Defibrillation

Recall Issues in CIED Hyung Wook Park Department of Cardiovascular Medicine, Chonnam National University Hospital, Gwangju, Korea

The Korean Society of Cardiology COI Disclosure Name of First Author: The authors have no financial conflicts of interest to disclose concerning the presentation 2017 Annual Spring Scientific Conference of the KSC in conjunction with KHRS, KSIC, KSE, and KSoLA

PIP (Poly Implant Prosthèse) French company founded in 1991 Illegally manufacturing and selling breast implants Cheaper industrial-grade silicone instead of the mandated medical-grade silicone Hundreds of thousands of unapproved implants sold globally by PIP from 2001 to 2010 500% higher risk of rupturing or leaking Several deaths due to systemic toxicity and several cases of induced breast cancer. Niederlander C, et al. Health Policy, 2013. 113(1 2): 20 37..

PIP (Poly Implant Prosthèse) http://www.pip-breast-implants.co.uk

Hip joint replacement Metal on metal (MoM) hip implants High level of toxic metals from defective hip implants High failure rate Necrosis (tissue death) Increased levels of cobalt and chromium ions Pain at the implant, sometimes spreading to the groin and back Osteolysis (bone loss) Fluid collections/solid masses around the hip joint Niederlander C, et al. Health Policy, 2013. 113(1 2): 20 37..

Definition and classification of medical device recall U.S. Food and Drug Administration (FDA) Class I: will cause serious adverse health consequences or death Class II: may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote Class III: is not likely to cause adverse health consequences http://www.fda.gov/medicaldevices/safety/listofrecalls/ucm329946.htm http://www.fda.gov/medicaldevices/deviceregulationandguidance/postmarketrequirements/recallscorrectionsandremovals/default.htm

Definition and classification of medical device recall EU member: Field Safety Corrective Actions. Action taken by a manufacturer to reduce a risk of death or serious deterioration in the state of health associated with the use of a medical device that is already placed on the market. http://ec.europa.eu/health/medical-devices/files/meddev/2_12_1_ol_en.pdf

Number of cardiac implants and total recall reports Regulatory authorities Total cardiac implant recalls Total recall report Time period availability U.S. Food and Drug Administration (FDA) 12 335 2004 2014 Canada, Health Canada (HC-SC) 10 2486 2005 2014 Australia. Therapeutic Goods Administration (TGA) 12 1050 2012-2014 New Zealand. Medicines and Medical Devices Safety Authority (Medsafe) UK. Medicines and Healthcare Products Regulatory Agency (MHRA) 3 723 2012-2014 24 554 2004-2014 Ireland. Health Products Regulatory Authority (HPRA) 3 149 2004-2014 Switzerland. Swiss Agency for Therapeutic Products (Swissmedic) 67 3697 2005-2014 Germany. Federal Institute for Drugs AND Medical Devices (BfArM) 96 6632 2005-2014 PR China. China Food and Drug Administration (CFDA) 6 195 2010-2014 China Hong Kong Health Department 29 788 2005-2014 Saudi Arabia. Saudi Food and Drug Authority (SFDA) 38 5103 2011-2014 Zhang S, et al. Plos one 2015; 10(5): e0125987.

Recall ratio of different categories of cardiac implant medical devices Zhang S, et al. Plos one 2015; 10(5): e0125987.

Recall reasons among cardiac implant medical devices Regarding different problems causing the recall - Device battery; 33.0% - Incorrect therapy delivery; 31.1% - Software problems; 15.5% - Connection problems; 14.6% - Deliver correct output data; 5.8% Zhang S, et al. Plos one 2015; 10(5): e0125987.

Ratio of recall reasons among cardiac implant medical devices Categories Sub-categorizes ICD CRT Pacemaker Stent Leads Implantable artificial organs Battery Capacitor 10 6 16 Software Voltage 2 2 Connection 2 1 1 4 Battery defect 3 3 Reporting 2 2 Premature battery depletion 4 2 1 7 Performance inconsistency problem 5 1 1 7 Inappropriately set 2 1 1 4 Lead to battery defect 2 2 4 Influence by environment 1 1 Output data Incorrect express 1 1 2 No output 1 1 No or incorrect feedback 3 3 Total number Zhang S, et al. Plos one 2015; 10(5): e0125987.

