe Medical Device Directive 93/42/ECC (MDD) as amended by MDD 2007/47/EC.It will also provide guidance on the post-market clinical monitoringrequirements if a PMCFS is not required.Figure 5-1: High-Level Process Overview for Post-Market Clinical Follow-UpPMCFSDetermination5.1.General Requirements5.1.1.Prior to M3 sign-off, the Product Regulatory Affairs Representative inconsultation with the Research Manager or designee and the DesignEngineering and/or Engineering Representative shall determine for agiven project/program whether a PMCFS is required. They shall alsodetermine the post-market clinical follow-up plan.5.1.2.A PMCFS may not be required for products for which medium/long-termclinical performance and safety is already known from previous use of the device or where other appropriate post-market surveillanceactivities would provide sufficient data to address the risks.5.2.Determining the Type of Post-Market Clinical Follow-UpRequiredPost-market clinical monitoring shall have one of two outcomes, (1) PMCFS required or (2) no PMCFS required.The need for a PMCFS shall be based on a combination of several factors detailed in this section.5.2.1.The Product Regulatory Affairs Representative in consultation with theResearch Manager or designee and Design Engineering and/or Engineering Representative shall determine whether an equivalent device exists.Equivalence shall be demonstrated in all the essential characteristics precisely defined below. Equivalence means:▪Clinical▪Used for the same clinical condition or purpose;▪Used at the same site in the body;▪Used in similar population (including age, anatomy,physiology);▪Have similar relevant critical performance according toexpected clinical effect for specific intended use▪Technical▪Used under similar conditions of use;▪Have similar specifications and properties;▪Be of similar design;▪Use similar deployment methods▪Have similar principles of operation▪Biological▪Same or similar use of materials in contact with human tissues or body fluids5.2.2.Products for which the medium/long term clinical performance and safetyis already known from previous use of the device, or from fullytransferable experience with equivalent devices shall not require aPMCFS.NOTE: If the device quoted as the “equivalent” requires a PMCFS, then the new product shall be subject to the same requirement.5.2.3.The need for a PMCFS shall be determined based on the identification ofresidual risks that may impact the risk/benefit ratio. A study shouldalways be considered for devices where the identification of possible emerging risks and the evaluation of long term safety and performance are essential. The Product Regulatory Affairs Representative inconsultation with the Research Manager or designee and Design Engineering and/or Engineering Representative shall identify such emerging risk, the following criteria should be taken into account:▪innovation, e.g., where the design of the device, the materials, the principles of operation, the technology or the medicalindications are novel;▪high risk anatomical locations (i.e., heart, central nervous system, etc.);▪severity of disease/treatment challenges;▪sensitivity of target population (i.e., infants, children, pregnant women, etc.);▪identification of an acceptable risk during the pre-CE clinical evaluation, which should be monitored in a longer term and/orthrough a larger population;▪well known risks identified from the literature or similar marketed devices;▪discrepancy between the pre-market follow-up time scales and the expected life of the product;5.2.4.A properly conducted risk analysis is essential in determining whatclinical evidence may be needed for a particular device. Any risks identified as an “unacceptable” risk at the conclusion of thedevelopment process shall require a PMCFS. A study should also beconsidered for risks identified as “acceptable” or “risk mitigation required” if the device meets any of the other characteristicsidentified in 5.2.1 and 5.2.2. The risk assessment shall be performed according to the Risk Management Procedure. The Product RegulatoryAffairs Representative shall review the risk assessment.5.2.5.The Product Regulatory Affairs Representative shall complete the PostMarket Clinical Follow-Up Study Determination Form (Appendix A) once the decision regarding the need for a study has been determined. NOTE:This form may also be used as a guide in making the determination about the need to perform a PMCFS.5.2.6.The Product Regulatory Affairs Representative shall complete thePost-Market Clinical Follow-Up Plan (Appendix B) that details the plan for post-market clinical follow-up.5.2.7.The Research Manager or designee and Medical Affairs Representative shallreview the Post-Market Clinical Follow-Up Justification Form and ThePost-Market Clinical Follow-Up Plan to confirm the decisions regarding post-market clinical monitoring.5.3.No Post Market Clinical Follow-Up Study Required5.3.1.If it was determined that no PMCFS is required (based on section 5.2),post-market clinical monitoring is still required for the medical device.5.3.2.Justification regarding the decision not to perform a PMCFS must beclearly documented and maintained in the design history/technical file (see 5.2.5).5.3.3.Post-Market Clinical Monitoring Requirements (minimum)5.3.3.1.At a minimum, the following post-market clinical monitoringactivities shall be completed according to TDI Foot/Ankle Array 8chestablished procedures/work instructions. These elements will beinputs into the Post-Market Literature Evaluation and Market Analysis Report.