Ratio of recall reasons among cardiac implant medical devices Categories Sub-categorizes ICD CRT Pacemaker Stent Leads Implantable artificial organs Total number Therapy delivery Background influence 1 1 Pacing inhibition 4 1 5 Inappropriate therapy 2 2 4 Equipment malfunction 3 1 1 5 Fractured 6 1 7 Failed or partial deployment 6 6 Leak 1 1 Inadequate size 2 1 3 Connection Weakened bond 1 1 2 Partially or fully separated 1 1 Separation of wires 2 2 4 Bend relief 1 1 Lead insulation abrasion 5 5 Materials detached from guide wires 2 2 Total number 43 13 15 15 10 8 103 Zhang S, et al. Plos one 2015; 10(5): e0125987.

Implantable cardioverter defibrillator (ICD) 42 recalled ICD reports - 50%; battery problems - 23.8%; therapy delivery - 21.4%; software malfunctions 10/21 reports of battery problems - Capacitor issues - Accelerated degradation of the capacitors, increasing the risk of faulty therapy delivery http://www.mhra.gov.uk/publications/safetywarnings/medicaldevicealerts/con316337 UK. Medicines and Healthcare Products Regulatory Agency (MHRA). Medical Device Alert: Implantable cardioverter defibrillators (ICD) and cardiac resynchronisation therapy devices

Pacemaker 15 reported pacemaker recalls - 33.3%; software malfunction - 20.0%; battery problems - 20.0%; therapy delivery inhibition Software malfunction issue - Pacemakers did not provide a change in sensor driven (rate responsive) pacing rates in response to patient s physical activity. Swiss Agency for Therapeutic Products. St. Jude Medical Accent SR Model PM1110 and Accent DR Model 2112 Pacemakers Potential for the Inability to Provide Rate Responsive Sensor Driven Pacing Rates. 2012 [cited 7 December 2012]. Available: https://www.swissmedic.ch/recalllists_dl/07073/vk_20121212_02-e1.pdf. JAMA. 2006;295(16):1929-1934. doi:10.1001/jama.295.16.1929

Coronary stent 15 recalled coronary stent reports - Therapy delivery problems - Fracture of the device - Partially deployed or failed therapy - Inadequate size of the coronary stent U.S. Food and Drug Administration. Boston Scientific To Recall Additional Coronary Stent Systems. 2004, 29.Nov.2012 [cited 16 July 2004]. Available: http://www.fda.gov/medicaldevices/safety/ ListofRecalls/ucm133098.htm. U.S. Food and Drug Administration. Boston Scientific Express2TM (bare metal) Coronary Stent. 2004, 02.May.2014 [cited 16 Jul 2004]. Available: http://www.fda.gov/medicaldevices/safety/listofrecalls/ ucm064772.htm. U.S. Food and Drug Administration. Boston Scientific Taxus Express2TM Coronary Stent. 2004, 02. May.2014 [cited 1 July 2004]. Available: http://www.fda.gov/medicaldevices/safety/listofrecalls/ ucm064778.htm.

Coronary stent 1 death and 18 serious injuries with the TAXUS stent 2 deaths and 25 serious injury with the Express2 stent Both design did not allow the balloon to deflate, which resulted in the impeded removal of the balloon after stent placement U.S. Food and Drug Administration. Boston Scientific To Recall Additional Coronary Stent Systems. 2004, 29.Nov.2012 [cited 16 July 2004]. Available: http://www.fda.gov/medicaldevices/safety/ ListofRecalls/ucm133098.htm. U.S. Food and Drug Administration. Boston Scientific Express2TM (bare metal) Coronary Stent. 2004, 02.May.2014 [cited 16 Jul 2004]. Available: http://www.fda.gov/medicaldevices/safety/listofrecalls/ ucm064772.htm. U.S. Food and Drug Administration. Boston Scientific Taxus Express2TM Coronary Stent. 2004, 02. May.2014 [cited 1 July 2004]. Available: http://www.fda.gov/medicaldevices/safety/listofrecalls/ ucm064778.htm.

Cardiac resynchronization therapy (CRT) 13 recall reports of CRT - 9 reports; battery issues (6 capacitor malfunction, 2 premature battery depletion) - 2 reports; software problems - 2 reports; delivery problems Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM). Important Safety Information for COGNIS CRT-Ds and TELIGEN ICDs, Boston Scientific. 2013 [cited 10 September 2013]. Available: http://www.bfarm.de/shareddocs/kundeninfos/en/01/2013/5149-13_kundeninfo_en.pdf? blob = publicationfile&v=2

Leads 10 recall reports - 9 connection problems - 2 separation of wires - 5 lead insulation abrasion - 2 coating materials detaching - 1 fracture of the device Swiss Agency for Therapeutic Products. Urgent Medical Device Field Safety Notice ISOLINE defibrillation leads, model 2CR5, 2CR6 and 2CT6. 2013 [cited 28 January 2013]. Available: https://www.swissmedic.ch/recalllists_dl/07246/vk_20130130_10-e1.pdf.

Leads Internal insulation breach under the right ventricular (RV) and the Superior Vena Cava (SVC) defibrillation coil electrode - resulting in low pacing impedance, ventricular oversensing and inappropriate therapies Swiss Agency for Therapeutic Products. Urgent Medical Device Field Safety Notice ISOLINE defibrillation leads, model 2CR5, 2CR6 and 2CT6. 2013 [cited 28 January 2013]. Available: https://www.swissmedic.ch/recalllists_dl/07246/vk_20130130_10-e1.pdf.

The death and serious injury reports from 103 identified recall reports Recall date Product name Announced regulatory authority 2011/11 /28 Riata and Riata ST Silicone Endocardial Defibrillation Leads FDA, Swissmedic, BfArM Distribution Volume Effect Worldwide 79,000 implanted worldwide 3 deaths and 2 serious injuries 2008/06/23 Stent, cardiovascular Swissmedic, Worldwide 7 complaint reports 2 serious injuries 2007/10 /15 Sprint Fidelis Defibrillator Leads 2004/07/01 Express2paclitaxel drug-eluting & bare metal coronary stent system 2004/04 /04 Micro Jewell II Model 7223Cx and GEM DR Model 7271(ICD) FDA, HC-SC IMB, MHRA, Swissmedic, China HK, BfArM Worldwide 268,000 implanted worldwide FDA Worldwide Model 1: 500,000 manufactured, recall 85,000Model 2:600,000 manufactured, recall 11,000 FDA, MHRA Worldwide 6,268 manufactured, 1,800 implanted 5 deaths Model 1: 1 death and 18 injured;model 2: 2 deaths and 25 injuries 1 serious injuries and 4 deaths Swiss Agency for Therapeutic Products. Urgent Medical Device Field Safety Notice ISOLINE defibrillation leads, model 2CR5, 2CR6 and 2CT6. 2013 [cited 28 January 2013]. Available: https://www.swissmedic.ch/recalllists_dl/07246/vk_20130130_10-e1.pdf.

Different recall management according to the same recall event in different regulatory authorities Regulatory Authority Recall Date U.S. FDA 2007/ 10/15 Recall Level Volume Effect Recall Reasons Class I 268,000 implanted worldwide, 172,000 in U.S less than 1% defected, no specific number of deaths and injuries Background Information Patient contact Methods yes yes Toll-free number Outcome of the recall no Canada. HC-SC 2007/ 11/05 Ireland. IMB 2007/ 10/15 Recall 268,000 5 deaths, none in Canada Recall 1,178 implanted in Ireland yes yes Phone no N/a yes yes Phone no UK. MHRA 2007/ 10/19 Immediate action 6900 leads distributed in the UK 23 reports of leads fracture in UK yes yes Phone Deadline (action complete): 28.12.2007 SwitzerlandSwi ssmedic 2007/ 10/19 Recall 268,000 implanted worldwide 665 chronic fractures in returned leads yes yes Phone no China HK 2007/ 10/15 Recall More than 200 distributed in HK no serious injury or death in HK yes yes Phone no Germany BfArM 2007/ 10/15 Field Safety Corrective Action 268,000implanted worldwide, 16,000 in Germany 665 chronic fractures in returned leads, 350 fractured in Germany yes yes Phone no Zhang S, et al. Plos one 2015; 10(5): e0125987.