▪Review of product complaints according to Complaint Handling Procedure▪Review of post market adverse events according to Post Market Event Reporting Procedure▪Literature review according to TDI Foot/Ankle Array 8ch Evaluation of Clinical Data to Support CE Marking Work Instruction .5.3.3.2.Review of product complaints, post market adverse events and theliterature review shall be completed at the intervals specified in Table 5-1. The timing outlined provides the minimum requirements. TheProduct Regulatory Affairs Representative and/or the Research Manager or designee can determine that clinical data shall be reviewed more often.Table 5-1: Timing for Review of Clinical Data based on Medical Device Class5.3.3.3.At the interval outlined in Table 5-1, the Research Manager ordesignee shall complete a literature review and analysis of post-market experiences (i.e. complaints and adverse events) and re-evaluate if aPMCFS needs to be conducted based on this data. The Post MarketLiterature Evaluation and Market Analysis Conclusion form (Appendix D) shall be completed and maintained as part of the device’s designhistory/technical file. The Product Regulatory Affairs Representative and Medical Affairs Representative shall review and approve thisdocument.NOTE:The literature review shall be executed according to the Evaluation of Clinical Data to Support CE Marking Work Instruction, section 5.5. However, the following forms/templates shall be used in place of those specified in this work instruction:a.Instead of using The Literature Evaluation Plan template referenced, usethe Post Market Literature Evaluation and Market Experience Plan form(Appendix C)b.Instead of using The Literature Evaluation Report and Conclusion template,use the Post-Market Literature Evaluation and Market Analysis Report andConclusion form (Appendix D)5.4.Post Market Clinical Follow-Up Study Required5.4.1.If it was determined that a PMCFS is required, in addition to therequirements listed under 5.3.3, studies such as extended follow-up of patients enrolled in the pre-market trials, prospective study of arepresentative subset of patients after the device is placed on the market, or an open registry may be performed.5.4.2.The PMCFS shall be carried out in accordance with TDI Foot/Ankle Array8ch’s Research Involving Human Subjects Procedure5.4.3.The Research Manager or designee in consultation with the RegulatoryAffairs Representative and the Design Engineering and/or EngineeringRepresentative will determine the type of PMCFS that will be implemented.5.4.4.The study should take into account the following:▪Results of the clinical investigation including adverse events identified▪Average life expectancy of the device▪The claims made by the manufacturer for the device▪Performances for which equivalence is claimed▪New information becoming available5.4.4.1.At the interval outlined in Table 5-1, the Research Manager ordesignee shall complete a literature review and analysis of post-market experiences (i.e. complaints and adverse events) and review the ongoing results/data of the PMCFS. The Post Market Literature Evaluation and Market Analysis Conclusion form (Appendix D) shall be maintained as partof the device’s design history/technical file. The Product Regulatory Affairs Representative and Medical Affairs Representative shall review and approve this document.NOTE:The literature review shall be executed according to the Evaluation of Clinical Data to Support CE Marking Work Instruction, section 5.5. However, the following forms/templates shall be used in place of those specified in this work instruction:a.Instead of using The Literature Evaluation Plan template referenced, usethe Post Market Literature Evaluation and Market Experience Plan form(Appendix C)b.Instead of using The Literature Evaluation Report and Conclusion template,use the Post-Market Literature Evaluation and Market Analysis Report andConclusion form (Appendix D)5.5.Elements of a post-market clinical follow-up study5.5.1.Post-market clinical follow-up studies are performed on a device withinits intended use/purpose(s) according to the instructions for use.5.5.2.A PMCFS shall include the elements defined in the Writing ClinicalInvestigational Plans and Protocols Work Instruction.5.5.3.The objective(s) of a PMCFS should be stated clearly and should addressthe residual risk(s) identified. It should be formulated to address one or more specific questions relating to the clinical safety or performance of the device.5.5.4.Post-market clinical follow-up studies should be designed to address theobjective(s) of the study. The design may vary based on the objective(s) and should be scientifically sound to allow for valid conclusions to be drawn.5.5.5.The study design can take several forms, for example:▪the extended follow-up of patients enrolled in pre-marketinvestigations;▪ a new clinical investigation;▪ a review of data derived from a device registry;▪ a review of relevant retrospective data from patients previously exposed to the device.▪the analysis plan including any interim reporting; and▪procedures for early study termination.5.5.6.The data and conclusions derived from the PMCFS are used to provideclinical evidence to support the post-market surveillance program. This process may result in the need to reassess whether the device continuesto comply with the Essential Principles. Such assessments may result in corrective or preventive actions.6.APPENDIX6.1.Appendix A: Post-Market Clinical Follow-Up StudyDetermination6.2.Appendix B: Post-Market Clinical Follow-Up Plan6.3.Appendix C: Post Market Literature Evaluation and MarketExperience Analysis Plan6.4.Appendix D: Post-Market Literature Evaluation and MarketAnalysis Report and Conclusion。