의료기기법 - 의료기기회수 폐기등업무처리지침 구분 의료기기법 - 제 31 조 ( 부작용관리 ) 관련규정 - 제 34 조 ( 회수 폐기및공포명령등 ) 의료기기법시행령 - 제 13 조 ( 권한의위임 ) - 제 52 조 ( 위해의료기기회수기준및절차등 ) 의료기기법시행규칙 - 제 53 조 ( 회수계획의공표등 ) - 제 54 조 ( 회수대상의료기기의폐기등 ) - 제 57 조 ( 회수 폐기및공표명령등 )

의료기기법시행규칙 제 51 조 ( 부작용보고등 ) 1 법제 31 조제 1 항에따라의료기기의부작용에관한사항의보고를하려는자는다음각호에서정하는바에따라하여야하고관련자료를 2 년간보존하여야한다. 1. 사망이나생명에위협을주는부작용을초래한경우에는 7 일이내. 이경우상세한내용을최초보고일부터 8 일이내에추가로보고하여야한다. 2. 다음각목에서정한부작용을초래하거나이상사례가나타난경우 15 일이내가. 입원또는입원기간의연장이필요한경우나. 회복이불가능하거나심각한불구또는기능저하를초래하는경우다. 선천적기형또는이상을초래하는경우 2 식품의약품안전처장은법제 31 조제 4 항에따라의료기관개설자에게부작용과회수계획등을알릴때에는방문, 우편, 전화, 전자우편또는팩스등의방법으로한다. 3 법제 31 조제 5 항에따라환자에게부작용과회수계획을등을알린의료기관개설자는별지제 42 호서식의환자통보확인서를작성하여식품의약품안전처장에게제출하여야한다. 4 제 1 항부터제 3 항까지에서규정한사항외에부작용보고및관리에관한세부사항은식품의약품안전처장이정하여고시한다.

의료기기법시행규칙 제 52 조 ( 위해의료기기의회수기준및절차등 ) 1 법제 31 조제 2 항에따라의료기기수리업자 판매업자및임대업자는수리 판매또는임대하는의료기기가인체에위해를끼치거나끼칠위험이있는의료기기 ( 이하 " 회수대상의료기기 " 라한다 ) 로의심되는경우에는해당의료기기의수리 판매또는임대를즉시중단하고그사실을해당의료기기의제조업자또는수입업자 ( 이하 " 회수의무자 " 라한다 ) 에게알려야한다. 2 법제 31 조제 2 항에따라회수의무자는그가제조또는수입하여판매 임대한의료기기중회수대상의료기기로의심되는의료기기와제 1 항에따라통보받은의료기기가다음각호의어느하나에해당하는의료기기인지를확인하여야한다. 1. 의료기기의사용으로완치될수없는중대한부작용을일으키거나사망에이르게하거나, 그러한부작용또는사망을가져올우려가있는의료기기 2. 의료기기의사용으로완치될수있는일시적또는의학적인부작용을일으키거나, 그러한부작용을가져올수있는의료기기 3. 의료기기의사용으로부작용은거의일어나지아니하나법제 19 조에따른기준규격에부적합하여안전성및유효성에문제가있는의료기기

의료기기법시행규칙 3 회수의무자는제 2 항에따른확인결과해당의료기기가제 2 항각호에해당하면즉시해당의료기기의판매를중지하는등의조치를하고, 제 2 항에따라확인된날부터다음각호의구분에따른기간이내에별지제 43 호서식의회수계획서를회수의무자의소재지를관할하는지방식품의약품안전청장에게제출하여야한다. 이경우회수의무자는식품의약품안전처장이정하는전산프로그램을이용하여회수계획서를제출할수있다. 1. 제 2 항제 1 호의의료기기 : 5 일이내 2. 제 2 항제 2 호및제 3 호의의료기기 : 15 일이내 4 회수의무자가제 3 항에따라회수계획서를보고할경우에는다음각호의서류를첨부하여야한다. 1. 해당품목의제조 수입기록서사본및판매처별판매량 판매일, 임대인별임대량 임대일등의기록 2. 제 53 조제 3 항에따라통보할회수계획통보서 3. 회수사유를적은서류 4. 회수대상의료기기가제 2 항제 1 호에해당하는경우에는해당의료기기를사용한의료기관명칭, 소재지및개설자성명등의료기기개설자에관한정보 5 회수의무자는제 3 항에따른회수계획서를작성할경우회수종료예정일을회수가시작된날부터 30 일이내로하여야한다. 다만, 그기한내에회수하기어렵다고판단되는경우에는그사유를밝히고회수기한을 30 일을넘어정할수있다. 6 지방식품의약품안전청장은제 3 항및제 4 항에따라보고받은회수계획이미흡하다고판단되는경우에는해당회수의무자에게회수계획의보완을명할수있다.

의료기기법 - 의료기기회수 폐기등업무처리지침 제 53 조 ( 회수계획의공표등 ) 1 회수의무자는법제 31 조제 3 항에따라지방식품의약품안전청장으로부터회수계획공표명령을받으면다음각호의구분에따라그회수계획을공표하여야한다. 1. 제 52 조제 2 항제 1 호의의료기기 : 방송법 제 2 조제 1 호에따른방송, 신문등의진흥에관한법률 제 9 조제 1 항에따라등록한전국을보급지역으로하는일반일간신문 [ 당일인쇄 보급되는해당신문의전체판 ( 版 ) 을말한다 ] 또는이와같은수준이상의대중매체 ( 회수대상의료기기의사용목적, 사용방법등을고려하여식품의약품안전처장이인정하는매체를포함한다 ) 에공고 2. 제 52 조제 2 항제 2 호의의료기기 : 의학 의공학전문지또는이와같은수준이상의매체에공고 3. 제 52 조제 2 항제 3 호의의료기기 : 회수의무자의인터넷홈페이지또는이와같은수준이상의매체에공고 2 지방식품의약품안전청장은회수의무자의상호, 제품명, 제조번호, 제조일, 사용기한 유효기한및회수사유를인터넷홈페이지에게재할수있다. 3 회수의무자는회수대상의료기기를취급하는수리업자 판매업자 임대업자또는의료기관의개설자 ( 이하 " 회수대상의료기기의취급자 " 라한다 ) 에게방문, 우편, 전화, 전보, 전자우편, 팩스또는언론매체를통한공고등을통하여회수계획을알려야하며, 그통보사실을증명할수있는자료를회수종료일부터 2 년간보관하여야한다.

의료기기법 - 의료기기회수 폐기등업무처리지침 제 54 조 ( 회수대상의료기기의폐기등 ) 1 회수의무자는회수하거나반품받은의료기기를폐기하거나그밖에위해를방지할수있는조치를하고, 그에대하여별지제 45 호서식의회수평가보고서를작성하여야한다. 2 회수의무자는제 1 항에따라회수대상의료기기를폐기하는경우에는별지제 46 호서식의폐기신청서에다음각호의서류를첨부하여관할시 도지사에게제출하고관할특별시 광역시 도 특별자치도 ( 이하 " 시 도 " 라한다 ) 관계공무원의입회하에환경관련법령으로정하는바에따라폐기하여야하며, 별지제 47 호서식의폐기확인서를작성하여 2 년간보관하여야한다. 1. 별지제 43 호서식의회수계획서사본 2. 별지제 44 호서식의회수확인서사본 3 회수의무자는회수가끝난경우에는별지제 48 호서식의회수종료보고서에다음각호의서류를첨부하여회수의무자의소재지를관할하는지방식품의약품안전청장에게제출하여야한다. 1. 별지제 44 호서식의회수확인서사본 2. 별지제 45 호서식의회수평가보고서사본 3. 별지제 47 호서식의폐기확인서사본 ( 폐기한경우만해당한다 )

Conclusion Traceability and transparency of safety hazards information is crucial. Efficient safety-reporting system for monitoring the patients safety. The public and relevant stakeholders such as physicians, manufacturers, regulatory authorities should be prepared to appropriately deal with related issues in the context of patient safety.

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